GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY  Soya food (taho, tokwa, soy sauce)

 Most common enzymatic deficiency in red blood cells  Tonic water – is a bitter carbonated soft drink made with quinine (malarial medication) it
 7.5% of world population deficient is used especially as a mixer with gin and other liquors.
o 60-70% kurdish jews  Bitter melon/ampalaya
o 35% prevalence in certain areas of africa
 Inherited, x-linked recessive disorder. Rare in female. SYMPTOMS
 In severe cases it can lead to kidney failure or death. Do not display any signs of the disease until exposed to certain chemicals in food or medicine.
 G6pd enzyme helps red blood cells work properly.  Dark tea-colored urine – due to increased level of bilirubin in urine
 Too little g6pd leads to the destruction of red blood cells. This process is called hemolysis. When  Back pain (kidney damage)
this process is actively occurring, it is called a hemolytic episode.  Enlarged spleen
 3 main triggering factors: infections, certain foods and certain drugs.  Anemic symptoms (fatigue, hypotension, tachycardia and confusion)
CAUSE  Rapid heart rate or shortness of breath
 G6pd deficiency is cause by mutations in g6pd gene.  Yellow skin color (jaundice)
 The defective gene that causes this deficiency is on the x chromosome, which is one of the two sex
chromosomes. Men have only one x chromosome, while women have two x chromosomes. In males, DIAGNOSIS
one altered copy of the gene is enough to cause g6pd deficiency.  Screening tests
 In females, however, a mutation would have to be present in both copies of the gene.  Fluorescent spot test (most reliable and sensitive) -it detects the fluorescence of NADPH
PATHOPHYSIOLOGY  Methemoglobin reduction test
 G6pd is an enzyme involved in the production of nadph in the hexose monophosphate shunt  Confirmatory tests - If positive screening test , To asses or check the level of g6pd enzyme and
pathway/pentose phosphate pathway generated nadph
 Nadph is necessary for reduced glutathione, which protects hemoglobin from oxidase damage  Blood tests
 When g6pd is deficient, reduced glutathione is absent  Complete blood count (cbc) – Hgb and Hct (decreased)
 Without reduced glutathione, hemoglobin is oxidized and forms heinz bodies in rbc  Reticulocyte count - Increased
 Heinz bodies cause damage to the rbc membrane and these damaged rbcs are removed in the  Molecular test - Detection of g6pd gene mutation
spleen, leading to anemia.
Note: Without G6PD there is no NADPH, if there is no NADPH our red blood cells will never be safe BLOOD FINDINGS
CLASSIFICATIONS  Anemia (normochromic and normocytic)- Normochromic and normocytic meaning there is no
 Class i - <10% of normal; chronic change in rbcs or the rbcs are typically normal.
 Anisocytosis – there are different shapes of rbcs ( some are smaller and some are bigger)
 Class ii - <10% of normal; intermittent
 Poikilocytes – different shapes
- G6pd mediterranean  Heinz bodies and bite cells
 Class iii – 10-60% normal; intermittent
- G6pd a allele TREATMENT
 Class iv – wild type: g6pd b (normal individuals)  Avoid/remove known triggers
 Class v- 2x normal activity  Folic acid supplementation (patients with chronic hemolysis)- 1mg/day
CLINICAL PRESENTATION  Blood transfusion (if hemolysis is severe)
 Majority asymptomatic - No hemolysis, no anemia
 Neonatal jaundice/ hyperbilirubinemia - Appearing 1-4 days after birth
 Chronic hemolytic anemia (very rare)
 Acute hemolytic anemia
 Trigger factors
-red blood cell destruction can be triggered by infections, certain foods and certain
HEMOLYTIC DISEASES OF NEW BORN (HDN)
medicines:
• Is a blood problem in newborn babies it occurs when the baby’s red blood cell breakdown at a fast
o Medication: dapsone – medication for leprosy
rate. It is also called Eythroblastosis fetalis.
nitrofurantoin
primaquine – a malarial medication • It is a condition in which the neonate or the fetus red blood cell (rbc) are destroyed by
methylene blue immunoglobulin G (IgG) produce by the mother.
dimercaperol
o Foods to avoid CAUSES OF HDN:
 Fava beans (abitsuelas, garbanzos, kadyos, munggo) 1. Rh Incompatability
- Fava beans is a type of legumes consumed worldwide that contains high amount • HDN is occurred when a mother with Rh-negative blood becomes pregnant with Rh-
of divicine, convicine, and isouramil-chemicals that are suspected to be highly positive baby that inherited from a Rh-positive Father
oxidative. • It occurs when anti-D is stimulated in mother plasma due to mother’s immune response
 Red wine to the antigen D on fetal red blood cell
 Blueberry
 • This is due to the Anti-D that capable to cross placenta hence delivered to fetal • Coombs test
circulation • Percutaneous umbilical cord blood sampling
• Rh caused HDN in less common but more severe. - AKA: Fetal Blood Sampling
2. ABO incompatability - This is done to check if your baby needs an intrauterine blood transfusion.
• HDN is aroused when a mother of blood type O become pregnant with a fetus with
different blood types A, B or AB. PREVENTION:
• ABO caused HDN is common but less severe. • Determine Rh status of the mother
• If the mother is not sensitized, reduce the risk of future sensitization
LESS COMMON CAUSE: • If the mother is sensitized, determine whether the fetus is at risk and monitor accordingly
3. other unexpected immune antibody (other than anti-D)
- Other Rh Antibodies
 Anti- E (second most common, mild disease)
 Anti- c (third most common, mild to severe)
 Anti- C and Anti- e (Rare)
- Other Antibodies
 Kell system antibodies (uncommon causes)
 Duffy, MNSs and Kidd system antibodies (rare causes)
SYMPTOMS:
note: during pregnancy you won’t notice any symptoms
DURING PRENATAL TEST:
• Yellow coloring amniotic fluid
• The baby may have big liver, spleen or heart
• Hydrops fetalis
AFTER BIRTH SYMPTOMS:
• Pale looking skin
• Jaundice- Yellow coloring of the baby’s umbilical cord, skin and the white of
his/her eyes
• A new born with hydrops fetalis
• Kernicterus

KERNICTERUS
- is a rare neurological disorder characterized by excessive levels of bilirubin in the blood
during infancy results from high levels of unconjugated bilirubin in the fetus blood which HODGKIN DISEASE
is more than 20 mg/dl  First described in 1832 by Dr. Thomas Hodgkin. It is also called Hodgkin lymphoma.
- Because the unconjugated bilirubin are lipid soluble and toxic it can crosses the blood  a type of blood cancer that develops when white blood cells called lymphocytes(B cells) grow out of
brain barrier and it will penetrates neuronal and glial membrane thus causes toxicity control.
- Patients surviving kernicterus have severe permanent neurologic symptoms such as:  These lymphocytes divide in an abnormal way or do not die when they should.
- Choreoathetosis  It most often spreads through the lymph vessels via lymph nodes but can invade the bloodstream and
- Spasticity metastasize to areas including the liver, lungs, spleen, and bone marrow.
- Muscular rigidity  The most common sites of occurrence are in the chest, neck, groin, or armpit.
- Ataxia  Bimodal peak: 25-30 yrs. Old and 55 yr. old and above.
- Deafness
 Slightly predominance in male. Rare in children younger than 10 years.
- Mental retardation
There are two types of Hodgkin lymphoma
HYDROPS FETALIS
 classical Hodgkin lymphoma
• As the fetus anemia got worsen the fetus accelerates red cell production
 Nodular lymphocyte- predominant Hodgkin lymphoma (NLPHL)
• Liver and spleen increase in size due to increase of rbc
1. Classical Hodgkin lymphoma
• As a result, portal hypertension occurs, causing the liver to reduce its albumin production
- contains particular cells called Reed–Sternberg cells. These are large, abnormal lymphocytes that
• This turn result in edema
look a bit like owl eyes under a microscope.
• Edema- is an abnormal accumulation of fluid beneath the skin
- It also contains Hodgkin cells, which have similar proteins and DNA to Reed–Sternberg cells but
don’t look like owl eyes
DIAGNOSIS:
Four subtypes of CHL:
• Blood test
• Nodular sclerosis – most common in female
• Ultrasound
• Mixed cellularity- eosinophil's, plasma cells, histiocytes
• Amniocentesis
 • Lymphocyte rich classical- very good prognosis Stage 2 – involves a minimum of two lymph node regions on the same side of the body (determined by
• Lymphocyte depleted – has poorest survival their location relative to the diaphragm), or the spread of cancer from one lymph node into one nearby.
2. Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) Stage 3 – involves affected lymph node regions on both sides of the body with further characterization
- Around 1 in 10 people with Hodgkin lymphoma have NLPHL. contains variants of Reed–Sternberg dependant on the affected areas.
cells called lymphocyte-predominant cells (LP cells). They are sometimes known as ‘popcorn cells’ Stage 4 - involves both spread in areas outside the lymphatic system (metastasis), and lymphatic system.
because they look a bit like pieces of popcorn under a microscope. LP cells make a protein called ‘CD20’. Staging can also be determined by the presence or absence of some symptoms.
This is more commonly found in non-Hodgkin lymphomas.  Asymptomatic (A) - No fever, night sweats, or weight loss.
RISK FACTORS  Symptomatic (B) - Symptoms include fever, night sweats, or weight loss.
 Medical conditions that weaken the immune system
 Immunosuppressant medications TREATMENT
 Certain viral infections – there is a positive correlation seen between Hodgkin disease and Classical Hodgkin lymphoma
infection by viruses such as the Epstein-Barr virus (responsible for Infectious  Chemotherapy
 radiotherapy
mononucleosis), and human immunodeficiency virus (HIV)
NLP Hodgkin lymphoma
 EBV- is very common virus that cause glandular fever.  Surgery
 There’s a higher risk of developing HL if the person have been infected with the  Radiotherapy
virus.  Chemotherapy combined with antibody therapy
 Family history - if a first-degree relative (such as a parent, child, or sibling) has suffered the
condition.
SYMPTOMS IRON DEFICIENCY ANEMIA (IDA)
 Nontender lymph nodes enlargement (localized)  A common type of anemia
 neck and supraclavicular area  As the name implies, it is due to insufficient iron.
 Lymphodenopathy(painless) IDA occurs when the body doesn't have enough iron to produce haemoglobin, a part of RBCs that gives
 B symptoms blood its red color and enables the RBCs to carry oxygenated blood throughout the body.
 fever SIGNS AND SYMPTOMS
 night sweats
 Initially, iron deficiency anemia can be so mild that it goes unnoticed.
 unexplained weight loss
 other symptoms  As the body becomes more deficient in iron and anemia worsens, the signs and symptoms intensify.
 fatigue, weakness, pruritus o Extreme fatigue
 cough , chest pain, shortness of breath, vena cava syndrome o Weakness
 abdominal pain, bowel disturbances, ascites o Pale skin
 bone pain o Chest pain, fast heartbeat (tachycardia) or shortness of breath
o Headache, dizziness or lightheadedness
DIAGNOSIS o Cold hands and feet
 Lymph node biopsy o Inflammation or soreness of the tongue
 is the only way to tell for certain whether or not a lump is lymphoma. This means taking a sample o Brittle nails
from a swollen lymph node to be examined in a lab. o Unusual cravings for non-nutritive substances, such as ice, dirt or starch
 The exact procedure depends on where the swollen lymph node is. o Poor appetite, especially in infants and children
There are different types of biopsy. CAUSES
• Excision biopsy  iron loss, iron intake, iron absorption
- involves a minor operation to remove a swollen lymph node. If the lymph node is very large, only Iron deficiency anemia will eventually develop when
part of it might be removed.  One is losing too much iron
• Needle core biopsy  One doesn’t consume enough iron
-a small sample of the cells in a swollen lymph node is taken using a special needle.  The body can't produce enough haemoglobin
It is often done at the same time as an ultrasound or CT scan under local anaesthetics. BLOOD LOSS
 Blood tests - Blood contains iron within the RBCs. Losing blood means losing some iron.
 Computed tomography (CT) scans - Heavy menstrual periods
 Positron-emission tomography (PET) scans - Slow, chronic blood loss (peptic ulcer, a hiatal hernia, a colon polyp or colorectal cancer)
 Ultrasound scans- use to examine swollen lymph node that are near the surface of skin. - Medications- Gastrointestinal bleeding can result from regular use of some over-the-counter
pain relievers, especially aspirin.
 X-rays –use to assess what parts of the body are affected by lymphoma.
LACK OF IRON IN THE DIET
 Magnetic resonance imaging (MRI) scans - The body regularly gets iron from the food we eat.
 Bone marrow biopsy - Consuming too little iron, over time the body can become iron deficient.
Staging is a process in which the extent of cancer spread is determined - this is useful in indicating what - Examples of iron-rich foods include meat, eggs, leafy green vegetables and iron-fortified
level of treatment will be most appropriate. foods.
- For proper growth and development, infants and children need iron from their diet.
METHOD OF STAGING HODGKIN LYMPHOMA IS THE FOLLOWING: INABILITY TO ABSORB IRON
Stage 1 – involves one affected lymph node region. - Iron from food is absorbed into the bloodstream in the small intestine.
 - An intestinal disorder, such as celiac disease, affects the intestine's ability to absorb
nutrients from digested food.
- If part of the small intestine has been bypassed or removed surgically, it may affect the PREVENTION
ability to absorb iron and other nutrients. Foods rich in iron include:
PREGNANCY- Without iron supplementation, iron deficiency anemia occurs in many pregnant women  Red meat, pork and poultry
because their iron stores need to serve their own increased blood volume as well as be a source of  Seafood
hemoglobin for the growing fetus.  Beans and Peas
 Dark green leafy vegetables, such as spinach
 Dried fruit, such as raisins and apricots
 Iron-fortified cereals, breads and pastas
The body absorbs more iron from meat than from iron-rich plant-based foods.
Enhance the body's absorption of iron by drinking citrus or orange juice or eating foods rich in
vitamin C.
RISK FACTORS  Broccoli, Grapefruit, Kiwi, Leafy greens, Melons, Peppers, Strawberries, Tangerines, Tomatoes
These groups of people may have an increased risk of iron deficiency anemia:
Women - They lose blood during menstruation, women in general are at greater risk of iron deficiency
anemia.
Infants and children - Infants, especially with low birth weight or born prematurely, who don't get
enough iron from breast milk or formula may be at risk of iron deficiency. Children need extra iron during
growth spurts.
Vegetarians- People who don't eat meat may have a greater risk of iron deficiency anemia if they don't eat
other iron-rich foods.
Frequent blood donors- People who routinely donate blood may have an increased risk of iron
deficiency anemia since blood donation can deplete iron stores. Low hemoglobin related to blood
donation may be a temporary problem remedied by eating more iron-rich foods.
DIAGNOSIS
 Complete Blood Count
 Red blood cell size and color. With IDA, red blood cells are smaller and paler in color than normal.
 Hematocrit. This is the percentage of the blood volume made up by the RBCs. Normal levels are
generally between 35.5 and 44.9 percent for adult women and 38.3 to 48.6 percent for adult men.
These values may change depending on the age.
 Hemoglobin. Lower than normal hemoglobin levels indicate anemia. Male: 13-18g/dL. Females:
12-16g/dL
 Mean Corpuscular Volume (MCV). Lower than normal when RBCs are too small. This condition
is called microcytic anemia. Microcytic anemia may be caused by: iron deficiency.
 Ferritin. This protein helps store iron in the body, and a low level of ferritin usually indicates a low
level of stored iron.
ADDITIONAL DIAGNOSTIC TESTS TO IDENTIFY AN UNDERLYING CAUSE
 Endoscopy.  A thin, lighted tube equipped with a video camera is passed down the throat to Preventing iron deficiency anemia in infants
the stomach to view the esophagus and stomach to look for sources of bleeding from a hiatal hernia  FIRST YEAR- Feed the baby breast milk or iron-fortified formula.
or an ulcer in the stomach.
 UNDER 1 YEAR- Cow's milk isn't a good source of iron for babies and isn't recommended for
 Colonoscopy. To rule out lower intestinal sources of bleeding. A thin, flexible tube equipped
with a video camera is inserted into the rectum and guided to the colon to view inside some or all of infants.
the colon and rectum to look for internal bleeding. Patient is sedated during this test.  AFTER AGE 6 MONTHS, start feeding the baby iron-fortified cereals or pureed meats at least twice
 Ultrasound. Pelvic ultrasound for women to look for the cause of excess menstrual bleeding, a day to boost iron intake.
such as uterine fibroids.  AFTER ONE YEAR, children should not drink more than 20 ounces (591 milliliters) of milk a day.
Too much milk often takes the place of other foods, including those that are rich in iron.
COMPLICATIONS OF IDA
TREATMENT
 Mild iron deficiency anemia usually doesn't cause complications.
Blood transfusion in severe cases - If iron deficiency anemia is severe, iron maybe given intravenously
 If left untreated, IDA can become severe and can lead to the following:
or a need for blood transfusion to help replace iron and hemoglobin quickly.
Heart. IDA may lead to a rapid or irregular heartbeat. The heart must pump more blood to compensate for
Iron supplementation
the lack of oxygen carried in the blood. This can lead to cardiomegaly or heart failure.
- Correct dosing to replenish the iron stores in the body.
Pregnancy. Severe iron deficiency anemia has been linked to premature births and low birth weight
babies. It is preventable by iron supplements as part of the prenatal care. - Iron is available in liquid form for infants and children.
Growth problems. In infants and children, severe iron deficiency can lead to anemia as well as delayed - To improve the chances that the body will absorb the iron in the tablets
growth and development. IDA is associated with an increased susceptibility to infections. Take iron tablets on an empty stomach. May need to take iron tablets with meals if it upsets the
stomach.
Don't take iron with antacids. Medications like antacids can interfere with the absorption of iron. Take  Halt cell division causing the cell lysis which increases apoptosis resulting in peripheral
iron two hours before or four hours after you take antacids. pancytopenia.
Take iron tablets with vitamin C. Vitamin C improves the absorption of iron. It is recommended to take Pancytopenia: a decreased in all blood cell types
 Some of the erythroid progenitor cells may manage to survive and continue abnormal
iron tablets with a glass of orange juice or with a vitamin C supplement. Generally, patients start to feel
maturation then released into circulation.
better after a week or so of treatment. Blood is rechecked after treatment to measure iron levels. CAUSES OF MEGALOBLASTIC ANEMIA
 Two most common cause:
TARGET is to TREAT UNDERLYING CAUSE OF IRON DEFICIENCY 1. Vitamin B12 deficiency
- If iron supplements don't increase blood-iron levels, it's likely the anemia is due to a source of bleeding 2. Folate deficiency
or an iron-absorption problem that has to be investigated and treated.  These two nutrients are needed for the production of thymidine nucleotides for DNA synthesis to be
- Depending on the cause, iron deficiency anemia treatment may involve: able to generate normal erythropoiesis.
 Medications, such as oral contraceptives to lighten heavy menstrual flow  Other Causes of megaloblastic erythrocytes: Dysplastic erythroid cells in Myelodysplastic syndrome
 Antibiotics and other medications to treat peptic ulcers (MDS)
 Surgery to remove a bleeding polyp, a tumor or a fibroid Vitamin B12 Folate
- Vitamin B12 is known as cobalamin. - A vitamin B9
- A water-soluble vitamin found in some - Folic acid: synthetic form of
foods like meat, fish, eggs, dairy supplements.
products as wells as fortified cereals - Folate: They are naturally found in
and supplements. foods.
ADDITIONAL NOTES: - Vitamin B12 is not destroyed by - Source: leafy green vegetables, dried
DO NOT self-diagnose or treat. cooking. beans, fortified breakfast cereals, some
If a person develops signs and symptoms that suggest iron deficiency anemia, seek medical - It is coabsorbed with intrinsic factor, a fruits like oranges
attention. product of stomach parietal cells, - Folate are heat labile and overcooking
Self- medication may lead to overloading with iron which can be dangerous, excess iron absorb by the terminal ileum after being of foods can diminish their nutritional
accumulation can damage the liver and cause other complications. extracted by gastric acid. value.
Iron supplements can cause constipation; a stool softener is also recommended.
Iron may turn stools black, which is a harmless side effect. ABSORPTION OF VITAMIN B12 AND FOLATE
Iron deficiency can't be corrected overnight. Take iron supplements for a month or longer to
replenish iron reserves. • Dietary intake of Vitamin B12 and Folate
• Intrinsic Factor is a glycoprotein secreted by parietal cells of stomach mucosa.
• Cobalamin splits from dietary protein & combines with IF to form vitamin-IF complex.
• Vitamin-IF complex remains stable and unabsorbed until it reaches the ileum
• In ileum, vitamin-IF complex attaches to specific receptor sites present in the microvillus
membrane
• Release of this complex from the mucosal cells with subsequent transport to the tissue depends
on the Transcobalamin II
• TC II is a plasma polypeptide synthesized by the liver, bone marrow and probably other
tissues. TC II acts as the acceptor and principal carrier of the vitamin to the liver & other
tissues
WHAT CAUSES THE DEFICIENCIES?
A. Vitamin B12 Deficiency
1. Decreased intake in strict vegetarian
2. Malabsorption
 Lack of Intrinsic factor: IF is produced in the gastric parietal cells of the stomach,
its secretion parallels that of hydrochloric acid
 Lack of intrinsic factor can be due to immune system producing antibodies that mistakenly attacks
gastric parietal cells of the stomach leading to pernicious anemia.
MEGALOBLASTIC ANEMIA
 Pernicious anemia
 Characterized by impaired DNA synthesis and distinct megaloblast in the bone marrow.  Hereditary intrinsic factor deficiency, a rare autosomal recessive disorder characterized by the absence or
 Impaired DNA synthesis: due to deficiency of vitamin B12 or folate. nonfunctionality of intrinsic factor.
 Impaired DNA synthesis leads to depletion of thymidine nucleotide which leads to retarded mitosis.  Post gastrectomy: a surgical removal of stomach parts which results in removal of intrinsic factor-
 There is a delayed nuclear maturation→resulting in megaloblasts →macrocytes producing parietal cells
 Megaloblast: abnormally large nucleated erythroid precursors  Celiac disease
 Macrocytes: RBCs are larger than normal  Ileal resection
 It affects all rapidly dividing cells of the body including skin, epithelium of GI tract, and  Crohn disease: a type of inflammatory bowel disease which causes inflammation in the digestive tract.
hematopoietic tissues.  Bacterial or parasitic competition for vitamin B12
 Ineffective erythropoiesis occurs: where in megaloblast precursors undergo intramedullary  Bacterial overgrowth: Helicobacter pylori infection resulting in loss of parietal cells.
destruction
  Infestation of fish tapeworm Diphyllobothrium latum is able to split vitamin B12 from intrinsic  Neuropsychiatric symptoms may also be present, Including personality changes and psychosis
factor. (delusions and hallucinations). These symptoms seem to be the result of demyelinization of the
3. Increased Demand: pregnancy, lactation, infants and children growth due to vigorous cell spinal cord and peripheral nerves, but the relationship of this demyelinization to vitamin B12
replication deficiency is unclear.
B. Folate Deficiency In folate deficiency
1. Decreased intake: Especially old age, poverty, poor diet  Depression, Folate levels appear to influence the effectiveness of treatments for depression.
2. Malabsorption: due to tropical sprue  Folate deficiency during pregnancy can result in impaired formation of fetal nervous system
3. Excessive loss of folate: Hemodialysis resulting in neural tube defects such as spinal bifida. Pregnancy requires an increase in folate to
 Renal dialysis, however patients are routinely provided with supplemental folic acid fulfill the requirements related to rapid fetal growth, uterine expansion, placental maturation, and
to prevent megaloblastic anemia. expanded blood volume.
4. Increased demand: Pregnancy, Lactation, Infants LABORATORY FINDINGS
 Markedly increased in hematopoiesis SCREENING TEST
5. Impaired utilization due to: 1. Complete Blood Count
 Drugs that are folate antagonist:  Hemoglobin and hematocrit (PCV): reduced
o anticonvulsant such as carbamazepine, phenytoin  Normal Hgb values for Male: 13-18g/dL. Females: 12-16g/dL
o anti-cancer such as methotrexate, hydroxyurea  Red cell indices
 Mean Corpuscular Volume (MCV): increased, above 100 fL (Normal MCV 82-98 fL)
 Mean Cell Hemoglobin (MCH): increased (normal 27-32 pg)
 Mean Cell Hemoglobin Concentration (MCHC): normal (31-36 g/dL)
2. Reticulocyte count: decreased
3. WBC Differential Count: hypersegmented neutrophils with 6 or more lobes, bands can also be seen
4. Bilirubin and Lactate Dehydrogenase Levels
 Serum total and indirect bilirubin – increased
 Serum lactate dehydrogenase (LDH) – increased

PERIPHERAL SMEAR MORPHOLOGY

RBCs- Macro-ovalocytes & Megaloblast, Most macrocytes lack central pallor, Marked variation in the
size and shape of red cell, Evidence of dyserythropoiesis: basophilic stippling,cabot ring and Howell Jolly
bodies
WBCs - Hypersegmented neutrophils with more than 5 nuclear lobes. This is a specific morphological
PERNICIOUS ANEMIA (PA) sign of megaloblastic anemia
 An autoimmune disease due to deficiency of intrinsic factor causing impaired absorption of vitamin Platelets: - Decreased
B12. Lack of intrinsic factor is secondary to gastric atrophy. Dimorphic anemia - Combined vitamin B12/folate and iron deficiency Peripheral smear shows two
 Stomach shows damage to parietal cells leading to→ chronic atrophic gastritis → which causes the populations of RBCs namely: macro-ovalocytes and microcytic hypochromic
failure of production of intrinsic factor and HCl acid. HCl acid constitutes achlorhydria. SPECIFIC DIAGNOSTIC TEST
 Atrophic gastritis is most often the result of a bacterial infection caused by H. pylori 1. Bone Marrow Examination
bacterium. Due to ineffective erythropoiesis: Intramedullary hemolysis occurs , Bone marrow is markedly
 Presence of autoantibodies in PA hypercellular, Megaloblast, Cytoplasm appears pinkish-blue
1. Anti-intrinsic factor antibody  Neutrophils: Giant metamyelocytes & band forms
o Type I (blocking) antibody: blocks the binding of vitamin B12 to IF. Present in 50-75% of the  Bone marrow aspiration is confirmatory for megaloblastic morphology however it does not identify
cases. its cause.
o Type II (binding) antibody: attaches to the IF-vitamin B12 complex and prevent its binding to 2. Assays for folate and vitamin B12
receptors in the ileum. Present in about 40% of patients. Vitamin B12 deficiency assay
2. Parietal cell (Type III) antibody: It is found in 90% of patients. • Serum vitamin B12 – decreased
CLINICAL SIGNS AND SYMPTOMS • Serum methylmalonic acid (MMA) and homocysteine– increased
 Fatigue, Weakness, Shortness of breath, Lemon-yellow skin color, Atrophic glossitis: painful Folate deficiency Assay
red “beefy” tongue, Dyspnea, Dizziness Angina • RBC folate – decreased
OTHER CLINICAL SIGNS AND SYMPTOMS 3. Gastric analysis and Serum gastrin
In vitamin B12 deficiency • Gastric analysis used to confirm achlorchydria in pernicious anemia
 Vitamin B12 deficiency in infants can cause neurological symptoms. If untreated, permanent  Serum gastrin can be markedly elevated due to gastric achlorhydria
neurological damage can occur in breast-fed infants whose mother had undiagnosed pernicious 4. Antibody Assays
anemia.  Serum antibodies to intrinsic factor: highly specific for pernicious anemia
 Neurological symptoms may occur: ELISA – detect intrinsic factor–blocking antibodies but not clinically useful in diagnosis of PA
 These include memory loss, 6. Stool analysis for parasites
 numbness and tingling in toes and fingers,  Diphyllobothrium latum may be the cause of vitamin B12 deficiency
 and loss of balance 7. Schilling test for vitamin B12 absorption to detect lack of intrinsic factor in PA.
  Oral administration of Radioactive vitamin B12. Then measure radioactivity in a 24-hour 2 types:
sample of urine to assess the status of intrinsic factor and vitamin B12. – MDS-EB1: blasts make up 5% to 9% of the cells in the bone marrow, or 2% to 4% of the cells
 Consist of step by step procedure. in the blood
TREATMENT – MDS-EB2: blasts make up 10% to 19% of the cells in the bone marrow, or 5% to 19% of the
 Proper diagnosis prior to treatment is important. cells in the blood
 Lifelong supplementation with vitamin B12 is necessary * one of the types most likely to turn into AML3, with the risk being higher for MDS-EB2 than for MDS-
 Vitamin B12 is administered intramuscularly to bypass the need for intrinsic factor. EB1.
 Folic acid can be administered orally. 5. MDS with isolated del(5q) the chromosomes of the bone marrow cells are missing part of
 When proper treatment is initiated then the body’s response is prompt and brisk chromosome number 5. Low numbers of 1 or 2 types of blood cells (usually red blood cells). Dysplasia in
 The bone marrow morphology will begin to revert to normoblastic appearance within 8-12 hours. at least 1 cell type in the bone marrow. This type of MDS is not common. It occurs most often in older
 A reticulocyte response is apparent at about 1 week, with hemoglobin increasing toward normal women. Patients with this type of MDS tend to have a good prognosis. They often live a long time and
levels in about 3 weeks rarely go on to develop AML4.
 Reticulocytosis typically increases MCV but will decrease after 3 to 4 days.
 Hypersegmented neutrophils disappear from the peripheral blood within 2 weeks of initiation of 6. MDS, unclassifiable (MDS-U) This type of MDS is also not common. This type is rare. The findings
treatment in the blood and bone marrow don’t fit any other type of MDS
 Hematocrit increases in 1 week and will normalize within 4 to 8 weeks. CLASSIFICATION OF MDS:
 Treatment for neurological abnormalities is dependent on the duration of loss. Maximal MDS can also be classified based on the underlying cause called/known as clinical classification. If no
improvement of neurological symptoms is within 6 months of initiation of therapy. cause can be identified, it's called primary MDS. (This type is more common.) When the cause of the
disease is known, it's called secondary MDS. Secondary MDS is often related to prior cancer treatment, or
it develops in someone who already had a different bone marrow disease. NOTE: Identifying MDS as
MYELODYSPLASTIC SYNDROMES primary or secondary is important because the secondary type is much less likely to respond to
Myeloid – from bone marrow, the myeloid lineage. treatment.
- Dys – difficulty/abnormalities, Plasia/plastic –growth CAUSES OF MDS:
- Syndrome –a specific group of signs and symptoms that a company a disease.  The exact cause of MDS are still unknown.
Myelodysplastic syndromes are a rare group of disorders in which your body no longer makes enough  Potential triggers or causes includes:
healthy blood cells/mature blood cells. Heterogeneous group of hematologic disorder. – Radiation and chemotherapy
- Cytopenia – Anemia, Leukocytopenia, Thrompocytopenia – Long term exposure to certain industrial chemicals, such as benzene.
• Acute myeloid leukemia (AML)- MDS may lead to AML if not properly treated (30 % of cases.) – Environmental factors
• Acquired colonal disorder: De novo mutation., Environmental exposure – Other existing blood disorder.
• Common in males with age of 50-80 with median of 60 years old or older (75%). Can also affect – Inherited Genes
children and young adults.  Other existing blood disoder:
• MDS survival rate: – Fanconi anemia
– 6 years for lower risk patients(who do not receive a bone marrow transplant) – Shwachman-Diamond syndrome
Approximately 5 months for high risk. – Diamond Blackfan anemia
TYPE OF MDS – Familial platelet disorder with a propensity to myeloid malignancy
1. MDS with multilineage dysplasia (MDS-MLD)- Also called refractory cytopenia with – Severe congenital neutropenia
multilineage dysplasia(RCMD). Dysplasia is seen in at least 10% of the early cells of 2 or 3 cell – Dyskeratosis congenital
types low numbers of at least 1 type of blood cell. There is a normal number (less than 5%) of very SIGNS AND SYMPTOMS:
early cells called blasts in the bone marrow. Feeling tired, Dizzy, Weak, Shortness of breath, Pale skin. Frequent/ severe infections, Easy bruising and
2. MDS with single lineage dysplasia (MDS-SLD)- This type of MDS is not common Dysplasia is bleeding, Frequent or severe nosebleeds or bleeding from the gums(for some people). Other symptoms:
seen in at least 10% of the early cells of 1 cell type. Low numbers of 1 or 2 types of blood cells. Weight loss, Feve, Bone pain, Loss of appetite
There is a normal number (less than 5%) of very early cells called blasts in the bone marrow. This RISK FACTORS:
type of MDS can often live a long time, even without treatment. Referred to as refractory cytopenia  AGE- most important risk factors for MDS. . MDS is uncommon in people younger than 50. Most
with unilineage dysplasia (RCUD). It includes refractory anemia (RA), refractory neutropenia (RN), cases are found in people in their 60s to 80s.
and refractory thrombocytopenia (RT), depending on which cell type is affected.  SEX- MDS is more common in men than in women.
3. MDS with ring sideroblast (MDS-RS) referred to as refractory anemia with ring sideroblasts  TREATMENT FOR CANCER- another important risk factor for MDS. Patients who have been
(RARS). Also not common and rarely turn to AML II Early red blood cells are ring sideroblasts. treated with certain chemo drugs for cancer are more likely to develop MDS later on.
15% of the early red blood cells must be ring sideroblasts (or at least 5% if the cells have a mutation  Genetic/Familial MDS- People with certain inherited syndromes are more likely to develop MDS.
in the SF3B1 gene) Families with history of MDS is more likely to acquired it.
Divided into 2 types : based on how many of the cell types in the bone marrow are affected by DIAGNOSIS FOR MDS:
dysplasia: BLOOD TEST
 MDS-RS with single lineage dysplasia (MDS-RS-SLD) dysplasia in only one cell type COMPLETE BLOOD COUNT- measures the levels of red blood cells, white blood cells, and platelets
 MDS-RS with multilineage dysplasia (MDS-RS-MLD) dysplasia in more than one cell in your blood.
type • Increase in MCV
4. MDS with excess blasts (MDS-EB) more blasts than normal in the bone marrow and/or blood, low • Decrease in reticulocyte
numbers of at least one type of blood cell. It may or may not be severe dysplasia. Accounts for about • Decrease in platelet count
1 in 4 cases of MDS. This was previously referred to as refractory anemia with excess blasts • Decrease in leukocyte
(RAEB). PERIPHERAL BLOOD SMEAR
  Psuedo-Pelger-Huet Segmented Nucleus  GROWTH FACTORS
 Basophilic Stippling of RBCs  CHEMOTHERAPY
 Large Agranular Platelets  IMMUNOLATING AGENTS
 Ringed Sideroblast (Nucleated)  STEM CELL TRANSPLANT
 Dimorphic RBCs (microcytic and macrocytic = increase in Red Cell Distribution Width) – ALLOGENIC
– AUTOLOGOUS
SUPPORTIVE THERAPY
BONE MARROW TESTS- Bone marrow samples are obtained from a bone marrow aspiration and  For Anemia - Blood Transfussion, Can cause iron overload- to prevent iron overload stop taking iron
biopsy, tests that are usually done at the same time. The samples are usually taken from the back of the supplement or take chelation medicine such as deferasirox and deferoxamine. Human growth factor-
pelvic (hip) bone. These tests are used first for diagnosis and classification. In MDS: Blasts <20%, if the Erythropoietin.
presence of blast is more than 20% it may lead to AML.  For Thrombocytopenia - Human Growth factor, Platelet transfusion, Aminocoproic acid
- Also, MDS is hypercellular Other types of lab tests can also be done on the bone marrow or  For Leukopenia - Human Growth Factor
blood samples to help diagnose MDS: GROWTH FACTORS
FLOW CYTOMETRY • For RBC Growth Factor – Erythropoietin & Darbepoietin alpha
IMMUNOCYTOCHEMISTRY - For both flow cytometry and immunocytochemistry, samples of cells • For Platelets Growth Factor – Romiplostim & Eltrombopag
are treated with antibodies, which are proteins that stick only to certain other proteins on cells. For • For WBC Growth Factor - G-CSF-(PEGFILGRASTIM) & GM-CSF
immunocytochemistry, the cells are then looked at under a microscope to see if the antibodies stuck to CHEMOTHERAPY
them while for flow cytometry a special machine is used.These tests can be helpful in distinguishing • Hypomethelating agents-
different types of MDS or leukemia from one another and from other diseases. – Pyrimidine Analogues
CHROMOSOME TEST - These tests look at the chromosomes (long strands of DNA) inside the cells. • MDS TO Mature BLOOD CELLS – AZACITIDINE & DECCITABINE
Each cell should have 46 chromosomes (23 pairs). Abnormal chromosomes are common in MDS. STANDARD CHEMOTHERAPY(HIGH RISK)
– CYTOGENICTS • Cytarabine (ARA-C)
– FLOURESCENT IN SITU HYBRIDIZATION (FISH) • Idarubicin
– POLYMERASE CHAIN REACTION (PCR): • Daunorubicin
CYTOGENETIC - In this test, the cells are looked at under a microscope to see if the chromosomes have IMMUNOLATING AGENTS - Linalidomide (5q deletion)
any abnormalities. A drawback of this test is that it usually takes about 2 to 3 weeks because the cells must IMMUNOSUPPRESANTS - Anti-thymocyte Globulin & Cyclosporine
grow in lab dishes for a couple of weeks before their chromosomes can be viewed. The results of STEM CELL TRANSPLANT - A stem cell transplant (SCT) currently offers the only realistic chance to
cytogenetic testing are written in a shorthand form that describes which chromosome changes are present. cure myelodysplastic syndrome (MDS), although many patients with MDS might not be eligible to have
It can be deletion, addition or translocation. Certain chromosome changes in MDS cells can help predict one.
the likely course of MDS. Usually a deletion of a part of chromosome 5, or del(5q) is present in MDS. • There are 2 main types of SCT:
- ALLOGENIC STEM CELL TRANSPLANT- after the bone marrow is destroyed, the patient
HOW TO WRITE CYTOGENTIC STUDY REPORT: receives blood-forming stem cells from another person. This is the type of transplant typically
ADDITIONAL NOTES: used for MDS.
• A minus sign (-) or the abbreviation “del” is used to mean a deletion. For example, if a copy of - AUTOLOGOUS STEM CELL TRANSPLANT- The patient gets back their own stem cells
chromosome 7 is missing, it can be written as -7 or del(7). Often, only a part of the chromosome is (which were removed before treatment). This type of transplant is not typically used for
lost. There are 2 parts to a chromosome, called p and q. The loss of the q part of chromosome 5 is patients with MDS because the patient's bone marrow contains abnormal stem cells
written 5q- or del(5q). SIDE EFFECTS OF SCT
• A plus sign is used when there is an addition (an extra copy of all or part of a chromosome). +8, for Most serious side effects is low blood counts, which can lead to risks of serious infections and bleeding.
example, means that chromosome 8 has been duplicated, and there are too many copies of it within Graft-Versus-Host Disease (GVHD) - Another possible serious side effect from allogeneic transplants
the cell. This occurs when the new immune cells (from the donor) see the patient’s tissues as foreign and attack
• The letter t is used to indicate a translocation, in which parts of two chromosomes have traded them. GVHD can affect any part of the body and can be life threatening.
places with each other. For example, if chromosomes 8 and 21 have swapped pieces, it would be PREVENTION FOR MDS:
written as t(8;21) There is no sure way to prevent myelodysplastic syndromes (MDS). But there are things you
FLOURESCENT IN SITU HYBRIDIZATION - This test looks more closely at cell DNA using can do that might lower your risk.
fluorescent dyes that only attach to specific gene or chromosome changes Results within a couple of days. – Not smoking
FISH is very good for finding translocations – it can even find some that may be too small to be seen with – Avoiding exposure to radiation
usual cytogenetic testing. – Avoiding certain chemicals(benzene)
Polymerase chain reaction (PCR) - This is a very sensitive DNA test that can also find some chromosome
changes too small to be seen under a microscope, even if there are very few abnormal cells in a sample.

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

- A type of hemolytic anemia. a rare blood disease that causes red blood cells to break apart. An
acquired, clonal disorder caused by a non malignant clonal expansion of one or more stem cells
with mutated gene called PIG-A (phosphatidyl glycan class A) in the bone marrow.
PIGA gene - provides instructions for making a protein called phosphatidylinositol glycan class A. This
protein takes part in a series of steps that produce a molecule called GPI anchor.
TREATMENT FOR MDS:
- Glycosylphosphatidylinositol (GPI) anchors attach specific proteins to the cell surface of
 SUPPORTIVE THERAPY
hematopoietic cells.
 - PNH results in a deficiency of cell-surface glycosyl phosphatidylinositol anchored proteins
(GPI-Aps)
Absence of a GPI-anchored receptor prevents several protiens from binding to the red cell membrane.
This include the complement-regulatory proteins, CD55 and CD59, whose absence results in enhanced
complement-mediated lysis.
Characterized by:
 destruction of red blood cells (hemolytic anemia),
 blood clots (thrombosis), and
 impaired bone marrow function (not making enough of the three blood components)
Hemolytic anemia (destruction of cells)- It happens because the surface of a person’s blood cells is
missing a protein that protects them from the body's immune system.
Bone marrow failure - Happens when the marrow does not produce enough red cells, white cells or
platelets, or the blood cells that are produced are damaged or defective. This means the body can not
supply itself with the blood it needs.Leads to pancytopenia.
Thrombosis (Blood clots)- Blood clots occur almost exclusively in veins, as opposed to arteries, and are
the leading cause of death in PNH. The most common sites for blood clots are in the hepatic vein (a vein
that drains the liver). Clots here are also referred to as Budd-Chiari syndrome) and in the sagittal vein (a
vein in the head). However, they can occur in any vein, especially those in the abdomen
- Paroxysmal -occurs Irregularly
- Nocturnal -means “at night”
- Hemoglobinuria -means “hemoglobin in urine” hemoglobin, the red part of red blood cells,
makes urine look dark.
EPIDEMIOLOGY
- 25% of cases will evolve into or from aplastic anemia. Approximately 5% to 10% of patients will have
terminal acute myelogenous leukemia. The median age of patients at diagnosis is 42 years ( range, 16 to
75 years).
RISK FACTORS OF PNH
- Having aplastic anemia is the only known risk factor for developing PNH. More than 10 out of every
100 people with aplastic anemia will develop PNH.
- People with PNH can share symptoms with aplastic anemia patients, such as low blood cell counts.
CLINICAL SIGNS AND SYMPTOMS
- HEMOGLOBINURIA - morning hours, Dyspnea, Fatigue -mild to severe, Abdominal pain, Chest Pain,
Headache, Jaundice , Bruising or bleeding easily, Recurring infections and/or flu-like symptoms,
Difficulty in controlling bleeding, even from very minor wounds, The appearance of small red dots on the
skin that indicates bleeding under the skin, Fever due to infection, Vascular nitric oxide depletion
(increased smooth muscle tone, Dysphagia, Erectile dysfunction), Renal insuffieciency and pulmonary
hypertension (may occur due to prolonged free hemoglobin in the blood), Blood clots (thrombosis)
 The leading death in PNH is thrombosis.
LABORATORY FINDINGS
- Most patients have severe anemia with hemoglobin concentration less than 6g/dL.
- Peripheral blood smears may reveal hypochromic, microcytic red cells .
Laboratory tests that should be performed in all cases of suspected PNH to assess anemia:
• CBC - To check the numbers of red and white blood cells
• RETICULOCYTE COUNT - Recommended to assess the bone marrow response to anemia.
-increased reticulocytes
• COOMBS TEST - should be perform to rule out other causes of anemia, given that the PNH
is coombs negative.
Useful in assessing hemolysis:
• Serum lactate dehydrogenase (LDH): MARKEDLY INCREASED
• Bilirubin: USUALLY INCREASED
• Haptoglobin tests: MARKEDLY DECREASED
DIAGNOSIS
Flow cytometry - Gold standard for diagnosing PNH
 evaluate for the presence of GPI-linked antigens on blood cell.
 enables calculation of the percentage of red blood cells (RBCs) or white blood cells
(WBCs) that entirely or partially lack GPI-linked antigens compared with normal cells; this
percentage is referred to as the PNH clone size.
Specimen: Peripheral blood is the preferred specimen, and the use of multiple specific GPI-linked
reagents is recommended
Sucrose hemolysis test- is confirmatory test for paroxysmal nocturnal hemoglobinuria when the sugar test
is positive. most commonly used screening test for PNH.
Procedure: Blood is collected in heparinized tubes, and red cells are separated and washed. An isotonic
sucrose solution allows complement to aggregate on the red blood cell surface in the presence of type-
compatible serum. After 1 hour of incubation, lysis greater than 5% of the red blood cells is compatible
with the diagnosis of PNH.
TREATMENT
 Some patients will experience few or no symptoms from PNH and do not require treatment other
than folic acid and sometimes iron supplementation to increase red blood cell production.
 Over time, the disease may progress and more aggressive supportive care may be indicated
depending on the patients' symptoms.
Note: Medications that increase the risk for thrombosis, such as oral birth control pills, should be avoided.
Bone marrow transplantation: Allogeneic bone marrow transplantation is the only cure for PNH. A
transplant replaces all of the bone marrow stem cells with those of a healthy sibling.
Medical Therapy: The mainstay of PNH treatment is the drug eculizumab (Soliris). This drug is
effective in reducing hemolysis and reducing the risk for thrombosis in PNH patients Blood thinners
(anticoagulants) may be used on some patients to help reduce the chance of    having blood clots
Immunosuppressive therapy:  Lowers your body's immune response and is appropriate for PNH
patients who also have aplastic anemia. uses medicines to keep the immune system from attacking the
bone marrow. Antithymocyte globulin  (ATG) and cyclosporine are the medicines typically used.
Blood transfusionsalleviate some of the symptoms, generally only use transfusions if the patient has
symptoms of anemia.
Folic acid is a vitamin needed by the bone marrow to help make blood cells.
• the bone marrow often produces more red blood cells than normal to try to
compensate for the blood cells being destroyed in the bloodstream.
RED BLOOD CELLS ABNORMALITIES
Morphology associated membrane defect
A. ACANTHOCYTE
 The acanthocyte is an abnormally crenated RBC.
 It is the consequences of a defect in the cell membrane.
Observed in:
- Abetalipoproteinemia - is an inherited disorder that impairs the normal absorption of fats and certain
vitamins from the diet. Many of the signs and symptoms of abetalipoproteinemia result from a
severe shortage (deficiency) of fat-soluble vitamins (vitamins A, E, and K).
- Liver disorders- eg. hepatitis
- Lipid metabolism disorders - Lipid metabolism disorders, such as Gaucher disease and Tay-Sachs
disease, involve lipids. Lipids are fats or fat-like substances. They include oils, fatty acids, waxes,
and cholesterol. If you have one of these disorders, you may not have enough enzymes to break
down lipids.
B. SPHEROCYTE
 The spherocyte is an erythrocyte in which the biconcave disc profile is lost.
 It appears as a smaller and denser RBC.
Observed in:
- Immune induced hemolysis- This happens because the immune system mistakenly recognizes these
blood cells as foreign
- Post blood transfusions
- Congenital anemia- is one of many types of anemia, characterized by ineffective erythropoiesis, and
resulting from a decrease in the number of red blood cells (RBCs) in the body and a less than normal
quantity of hemoglobin in the blood.
C. STOMATOCYTE - Stomatocyte is characterized by a slit-like or narrow rectangular area of pallor in
the cell.
 It is observed in: Liver disease, Alcoholism, Electrolyte imbalance, Hereditary stomatocytosis, Infectious
mononucleosis, Lead poisoning, Malignancies, Thalassemia minor.
D. ELLIPTOCYTE
 There is known to be a hereditary defect present in the RBC cytoskeletal proteins (the spectrin
chain).
 These cells observed in varying percentages in:
- Iron deficiency anemia- is due to insufficient iron. Without enough iron, your body can't
produce enough of a substance in red blood cells that enables them to carry oxygen
(hemoglobin).
- Leukemia associated anemias.
- Thalassemia - is an inherited blood disorder that causes your body to have less hemoglobin
than normal. Hemoglobin enables red blood cells to carry oxygen.
- Dyserythropoiesis - refers to the defective development of red blood cells, also called
erythrocytes. This problem can be congenital, acquired, or inherited.
 Patients with congenital elliptocytosis may demonstrate up to 90% distinctly oval shaped cells.
CONDITION ASSOCIATED IN HEMOGLOBIN DEFECT
A. HbC Crystal
 Hemoglobin C- dense rectangular structures composed of precipitated hemoglobin crystals.
 If the condition is severe,then up to 10% of the RBC’s may contain these crystals.
B. SICKLE CELL -
 There are two basic types of sickle cells:
1. the oat cell, slightly sickled variation, and/or holly leaf.
2. The second type form very distorted filamentous forms.
 In the presence of a reduced oxygen atmosphere these cells form, but when the oxygen pressure is
normalized, they do NOT revert back to the normal discoid shape.
RBC INCLUSION BODIES
A. BASOPHILIC STIPPLING -
 Basophilic stippling (also called punctate basophilia), is characterized by the presence of
numerous granules in the erythrocyte.
 They are observed in:
 Lead poisoning.
 Hemoglobinopathy - is the medical term for a group of blood disorders and diseases that
affect red blood cells.
 Alcoholism.
 Megaloblastic anemias - is a condition in which the bone marrow produces unusually
large, structurally abnormal, immature red blood cells (megaloblasts).
B. CABOT RING
 The Cabot ring is a purple staining ring-like filament or figure-8 and is thought to be formed
from the microtubules of the mitotic spindle.
 It is most likely to be seen in:
 Severe anemias (example: pernicious anemia) and lead poisoning.
C. HEINZ BODIES
 These consist of precipitate globins chain of hemoglobin.
 They occur when there is defective reducing capacity in the cell as in glucose -6- phosphate
dehydrogenase deficiency.
 Particularly after drugs which stress this pathway (Drugs acting as oxidants also cause Heinz
body formation, important examples being acetaminophen, vitamin K1, propafol, and
phenothiazine)
D. HOWELL-JOLLY BODY
 Is a cytopathological finding of basophilic nuclear remnants (clusters of DNA) in circulating
erythrocytes. During maturation in the bone marrow, late erythroblasts normally expel their
nuclei; but, in some cases, a small portion of DNA remains.
 They are usually observed in the mature erythrocyte, occurs when the spleen malfunctions.
 They are formed during the process of karyorrhexis, usually in the megaloblast.
 If more than two “HoJo bodies” are present in the red cells, then the patient may have
megaloblastic anemia.
 They are also observed in:
- Hemolytic anemias - is a disorder in which red blood cells are destroyed faster than they
can be made. The destruction of red blood cells is called hemolysis.
- Pernicious anemia - is a type of vitamin B12 anemia. The body needs vitamin B12 to
make red blood cells.
- Post-operative conditions.
- Splenectomy. Spleen removal
- Splenic atrophy.
E. Pappenheimer BODIES -
 Pappenheimer bodies are abnormal basophilic granules of iron found inside red blood cells on
routine blood stain
 These granules (which are aggregates of mitochondria, ribosomes and iron particles) seen in
hyposplenism and hemolytic anemia.
F. MALARIA PARASITE
 Observe in patient infected with malaria parasite of one of 4 species
 The cell may contain: Schizont, Trophozoite Gametocyte which depends on the type of species
OTHER ABNORMALITIES
A. TARGET CELL/CODOCYTES
 This cell is characterized by an abnormally thin membrane with an increase incorporation of
cholesterol into the cell membrane.
 It is observed in: Hemoglobinopathy, Hepatic diseases, Iron deficiency anemia, Hemolytic anemia,
Splenectomy
B. HYPOCHROMIC CELL -
 Hypochromic means that the red blood cells have less hemoglobin than normal. Low levels of
hemoglobin in your red blood cells leads to appear paler in color.
 In microcytic hypochromic anemia, your body has low levels of red blood cells that are both
smaller and paler than normal.
 Cell with low MCH (Mean Corpuscular Hemoglobin) MCH levels refer to the average amount of
hemoglobin found in the red blood cells in the body.
 Hemoglobin is a protein in the blood that allows red blood cells to deliver oxygen to the cells and
tissues in the body.
C. MICROCYTIC CELL
 Cell seen in: Low MCV (Mean Corpuscular Volume) is a laboratory value that measures the
average size and volume of a red blood cell associated with: (IDA, THALASSEMIA,
SIDEROBLASTIC, And ANEMIA OF CHRONIC DISORDER)
D. LEPTOCYTE - a red blood cell (erythrocyte) that is wafer-thin and generally large in diameter, with
the haemoglobin concentrated in a thin rim at the periphery. Leptocytes are seen in certain types of
anaemia. This cell is seen in liver disease and hypochromic anemias.
E. KNIZOCYTE Knizocytes are RBC’s with more than two concavities.
 They are observed in; hereditary spherocytosis - is an abnormality of red blood cells, or
erythrocytes. The disorder is caused by mutations in genes relating to membrane proteins that
allow for the erythrocytes to change shape. The abnormal erythrocytes are sphere-shaped
(spherocytosis) rather than the normal biconcave disk shaped.
 hemolytic anemia - is a disorder in which red blood cells are destroyed faster than they can be
made.
F. MACROCYTIC CELL - The term macrocytic is from Greek words meaning "large cell". A
macrocytic class of anemia is an anemia (defined as blood with an insufficient concentration of
hemoglobin) in which the red blood cells (erythrocytes) are larger than their normal volume.
This can be seen in: Vitamin B12 deficiency, Folic acid deficiency, Disease of the liver.
G. ECHINOCYTE CELL -
 Crenation is usually not an indicator of a pathological problem.
 It is usually an artifact due to:
1. loss of intracellular fluid.
 2. increased anti-coagulant blood ratios (due to a technique during a phlebotomy or - Microcytosis – the size of red blood cells are smaller than the normal.
manufacturing error in measuring anticoagulant in the vacutainer tube). - Some red blood cells are larger and some are smaller than the normal size.
3. slow drying of the blood film
4. the patient being dehydrated Morphologic Abnormalities of WBC’s
H. DIMORPHIC PICTURE - Involve either the nucleus or the cytoplasm -
 Dimorphic is a term used to describe two circulating red cell populations. One is the patient's basic red NUCLEAR CHANGES:
cell population; the other is a second population with distinct morphological features. The distinct  Hypersegmentation/ Hypersegmented forms
populations can be observed in the top image on the right.  Hyposegmentation
I. BURR CELL (Pelger-Huet nucleus)
 The burr cells are characterized by abnormal ytoplasmic projections, but not the same as that of  Barr body
the acanthocyte.  Pyknotic cell
 These cells are observed in: Uremia, Acute blood loss, Stomach cancer, Pyruvate kinase CYTOPLASMIC CHANGES:
deficiency  Toxic granulation (Hypergranulation)
J. OVALOCYTE - The cell become oval in shape, Condition which can be seen in pernicious anemia  Degranulation (Hypogranulation)
(macro ovalocyte).  Toxic vacuolation
K. ROULEAUX FORMATION  Cytoplasmic swelling
 They are sometimes present as”  Inclusions
 A slide artifact due to a delay in the spreading of blood  Dohle body
 Alder-Reilly granules
 The settling out phenomenon in the thick portion of the blood smear
 Chediak-Higashi granules
 Rouleaux appear in: Chronic inflammatory disorders, Multiple myeloma, Hyperproteinemia.,
 Auer body
Waldenström’s macroglobulinemia.
 May-Hegglin body
 Increased amount of fibrinogen in the blood can cause rouleaux formation.
 Phagocytized parasite
L. RBC POLYAGGLUTINATION- Clumping (agglutination) of red blood cells is frequently caused by
 Reactive Lymphocyte and Monocyte
cold agglutinins. Cold agglutinins are IgM antibodies that may arise following viral or Mycoplasma
infections, or in the setting of plasma cell or lymphoid neoplasms. Agglutination of red cells can interfere
with red blood cell indices.
M. TEARDROP CELL/DACROCYTE - Teardrop cells (dacrocytes) are frequently associated with
infiltration of the bone marrow by fibrosis, granulomatous inflammation, or hematopoietic or metastatic
neoplasms. They can also be seen in patients with splenic abnormalities, vitamin B12 deficiency, and
some other forms of anemia.

NUCLEAR CHANGES
 Poikilocytosis - Poikilocytosis is the medical term for having abnormally shaped red blood cells (RBCs)
HYPERSEGMENTATION
in your blood. Abnormally shaped blood cells are called poikilocytes.
- also referred as macropolycytes
Morphology:
 Larger than normal
Different types of poikilocytosis;  With 5 lobes or more
A. Spherocytes Found in:
B. Stomatocytes • Megaloblastic anemia
C. Codocytes/Target cells • Iron deficiency
D. Leptocytes • Chronic infection
E. Sickle cell • Liver disease
F. Elliptocytes • Uraemia
G. Ovalocytes ______________________________________________________________________________
H. Dacryocytes/Teardrop cell HYPOSEGMENTATION
I. Acanthocytes - Pelger Huet Nucleus
J. Echinocytes Morphology:
K. Schizocytes  Bilobed (pince-nez spectacles) nucleus
 More condensed chromatin
Found in:
Anisocytosis is the medical term for having red blood cells (RBCs) that are unequal in size. Normally, a • Pelger Huet Anomaly
person's RBCs should all be roughly the same size. Anisocytosis is usually caused by another medical • Idiopathic myelofibrosis
condition called anemia. • Chronic granulocytic leukemia
• Inherited Myelodysplastic syndromes
Different types of anisocytosis; • Severe infection
- Macrocytosis – the red blood cells are larger than the normal.
 Cytoplasmic Swelling
______________________________________________________________________________
BARR BODY - caused by actual osmotic swelling
Morphology: of the cytoplasm or by increased adhesion to the glass
 Appear as small drumstick-like projection on one of the lobes of the neutrophil in females slide by stimulated neutrophils. Regardless of the cause, the result is a variation in neutrophil size or
 Attached to the nuclear lobes by a single narrow stalk neutrophil anisocytosis
 Are the morphological expression of inactivated X-chromosome
 It is non-pathological unless associated with rare chromosomal disorders
_____________________________________________________________________________
___________________________________________________________________________
PYKNOTIC NUCLEI
- indicate imminent cell death CYTOPLASMIC INCLUSIONS:
Morphology:  Döhle body
 Nuclear water is lost Morphology:
 Chromatin is dense and dark  Irregular shaped pale blue cytoplasmic inclusions
 Filaments can still be seen between segments  often in the periphery of the cell.
 these inclusions represent remnants of free ribosome or Rough Endoplasmic
Neutrophil that has died Reticulum (RER)
Found in:
• Infective and inflammatory states
______________________________________________________________________________ • Severe burns
• Tuberculosis
CYTOPLASMIC CHANGES • Post chemotherapy
TOXIC GRANULATION
- hypergranulation
Morphology:
______________________________________________________________________________
 Increased granulation
 May-Hegglin body
 More basophilic
Morphology:
 Larger than normal
 multiple or single blue or pinkish inclusion
 darkly staining bluepurple
 Dohle like bodies but are larger and more defined
 coarse granules in the cytoplasm of neutrophils.
 the difference is that they contain glycogen and RNA, methyl green pyronine positive
Found in:
Found in:
• Severe bacterial infection
• May-Hegglin Anomaly
• Therapy with cytokines
- rare autosomal inherited dominant platelet disorder
• Chemical poisoning

____________________________________________________________________________
______________________________________________________________________________
HYPOGRANULATION
 Alder-Reilly granules
- degranulation
Morphology:
Morphology:
 Large, purple or purplish black and coarse azurophilic granules that covers the nucleus.
 Reduced granulation
Found in:
in neutrophil cytoplasm
• Alder-Reilly Anomaly
Found in:
- a rare hereditary anomaly of WBC
• Myelodysplastic syndromes
-result of abnormal polyssaccharide metabolism which prevents the formation of secondary
specific-staining granules.
_____________________________________________________________________________
¬¬¬¬¬-_____________________________________________________________________________
 Chediak-Higashi granules
TOXIC VACUOLATION
Morphology:
Vacuoles: represents the sites of digestion of the phagocytized material
 Red, blue or greenish gray granules of variable size
Sign of Activation of:
 These inclusions represents abnormal lysosomes
 Active Phagocytosis
Found in:
 Bacterial Infection
Chediak-Steinbrinck-Higashi syndrome
 Viral Infection, Sepsis or Some Types of Cancers
- hereditary autosomal recessive syndrome
- cells show not only a chemotactic defects but also impaired adhesion to artificial surfaces and
_____________________________________________________________________________
delayed killing of intracellular bacteria because of defective lysosomal emptying into phagocytic vacuoles.
 Alpha-thalassemia
 Four genes are involved in making the alpha hemoglobin chain. Two from each parent.
______________________________________________________________________________  If one inherits:
 Auer Body  One mutated gene
Morphology: o no signs or symptoms of thalassemia.
 Pink or red o a carrier of the disease and can be passed on to the children.
 Round or rod shaped
 These inclusions represents agglomeration of azurophillic granules  Two mutated genes
Found in: o signs and symptoms will be mild.
• Acute-lymphocytic anemia o This condition might be called alpha-thalassemia trait.
• Promyelocytic leukemia
• Fagot cell: a cell containing multiple Auer rods clumped together in the form of bundle
 Three mutated genes
o signs and symptoms will be moderate to severe.
______________________________________________________________________________
REACTIVE MONOCYTE
• Reactive changes may be seen in monocytes in infections, during recovery from bone marrow  Four mutated genes
aplasia, and after GM-CSF administration. o Rare and usually results in stillbirth.
• The nucleus can become thin and band-like in areas and may appear to be segmenting. o Babies born with this condition often die shortly after birth or require lifelong
• Reactive changes also include increased cytoplasmic volume, increased numbers of transfusion therapy.
cytoplasmic granules, and evidence of phagocytic activity o In rare cases, a child born with this condition can be treated with transfusions and a
stem cell transplant.
Beta-thalassemia
 Two genes are involved in making the beta hemoglobin chain.
 One gene is inherited from each parent.
 If one inherits:

 One mutated gene

o Mild signs and symptoms.
o This condition is called thalassemia minor or beta-thalassemia.

 Two mutated genes

o signs and symptoms will be moderate to severe.
o This condition is called thalassemia major, or Cooley anemia.
 Babies born with two defective beta hemoglobin genes usually are healthy at birth but
develop signs and symptoms within the first two years of life.
 A milder form, thalassemia intermedia, can also result from two mutated genes.
Symptoms

 There are several types of thalassemia.

 The signs and symptoms depend on the type and severity of the condition.
 Fatigue
 Weakness
THALASSEMIA
 Pale or yellowish skin
 An inherited blood disorder
 Facial bone deformities
 The body has less hemoglobin than normal.
 Slow growth
 Abdominal swelling
Causes
 Thalassemia is caused by mutations in the DNA of cells that make hemoglobin.  Dark urine
o The mutations associated with thalassemia are passed from parents to children.  Some babies show signs and symptoms of thalassemia at birth
 Others develop them during the first two years of life.
 Hemoglobin molecules are made of chains, the alpha and beta chains that can be affected by
 Some people who have only one affected hemoglobin gene don't have thalassemia symptoms.
mutations.
Risk factors
o In thalassemia, the production of either the alpha or beta chains are reduced,
Factors that increase the risk of thalassemia include:
resulting in either alpha-thalassemia or beta-thalassemia.
 Family history of thalassemia. Thalassemia is passed from parents to children through
 In alpha-thalassemia, the severity of thalassemia depends on the number of gene mutations
mutated hemoglobin genes.
inherited from the parents. The more mutated genes, the more severe the thalassemia.
 In beta-thalassemia, the severity of thalassemia depends on which part of the hemoglobin  Certain ancestry. Thalassemia occurs most often in African Americans and in people of
molecule is affected. Mediterranean and Southeast Asian descent.
Complications
Possible complications of moderate to severe thalassemia include:
Iron overload 
 People with thalassemia can get too much iron in their bodies, either from the disease or from
frequent blood transfusions.
 Too much iron can result in damage to the heart, liver and endocrine system, which includes
hormone-producing glands that regulate processes throughout the body.
Infection  Frequent blood transfusions
 People with thalassemia have an increased risk of infection.
 This is especially true if the patient had splenectomy.
In cases of severe thalassemia, the following complications can occur:
 Usually done around the 16th week of pregnancy
 This test involves examining the amniotic fluid.
Treatment
 Mild forms of thalassemia trait don't need treatment.
 For moderate to severe thalassemia, treatments might include:
 More severe forms of thalassemia often require frequent blood transfusions, possibly every few
weeks.
 Over time, blood transfusions cause a build- up of iron in the blood, which can damage the
heart, liver and other organs.

Bone deformities  Chelation therapy

 Thalassemia can make the bone marrow expand, which causes the bones to widen.
o This can result in abnormal bone structure, especially in the face and skull.
o Bone marrow expansion also makes bones thin and brittle, increasing the chance of
broken bones.
Splenomegaly
 The spleen helps the body fight infection and filter unwanted material, such as old or damaged
blood cells.
 Thalassemia is often accompanied by the destruction of a large number of red blood cells.
o This causes splenomegaly and work harder than normal.
 Splenomegaly can make anemia worse, and it can reduce the life of transfused RBCs.
Splenectomy is suggested.
 Treatment used to remove excess iron from the blood as a result of regular transfusions.
 Some people with thalassemia who don't have regular transfusions can also develop excess
iron.
 Removing the excess iron is vital to the health.
 Oral medication, such as deferasirox (Exjade, Jadenu) or deferiprone (Ferriprox), to help rid
the body of the extra iron.
 Deferoxamine (Desferal), is given IM.
Stem cell transplant
 Also called a bone marrow transplant, a stem cell transplant might be an option in some cases.
 For children with severe thalassemia, it can eliminate the need for lifelong blood transfusions
and drugs to control iron overload.
 This procedure involves receiving infusions of stem cells from a compatible donor, usually a
sibling.

Prevention
Slowed growth rates  In most cases, thalassemia can't be prevented.
 Anemia can both slow a child's growth and delay puberty.  If the patient has thalassemia, or a carrier of thalassemia gene, a genetic counselor should be
consulted especially if desirous of children.
Heart problems  There is a form of assisted reproductive technology diagnosis, which screens an embryo in its
 Congestive heart failure and abnormal heart rhythms can be associated with severe early stages for genetic mutations combined with in vitro fertilization.
thalassemia. o This might help parents who have thalassemia or who are carriers of a defective
hemoglobin gene have healthy babies.
Diagnosis o The procedure involves retrieving mature eggs and fertilizing them with sperm in a
 Most children with moderate to severe thalassemia show signs and symptoms within their first dish in a laboratory.
two years of life. o The embryos are tested for the defective genes, and only those without genetic
 Confirm a diagnosis with blood tests if Thalassemia is suspected in a child. defects are implanted into the uterus.

Blood Test Additional Notes:

 CBC- Can reveal the number of red blood cells and abnormalities in size, shape or color.
 DNA analysis- to look for mutated genes. Lifestyle and home remedies
To help manage thalassemia by following the treatment plan and adopting healthy-living habits.
Avoid excess iron
 Unless recommended, don't take vitamins or other supplements that contain iron.
Healthy diet
Prenatal testing
 Can boost the energy.
 Done before a baby is born to find out if he or she has thalassemia and determine the severity.
 Folic acid supplement to help the body generate new RBCs.
 Tests used to diagnose thalassemia in fetuses include:
Keep healthy bones
 Chorionic villus sampling  Diet contains enough calcium and vitamin D.
o Usually done around the 11th week of pregnancy B vitamin
o This test involves removing a tiny piece of the placenta for evaluation.  To help build red blood cells.
Avoid infections
 Wash hands frequently and avoid sick people. This is especially important if patient had
splenectomy.
 Amniocentesis  Annual anti- flu shot and vaccines to prevent meningitis, pneumonia and hepatitis B.
  If fever or other signs and symptoms of an infection develop, consult a doctor immediately for shape RBC
treatment. Asymptomatic, do not show any symptoms Symptoms are chronic and severe such as painful
crises and organ damage
Coping and support Have a 50% chance of passing the gene onto their
 Coping with thalassemia can be challenging. Don't hesitate to ask for help. children
 Join a support group, which can provide both sympathetic listening and useful information.

RISK FACTORS
• Cold
• Lack of oxygen
• Lack of fluid in the body
• Hard exercise
Sickle Cell Anemia • High temperature (fever)
 Most severe form of sickle cell disease • Infection
 Inherited red blood cell disorder PATHOPHYSIOLOGY OF SCD
 A condition where there aren’t enough red blood cells to carry adequate oxygen throughout the Two interlinked mechanism
body 1. Anemia
• Normally, blood cells are flexible, round and move easily through the blood vessels • HbS Polymerization- HbS undergo polymerization under hypotoxic condition
• People with sickle cell anemia has rigid, sticky, and shaped like sickle or crescent moon red • Sickling- HbS distort the shape of the RBs causing them to become dense and sickle shape
blood cells • Hemolysis- inflexibility of sickled RBC contributes to their premature destruction
• Normal lifespan of RBC: 120 days • Anemia- decreased in no. of RBC, due to premature destruction, leads to lower hemoglobin
• Life span of sickled cells: 10-20 days level
o Body may have trouble in making enough new cells to replace one you lost 2. Vaso-occlusion
o Result in red blood cell deficiency known as anemia • Chronic Vascular Damage
• African- American have higher risk of sickle cell anemia than people of other races. Ongoing vascular damage and repeated injury to the blood vessel wall over time result in activation of
Hemoglobin endothelial cells
 Made up of four peptide chain • Inflammation and Cell Activation
 2 alpha hemoglobin The chronic inflammatory environment within blood vessels leads to increased expression of adhesion
 2 beta hemoglobin mediators, resulting in multicellular adhesion
 Faulty hemoglobin is called hemoglobin S (HgbS) as it replaces the normal hemoglobin which • Multicellular Adhesion
is called hemoglobin A (HgbA) Activated endothelial cells initiate a complex cascade of interactions with RBCs, white blood cells
 In all forms of SCD, at least one of the two abnormal genes causes a person’s body to make (WBCs), and platelets that leads to multicellular adhesion and ongoing vaso-occlusion
hemoglobin S. When a person has two hemoglobin S genes, Hemoglobin SS, the disease is • Vaso-Occlusion
called sickle cell anemia. This is the most common and often most severe kind of SCD. Multicellular adhesion reduces and blocks blood flow to organs
SCD FREQUENCY • Vaso-Occlusive Crises
• Most common in individual of African descents but seen also in Hispanic, Arabians, Indians, Ongoing, silent, vaso-occlusion may result in vaso-occlusive crises (VOCs)-the clinical hallmark of SCD.
and white There is tissue and organ damage.
• In united states the incidence is 1 in 635 live births to African- American is affected with sickle
cell anemia.
GENETICS OF SCD
• Changes in cell structure arises from a change in the structure of hemoglobin
Adhesion Mediators
• A single change in amino acid causes hemoglobin to aggregate.
P-selectin on activated endothelial cells and platelets
• Mutation in beta globin at 6th position (glutamic acid is replaced by valine)
• Mediates the capture and tethering of WBCs and sickled RBCs to the activated endothelium
• Expressed on platelets causing them to bind to WBCs that are clustered together
E-selectin on activated endothelial cells
• Binds WBCs to activated endothelial cells and promotes the capture of sickled RBCs
INHERITANCE PATTERN
L-selectin on the surface of WBCs
• If Each parent has normal A gene and one Hemoglobin S, which mean each children has:
• Mediates the recruitment and adhesion of additional WBCs to endothelial cells
 25% chance of inheriting two normal hemoglobin A gene, then child does not have sickle trait
or disease
SYMPTOMS
 50%- one normal A gene and one hemoglobin S gene- child has sickle cell trait
• Usually appear around 5 months of age
 25%- two hemoglobin s genes- child has sickle anemia
• Vary from person to person and change over time

• SCA is diagnosed in infants through newborn screening.
Sickle cell traits Sickle cell disease
1. Anemia
Carrier Affected • Sickle cells break apart easily and die leaving you with too few RBC.
Carry only one copy of the altered hemoglobin Carry two copies of altered hemoglobin genes • Shortage of RBC (anemia)
genes • Without enough RBC, your body can’t get enough oxygen, causing fatigue
SCD individual have both normal and some sickled Two copies of altered genes destroy RBC rapidly 2. Episodes of pain
  Periodic episodes of pain called pain crisis (major symptoms of sickle cell anemia) o fatal
 Pain develop when sickled RBC block blood flow to chest, abdomen, and joint • Splenic Sequestration (Pooling)
 Pain can also occur in bones (avascular necrosis) o spleen helps filter the blood of infection
 Pain varies in intensity and severe crisis requires hospital stay o Pooling of sickled cells causes spleen to enlarge and painful
 Chronic pain results to bone and joints damage, ulcers and other causes among o Become permanently damaged and become scarred due to repeated episodes
adolescents and adults o Symptoms: sudden weakness, pale lips, rapid breathing, excessive thirst, belly pain
3. Frequents infection and rapid heartbeat
 Sickle cell can damage spleen, leaving you more to vulnerable to infection o Requires emergency medical care
 Non-functional spleen- susceptible to encapsulated bacteria such as S. pneumoniae, H.
• Leg ulcer
influenzae, Neisseria meningitidis and Salmonella spp.
o open sores
 Infants and children are given vaccination and antibiotics to prevent life threatening infection
such as pneumonia
4. Delayed growth or puberty
• Gallstone
 RBC provide the body with oxygen and nutrient needed for growth
o Break down of RBC produces of bilirubin
 Shortage of RBC can slow the growth in infants and children, delay puberty in teenagers
5. Swelling of hand and feet o High level of bilirubin can lead to gallstone
 Dactylitis (inflammation of the digits) • Pregnancy Complication
 happens when sickled RBC blocks blood flow to hands and feet o SCA increases risk of high blood pressure and blood clot during pregnancy
 First symptoms in babies o Increases of miscarriage, premature and low birth weight babies
• Priapism
6. Sickled cells can also be stock in other bones causes sickle cell crisis which lead to o Sickle cell that block the blood vessels in the penis can lead to impotence over time
avascular necrosis of the bone o Painful, long-lasting erection

7. Vision problem • Blindness

 Tiny blood vessels that supply eyes is plugged with sickle cells o Tiny blood vessels that supply the eyes is blocked by sickle cells
 Damage retina (portion of the eye that process visual images), leads to vision problems o Over time, this can damage eye and lead to blindness
 Jaundice Diagnosis
1. Blood Test
Signs • to check for defective form of hemoglobin that underlies sickle cell anemia
• Fever- increased risk of infection can be first sign of fever • Part of routine newborn screening
• Unexplained episodes of severe pain- pain in the abdomen, chest, bones, or joints • Older children and adults: sample is drawn from a vein in the arm
• Swelling in the hands and feet • Young children and babies: collected from a finger or heel
• Abdominal swelling- if the area is tender to touch • Negative screening test: no sickle cell gene present
• Pale skin or nail beds • Positive screening test: further test is done to determine whether one or two sickle
• Yellow tint to the skin or whites of the eye cell gene are present
• Signs or symptoms of stroke- one sided paralysis, weakness in face, arm or legs, trouble • Check for low blood cell count will be done
walking or talking, sudden vision changes or unexplained numbness, severe headache, call 2. Peripheral blood smear-shows RBC appear irregularly contracted cells
your local emergency number right away
Complications 3. HB Electrophoresis- to confirm the diagnosis of sickle cell disease, measure the different
• Stoke types of hemoglobin
o Blocked blood flow in the area of the brain 4. Transcranial Doppler Ultrasound screening (TCD)- a painless procedure that uses sound
o Signs: seizures, weakness or numbness of arm and legs, sudden speech difficulties, waves to examine blood flow in the brain. Can asses risk of stroke
loss of consciousness
o Stroke can be fatal, seek medical treatment immediately Prenatal testing
• Acute chest syndrome 1.Amniocentesis
o A lung infection or blockage of blood vessels by sickle cells in the lungs result in  Done at 14- 16 weeks of pregnancy
chest pain, fever, and difficulty in breathing  Sample of amniotic fluid is for genetic defect (fluid and fetus has the same DNA)
o Occurs suddenly when body is under stress from infection, fever, dehydration  About 20 milliliters of fluid is withdrawn for lab evaluation
• Pulmonary hypertension  Results take 1-2 weeks
o High blood pressure in lungs in adults
o Symptoms: shortness of breath, fatigue 2. Chorionic villus sampling
o Fatal  Removal and testing of a very sample of the placenta during early pregnancy
 Placenta sample and fetus contains the same DNA
• Organ damage
 Sample can be obtained by catheter or a fine needle inserted in the cervix or through abdomen
o Sickle cells that block blood flow to organs deprive the effected organs of blood
when fine needle is used.
and oxygen
 Tissue is tested for genetic changes identified in affected family member
o Lack of oxygen-rich blood can damage nerves and organs including kidneys, liver
 Result is available within 2 weeks
and spleen Genetic counseling
 • Patients with sickle cell trait or parents of newborn babies diagnosed with sickle cell anemia or • Researchers are exploring whether inserting a normal gene into the bone marrow of people
sickle cell trait are often referred to genetic counseling. This helps prospective parents with sickle cell anemia will result in normal hemoglobin
determine the probability of future children inheriting the disease, and helps them make fully
informed reproductive decisions Lifestyle and Home remedies
• Drink plenty of fluid
• Take regular exercise (avoid over exertion)
Treatment • Eat healthy and balanced diet
• Aimed at avoiding crises, relieving symptoms, and preventing complications • Avoid getting cold
• Babies, children age 2 and younger: should make a frequent visit to a doctor • Treat infection and fever quickly
• Children older and adults: should see a doctor at least once a year according to Centers for • Do not take decongestants
Disease Control Prevention o May cause constriction of blood vessels and could trigger crisis
• Treatment includes: medications, blood transfusion and bone marrow transplant o Medicines that can provide a short-term relief for blocked or stuffy nose
Medications o Examples: Afrin, Dristan, Vicks Sinex (oxymetazoline), etc.
Antibiotics • Seek a doctor immediately if you feel unwell
 Children with sickle cell anemia may begin to take antibiotic penicillin when they are 2 months • Inform doctors or nurses that you have SCD
old until they are at least 5 years older
 Helps to prevent life threatening infections such as pneumonia
 For adults, if spleen is removed or had pneumonia, you might need to take penicillin
throughout life
Pain-Relieving medications
 To relieve pain during sickle cell crisis
 Hydroxyurea- taken daily to reduce frequency of painful crises and might reduce the need for
blood transfusion and hospitalization
 Hydroxyurea works by stimulating
Assessing stroke risk
 Special Ultrasound Machine (transcranial)
 To learn which children have a higher risk of stroke
 Painless test, uses sound wave to measure blood flow
 Used on children as young as 2 years
 Regular blood transfusions decrease stroke risk
Vaccination
 Childhood vaccination prevent disease or infection in all children
 For adults with sickle cell anemia- pneumococcal vaccine and the annual flu shot is important
Blood transfusion
 Given intravenously to person with sickle cell anemia
 Increases the number of normal red blood cells in circulation that helps to relieve anemia
 In children: regular blood transfusion decreases the risk
 Can carry risk including infection and excess iron buildup in the body damages heart, liver and
other organs
Nitric Oxide
 Helps keep blood vessels open and reduces the stickiness or RBC
 Treatment with inhaled nitric oxide might prevent sickle cell from clumping together
 Studies on nitric oxide shown little benefit
Bone Marrow Transplant
 Also known as stem cells transplant
 Only potential cure for sickle cell anemia
 Reserved for people younger than age 16 because risks increases for people older than 16
 Finding a donor is difficult, and procedures has serious risk associated with it including death
 Involves replacing bone marrow affected with sickle cell anemia with healthy bone marrow
from a donor
 If donor is found, the patient receives radiation or chemotherapy to destroy or reduce bone
marrow stem cells. Healthy stem cells from donor is injected intravenously into the
bloodstream of the patient and migrate to the bone marrow and begin generating new blood
cells
 After transplant, you will receive drugs to help prevent rejection of the donated stem cell
 If body rejects the transplant it may lead to a life-threatening complication.
Gene Therapy