Haematology Medicine

Medicine Notes by Chillers (Q-45, QAMC-Bahawalpur) Hematology
2020
Topic
FIRST EDITION
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CHILLER’s Q-45 (QAMC-BWP) presents:
“An Easy approach to Excel your Exams”
2020
CHILLER’S
Medicine Notes
Hematology
Editors
Sami Ur Rehman
Quaid-e-Azam Medical College, Bahawalpur
Q45 (2014-2019)
Haroon Ahmad Abdal
Q45 (2014-2019)
Muhammad Hamza Hassan
Q45 (2014-2019)
Muhammad Sohaib
Q45 (2014-2019)
Muhmmad Naveed
Q45 (2014-2019)
Hussnain Mehboob
Q45 (2014-2019)
Zain Ghaffar
Q45 (2014-2019)
ADDITIONAL RESOURCES AVAILABLE AT:

https://www.facebook.com/ChillersStudyCircleQ45QAMC
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Contents
* Basic Concepts of Hematology 04 15(C). Polycythemia Rubra Vera 13
(Davidson & Kaplan) (Kaplan & Davidson)
1. Iron deficiency Anemia 05 16. Acute Leukemias (ALL & AML) 14
(Davidson) (Kaplan & Davidson)
2. Megaloblastic Anemia 05 17. Chronic Myeloid Leukemia (CML) 15
3. Aplastic Anemia 06 18. Chronic Lymphocytic Leukemia (CLL) 16
4. Hereditary Spherocytosis 07 19. Hodgkin's Lymphoma (HL) 17
(Davidson & Kaplan) (Davidson)
5. Sickle Cell Anemia 07 20. Non-Hodgkin’s Lymphoma (NHL) 17
(Davidson) (Kaplan)
6. Beta– Thalassemia 08 21. Tumor lysis Syndrome 18
(Davidson) (Pervaiz Akbar)
7. Alpha Thalassemia 09 22. Multiple Myeloma 18
(Davidson) (Davidson)
8. HBS disease 09 23. Bleeding Disorders 19
(Davidson) (Davidson)
9. Anemia of chronic disease 10 23(A). Hemophilia A 19
(Kaplan) (Davidson)
10. Sideroblastic Anemia 10 23(B). Idiopathic Thrombocytopenia (ITP) 20
(Kaplan & Davidson) (Davidson & MTB by Cornard’s Fischer)
11. Hemolytic Anemia 10 23(C). Von-Willebrand disease 21
(Kaplan & Davidson) (Kaplan & Davidson)
12. Autoimmune Hemolytic Anemia (AIHA) 23(D). Disseminated intravascular coagula-
(Davidson & Kaplan) 11 tion (DIC) (Davidson) 21
13. Paroxysmal Nocturnal Hemoglobinuria 24. Venous Thrombotic Embolism (VTE)/
(Kaplan & Davidson) 12 Pulmonary Embolism (PE)/Deep Venous
14. Glucose 6-Phosphate Dehydrogenase Thrombosis (DVT) (Davidson) 22
(G6PD) Deficiency 13 25. Thrombotic Thrombocytopenic purpura &
(Davidson) Hemolytic uremic syndrome 24
15. Polycythemia 13 (Davidson & Kaplan)
(Kaplan & Davidson) 26. Heparin induced thrombocytopenia 24
15(A). True Polycythemia 13 (Kaplan & Davidson)
(Kaplan & Davidson) 27. Comparison of heparin & warfarin, Blood
15(B). Apparent Polycythemia 13 products and Transfusion, Bone marrow Trans-
(Kaplan & Davidson) plantation (Davidson) 25
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• Some basic concepts of Hematology:- Microcytic Macrocytic Normocytic

1. ANEMIA:- Low MCV Elevated MCV Normal
• Anemia is a condition characterized by following:- ( <80 fL) (> 100 fL) MCV (80-
A. Hematocrit < 41 in men & < 36% in women; or 100 fL)
B. Hemoglobin < 13.5 g/dl in men or < 12 g/dl in women. Causes: Causes: Causes:
• Clinical features: Symptoms based on the severity of disease; 1.Iron defi- 1. Vit. B12 or 1. Most
A. Early symptoms: fatigue& exercise intolerance. ciency anemia folic acid defi- forms of he-
B. As anemia worsens; dyspnea on exertion& light headedness. 2. Anemia of ciency molysis
C. Later, Confusion& altered mental status develop as hypoxia chronic disease 2. Toxic effects 2. Aplastic
of brain develops. 3. Thalassemia of alcohol anemia
D. Death from anemia is mostly caused by decreased oxygen 4. Sideroblas- 3. Chemothera- 3. Rheuma-
tosis peutic agents; toid Arthritis
delivery to heart and resulting MI. 5. Lead methotrexate.
poisoning 4. Drugs; AZT
2. Interpreting plasma iron studies:- or phenytoin.
Type of Anemia Iron (Fe) TIBC Ferritin Transferrin Soluble Trans-

saturation ferrin receptor
1. Iron deficiency anemia ↓ ↑ ↓ ↓ ↑
2. Anemia of chronic disease ↓ ↓ ↑ ↓ ↓ or ↔
3. Chronic hemolysis ↑ ↓ ↑ - -
4. Hemochromatosis ↑ ↓ or ↔ ↑ - -
5. Sideroblastic anemia ↑ ↔ or ↓ ↑ ↑ -
6. Thalassemia minor ↔ ↔ ↔ ↔ -
7. Pregnancy ↑ ↑ ↔ - -
Evaluation of pt.’s with Anemia
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3. Iron Deficiency Anemia (IDA) :-

• Causes:
1. Blood loss: Menorrhagia, GI-bleeding, Hookworm or Schistosomiasis & Chronic use of NSAIDs.
2. Poor diet.
3. Malabsorption.
• Investigations:
1. Hb level: low
2. MCV, MCH & MCHC: reduced
3. Plasma ferritin level: reduced (less than 10ng/ml) = Single best test to conform IDA. (mcq-uhs)
(*Ferritin levels may rise in acute phase responses & in liver diseases; in these conditions, ferritin level of up to 100 µg/L may
be compatible with low bone marrow iron stores.)
4. Serum iron level: reduced UHS Q: A 25 yrs. old female pre-
5. Total iron binding capacity (TIBC): increased sents in medical OPD with gener-
6. Transferrin saturation: low ( less than 16% consistent with IDA) alized body weakness, easy fatiga-
7. Immunoassay: increased transferrin receptors bility & paresthesia’s of hands
8. RBC Morphology: Microcytic hypochromic anemia &feet for 3 wks. On examination,
bald tongue & angular cheilosis
9. Bone marrow aspiration: in complex case (Micro-normoblastic hyperplasia) are present. On investigation, Hb is
10. Investigation of causes: a. For GIT: Endoscopy or barium studies, 7.8 g/dl& MCV 120 fl, peripheral
b. For celiac disease: Serum anti-gliadin & anti-endomysial antibodies blood film shows oval macro-
11. Stool & urine examination: for parasites. cytes& poikilocytosis.
• Management:- A. Diagnosis?, B. Three causes of
raised MCV. (A-2014)
1. Tab. Ferrous sulfate: 200 mg TID (3 times a day) for 3-6 months.
2. Incase of intolerance with dysphagia & altered bowel habit; Tab. Ferrous gluconate: 300mg BD for 3-6
months. (*Follow-up: After 1 week, Hb should rise by 1 g/dl or 10 g/L& retics response should be evident)
3. Pt.’s with malabsorption, chronic gut disease or inability to tolerate oral preparations: Parenteral Iron
therapy is given (Intramuscular Inj. Iron sorbitol, iron dextran, iron sucrose or iron isomaltose: 1.5 mg/
weight).
4. Blood transfusion: only in case of angina, heart failure or cerebral hypoxia. (*Observation for anaphylaxis
after initial test dose is recommended.)
4. Megaloblastic Anemia:- Neurological findings in B12 deficiency:
• Causes: ( Annual 2019-seq)
 Vitamin B12 deficiency:- 1.Peripheral nerves:
1. Dietary deficiency: Only occurs in strict vegans. Glove& stocking paresthesia, loss of ankle reflexes
2. Gastric factors: Gastric surgery (including gastrectomy). 2.Spinal Cord:
3. Pernicious anemia: An autoimmune disorder characterized Subacute combined degeneration of cord
by atrophy of the gastric mucosa. * Posterior column: ↓ vibration sensation & pro-
4. Small bowel factors: Terminal ileal disease (e.g. Crohn’s prioception. (cause of numbness& pins & needles)
disease) and ileal resection. (mcq-uhs) * Corticospinal tract: UMN signs
 Folate deficiency- 3.Cerebrum: Dementia, Optic atrophy
1) Diet, e.g. poor intake of vegetables, 4.Autonomic neuropathy
2) Malabsorption, e.g. coeliac disease,
3) Increased demand, e.g. pregnancy, hemolysis,
4) Drugs, e.g. phenytoin, contraceptive pill, methotrexate.
• Clinical features:-
Symptoms Signs
Malaise, Paresthesia, Wt. loss, Breathlessness, Sore mouth, Altered skin Smooth tongue, Vitiligo,
pigmentation, Impotence, Grey hair, Poor memory& depression, Personali- Angular cheilosis, Skin pigmentation,
ty changes, Hallucination, visual disturbance Heart failure, Pyrexia
• Investigations:-
1. Hemoglobin level: ↓
2. CBC: RBCs: low for degree of anemia; ↑ MCV, RDW& MCHC; WBCs & platelets are low or normal.
3. Reticulocyte count: low for degree of anemia
4. Serum indirect bilirubin level: increased
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5. Peripheral blood picture: Macrocytosis (oval macrocytes), Anisocytosis, Poikilocytosis, Hypersegmenta-

tion of neutrophils, Red cell fragmentation.
6. Bone marrow aspiration: Hypercellular fragments, ↑ iron stores, myeloid series shift to left, Giant
metamyelocytes, dysplastic megakaryocytes, Pathologic non-ring sideroblasts
7. Plasma LDH: elevated
8. Serum ferritin: elevated
9. Haptoglobin: decreased
10. Serum vit. B12 level: Decreased
11. Two part Schilling test: to rule-out the cause of vit b12 deficiency (pernicious)
12. FIGLO test: to differentiate ether anemia is due to vit b12 or folic acid.
13. Anti-parietal antibodies: +ve in case of pernicious anemia.
14. Serum folate level: low (*Red cell folate is a more accurate indicator of the body’s folate stores)
• Management:-
1. Before the result of lab tests: (Folic acid + vit. B12)= never treat folate deficiency alone in vit B12 defi-
ciency, it will precipitate subacute combined degeneration of spinal cord.
2. Vitamin B12 deficiency: ( Annual 2019)
• Inj. Hydroxy-cobalamin: 1000µg I/M, six doses; 2 or 3 days apart, followed by maintenance therapy:
1000µg every 3 months for life time.
• Follow-up: A. Retics count will peak at 5th-10th day & Hb level 1g/dl or 10g/l every week.
B. Response of marrow: Fall in K level & rapid depletion of iron.
C. If blood picture is dimorphic: add iron therapy
• Counselling: Sensory neuropathy may take 6-12 months to correct.
3. Folate deficiency:
• Tab. Folic acid 5mg OD for 3 wks. (acute deficiency) & 5mg weekly (maintenance).
• Prophylactic folic acid : Pregnancy, Autoimmune hemolytic anemia, Hemoglobinopathies
• Supraphysiologic supplementation: 400µg/day, ↓ risk of coronary& cerebral vascular disease by reducing
homocysteine.
4. Transfusion: In case of severe angina or heart failure.
3. Aplastic Anemia:-
• Causes:
1.Congenital: Fanconi’s anemia
2. Acquired:
1.Idiopathic or Unknown causes Camitta criteria (Severity of Aplastic anemia is graded
Primary aplas- according to it)
tic anemia:
1.Severe A.A.:
2. Secondary * Chemicals. e.g. Benzene,toluene misuse(glue- * Marrow cellularity <25% plus atleast two of:
Aplastic ane- sniffing) A. Neutrophils <0.5* 109 /L
mia: * Drugs. e.g. Antibiotics B. Platelets <20 * 109/L
(sulfonamides,azathiopurine,etc), Anti- C. Retics count <20* 109/L
rheumatics, Anti-thyroid drugs, Anti-
2. Very severe: A.A.:
convulsants, Immunosuppressants As for severe A.A. but neutrophils <0.2* 109/L
*Insecticides
* Ionizing radiation 3. Non-severe A.A.:
*Infections: HIV,EBV, Viral Hepatitis A.A. not fulfilling criteria for both above.
*Pregnancy, * SLE, * Paroxysmal nocturnal he-
moglobinuria UHS Q: A 60 yrs old female presented with weak-
ness &shortness of breath on exertion. She is diabet-
• Clinical features:- ic& mild depression. Her examination reveals eden-
1. Anemia (Fatigue, pallor, dyspnea): due to low RBC’s tulous patient with moderate degree of mucosal pal-
or.You request for her routine tests which reveal that
2. Infections of mouth, sore throat : due to low WBC’s she has Hb 6.5g/dl with MCV 124 fl.The blood film
3. Bleeding (Petechiae & ecchymosis): due to low platelets. shows cells are megaloblastic. Her renal function is
• Investigations:- normal A.How will u differentiate the 2 causes of
1. CBC: Pancytopenia, often macrocytosis. megaloblastic anemia?, B.Which micronutrient will
2. Reticulocyte count : low you replace first if you r not clear as to what is cause
of anemia. (S-2017 held in 2018)
3. Peripheral picture: Normocytic Normochromic anemia.
4. Bone marrow biopsy: Trephine biopsy, hypocellularity with increase fat spaces.
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• Management:
1. Supportive:- (Asymptomatic pt.'s don’t need much except for supportive treatment)
A. Packed cell volume & platelets transfusion for bleeding (supports blood count)
B. Vigorous antibiotics for infections (like parvo-virus B19 in sickle cell pt.’s)
C. Remove exposure to hazardous drugs & toxins.
2. Curative:-
A. Treatment of choice in younger pt.’s(<35yrs) who are severely affected is allogenic HSCT from HLA-
matched sibling.
B. Drug of choice in older people & who don’t have suitable allogenic donor: Immunosuppressive therapy
(IST): (Anti-thymocyte globulin, cyclosporin & corticosteroids): response usually occurs in 4-12 wks.
*cyclophosphamide in resistant cases.
C. Pt.’s who fail IST are considered for unrelated donor allograft or TPO-RA like eltrombopag.
D. Pt.’s with aplastic anemia should be followed long-term.
4. Hereditary Spherocytosis:- (Autosomal dominant condition)
• De-novo in patients over 65 yrs.
• Chace finding on blood count.
• Clinical features:-
1.Asymptomatic, 2. Jaundice, 3. Splenomegaly, 4.Hemolytic crisis: Jaundice , splenomegaly & anemia. 5.
Aplastic crisis: due to infection of parvo-virus., 6. Megaloblastic crisis: due to folic acid deficiency (first
presentation of disease in pregnancy), 7. Leg ulcers & liability to form gall stones( in 50% pt.’s).
1. Screened for features of compensated hemolysis.(Eosin-5-malemide binding test).
2. Anemia: mild, (CBC: RBC↓, MCHC & Reticulocyte count ↑ )
* Causes of Pancytopenia:
3. Blood film shows spherocytosis & reticulocytes. 1. Bone marrow failure: Aplastic anemia, Inherit-
4. Osmotic fragility test: +ve (lysis in hypotonic saline solution) ed, Idiopathic, Viral, Drugs
5. Electrophoresis to detect abnormal proteins : confirmatory. 2. Bone marrow infiltrates: Leukemia, Lympho-
6. Coomb’s test : -ve ma, Cancer
3. Infective hematopoiesis: Megaloblastic, AIDS
• Management:- 4. Peripheral pooling/destruction: Hypertension,
1. Splenectomy: indicated in following conditions: SLE
* Anemia causes persistent impairment of health.
* Severe hemolytic crisis UHS Q: A 28 yrs boy presents with shortness of
* Presence of gall stones. breath,pallor7bleed from gums&nose.On investigation,
2. In hemolytic crisis: blood transfusion. his Hb is 7g/dl,platelet count 12000 & TLC is 12*10 9/L
& absolute neutrophil count <0.5*109/L.Bone marrow is
3. Prophylactic folic acid: 5mg weekly. hypocellular&he is diagnosed as aplastic anemia.
A.How you asses the severity of aplastic anemia in this
5. Sickle Cell Anemia:- (Autosomal recessive trait) patient?, B.How will u manage?, C. Into which condi-
tions, aplastic anemia can evolve? (A-2017)
• Clinical features:
1. HbF protects from its complications, usually asymptomatic.
2. Painful vaso-oclusive crisis: Acute severe bone pain, dactylitis in children (painful swelling on dorsal sur-
faces of hands & feet), tachycardia, sweating &fever. Rx: see treatment
3. Stroke in 10% children, Diagnosis: Transcranial doppler USG, Rx: hydroxycarbamide.
4. Sickle chest syndrome: most common cause of death in adults with this disease. Rx: see treatment
5. Sequestration crisis: mainly affects children, pooling of blood in spleen±liver with organomegaly, severe
anemia & shock. Priapism is complication on males. Rx: urgent transfusion.
6. Aplastic crisis: due to Parvo-virus B19. Rx: Transfusion may be needed.
• Complications:
1.Spleenic infarction before 2 yrs old (Rx is zinc supplement), 2. Poor growth, 3. Chronic renal failure, 4. Gall-
stones, 5. Retinal disease, 6. Iron overload, 7. Lung damage.
1. Blood Complete picture: Compensated anemia, Hb: 6-8g/dl, Hematocrit usually 20-30%, High retics
count, Sickle cell comprising 5-50% of red cells, WBC & platelets elevated.
2. Serum bilirubin level: indirect bilirubin level is high
3. Hb Electrophoresis: 85-98% HbS, no HbA, 2-20% HbF
4. Blood film: sickle cells, target cells & features of hyposplenism from a younger age.
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5. Both parents of the affected individual have sickle cell trait.

6. Emergency screening test: By exposing red cells to a reducing agent (sodium dithionite), HbA gives clear
solution & HbS produce turbid solution.
• Treatment:- UHS Q: A 45 yrs lady presented with
1. Supportive: progressive shortness of breath for last
6 mnths,Lab data shows: Hb 3.8g/
A. protect the patient from gram +ve sepsis (Penicillin V) dl,TLC:3000/cm3.Platelets:45,00/
B. Avoid ppting factors like hypoxia, dehydration & acidosis. cm3,MCV:112fl,PCV0.15,retics:3%
C. In hemolytic anemia: I/v fluids, oxygen,antibiotics,analgesia&transfusion. A.Diagnosis?, B. What further investi-
D. Folic acid: 5mg daily gations are required?, C. Treatment?
E. Vaccination for influenza, Hep. B, Pneumococcus, meningococcus. (Annual 2010)
2. Hydroxyurea: 500-750 mg/day, increases the level of HbF.
3. Regular Transfusion: in pt.’s with recurrent severe complications, like CVA in children & chest syndrome
in adults.
4. Treatment of vaso-oclusive episodes: 1. Analgesia for pain, 2. Aggressive rehydration, 3. O2 therapy, 4.
Antibiotics, 5. Transfusion with packed cell volume, if HCT is low, 6. Exchange transfusion, if HCT is
high (*Acute chest syndrome has same treatment as of vaso-oclsive episodes + Bronchodilators)
5. Allogenic bone marrow transplantation.
6. Life threatening crisis/Preparation for surgery: Exchange transfusion
7. Aplastic crisis/Sequestration crisis: Simple top-up transfusion.
6. Beta– Thalassemia:
• Inherited disorder (autosomal recessive) of microcytic hemolytic anemia characterized by “absence or de-
creased synthesis of the beta globin chain of hemoglobin”. Risks to the baby
• Types: born to thalas-
1) Heterozygous states: Thalassemia minor (1 normal β-globin gene and 1 thalassemia gene) semic parents
2) Homozygous states: Thalassemia major(early onset) & Thalassemia minor(late onset) 1. Thalassemia
 Thalassemia minor: carrier state, usually asymptomatic. Mild well-tolerated anemia major.
(Hb >9g/dl), which my worse in pregnancy. MCV>75fL, HbA2 >3.5%, slight HbF ↑. 2.Abortion, hy-
Often confused with iron deficiency anemia. drops fetalis
3. IUGR, IUD
 Thalassemia major (Cooley’s Anemia): denotes abnormalities in both β-globin genes
& presents in first year with severe anemia & failure to thrive. Extramedullary hematopoiesis occurs in re-
sponse to anemia causing characteristic head shape. e.g. skull bossing & hepatosplenomegaly due to hemol-
ysis.
β+ = reduced β-globin gene
• Clinical manifestations: βo = Absent β-globin gene
1. Parents are symptomatic by 12 months of age (often as early as 3 months)
2. Severe anemia & icteric tinge.
3. Mandibular prominence, depressed nasal bridge, frontal bossing
4. Abdomen become protuberance due to massive hepatosplenomegaly
5. Iron overload results in: Hepatic fibrosis & cirrhosis, Darkening of skin, sideroblastic cardiomyopathy
(arrythmias, CCF), & Endocrinopathies (DM, hypothyroidism).
• Diagnosis: Thalassemia Thalassemia
 CBC: 5-6 or less minor major
 Reticulocytes: increased (5-10%) 1. Mild ane- 1.Profound
 RBC morphology: microcytic hypochromic anemia, anisocytosis, poikilocy- mia hypochromic
tosis, Target cell, nucleated RBCs & Heinz bodies. 2.Microcytic anemia
 Hb electrophoresis: Diagnostic test hypochromic 2.Severe red
 Serum: Serum Fe is elevated, TIBC, Normal or elevated bilirubin. RBCs (not iron cell dysplasia
 X-ray: Hair on end pattern due to increase marrow activity & thinning of long deficient) 3.Erythroblasto
bone cortices. 3.Some target sis
cells. 4.HbA absent
 MRI: can monitor myocardial siderosis from iron overload. 4.Punctate ba- or reduced
 The film shows: Diagnostic features (see table) sophilia 5.Raised HbF
UHS Q: A 23 yrs old primigravida has been found to have mild anemia during outline antena- 5.Raised HbA2 6.Both parents
tal examination. Her husband, who is first cousin, also has mild anemia. Blood tests of pt. fraction are thalassemic
shows Hb 10.6g/dl with hypochromic microcytic picture. minor.
A. What further investigations required to determine cause of anemia?, B. Possible risks to
baby?, C. How could u prevent complications in baby? (S-2018)
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• Complications:
1. Iron Overload 1. Cardiomyopathy
2.Heart failure
3. Arrythmias
4.Hepatic fibrosis, cirrhosis
5.Endocrinopathy (Hypothyroidism, Hypoparathyroidism, DM, Hypogonadism, Delayed Pu-
berty)
2. Bone disease 1. Osteopenia
2.Osteoporosis
3. Infections HBV, HCV, Yersinia enterocolitis
4. Hyper coagulopathy Pulmonary embolism, Cerebral ischemia, DVT
5. Alloimmune & RBC
autoimmunization
• Management:
1. General:
* Discuss with the parents about nature, prognosis & Rx.
* Goals of therapy: maintain normal Hb level, prevent iron accumulation & promote iron excretion.
2. Transfusion Therapy:
* Packed RBC transfusion (15-20 ml/kg) should be given every 4-8 wks to maintain Hb level above 10g/dl
(mcq-uhs) or above 12g/dl.
* Required amount of packed cells: Formulae:
Desired Hb - present Hb * wt. in kg * 3
* Each unit of blood contains 200 mg iron.
3. Chelation therapy:
* Deferoxamine (Desferal) 20-60 mg/kg SC over 8 hrs by an infusion pump for a minimum of 5 nights /wk.
* Deferoxamine is initiated b/w 4-5 yrs of age when serum ferritin is greater than 1000 ng/ml & transferrin is
50% saturated.
4. Ascorbic acid, folic acid acid(5 mg daily).
5. Splenectomy: for splenomegaly causing mechanical problems, & excessive transfusion needs.
6. Bone marrow transplantation.
7. Hydroxy-urea
• Prevention:
1. Genetic counselling.
2. Fetal DNA analysis by chorionic villus sampling in 1st trimester or amniocentesis in 2nd trimester.
3. By fetal DNA analysis, diagnosis can be made before the 10th wk. of gestation.
UHS Q: A 58 yrs old lady is complaining of
7. Alpha Thalassemia: easy fatigue,breathlesssness as wel as numb-
• 4 α genes. ness&pins in her feet & legs. She also says that
• If one is deleted, no clinical effect. immediately after meals she develops nausea,
bloating, sweating&palpitation.In her past medi-
• If two are deleted, mild hypochromic anemia. cal history, it was noted that she underwent par-
• If three are deleted, pt. has HbH disease. tial gastrectomy 7 yrs ago. Her Hb 8.8g/
dl&MCV 104fl.She is –ve for H. pylori.
• If all four are deleted, baby is still born (Hydrops Bart's/fetalis) A.What may be the cause of anemia?
• Treatment: same as of β-thalassemia. B.How would explain her post-prandial syn-
drome?, C.What is explanation of her numb-
ness&pins and needles?
8. HbH disease:
• Due to excess of β-chains, so the pt.’s rely on low levels of HbA for O2 transport.
• Treatment: same as of β-thalassemia.
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9. Anemia of Chronic disease: (Secondary Anemia or Anemia of inflammation)

• Commonest anemia in hospital pt.’s.
• 2nd most commonest anemia worldwide, after IDA.
• Hb usually in range of 8.5-11 g/dl.
• Defined as: “ A defect in body’s ability to make use of iron sequestered in stores within reticuloendothelial
system”.
• Pathology: Hepcidin, a regulator of iron metabolism, plays an important role in anemia of chronic disease.
In states where hepcidin level is abnormally high (e.g., inflammation), serum iron falls due to iron trapping
within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia
caused by an inadequate amount of serum iron being available for developing red cells.
• Clinical features: Symptoms are based on the severity of the anemia. The only other symptoms are
based on the specifics of the underlying disease.
• Diagnosis: UHS Q: A 23 yrs non-diabetic presents with h/o
1. Serum ferritin level is normal or elevated. paraehtesias in arms&legs.On examination, he is
markedly pale & beefy red tongue, he has got loss of
2. Serum iron level and total iron binding capacity (TIBC): ↓. touch, pain, proprioception& vibration in glove stock-
3. Reticulocyte count is low. ing distribution. Her planters are down going &ankle
4. MCV normal usually (normocytic, normochromic). reflexes are diminished with preserved other deep
5. Hb level >8g/dl. reflexes. A. what is the cause of these symptoms?,
B.How will you treat these pt’s?, C.What is the signif-
• Treatment: icance of vitiligo in these pt.’s? (S-2014)
1. Correct the underlying disease.
2. Iron supplementation and erythropoietin will not help, except in renal disease and anemia caused by chem-
otherapy or radiation therapy.
3. Iron give parenterally can safely overcome functional iron deficiency anemia.
10. Sideroblastic Anemia:

• Microcytic anemia caused by a disorder in the synthesis of hemoglobin, characterized by trapped iron in
the mitochondria of nucleated RBCs.
Hereditary Acquired form
• Associated with myelodysplastic syndromes and refractory anemia. form
Sideroblastic anemia may progress to acute myelogenous leukemia
• Clinical features: Symptoms are related to the severity of the anemia. 1. Due to a de- 1. Due to drugs
fect in ami- such as chloram-
• Diagnosis: nolaevulinic acid phenicol, isoniazid,
1. Serum ferritin level is elevated. Transferrin saturation is very high, and synthase. “or” 2. or alcohol. 2.
thus TIBC is very low. Serum iron level is high. An abnormality Lead poisoning can
2. The most specific test is a Prussian Blue stain of RBCs in the marrow that in vitamin B6 cause sideroblastic
will reveal the ringed sideroblasts. Marrow reticuloendothelial iron is metabolism. anemia as well.
strikingly increased. *Sideroblastic anemia is the only microcytic ane-
mia in which serum iron is elevated.
• Treatment:
1. Remove the offending drug. Some patients, especially those with INH-associated sideroblastic anemia, will
respond to pyridoxine therapy 2-4 mg per day.
2. Consider transfusion for serious cases and BMT for refractory cases.
11. Hemolytic Anemias:

caused by decreased RBC survival from increased destruction of the cells. (The destruction may be inside the
blood vessels (intravascular) or outside (extravascular), which generally means inside the spleen).
• Hemolytic anemia may be:
1. Chronic (sickle cell disease, paroxysmal nocturnal hemoglobinuria, and hereditary spherocytosis) or
2. Acute (drug-induced hemolysis, autoimmune hemolysis, or G6PD deficiency).
UHS Q: A 15 yrs boy is brought to you with fever,palor&dyspnea.O/E, there I marked pallor but no hepatosplenomeg-
aly&lymphadenopathy.Hb 6.5g/dl,TLC:1800/cumm, DLC: Polys20%,Lymphos78%,monocytes2%,eosinophils
0%,basophils0%,platelets 25,000/mm3.No blast cells or other premature cells on smear.
A.Most likely Diagnosis?, B.Investigations required to establish diagnosis?, C.Treatment required in this case? (A-2008)
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• Clinical Features: The usual symptoms of anemia are present based on the severity of the disease, not
necessarily the etiology. Fatigue and weakness occur with mild disease. Dyspnea and later confusion
occur with more severe disease. The major difference between hemolytic anemia and the micro- and
macrocytic anemias is that hemolysis is more often the etiology when the onset is sudden. This is, of
course, provided that simple blood loss has been excluded. Hemolysis is often associated with jaundice
and dark urine as well. Fever, chills, chest pain, tachycardia, and backache may occur if the intravascular
hemolysis is particularly rapid.
• Classification of Hemolytic anemias:
Hereditary Anemias Acquired Anemias
Immune
• Autoimmune: warm antibody type,
cold antibody type
Membrane: hereditary spherocytosis,
• Alloimmune: hemolytic transfusion reactions,
hereditary elliptocytosis
hemolytic disease of the newborn, allografts
(especially stem cell transplantation)
• Drug-associated
Metabolism: G6PD deficiency, pyruvate
Red Cell Fragmentation Syndromes
kinase deficiency, Pyrimidine 5’-nucleotidase
Hemoglobin: genetic abnormalities
Infections: malaria, clostridia
(Hb S, Hb C, unstable)
Chemical and Physical Agents: drugs, Indus
trial/domestic substances, burns
Secondary: liver and renal disease
Paroxysmal Nocturnal Hemoglobinuria
Mechanical: prosthetic valves, HUC, DIC, March Hburia
• Diagnosis:- * Investigation results indicating active hemolysis:-

Diagnosis of Extravascu- Diagnosis of intra-
lar Hemolysis vascular hemolysis Hall marks of hemolysis Additional features of
* Pt. RBCs are labelled * ↓ Haptoglobin intravascular hemolysis
with 51Cr .These are re- ↓ Hb ↓ Haptoglobin
injected to determine red * Methemoglobin de- ↑ Unconjugated bilirubin ↑ methemoglobin
cell survival. tected spectrophoto- ↑ LDH +ve urinary hemosiderin
This test indicates whether metrically in Shumm’s ↑ Reticulocytes Hburia
spleen or liver is the main test. ↑ Urinary urobilinogen
source of RBC destruc-
tion.
• Treatment:-
1. Transfusion is needed in all anemias, when hematocrit is low.
2. Hydration to protect kidney from toxicity of free hemoglobin.
3. Specific Therapy:
4. Pt.’s with chronic hemolytic anemia need to be maintained on chronic folic acid therapy, as there is an
increase in cell turnover.
12. Autoimmune Hemolytic Anemia (AIHA):-

• Various forms of acquired hemolytic anemias can result from the production of IgG, IgM, or activation of
complement C3 against the red cell membrane. The destruction of the cells most often occurs through mac-
rophages in the spleen or by Kupffer cells in the liver.
• Causes:- (1) Idiopathic.(2) Various forms of leukemia, especially chronic lymphocytic leukemia (CLL),
myeloma.(3) viral infections.(4) lymphoproliferative disorders.(5) collagen vascular diseases like lupus.
(6) Drugs: Penicillin, cephalosporins, sulfa drugs, quinidine, methyldopa, procainamide, rifampin, and thia-
zides.(7) Ulcerative colitis can also lead to autoimmune hemolytic anemia.(8) Autoimmune (SLE, RA).
11
• AIHA may be warm AIHA (at body temperature) or cold AIHA(at <4 0C).
• Warm AIHA: It is IgG mediated and binds to red cells at body temperature (37 0C).
• Cold AIHA: is an IgM antibody produced against red cell(bind at ↓ temperature.i.e <4 0C) in association
with malignancies such as lymphoma or Waldenstrom macroglobulinemia, and infections such as EBV,
mononucleosis or mycoplasma.Occurs predominantly in liver. Presents often with Raynauds phenomenon.
• Clinical Features:
* Symptoms are generally related to the severity of the anemia, not the etiology.
* The onset may be very sudden resulting in fever, syncope, congestive failure, and hemoglobinuria.
* Mild splenomegaly occurs when the disease has occurred long enough for the time it takes spleen to enlarge.
* The drug history is often the clue with drug-induced varieties.
* Cold agglutinin disease results in cyanosis of the ears, nose, fingers, and toes.
* Weakness, pallor, jaundice, and dark urine may occur in all forms of hemolysis of sufficient severity.
• Diagnosis: UHS Q: 32 yrs old with recent onset complains of low grade fever, yellowish discolora-
1. Normocytic anemia tion of eyes&urine & palpable spleen.Hb 8g/dl with retics 5%.Bilirubin 5mg/dl with
2. Reticulocytosis 4mg indirect bilirubin. Urinary urobilinogen +ve while HbsAg & Anti-HCV –ve.
3. ↑ LDH A) Diagnosis? & write 4 possible causes if disease is caused by auto-antibodies without
infection., B) What abnormalities seen on peripheral blood picture?, C) How will you
4. Absent or ↓ Haptoglobin. treat this case?
5. Increased indirect bilirubin.
6. Coombs test: direct combs test is Diagnostic. (*-ve in brisk hemolysis)
7. Peripheral Blood picture: Spherocytes, raised retics, polychromasia
• Treatment:
Cold AIHA Warm AIHA
1. Keep warm 1. Steroids.
2. Chlorambucil may help. 2. Splenectomy.
3. Rituximab & plasmapheresis. 3.Immunosuppressants.
* Liver mediated destruction is not affected by steroids. 4. Severe hemolysis by IVIG, if no response to steroids.
13. Paroxysmal Nocturnal Hemoglobinuria(PNH) “or” (Marchiava-Micheli disease) :-

• It is a red cell membrane defect leading to intermittent dark urine and venous thrombosis and a chronic
form of hemolysis.
• A red cell membrane defect in phosphatidyl-inositol glycan A (PIG-A) allows increased binding of com-
plement to the red cell, leading to increased intravascular hemolysis .
• It is a clonal stem-cell disorder, and so can develop into aplastic anemia, leukemia, bone marrow failure &
myelodysplastic syndrome.
 Clinical Presentation.
1. s/s of anemia,
2. Pt.’s present with dark urine from intravascular hemolysis.
3. Thrombosis of major venous structures, particularly the hepatic vein (Budd-Chiari syndrome), is a com-
mon cause of death in these patients.
4. Hemoglobinuria is most common in the first morning urine because the hemolysis occurs more often when
patients develop a mild acidosis at night due to hypoventilation.
 Investigations:
1. Increased LDH, bilirubin, and reticulocyte count.
2. Low haptoglobin and hemoglobin in the urine.
3. Hemosiderinuria occurs when the capacity of renal tubular cells to absorb and metabolize the hemoglobin is
overwhelmed, and the sloughed off iron-laden cells are found in the urine.
4. The gold standard test is flow cytometry for CD55 and CD59 on white and red cells. In PNH, levels are
low or absent.
 Treatment: depends on the severity of symptoms.
1. Some patients with few or no symptoms require only folic acid and possible iron supplementation.
2. In the anemic patient with signs of hemolysis, prednisone is given to slow the rate of RBC destruction.
3. In the patient with acute thrombosis, thrombolytic therapy (streptokinase, urokinase, or tissue plasminogen
activator) is often administered, followed by long-term anticoagulants to help prevent further blood clots.
12
4. Antiplatelet agents such as aspirin and ibuprofen may also help prevent blood clots.
5. Avoid medications that increase the risk for thrombosis, such as oral birth control pills.
6. Allogenic bone marrow transplantation is main stay curative therapy.
7. Eculizumab (Anti-complement C5 monoclonal antibody) *Pt. should get vaccinated against N. meningitidis.
14. Glucose-6-Phosphate Dehydrogenase(G6PD) Deficiency:

 Most common human enzymopathy.
 A hereditary deficiency of an enzyme for producing the reducing capacity necessary for neutralizing oxi-
dant stress to the red cell resulting in acute hemolysis.
Oxidant stresses:
• Clinical features: Patients are normal until exposed to the stress. 1. Infections (most com-
1. Neonatal jaundice: features of β– enzyme. mon).
2. Favism ( after eating bread beans). 2. Most commonly impli-
3. A sudden, severe, intravascular hemolysis can occur including jaundice, dark urine, cated drugs are sulfa
drugs, primaquine, dap-
weakness, and tachycardia. sone, quinidine, and ni-
* The history of recent drug ingestion is the main clue to the diagnosis. trofurantoin.
• Diagnosis: 3. Hinna (Mehndi)
1. Blood film: High LDH, bilirubin, and reticulocyte count with a normal MCV, low
haptoglobin, and hemoglobinuria. Heinz bodies are precipitated hemoglobin inclusions seen in red cells.
Bite cells are seen on smear indicating the removal of the Heinz bodies. Polychromasia reflecting reticulo-
cytosis. Blister cells.
2. Definitive test is the G6PD level, which can be falsely normal immediately after an episode of hemolysis.
Hence, the level is best tested about 1 week after the event.
• Treatment: 1. No specific therapy. 2. Hydration 3. Transfusion,if the hemolysis is severe. 4. The main
therapy is to avoid oxidant stress in the future.
15. Polycythemia: A disorder of red cell production. Red cells are produced in excessive amounts.
 Male: Hb >18g/dl or HCT >0.60
 Female: Hb >16.5 g/dl or HCT >0.56
Primary causes Secondary causes
15a. True Polycythemia: Myeloproliferative 1.Increased Epo (erythropoietin) due to tissue hypoxia,
• ↑ RBCs, plasma volume normal disorder .i.e. poly- high altitude, lung disease.
• Causes: see table cythemia rubra 2.Inappropriately increased Epo: renal disease, hydro-
vera, PPP nephrosis, cyst, tumor
15b. Apparent/Relative or Low volume Polycythemia:
• ↓ plasma volume, RBCs normal
• Causes: Diuretics, Smoking, Obesity, Alcohol, Gaisbock’s syndrome
15c. Polycythemia Rubra Vera:

 Red cells are produced in excessive amounts in the absence of hypoxia or increased erythropoietin levels.
 Mainly in pt.’s over 40 years of age.
• Clinical Presentation: Patients present with: UHS Q: A 62 yrs retired accountant presents with
1. Markedly elevated hematocrit. excessive tiredness, visual disturbance& dull pain in
left upper abdomen.O/E,he is plethoric with congest-
2. Splenomegaly. ed conjunctiva & has 8cm palpable spleen. (S-2012)
3. Lassitude, loss of concentration, black-out, headache. A.Give 3 most likely possibilities for gentlemen
4. Sometimes elevation of the platelet and white cell counts. condition?, B.Give three appropriate investigations?
5. Thrombosis. C.Give 3 most important steps in treatment?
6. “Plethora” or redness and fullness of the face.
7. Pruritis (approximately 40% of patients), particularly after exposure to warm water such as in a shower or
bath; possibly caused by abnormal histamine or prostaglandin production.
• Diagnosis: (1) High hematocrit in the absence of hypoxia, carbon monoxide poisoning, or elevated
erythropoietin level.
(2) The most specific test is the Janus Kinase or JAK-2 mutation. (+ve in 95% cases).
13
• Treatment: (1) Phlebotomy is the primary treatment.

(2) Hydroxyurea may be used in higher risk pt.’s(age >60 yrs). UHS Q: An 8yrs girl presented with ex-
treme pallor, gum bleeds, purpura with lym-
(3) Aspirin is used to reduce the risk of thrombotic events. phadenopathy &hepatosplenoegaly.She con-
(4) Aim is to keep HCT <0.45 to reduce the risk of thrombosis. sult her physician who referred her to
(5) In younger pt.’s at low risk, venesection is done. THQ,where investigations carried out. Only
a week later, she was ill again with fever,
severe headache &extreme lethargy.
16. Acute Leukemia: A.Diagnosis?, B.Investigations?,
 Failure of cell maturation is called as leukemia C.Treatment options? (A-2015)
 Acute Lymphocytic leukemia(ALL) is more common in children.
 Acute myelogenous leukemia(AML) is more common in adults.
Sign & symptoms of ALL Sign & symptoms of AML
1.Marrow failure: Anemia, infection, bleeding 1. Same s/s as of ALL except of CNS involvement and lymphade-
2.Infiltration: Hepato & splenomegaly, lymphadenopa- nopathy.
thy, orchhidomegaly, CNS involvement(CN palsy, menin- 2. DIC may occur in a subtype of AML (acute promyelocytic leu-
gism) kemia t15;17) (mcq-uhs)
3. Gum hypertrophy & skin involvement.
• Investigations:
1. CBC: Anemia with normal or raised MCV, (pancytopenia+blasts), WBC count is often increased but can
be normal or even low.
2. Blood smear/Peripheral picture: Blast cells are diagnostic => best initial test.
3. Bone marrow: Hypercellular, with replacement of normal elements by leukemic blast cells in varying de-
grees.=> most valuable diagnostic test.
4. Trephine biopsy: If now marrow is obtained, blast cells more than 20%. * Common infections:
1.Especially Chest, mouth, perianal &
5. Auer rods are present in myeloblastic type of leukemia (AML). skin,
6. Serum uric acid level ↑ 2.Bacterail septicemia (Staph Aureus,
7. Serum calcium Staph. epidermidis)
8. Blood culture 3. Zooster, 4.CMV, 5.Candidiasis,
9. X-ray Chest(CXR): Lymphoblastic leukemia has a mediastinal mass. 6.Measles,7.Pnemocystis pneumonia
10. CSF: meningeal leukemia have blast cells in CSF
11. Flow cytometry: Most accurate test. It will distinguish different subtypes of acute leukemia. It is the
method of detecting CD-subtypes with each type of leukemia. Myeloperoxidase is characteristic of AML.
Phase ALL AML
• Management:
A. Supportive: Remission induction: Vincristine (I/V) Daunorubicin (I/V)
1. Anemia:Red cell concentrate transfusion In this phase, a fraction Prednisolone (oral) Cytarabine (I/V)
2. Thrombocytopenia: Platelet transfusion of tumor is destroyed by Daunorubicin (I/V) Etoposide (I/V)
3. Infections: Immediate antibiotics, start a combination therapy. Methotrexate(intrathecal) Altran's retinoic acid
Imatinib (oral) Arsenic trioxide
neutropenic regimen. L-asparaginase (ATO)
Bacterial: Empirical therapy (gentamicin+
tazobactam) for 9 days. Co-trimoxazole dur- Consolidation phase: Daunorubicin (I/V) Cytarabine (I/V)
ing chemotherapy as prophylaxis for P. jiro- If remission has been Cytarabine (I/V) Amsacrine (I/V)
vecii. achieved, residual dis- Etoposide (I/V & oral) Mitoxantrone (I/V)
Fungal: I/V nystatin, amphotericin, capso- ease is attacked by thera- Methotrexate (I/V)
py during this phase.
fungin/voriconazole
Viral: Acyclovir Maintenance phase Prednisolone (oral) -
4. Metabolic problems: Fluid balance with Vincristine (I/V)
Methotrexate (oral)
allopurinol/rasburicase (prevents tumor Imatinib (oral)
lysis syndrome) Mercaptopurine (oral)
5. Psychological support.
Relapse Fludarabine Fludarabine
Cytarabine Cytarabine
B. Specific treatment: (See table) Idarubicin Arsenic trioxide
C. Bone marrow transplantation. (ATO)
14
• Outcome in Adults Acute leukemia:

Poor risks Good risks Intermediate risk
AML Cytogenic abnormalities Promyelocytic leukemia(t15;17) AML with none of the above
-5, -7 deletions t(8;21)
5q, abn(3q), complex (>5) Inv 16 or t(16;16)
Poor risk Standard risk
ALL Philadelphia chromosome ALL with none of the above
High WCC >100 *109/L
Abnormal short arm of chromosome 11 t(1;19)
17. Chronic Myeloid Leukemia (CML):

 Chromosomal abnormality: Philadelphia(Ph) chromosomes (defining characteristic).This is shortened
chromosome 22 resulting from a reciprocal translocation of material with chromosome 9(BCR-ABL gene
fusion).
 Usually b/w age 30-80 years.
UHS Q: A 50 yrs old man
• Clinical features: presented to OPD with
1.Chronic phase: weakness, shortness of
A. non-specific: fatigue, night sweats, low grade fever, gout, wt. loss breath,wt. loss&fever for
B. Abnormal fullness: splenomegaly last 1 month.O/E,he was
Examination: a. Splenomegaly in 90% and may extend 15cm below costal margin. pale looking&no lymphad-
enopathy. His speen was
b. Sternal tenderness due to marrow over-expression moderately enlarged. His
c. Hepatomegaly 50% Hb 7g/dl,TLC:80,000/
d. A friction rib may be heard in cases of splenic infarction. cm3,Neutrophils70%,lymp
2.Accelerated phase: hocytes15%,platelets↑.
A. fever A.Diagnosis?Give 2 other
causes of large spleen?,
B. bone pain B.Chromosomal abnor-
C. splenomegaly mality in this dis-
D. pruritis after hot bath due to histamine release from basophils. ease?,C.Drug treat-
3.Blast crisis: Bleeding and infection ment&curative treatment?
(S-2015 held in 2016)
• Investigations:
Chronic phase:
1. CBC: Normocytic normochromic anemia, elevated WBCs=150,000/µL, greatly increased neutrophils,
blast cells are usually less than 5%, Platelet count normal or elevated(2000 * 109/L), Basophilia tends to
increase as disease progress
2. Peripheral blood picture: nucleated RBCs, full range of granulocyte precursors, but predominant are neu-
trophils and myelocytes.
3. Bone marrow biopsy: hypocellularity with left shifted myelopoiesis
4. Neutrophil alkaline phosphatase: LAP score is low.
5. Serum vitamin B12: high due to increase secretion of transcobalamin.
6. Philadelphia chromosomes and RNA analysis: BCR & ABL genes done by PCR or FISH.
7. LDH level: Elevated due to breakdown of cells
• Treatment:
 Drug Treatment:
1. Chronic Phase:
A) Inhibitors of Tyrosine kinase(1st line therapy):
1st line: Imatinib, Nilatinib & Dasatinib 2nd line: Bosutinib & Ponatinib
*Normalizes blood count within a month & within 3-6 months produce complete cytogenic response
(disappearance of Philadelphia chromosome) in 90% of pt.’s.
*Imatinib 400 mg/dl reduce 76% Ph chromosome for 18 months & PCR after every 3 months for BCR-ABL
mRNA transcripts in blood. A sample of bone marrow is taken at 6 months to conform complete cytogenic re-
sponse.
B) α-interferon: Alone or in-combination with Ara-c 75%, reduce 20% Ph chromosome in women planning
pregnancy.
15
C) Hydroxyurea: Hydrea 500 g was previously used.

D) Bone marrow transplantation.
2. Treatment of accelerated & blast crisis: *When blast transformation occurs, type of blast
A) Imatinib: If not indicated already in chronic phase. is determined. Acute leukemia treatment with 2nd
B) Hydroxycarbamide: Effective single agent or 3rd generation TKI such as dasatinib.
C) Cytarabine
 Curative Treatment:
Allogenic hematopoietic stem cell transplantation(HSCT) => in younger & fitter pt.’s if return to chronic
phase is achieved.
18. Chronic Lymphocytic Leukemia(CLL): (most common variety of leukemia)

 male: female = 2:1
Stage A No anemia or
 Median age: 65-70 years thrombocytope-
• Clinical features: nia and less
1.Insidious onset. than three areas
2.Mostly pt.’s are asymptomatic and presents with painless lymphadenopathy. of lymphoid
enlargement.
3.Splenomegaly
4.Hepatomegaly. Stage B No anemia or
thrombocytope-
• Investigations: nia and with
1. CBC: Mild anemia, platelets count usually normal, mature lymphocytosis three areas of
2. Bone marrow: not necessary for diagnosis, but for prognosis and monitoring. lymphoid en-
3. Reticulocyte count: largement.
4. Direct comb test: as autoimmune hemolytic anemia Stage C Anemia &
5. Immunophenotyping: b-cell antigen: CD19, CD23, T-cell antigen CD5 thrombocytope-
6. Serum immunoglobulin level(to check degree of immunosuppression): low nia, regardless
of no. of areas
• Treatment: of lymphoid
 Stage A: No specific treatment required, until progression occurs. Life expectancy enlargement.
normal in older pt.’s.
 Progressive stage A, stage B &
stage C: depends on:
age, fitness & TP3 mutation status.
 Supportive care:
1. Anemia/ Thrombocytopenia: transfusions
2. Infections: antibiotics
3. Hypogammaglobulinemia: Immunoglobulins replacement
4. Lymphadenopathy/Symptomatic splenomegaly: radiotherapy
5. Low blood count due to autoimmune destruction: splenectomy
6. Bone marrow failure/Autoimmune cytopenia's: Glucocorticoid treatment
UHS Q: 70 yrs old with 3 months h/o fever, bone apins in back&ribs, wt. loss & recurrent UTI’s. Tenderness in bilateral flanks.ESR
110mm,calcium 12(8-10),total proteins 11g/dl,albumin 3g/dl&globulin 8/dl.
A.Diagnosis?, B.Four investigations to conform diagnoses?, C.Four reasons for renal impairment? (A-2018, A-2016)
UHS Q: A 65 yrs man presents with low grade fevr for last 6 wks. He also complains of bone pains, weakness&early fatigue. His
workup reveals ESR 112 mm fall in 1st hr, Hb 10.2g/dl,normal TLC,DLC&platelets.His serum Ca was found to be elevated with a
normal alkaline phosphatase.X-ray reveals multiple round to oval lytic lesions in his bones. (S-2011)
A. Most likely diagnosis?, B.What three investigations will help to make a diagnosis?, C.What three specific therapies ay be helpful?
16
19. Hodgkin’s Lymphoma: Histological sub-types

Histological Subtypes of Hodgkin’s Lymphoma
• A neoplastic transformation of lymphocytes particularly in the Nodular sclerosing 70% Young& wom-
lymph node. It is characterized by the presence of Reed- en
Sternberg cells on histology.
Mixed cellularity 20% Elderly
• Median age: 31 years, 1st peak at 20-35 yrs and 2nd at 50-70 yrs.
• Three times more likely with past history of inf. Mononucleosis. Lymphocyte rich 5% Men
 Clinical features: Lymphocyte depleted rare Poorest progno-
1. Painless rubbery lymphadenopathy at neck and supraclavicular sis
fossa. Lymphocyte predomi- 5%
2. Mediastinal masses: dry cough & breathlessness in younger pt.’s nant
with nodular sclerosis.
3. Hepatosplenomegaly. Clinical stages of Hodgkin lymphoma
(Ann Arbor classification)
 Investigations:
I Involvement of a single lymph node re-
1. CBC: Normal,normocytic anemia & lymphopenia:bad gion or extralymphatic site
prognostic
2. ESR: may be raised II Involvement of two or more lymph node
regions or an extralymphatic site and
3. Renal function test: checking for treatment lymph node regions on the same side of
4. LFT’s: may be infiltration the diaphragm
5. LDH: raised: bad prognostic
III Involvement of lymph node regions on
6. CT-scan: for staging bulky disease (greater than 10cm in both sides of the diaphragm with or with-
single nodal mass is an adverse prognostic factor) out localized extralymphatic involvement
7. Lymph node biopsy: Undertaken surgically or by percuta- or involvement of the spleen or both
neous needle biopsy under radiological guidance. IV Diffuse involvement of one or more ex-
8. PET: allows more accurate staging. tralymphatic tissues, e.g. liver or bone
 Treatment: marrow
 Stage I & II: Radiotherapy and Chemotherapy :- *Each stage is sub-classified as A & B.
ABVD regimen: (Doxorubicin, vinblastine, Bleomycin, A No systemic symptoms
Dacarbazine) (4 courses)+ 30 Gy radiotherpay B Weight loss >10%, drenching sweats
*Prognosis is checked by CT & PET
 Stage III &IV: 6-8 cycles of ABVD regime; prognosis by PET.
 Bone marrow transplantation: resistant patients.
20. Non-Hodgkin's Lymphoma:

 The neoplastic transformation of both the B and T cell lineages of lymphatic cells.
 The Reed-Sternberg cell is absent.
 Etiology:
Infections such as HIV, hepatitis C, Epstein-Barr, HTLV-I, and Helicobacter pylori. HIV and Epstein-Barr are
both more often associated with Burkitt lymphoma.HIV can also be associated with immunoblastic lymphoma.
 Clinical Presentation:
1. Enlarged, painless, rubbery, nonerythematous, nontender lymph nodes are the hallmark of the disease.
2. Patients may also develop “B” symptoms, which are drenching night sweats, 10% weight loss, and fevers.
3. Although pruritus is common in the disease, it is not one of the “B” symptoms.
 Difference b/w HL and NHL:
The Hodgkin disease is localized to cervical and supraclavicular nodes 80–90% of the time, whereas NHL is
localized only 10–20% of the time. NHL is far more likely to involve extralymphatic sites as well as to have
blood involvement similar to chronic lymphocytic leukemia. CNS involvement is also more common with
NHL. HIV-positive patients often have CNS involvement. The staging system for NHL is the same as for HL.
 Investigations:
1.Initially on an excisional lymph node biopsy.
2.After this, the most important step is to determine stage of the disease to determine therapy. NHL is far more
likely to be widespread at initial presentation. Lymphangiography is never necessary, and staging laparotomy
is rarely needed.
3.The bone marrow biopsy is more central as an initial staging tool.
4.As with HL, leukopenia, eosinophilia, high LDH, and high ESR often accompany the disease.
17
5.PET scanning is highly sensitive and specific for Rituximab is an anti-CD20 antibody that has limited toxicity and
nodal and extranodal sites but not for bone marrow adds survival benefit to the use of CHOP. Thus, R-CHOP would
disease. then become first-line therapy. Prior to using R-CHOP, always
test completely for hepatitis B and C, as rituximab can cause ful-
• Treatment: minant liver injury in those with active hepatitis B or C disease.
1. Stage IA & stage IIA: predominantly radiotherapy.
2. All those with “B” symptoms as well as stages III and IV: Combination chemotherapy.
The initial chemotherapeutic regimen for NHL is CHOP (cyclophosphamide, hydroxy-Adriamycin, oncovin
[vincristine], prednisone).
3. CNS lymphoma is often treated with radiation, possibly in addition to CHOP.
4. Relapses of NHL can be controlled with autologous bone marrow transplantation.
5. Some patients with NHL express CD20 antigen in greater amounts. When this occurs, monoclonal antibody
rituximab should be used.
21. Tumor Lysis Syndrome:

• It is an oncotic emergency caused by massive tumor lysis, with the release of large amount of potassium,
phosphate and uric acid into the systemic circulation. Follows initiation of cancer treatment.
• Hyperkalemia, Hyperphosphatemia, Hyperuricemia, Hypocalcemia & Acute renal failure.
• S/S: Lethargy, edema, fluid overload, CHF, cardiac arrythmias, syncope & sudden death.
• Investigations: a) BUN, b) creatinine, c) uric acid ↑, d) K+ ↑, e) Ca+2 ↓, f) P-4 ↑, g) LDH
• Treatment:
1. Allopurinol: for hyperuricemia
2. Hydration: Aggressive I/v hydration
3. Urine alkalization: to solubilize & to minimize intratubular precipitation of uric acid.
4. Rx of hyperkalemia: Restrict dietary K+, I/V infusion of glucose+insulin, Ca-gluconate
5. Dialysis: if the above treatment fails.
• 22. Multiple Myeloma: (Male: female = 2:1)

• Malignant proliferation of plasma cells. In myeloma, plasma cells produce immunoglobulins of single
heavy and light chain, a monoclonal protein referred to as paraprotein.
• Median age of diagnosis: 60-70 years
• Classification:
Type of paraprotein Relative frequency
IgG 55%
IgA 21%
Light chain only 22%
Others (D, E, non-secretory) 2%
• Clinical features: * β2-macroglobulins correspond
1. Bone pain: particularly in ribs and axial skeleton. to the severity of the disease.
2. Infections * Myeloma has decreased anion
3. Symptoms of anemia & pancytopenia due to marrow involvement. gap.
4. Bleeding * Rouleaux in peripheral blood
5. Renal disorder picture/blood smear.
6. Features of hypercalcemia. E.g. Thirst & polyurea * Reasons of Renal Impairment:
7. Skin changes: purpura, pruritis. 1. Paraprotein deposition.
8. Hyperviscosity syndrome: Blurred vision, headache, Vertigo, Stupor & coma. 2. Hypercalcemia
9. Anorexia, vomiting, hyperuricemia 3. Amyloid
• Investigations: Diagnosis of multiple myeloma requires two of following: 4. Infections.
5. NSAIDs
1. X-rays (skeletal survey): Presence of lytic (punched-out) lesion, bone fractures
2. Blood & urine protein electrophoresis: Presence of urine/plasma paraprotein
3. Bone marrow aspiration & trephine biopsy: Presence of >10% plasma cells in bone marrow.
4. Plasma Immunoglobulins level
18
• Management:
* Treatment is administered until paraprotein levels have stopped falling. This is termed “plateau phase” & can
last for weeks or years.
A. Supportive/Immediate treatment:
1. High fluid intake to treat renal impairment & hypercalcemia. Prognosis: Survival
(International staging system-ISS)
2. Analgesia for bone pain.
3. Bisphosphonates for hypercalcemia, prevents fracture. ISS-stage 3 High β2 macroglobulinemia 29 months
4. Allopurinol to prevent urate nephropathy. Low albumin
5. Plasmapheresis for hyperviscosity. ISS-stage 1 Normal albumin 62 months
B. Specific treatment: Low β2 macroglobulin
1. Chemotherapy:
In Older Pt.’s In Young Pt.’s
1. Thalidomide with alkylating agent, melphan & predniso- 1. Standard treatment includes first line therapies such as
lone (MTP). (cyclophosphamide, thalidomide & dexamethasone) or (Bortezomib,
2. Lenalidomide for pt.’s not eligible for transplantation & thalidomide & dexamethasone) to maximum response.
intolerant to above therapy. 2. And then analogous HSCT that improves only survival.
3. VAD (vincristine, Adriamycin, dexamethasone) can also be given.
2. Radiotherapy:
* Effective for localized bone pain not responding to analgesia & for pathological fractures.
* Emergency treatment of spinal cord compression complicating extradural plasmacytomas.
3. Transplantation:
* Autologous stem cell transplant under 65 years of age.
* Allogenic stem cell transplant is effective under 55 years of age.
23. Bleeding Disorders:

Bleeding disorder Bleeding time Clotting time PT APTT
Hemophilia A normal ↑ normal ↑
ITP ↑ - normal Normal
Von Willebrand disease ↑ - Normal ↑
DIC - - ↑ ↑
23(A). Hemophilia A:- (X-linked recessive disorder) most common congenital coagulation disorder.
1. Skin: Bruising, mucus membrane bleeding
2. Muscles: Hematoma,mostly in calf & psoas muscles.
3. Joint: hemarthosis (most crippling hallmark of Hemophilia A)
• Diagnosis:
1. +ve family history (diagnosis is usually made after 6 months when babies become more mobile)
2. APTT: ↑
3. BT: normal
4. PT: normal
5. CT: ↑
6. vWF: normal
7. Conformed by decreased level of factor VIII activity with normal vWF.
8. Molecular genetic techniques & ratio of factor VIII to vWF(carrier).
• Management:
* Key to management of severe hemophilia A is prophylactic coagulation factor replacement.
* The aim of treatment is to maintain trough levels of factor VIII (IX in Hemp. B) above 0.02 U/ml.
A. Supportive:
1. Prevention of trauma.
2. Avoid aspirin. 3. Immunization for Hepatitis A & B.
19
B. Specific: * For life threatening bleeding, levels of 80-100% of normal factor VIII
1. Desmopressin acetate. necessary.
2. Aminocaproic acid + Tranexamic acid. * For mild to moderate bleeding, episodes(e.g. hemarthrosis), a 40% level
3. Administration of factor VIII concentrate. for factor VIII is appropriate.
4. Cryoprecipitate: (fibrinogen + VIII + XIII) dose calculation= desire * wt. * 0.5
5. If factor VIII concentrate not available, then fresh blood & fresh frozen plasma can also be given.
C. Prevention:
1. Genetic counselling. UHS Q:A 29 yrs woman presents to her
2. Antenatal diagnosis. gynecologist with menorrhagia. Her doctor
noticed her to have purpura over forearms,
• Complications: Blood complete examination: normal except
1. Intracranial hemorrhage a low platelet count.
2. Hemarthrosis A.Diagnosis?, B.What immediate treatment
3. Large I/M hematoma you can start?, C.What do u expect to show
on bone marrow examination?, D.What is
4. Development of antibodies to factor VIII, ↑ dose of factor short term& long term treatment? (S-2013)
VIII.
5. Therapy related: Common infection; HIV, hepatitis B& C.
6. Mononeuropathy, resulting from pressure of hematoma. (Compartment syndrome)
7. Atrophy of muscles.
8. Atrophy of large joints. e.g. Knee, elbows, etc.
9. Encephalopathy
10. Massive retroperitoneal hemorrhage.
23(B). Idiopathic Thrombocytopenic Purpura:

• Immune mediated with involvement of autoantibodies, most often directed against membrane glycoprotein
IIb/IIIa, which sensitize the platelet, resulting in premature removal from cir-
culation by cells of reticuloendothelial system. * Causes:
1. Connective tissue disease
• Clinical features: 2. HIV infection
1. Spontaneous bleeding (when platelets <20 * 109/L) 3. Pregnancy
2. Bruising 4. Certain drugs.
3. Epistaxis
4. Acute ITP in children 2-3 week after viral infection.
5. Chronic ITP in adult women20-50 yrs.
• Diagnosis: * D/D:
1. Leukemia (blast cells)
1. CBC: Anemia, ↓ platelets, WBC normal 2. Aplastic anemia (pancytopenia)
2. Peripheral blood picture: Normal 3. DIC (PT & APTT↑
3. Infection: rule out HIV 4. Lymphoma: (lymphadenopathy)
4. Connective tissue disorder: ANA, Double strand DNA 5. SLE
5. BT: ↑
6. PT & APTT: normal
7. Bone marrow aspiration: Megakaryocytes ↑ (To look for accompanying β-cell malignancy in pt.’s over 65
yrs age)
8. Platelet associated IgG and Ig M.
9. Detection platelet autoantibodies. 10. USG or CT-scan to exclude hypersplenism.
UHS Q: A 31 yrs female who previously developed meneorrhagia, epistaxis & petechia over legs. O/E,she is febrile& has blood
filled bulla in her mouth& subconjunctival hemorrhage. Her spleen is not palpable. No h/o arthritis or any drug intake. Her lab
shows Hb 12.4, WBC 8200* 109/L,Bone marrow examination reveals normal finding with slightly increased number of megakaryo-
cytes. ANA is –ve.
A.Diagnosis?, B. What immediate therapeutic measures has taken?, C. If medical therapy is unsuccessful, what surgical measures
may be hepful? (Model paper 2007)
UHS Q: A middle aged female has h/o easy bruisability &bleeding from the gums for past 3 months.O/E,she has multiple small red
spots which donot blench on pressure, Investigations reveal increased bleeding time, with normal PT, platelet count is 50,000/cmm.
A. Diagnosois?, B.How will you investigate the patient? (S-2007)
UHS Q:A 25 yrs old girl presented with 3 mnths h/o bleeding gums, menorrhagia, bruising in the skin without significant gtrau-
ma.O/E, papable lymphadenopathy ot splenomegaly. She doesnot complain of joint pains or skin rash or loss of hair. Her blood film
shows: Microcytic hypochromic anemia, normal TLC with any immediate any immature cells. Bone marrow shows normal triline-
age cell lines without any evidence of neoplasm. Megakaryocytes were however increased in number.
A.How would you manage her? (A-2009)
20
• Treatment:
Presentation Management
1.No bleeding (platelet count >30,000) No Rx, except at times of surgery & biopsy.
2.Mild bleeding (spontaneous bleeding) *Prednisolone(1 mg/kg daily)
(platelet count <20,000) *Dexamethasone(40 mg daily for 4 wks.)
3.Severe hemostatic failure (GI/CNS) IVIgG, Anti-Rho(Anti-D)+ Glucocorticoids
4.Persistent/Potentially life threatening bleeding Platelet transfusion + above
5.In case of relapse Reintroduce glucocorticoids
6.In case of 2 relapses or primary refractory Splenectomy + immunosuppression(rituximab, ciclosporin, mycophenolate, tacro-
disease limus)
7. Splenectomy/ Steroids not effective TPO-RA (eltrombopag & romiplostim)
23(C). Von-Willebrand disease: (mostly Autosomal Dominant inheritance pattern)

1. Superficial bleeding. Reduced level of vWF is present in people
2. Bruising. with blood group “O”.
3. Epistaxis.
4. Menorrhagia * Contraindications to the use of desmopressin:
5. GIT Bleeding 1. Young children
• Diagnosis: 2. Severe arterial disease
1. vWF (Von-Willebrand factor) ↓ 3. Type 2B: Thrombocytopenia
2. Factor VIII ↓
3. Prolongation of BT, APTT
4. Ristocetin-induced platelet aggregation (RIPA): It is test of function to determine binding to glycoprotein
Ib): ↓ aggregation “or” Hypoactive agglutination occurs
5. PT normal and INR also normal.
• Management:
1. Mild hemorrhage: Desmopressin acetate which increases vWF with secondary increase in VIII.
2. Tranexamic acid: may be useful in case of mucosal bleeding.
3. Massive hemorrhage: selected factor VIII concentrate.
4. Cryoprecipitate can control bleeding in all types but only over 2-3 hrs.
5. Bleeding in type 3 pt.’s correspond only to factor VIII/vWF concentrate.
• Classification:
Type Defect Inheritance Investigation
1 Partial quantitative AD(Autosomal dominant) ↓ vWF, Ag & VIII
2A Qualitative AD Absent HMW of vWF
Ratio of vWF activity to antigen <0.7
2B Qualitative AD Reduced HMW, RIPA
2M Qualitative AD Normal HMW, interaction abnormal
2N Qualitative AR(Autosomal recessive) Defective binding of vWF to VIII
3 Severe Quantitative AD/CH 1 & 2A
UHS Q:A young boy of 12 yrs is referred by dentist for persistent bleeding after tooth extraction. There is previous h/o in-
creased bleeding from minor cuts in past few years. On investigation: increased bleeding time&APTT.Platelt count is normal
A.Diagnosis?, B.How will you treat this boy? (A-2007)
23(D). Disseminated intravascular coagulation (DIC):

1. Bleeding Promyelocytic leukemia(M3) is a
2. Thrombosis classical association.
21
• Diagnosis: * Causes/Underlying conditions:

1. Platelets ↓ 1. Infections/sepsis
2. APTT & PT prolonged 2. Trauma
3. Fibrinogen degradation products ↑ 3. Tissue destruction (pancreatitis, burn)
4. D-dimer ↑ 4. Obstetrics.e.g.Amniotic fluid embolism,pre-eclampsia
5. Severe liver failure
5. Thrombocytopenia 6. Malignancy.e.g. Solid tumors & leukemia
6. Anti-thrombin III level: may be very low 7. Vascular abnormalities (vascular aneurysms)
7. Reduction of clotting factors, particularly fibrinogen & 8. Toxic/Immunological(ABO incompatibility,snake bite)
factor II, V & VIII. Protein C↓
• Treatment:
ISTH scoring system for diagnosis
1. Treat the underlying cause of DIC is given on Davidson. If
2. General measures: anyone has to do it, please have a
Intensive care for:- acidosis, dehydration, renal failure, hypoxia look there. From exam point of
3. Replacement therapy: view, it is unimportant.
a) Platelet transfusion: to maintain platelets above 50,000/ul
b) Fresh frozen plasma(7-14 units): to correct coagulation factor deficiency
c) Cryoprecipitate: to replace fibrinogen
d) Packed red cell: Bleeding
4. Prophylactic dose of unfractioned heparin: for thrombosis
5. Activated protein C concentrate: for sepsis+ DIC
6. Tranexamic acid is contraindicated.
24. Venous Thrombotic Embolism (VTE)/ Pulmonary Embolism (PE)/

Deep venous Thrombosis (DVT):
• Risk factors:
Surgery Major abdominal/pelvic surgery; hip/knee surgery; postoperative intensive care
Pregnancy/puerperium
Cardiorespiratory disease COPD, congestive cardiac failure or other disabling disease
Lower limb problems Fracture; varicose veins; stroke/spinal cord injury
Malignant disease Abdominal/pelvic; advanced/metastatic; concurrent chemotherapy
Miscellaneous Increasing age, previous proven VTE, immobility, thrombotic disorders, trauma
• Investigations:
1. Chest X-ray(CXR): most cases have a normal CXR. It excludes heart failure, pneumonia or pneumothorax.
2. ECG: The most common findings in PE are sinus tachycardia and anterior T-wave inversion.larger emboli
may cause right heart strain with an S1Q3T3 pattern, ST-segment and T-wave changes, or right bundle
branch block
3. ABGs: a reduced PaO2 and a normal or low PaCO2, Metabolic acidosis may occur in acute massive PE
with shock.
4. D-dimer
5. CTPA(CT-pulmonary angiography): first line diagnostic. Contrast media should be taken with care in pa-
tients with renal impairment because of their nephrotoxic effect.
6. Ventilation/perfusion scanning: seldom used nowadays
7. Doppler USG of leg veins: investigation of choice in patients with suspected DVT but may also be used in
patients with suspected PE
8. Echocardiography: helpful in the differential diagnosis and assessment of acute circulatory collapse
9. Pulmonary angiography: now replaced by CTPA.
22
• Algorithm for the investigation of patients with suspected pulmonary throm-

boembolism :
• Treatment:
A) General:
1.Sufficient oxygen should be given to all hypoxemic patients to restore SpO2 to >90%
2.Hypotension is treated using IV fluid or plasma expander; diuretics and vasodilators should be avoided.
3.Opiates may be necessary to relieve pain and distress but should be used with caution.
4.External cardiac massage is successful in moribund patient by dislodging and breaking large central embolus
B)Specific: * Patients with persistent risk factors or previous VTE:

1.Anticoagulation: should be anticoagulated for life.
* LMWH followed by coumarin, like warfarin is * Patients with a reversible risk factor: 3 mths of therapy.
one of the options & continued for 5 days. * Patients with cancer-associated VTE: LMWH is more
* Direct oral anti-coagulant(DOAC): effective than warfarin.
Rivoraxaban & apixaban immediately after * Patients with unprovoked VTE: prolonged therapy should
diagnosis without the need of LMWH be considered, particularly in males, those in whom the D-
Dabigatran & Edoxaban after 5 day treatment dimer remains elevated 1 mnth. after stopping warfarin, and
with LMWH. those in whom recurrent PE may be fatal
2.Thrombolytic therapy:
Thrombolysis improves outcome when acute massive PE is accompanied by shock (systolic BP <90 mmHg)
but shows no advantage over heparin in normotensive patients.
3.Caval filters: Selected patients with recurrent PE despite adequate anticoagulation or those in whom antico-
agulation is contraindicated may benefit from insertion of a filter in the inferior vena cava below the origin of
the renal veins.
4.Mechanical Treatment for DVT:
) Intermittent pneumatic compression
Post-thrombotic syndrome: is due to damage to venous valves
) Graduated compression stockings by thrombus, in 30% pt.’s with proximal lower limb DVT & re-
) Mechanical foot pumps sults in ulceration around medial malleolus.
23
• Some Additional topics:
25. Thrombotic Thrombocytopenic purpura/Hemolytic

uremic syndrome:
• Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome
(HUS) are two varieties of the same disease process with considerable overlap.
There is no specific diagnostic test, so the diagnosis is based on the clinical triad
(HUS) or pentad (TTP).
• Primary TTP is idiopathic and arise from inhibition of the enzyme
ADAMTS13, which is responsible for cleaving large multimers of von Wil-
lebrand factor into smaller units.
• Secondary TTP: is caused by;
1) specific diseases (cancer, HIV)
2) drugs (ticlopidine, clopidogrel, cyclosporine, and interferon)
*ADAMTS13 activity is generally not as depressed in secondary TTP.
• HUS: predominantly affects children. Most cases are caused by a shiga-like toxin
produced by E. coli O157:H7 although Campylobacter, Shigella, and some viruses
have also been implicated. It is one of the most
• Diagnosis: * Do not give antibiotics to those with possible
1. The anemia in both will be intravascular in nature and will HUS; if antibiotics are given, organism may release
have an abnormal blood smear showing schistocytes, helmet more toxins as it dies and may worsen the disease.
cells, and fragmented red cells. * Do not transfuse platelets. Even if the platelet
count is low, administering platelets can actually
2. LDH and reticulocyte count ↑ and haptoglobin ↓. worsen the CNS and renal abnormalities by giving
• Treatment: more platelets as a substrate to precipitate. Small
1) Plasmapheresis. Plasmapheresis is used to treat severe cases platelet plugs are actually the cause of the problem.
of HUS but is not established in the treatment of mild disease.
2) Mild disease resolves spontaneously.
3) Dipyridamole may help treat TTP by preventing platelet aggregation.
4) Glucocorticoids, aspirin & rituximab have a role in management.
26. Heparin-induced Thrombocytopenia:

Heparin-induced thrombocytopenia (HIT), a complication of heparin therapy, can occur with any form of hep-
arin. It is more common with IV unfractionated heparin than with low molecular weight (LMW) heparin.
* Type 1 HIT presents within first 2 days after exposure to heparin.
1. Non-immune-mediated disorder that results from the direct effect of heparin on platelet activation
2. This form of thrombocytopenia is benign, self-limited, and not associated with bleeding or increased risk of
thrombosis
* Type 2 HIT (generally referenced as HIT) occurs 4-10 days
after exposure to heparin. * Suspect HIT when a patient who is re-
1. Immune-mediated disorder ceiving heparin has a decreased platelet
2. Has life and limb-threatening thrombotic complications (low count, particularly if the drop is >50% of
platelet count causes embolism, paradoxically) the baseline count, even if the platelet
* Diagnosis of HIT is based on the combined clinical findings, count nadir remains >150,000. Clinically,
thrombocytopenia characteristics, and lab studies of HIT antibod- HIT is not often marked by bleeding; the
ies (positive in ~85% of patients with type 2 HIT). most common complication is venous
* Treatment : thromboembolism (deep venous throm-
1) Discontinuation of all heparin products (including heparin bosis, pulmonary embolism), and less of-
flushes of intravenous catheters), ten, arterial thrombosis (stroke, myocardi-
2) Administration of an alternative anticoagulant such as ar- al infarction). For that reason, the disorder
gatroban or lepirudin. is sometimes called heparin-induced
3) Patients diagnosed with HIT should avoid all forms of heparin thrombocytopenia and thrombosis
for life. (HITT). Thrombosis develops in approxi-
mately 20% of patients with HIT, with
mortality as high as 30%.
24
 Comparison of Heparin and Warfarin:
HEPARIN WARFARIN
DURATION Effects fade quickly Effects persist for days
MONITORING aPTT PT
ANTIDOTE PROTAMINE SULFATE VITAMIN K
 Complications of transfusion reaction:

1. Immediate: Hemolytic transfusion reaction presenting as fever, shivering, restlessness, nausea, vomiting.
Pulse raised & B.P. fall & shock
2. Delayed hemolytic transfusion reaction Blood products
3. Non-hemolytic febrile reaction
Red cell concentrate: Used to increase red cell
4. Urticarias & anaphylactic reaction mass in patients with anemia and in acute blood
5. Transmission of infection: HIV& hepatitis, malaria loss. ABO compatibility with the patient is essen-
6. Virus overload…...pulmonary edema tial.
7. Iron overload Platelet concentrate: Used to treat and prevent
8. Bleeding bleeding due to thrombocytopenia.
9. Thrombophlebitis
Fresh frozen plasma (FFP): Used to replace
10. Air embolism coagulation factors.
• Management:
1. Stop transfusion, send again for grouping & cross-matching. Cryoprecipitate: Obtained from plasma and con-
tains proteins, including fibrinogen, factor VIII
2. Inj. Hydrocortisone 100mg I/v and von Willebrand factor (vWF). It is used to
3. Inj. Avil 10mg I/v replace fibrinogen.
4. Diuretics e.g. Inj. Mannitol 100ml I/v
Coagulation factor concentrates: Used to treat
5. Treatment of shock hemophilia and von Willebrand disease (factors
VIII and IX). Recombinant manufactured factors
 Bone marrow transplantation: are preferred, as they avoid infection risk.
• Indications: IV immunoglobulin: Used to prevent infection in
A. Allogenic transplant: patients with hypogammaglobulinemia. It is also
1. Acute myeloid leukemia (CR1 & CR2) used in idiopathic thrombocytopenic purpura and
2. Adult acute lymphoblastic leukemia (ALL,AML) Guillain–Barré syndrome
3. Chronic myeloid leukemia (CML)
4. Myelodysplastic syndrome Every blood donation must be reliably tested to
5. Sever aplastic anemia exclude those containing transmissible agents. In
the developed world, this includes:
6. Myelofibrosis ● Hepatitis B. ● Hepatitis C. ● HIV. ● Human T
7. Severe immune deficiency syndrome lymphotrophic virus (HTLV).
B. Autologous Transplant:
1. AML (CR2)
2. Myeloma PT: Assesses the extrinsic system and is pro-
longed by deficiencies of factors II, V, VII and X,
3. Poor risk Hodgkin's lymphoma and by liver disease.
4. High grade Non-Hodgkin's lymphoma APTT: Assesses the intrinsic system and is sensi-
5. Mantle cell lymphoma tive to deficiencies in factors II, V, VIII, IX, X,
• Complications: XI and XII.
1. mucositis International normalized ratio (INR): Used to
2. Infections assess the control of warfarin treatment, and is the
ratio of the patient’s PT to a normal control using
3. Bleeding an international reference thromboplastin.
4. Cataract
5. Pneumonitis
6. Infertility
7. Chronic graft versus host reaction
8. Acute graft versus host reaction
9. Secondary malignant disease
25

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Medicine Notes by Chillers (Q-45, QAMC-Bahawalpur) Hematology

CHILLER’s Q-45 (QAMC-BWP) presents:

“An Easy approach to Excel your Exams”

ADDITIONAL RESOURCES AVAILABLE AT:

• Some basic concepts of Hematology:- Microcytic Macrocytic Normocytic

Type of Anemia Iron (Fe) TIBC Ferritin Transferrin Soluble Trans-

Evaluation of pt.’s with Anemia

3. Iron Deficiency Anemia (IDA) :-

5. Peripheral blood picture: Macrocytosis (oval macrocytes), Anisocytosis, Poikilocytosis, Hypersegmenta-

5. Both parents of the affected individual have sickle cell trait.

9. Anemia of Chronic disease: (Secondary Anemia or Anemia of inflammation)

10. Sideroblastic Anemia:

11. Hemolytic Anemias:

Mechanical: prosthetic valves, HUC, DIC, March Hburia

• Diagnosis:- * Investigation results indicating active hemolysis:-

12. Autoimmune Hemolytic Anemia (AIHA):-

13. Paroxysmal Nocturnal Hemoglobinuria(PNH) “or” (Marchiava-Micheli disease) :-

14. Glucose-6-Phosphate Dehydrogenase(G6PD) Deficiency:

15c. Polycythemia Rubra Vera:

• Treatment: (1) Phlebotomy is the primary treatment.

• Outcome in Adults Acute leukemia:

17. Chronic Myeloid Leukemia (CML):

C) Hydroxyurea: Hydrea 500 g was previously used.

18. Chronic Lymphocytic Leukemia(CLL): (most common variety of leukemia)

19. Hodgkin’s Lymphoma: Histological sub-types

20. Non-Hodgkin's Lymphoma:

21. Tumor Lysis Syndrome:

• 22. Multiple Myeloma: (Male: female = 2:1)

23. Bleeding Disorders:

23(B). Idiopathic Thrombocytopenic Purpura:

23(C). Von-Willebrand disease: (mostly Autosomal Dominant inheritance pattern)

23(D). Disseminated intravascular coagulation (DIC):

• Diagnosis: * Causes/Underlying conditions:

24. Venous Thrombotic Embolism (VTE)/ Pulmonary Embolism (PE)/

• Algorithm for the investigation of patients with suspected pulmonary throm-

B)Specific: * Patients with persistent risk factors or previous VTE:

• Some Additional topics:

25. Thrombotic Thrombocytopenic purpura/Hemolytic

26. Heparin-induced Thrombocytopenia:

 Comparison of Heparin and Warfarin:

 Complications of transfusion reaction:

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