Indriani Silvia

Patologi Klinik
FK UNSWAGATI
2016
 Kelainan pada hematologi
Jenis kelainan hematologi
Gambaran kelainan hematologi pada
pemeriksaan laboratorium
Kelainan onkologi
Jenis pemeriksaan onkologi
Indikasi dan tujuan pemeriksaan
Interpretasi hasil pemeriksaan
 Transports oxygen, called oxyhemoglobin, when it
gives up its oxygen it is deoxyhemoglobin. 
 Also binds and transports carbon dioxide,
carbaminohemoglobin.
 Makes up ± 97 % of RBC  ± 250 million Hb
molecules per RBC
 Men: 14-18 mg/dl blood
 Women: 12-16 mg/dl blood
Types of Hemoglobin (Hb)
 Hb A
• 96% of adult Hb (α2 β2)
 Hb A2
• 3% of adult Hb (α2 σ2)
 Hb F
• 1 % of adult Hb (α2 γ2)
• Liver – contains phagocytic cells known as Kupffer
cells that act as a filter for damaged or aged cells in
a manner similar to, but less efficient than the
phagocytic cells in the spleen.
 If the bone marrow cannot keep up with the physiologic
demand for blood cells, the liver may resume the production
of blood cells that it began during fetal life
Blood Antigen Antibody Donor to Recipient
group from
A A Anti-B A A, O

B B Anti-A B B, O

AB AB Neither AB A, B, AB, O

O Neither Anti-A/Anti- O, A, B, AB O
B

Universal donor "O"       

Universal recipient "AB"
 
Acute Hemolytic Reaction
 Symptoms
• Fever, chills and fever, the feeling of heat along the vein in
which the blood is being transfused
• Pain in the lumbar region
• Constricting pain in the chest, tachycardia, hypo-tension
• Hemoglobinemia with subsequent hemoglo-binuria and
hyperbilirubin-emia.
 "feeling of impending doom"
Acute Hemolytic Reaction
 Causes
• Human error!
 Transfused red cells react with circulating antibody in the recipient
with resultant intravascular hemolysis
Acute Hemolytic Reaction
 Frequency
• Rare

 Prevention
• Proper identification of patients, pretransfusion blood
samples and blood components at the time of transfusion
Delayed Hemolytic Reaction
 Falling hematocrit
due to extravascular destruction of the transfused red blood
cells)

 Positive direct antiglobulin (Coombs) test (DAT)

 Occurs about 4-8 days after blood transfusion
 Patients may manifest fever and leukocytosis
Appearing to have an occult infection.
Febrile Transfusion Reaction
 Fever or chill fever
• temperature rise of 1.5 F or 1.0 C from the baseline
 Cytokines and antibodies to leukocyte antigens
reacting with leukocytes or leukocyte fragments
 1 in 8 transfusions
Allergic – urticaria
 Laryngeal edema and bronchospasm
 1% of recipients

• If coupled with another sign, such as fever, evaluation for a

hemolytic reaction may be indicated.
Allergic – Anaphylaxis
 Anaphylactic or anaphylactoid
• Respiratory involvement with dyspnea or stridor

 Cardiovascular instability
• hypotension, tachycardia, loss of consciousness, cardiac
arrhythmia, shock and cardiac arrest
Volume Overload
 Transfusion-related volume overload
 Infuse smaller volumes more slowly
Bacterial Contamination
 Hypotension, shock, fever and chills, nausea and

vomiting, and respiratory distress

 Gram stain and blood culture
Follow protocol for transfusion reactions
implemented by the institution
 Stop the transfusion immediately!
 Disconnect the intravenous line from the needle.
 Seek medical attention immediately. If the patient is
suffering cardiopulmonary collapse, and medical
attention is not immediately available, press for
“Code"
 Check to ensure that the patient name and registration
number on the blood bag label exactly with
information on the patient's identification

 Do not discard the unit of blood that has been

discontinued because it may be necessary for the
investigation of the transfusion reaction.
Reaction Type Treatment - Adult Pediatric Follow-up

Acute Diuretic therapy: Initially, give 40-80 Pediatric dose: 1-2 Treat shock and disseminated
Hemolytic mg Furosemide (Lasix) mg/kg/dose. intravascular coagulation with
Reactions intravenously. This dose can be May repeat once appropriate measures if and when
repeated once. Lack of response to at 2-4 mg/kg. they appear.
furosemide in 2-3 hours indicates
the presence of acute renal failure.

  Water loading: The patient should be Pediatric patients  

hydrated to maintain urinary should receive a
output of at least 100 mL/hr until smaller loading
urine is free of hemoglobin. volume of fluid
Infuse a loading dose of 0.9% sodium in proportion to
chloride or 5% dextrose in 0.45% their body
sodium chloride. Chart hourly surface area.
urine output. Maintain the urine
output by administering
intravenous fluid at 100 mL/hour
until the urine is free of
hemoglobin. If the patient's
urinary output does not increase,
with this hydration any additional
fluids should be infused with
caution.
Reaction Type Treatment - Adult Pediatric Follow-up

Delayed Specific treatment generally is not   Supplemental transfusion of blood lacking

Hemolytic necessary the antigen corresponding to the
Transfusion offending antibody may be necessary
Reactions to compensate for the transfused cells
that have been removed from the
circulation.
Reaction Type Treatment - Adult Pediatric Follow-up

Allergic Antihistamines(e.g., Benadryl). Give Pediatric dose: 1-2 Routine use of Benadryl as premedication
Transfusion 50-100 mg orally or intravenously. If mg/kg for all transfusions, regardless of a history
Reactions urticaria develops slowly, intramuscularly or of allergic reactions, is discouraged.
antihistamines may be given orally. intravenously for 25-
50 mg per average
dose.

  Aminophylline for wheezing, at a dose Pediatric dose: 3  

of 125-250 mg intravenously slowly mg/kg/dose in
over a period of about five minutes intravenous drip over
of 20 minutes.

  Epinephrine for severe, acute reactions Pediatric dose: 0.03  

including laryngeal edema or mL/M2 (0.03 mg/M2
bronchospasm Give 0.1-0.5 mg (0.1-0.5 of a 1:1000 solution)
mL of a 1:1000 solution) given subcutaneously.
subcutaneously. Subcutaneous dose A single pediatric
may be repeated at 10-15 minute dose should not
intervals. The total subcutaneous dose exceed 0.3 mg.
in a 24-hour period, with rare
exception, should not exceed 5 mg.
Reaction Type Treatment - Adult Pediatric Follow-up

Febrile Premedicate the patient with   Aspirin will adversely affect the patient's
Transfusion acetaminophen or other platelet function, so non-aspirin
Reactions antipyretic agents when previous antipyretic agents are preferable.
reactions have been extremely
bothersome. Pediatric dose: 10
mg/kg to a maximum of 600 mg.

Severe shaking (rigors) can be controlled by the   Note: Demerol may cause acute
Chills sedative effect of Benadryl or respiratory arrest. An opiate
Demerol (25-50 mg given antagonist (Narcan) should be
intramuscularly or intravenously immediately available.

Sepsis Due to Treatment of septic shock includes:

Bacterial terminating the suspected
Contamination transfusion immediately, cardio-
of Donor Blood vascular and respiratory support,
blood culture of the patient, and
administration of broad spectrum
antibiotics including anti-
pseudomonas coverage if the
blood component involved is Red
Blood Cells.
 Abnormally low number of RBC or Hb levels
 Reduced oxygen carrying capacity

Causes
 Blood loss
 Increased rate of red cell destruction
• Hemolytic anemia
 Deficient or impaired red cell production
Risk factors
 Poor diet
 Intestinal disorders
 Menstruation
 Pregnancy
 Chronic conditions
 Family history
 “NOT A DISEASE” but a symptom
• Dependent on severity, speed of development, age, health
status and compensatory mechanisms
• Associated with impaired O2 transport, alteration in RBC
structure or with chronic illness
• Not expressed until 50% of RBC mass is lost
Signs and symptoms
 The main symptom of most types of anemia is fatigue
• Weakness
• Pale skin
• Tachycardia
• Shortness of breath
• Chest pain
• Dizziness
• Cognitive problems
• Numbness or coldness in your extremities
• Headache
Iron Deficiency Anemia
 Most common form of anemia
• Affects about one in five women
• Half of pregnant women and 3 percent of men in the United
States.
 The cause is a shortage of the element iron
• Nutritional imbalance
• Slow, chronic bleeding disorders
• Inability to recycle plasma iron
Vitamin Deficiency Anemias
 Folate and vitamin B-12 deficiency
 Intestinal disorder that affects the absorption of
nutrients
 Fall into a group of anemias called megaloblastic
anemias, in which the bone marrow produces large,
abnormal red blood cells.
Anemia of Chronic Disease
 Interfere with the production of red blood cells,
resulting in chronic anemia
 Kidney failure also can be a cause of anemia
• The kidneys produce a hormone called erythropoietin,
which stimulates your bone marrow to produce red blood
cells.
 A shortage of erythropoietin, which can result from kidney failure or
be a side effect of chemotherapy, can result in a shortage of red blood
cells.
Aplastic Anemia
 Life-threatening anemia caused by a decrease in the
bone marrow's ability to produce all three types of
blood cells — red blood cells, white blood cells and
platelets
 Cause of aplastic anemia is unknown
• autoimmune disease
• Chemotherapy
• Radiation therapy
• Environmental toxins
Anemias associated with bone marrow disease
 Leukemia and myelodysplasia, can cause anemia by
affecting blood production in the bone marrow
 Effects vary from a mild alteration in blood
production to a complete, life-threatening shutdown of
the blood-making process
Myelodysplasia is a pre-leukemic condition that
can cause anemia.
Other cancers of the blood or bone marrow, such as multiple
myeloma, myeloproliferative disorders or lymphoma, can
cause anemia.
Hemolytic Anemias
 Red blood cells are destroyed faster than bone
marrow can replace them.
 Autoimmune disorders can produce antibodies to red
blood cells, destroying them prematurely
• Hemolytic anemias may cause yellowing of the skin
(jaundice) and an enlarged spleen.
Hereditary Spherocytosis
 Mutations in the ankyrin molecule with a secondary

deficiency of spectrin along the cell membrane

• Reduced red cell stability
 Does not affect oxygen carrying capacity
 Splenic sequestration
Sickle cell anemia
 Defective form of hemoglobin that forces red blood
cells to assume an abnormal crescent (sickle) shape.
• Mutation for the gene coding for the β-globulin chain
 Valine is substituted for glutamic acid HbS

 Red cells die prematurely, resulting in a chronic

shortage of red blood cells.
• Block blood flow through small blood vessels in the body,
producing other, often painful, symptoms.
 Single base pair mutation results in a single
amino acid change.
 Under low oxygen, Hgb becomes insoluble
forming long polymers
 This leads to membrane changes (“sickling”)
and vasoocclusion
 Sickle Cell Mutation
Chromosome 16   
5' 3'
Chromosome 11  G A   *
5' 3'

Normal (HbA)   Abnormal (HbS)

CCT GAG GAG   CCT GTG GAG
-Pro-Glu-Glu- A S -Pro-Val-Glu-
5 6 7 5 6 7

-O2 -O 2
+O 2 +O2
 Deoxygenation of SS erythrocytes leads to intracellular
hemoglobin polymerization, loss of deformability and
changes in cell morphology.

OXY-STATE DEOXY-STATE
α- Thalassemia
 Common in Asians
 Deletion of globulin chain loci
 4 possible degrees of α thalassemia:
• Silent carrier, loss of a single α globulin gene
• α thalassemia trait, loss of a pair of globulin gene
• HbH disease, only a single gene is present
• Hydrops fetalis, deletion of all α globulin
 The only treatments are stem cell transplant
and simple transfusion.
 Chelation therapy to avoid iron overload has to
be started early.
TALASSEMIA
 An acquired disorder of the bone marrow that causes
the overproduction of all three blood cell lines
• white blood cells, red blood cells, and platelets
 It is a rare disease that occurs more frequently in men
than women, and rarely in patients under 40 years old.
 causes is unknown
 Usually develops slowly, and most patients are
asymtomatic
• abnormal bone marrow cells proliferate uncontrollably
leading to acute myelogenous leukemia
 Patients have an increased tendency to form blood
clots that can result in strokes or heart attacks
• Some patients may experience abnormal bleeding because
their platelets are abnormal
Symptoms   
 Headache
 Dizziness
 Pruritus
 Fullness in the left upper abdomen
 Erythema (face)
 Shortness of breath
 Orthopnea
 Symptoms of phlebitis
 Collectively known as White Blood Cells (WBC)
 Formed elements of the blood with organelles and a
nucleus but lack hemoglobin
 Protect the body against microorganisms and remove
dead cells and debris from the body
 Per µl blood Per µl of blood

Total WBC count 5,000 – 10,000

Neutrophils 50 - 70% 2,000 – 7,000
Lymphocytes 20 - 40% 1,000 – 4,000
Monocytes 1 – 6% 50 – 600
Eosinophils 1 – 5% 50 – 500
Basophils 0 – 2% 0 - 100
 Leukopenia
• Decreased peripheral white cell count due to decrease
numbers of any specific types of leukocytes
 Leukocytosis
• Non–neoplastic elevation of WBC count
Neutropenia
 Reduction in the number of granulocytes (<1500/µl)
 Increased risk of infection
• Reduced phagocytosis response
Neutropenia
 Decreased or defective granulopoiesis
• Aplastic anemia
• Anti-neoplastic agents
• Other drugs: chloramphenicol, sulfonamides,
chlorpromazine
 Accelerated removal or destruction
• Aggressive and chronic infections
Manifestation of Neutropenia
 Infections

Signs and Symptoms

 Malaise, chills, fever
 Ulcerative necrotizing lesions of the mouth, skin

vagina and GI tract

Reactive Leukocytosis
 Increase number of WBC
 Common reaction due to a variety of inflammatory

states caused by microbial or non-microbial stimuli

 Usually non-specific
 Causes of Leukocytosis

Polymorphonuclear leukocytosis Acute bacterial infections

Eosinophilic leukocytosis Allergic disorders

Monocytosis Chronic infections

Lymphocytosis Chronic immunologic disease
 Leukemoid reaction – this is an extreme neutrophilia with a WBC count >
30 x 109/L
 Many bands, metamyelocytes, and myelocytes are seen
 Occasional promyelocytes and myeloblasts may be seen.
 This condition resembles a chronic myelocytic leukemia (CML), but can
be differentiated from CML based on the fact that in leukemoid reactions:
 There is no Philadelphia chromosome
 The condition is transient
 There is an increased leukocyte alkaline phosphatase score (more on this
later)
 Leukemoid reactions may be seen in tuberculosis, chronic infections,
malignant tumors, etc.
1. Leukemia – neoiplasms of the hematopoietic stem
cells
2. Malignant lymphomas – cohesive tumor lesions;
neoplastic lymphocytes
3. Plasma cell dyscrasias – arising from the bones;
localized disseminated proliferation of antibody
forming cells
4. Histocytoses – proliferative lesions of histiocytes
Leukemia
 Malignant neoplasm of the hematopietic stem cells
 BM replaced by unregulated, proliferating, immature

neoplastic cells  blood  leukemia  enter spleen,

lymph nodes
 Most common cancer in the paediatric age
 Leading cause of death in children between 3 and 14

years old
Classification of Leukemia
A. According to cell type and state of cell maturity
• Lymphocytic – immature lymphocytes and their
progenators
• Myelocytic – pluripotent myeloid stem cells and
interferes with maturation of all granulocytes, RBC and
platelets
B. Acute or Chronic
• Acute – immature cells (blast)
• Chronic – well differentiated leukocytes
 Congenital
• Pelger-Huet anomaly
 Bilobed and occasional unsegmented neutrophils
 Autosomal recessive disorder
• Neutrophil hyper-segmentation
 Rare autosomal dominant condition
 Neutrophil function is essentially normal
• May-Hegglin anomaly
 Neutrophils contain basophilic inclusions of RNA
 Occasionally there is associated leucopenia
 Thrombocytopenia and giant platelet are frequent
• Alder’s anomaly
 Granulocytes, monocytes and lymphocytes contain granules which stain purple
with Romanowsky stain
 Granules contain mucopolysaccharides
• Chediak-Higashi syndrome
 Autosomal recessive disorder
 Giant granules in granulocytes, monocytes and lymphocytes
 Partial occulocutaneous albinism
 Depressed migration and degranulation
 Recurrent pyogenic infections
 Lymphoproliferative syndrome may develop
 Treatment is BMT
 Acquired
 Toxic granulation
 Dohle bodies
 Pelger cells
 Hypersegmented neutrophils
 Leucocyte adhesion deficiency
 Chronic granulomatous disease
 Chediak-Higashi syndrome
 Primary immunodeficiency
 Severe combined immunodeficiency
 Common variable immunodeficiency
 Isolated IgA deficiency
 T-cell immunodeficiency
 Thymic aplasia (Di George syndrome)
 Block in the differentiation of leukemic cells with
prolonged genration time  clonal expansion of the
transformed stem cells + failure of maturation 
accumulation of leukemic blast  suppress normal
hematopoietic stem cells
Features
 Sudden onset (3 months)
 Depressed marrow function
 Bone pain and tenderness
 Generalized lymphadenophaty
 Splenomegaly, hepatomegaly
 CNS: headache, vomiting
 Most common leukemia in children (80%)
 Treatable and potentially curable
 Classified according to lymphocytes and state of
maturation
1. Early B cell
2. Pre-B cell
3. Mature B cell
4. Early T cell
5. Mature T cell
 Acute Non-lymphocytic Leukemia (ANLL)
 Most common in adults; >50% 60years old
 70% of adults will enter remission with induction
chemo
• 25-35% of those in remission will have a 5 year survival
rate
 BM transplant
Treatment
 Selective radiation
 Chemotherapy
1. Induction
2. Intensification
3. Maintenance and consolidation
 Bone marrow transplant
 Insidious onset
 Incidental findings during routine exam
 Proliferation and accumulation of mature
lymphocytes which are immunologically incompetent
• B cell line (US)
• T cell line (Asia)
 Hairy cell leukemia
 15% of all leukemias
 Chromosomal abnormality (Ph1)
 Mostly B cell disease
• Leukocytosis
• Splenomegaly
• Hepatomegaly
• Lympadenopathy
 Bone marrow transplant  5 year survival for 50-
75% of patients
Two distinct phases
 Chronic
• Last about 3-4 years
• Near end  accelerated phase: fever, night sweats, malaise
 Acute
• 2-4 months
• Poor prognosis, palliative management
 Primary solid tumors of the lymphoid system
 Cancers involving lymphocytes during maturation or
storage in the bone marrow
 Third most common malignacy in children
Hodgkin’s Lymphoma
 Disorders primarily involving the lymphoid tissues
 Anatomical spread
 Morphological presence of Reed-Sternberg cells
 60-90% cure rate
Manifestations of Hodgkin’s
 A symptoms
• Painless progressive enlargement of a single or group of
nodes (neck)
• May spread continuously through out the lymphatic system
 B symptoms
• Fever, night sweat, weight loss
• Fatigue, anemia
Treatment for Hodgkin’s
 Radiation
 Chemotherapy
Non-Hodgkin’s Lymphoma
 Involves lymphoid tissue and may spread to various

tissues
 Mostly B cell (80%)
 Cause may be viral or genetic
• EBV
• Immunosuppresed patients
 AIDS
 After organ transplant
Treatment
 Early stage  radiation
 Late stage  chemo and radiation
 BM transplant
 Transfuse for any severe anemia with
physiologic compromise.
 Decide early whether transfusion will be rare
or part of therapy.
 Avoid long-term complications by working
with your blood bank and using chelation
theraoy.