This document provides an overview of anemia, thrombocytopenia, and blood transfusions. It discusses the definition, causes, evaluation, and management of anemia and thrombocytopenia. For anemia, it classifies the different types and describes the approach to the anemic patient. For thrombocytopenia, it discusses the differential diagnosis and treatment with platelet transfusions. The document also summarizes a landmark study that found a restrictive transfusion strategy to be as effective and safer than a liberal strategy in critically ill patients.

1. Anemia,
Thrombocytopenia,
& Blood Transfusions
Dr. Rafi Ahmed Ghori
FCPS
Professor Medicine
Liaquat University of Medical & Health Sciences,
Jamshoro
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2. Objectives
• An overview and approach to the
anemic patient.
• An overview and approach to the
thrombocytopenic patient
• An overview of blood transfusions
with an evidence based approach
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3. Anemia
• A reduction below normal in the
concentration of hemoglobin or red
blood cells in the blood.
• Hematocrit (<40% in men,<36% in
women)
• Hemoglobin (13.2g/dl in men,
11.7g/dl in women)
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4. Symptoms of Anemia
• Nonspecific and reflect tissue
hypoxia:
– Fatigue
– Dyspnea on exertion
– Palpatations
– Headache
– Confusion, decreased mental acuity
– Skin pallor
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5. History and Physical in Anemia
• Duration and onset of symptoms
• Change in stool habits: Stool
Guaiacs in all
• Splenomegaly?
• Jaundiced?
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6. Components of
Oxygen Delivery
• Hemoglobin in red cells
• Respiration (Hemoglobin levels
increase in hypoxic conditions)
• Circulation (rate increases with
anemia)
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7. Classification of Anemia
Kinetic classification
• Hypoproliferative
• Ineffective Erythropoiesis
• Hemolysis
• Bleeding
Morphologic classification
• Microcytic
• Macrocytic
• Normocytic
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8. Anemia: A Kinetic Perspective
• Erythrocytes in circulation represent a
dynamic equilibrium between
production and destruction of red cells
• In response to acute anemia (ie blood
loss) the healthy marrow is capable of
producing erythrocytes 6-8 times the
normal rate (mediated through
erythropoietin)
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9. Reticulocyte Count
• Is required in the evaluation of all patients
with anemia as it is a simple measure of
production
• Young RBC that still contains a small amount
of RNA
• Normally take 1 day for reticulocyte to
mature. Under influence of epo takes 2-3
days
• 1/120th of RBC normally
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10. Absolute Retic count
• Retic counts are reported as a
percentage: RBC count x Retic % =
Absoulte retic count(normal: 40-
60,000/μl3)
• Absolute Retic counts need to be
corrected for early release ( If
polychromasia is present)
• Absolute retic/2 (for hct in mid 20’s)
• Absolute retic/3 (hct <20)
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11. Indirect Bilirubin: a marker of
RBC destruction
• 80% of normal Bilirubin production is a
result of the degradation of hemoglobin
• In the absence of liver disease Indirect
Bilirubin is an excellent indicator of RBC
destruction
• LDH and Haptoglobin are other markers
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12. Anemia
Low Retic count & Normal High Retic count & High
Bili/LDH Bili/LDH
Hypoproliferative Anemia Hemolytic Anemia
Low Retic count & High High Retic count & normal
Bili/LDH Bili/LDH
Ineffective Erythropoiesis
Blood Loss
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13. Hypoproliferative Anemias
• Iron deficiency anemia
• Anemia of chronic disease
• Aplastic anemia and pure red cell aplasia
• Lead poisoning
• Myelophthistic anemias (marrow replaced by
non-marrow elements)
• Renal Disease
• Thyroid disease
• Nutritional defieciency
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14. Lab Evaluation of
Hypoproliferative Anemias
Fe TIBC Ferritin
Fe Deficiency low High(>300) low
Anemia of low low Normal to
Chronic Dx high
Aplastic anemia High Extremely Normal to
high high
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15. Anemia of Chronic Disease
• “Excessive cytokine release” (aka,
infections, inflammation , and cancer)
• Pathophysiology
– Decreased RBC lifespan
– Direct inhibition of RBC progenitors
– Relative reduction in EPO levels
– Decreased availability of Iron
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16. Ineffective Erythropoiesis
• B12 and Folate Deficiency
– Macrocytosis
– Decreased serum levels
– Elevated homocysteine level
• Myelodysplastic Syndromes
– Qualitative abnormalities of platlets/wbc
– Bone marrow
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17. Hemolysis
• Thalassemia
– Microcytosis
– RBC count elevated
– Family history
• Microangiopathy
– Smear with schistocytes and RBC
fragments
– HUS/TTP vs. DIC vs. Mechanical Valve
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18. Hemolysis (cont.)
• Autoimmune (warm hemolysis)
– Spherocytes
– + Coomb’s test
• Autoimmune (cold Hemolysis)
– Polychromasia and reticulocytosis
– Intravascular hemolysis
– + cold agglutinins
– Hemoglobinuria/hemosiderinuria
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19. Bleeding
• Labs directed at site of bleeding and
clinical situation
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20. RBC Transfusion
• What is the best strategy for transfusion
in a hospitalized patient population?
• Is a liberal strategy better than a
restrictive strategy in the critically ill
patients?
• What are the risks of transfusion?
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21. Risks of RBC Transfusion
in the USA
• Febrile non-hemolytic RXN: 1/100 tx
• Minor allergic reactions: 1/100-1000 tx
• Bacterial contamination: 1/ 2,500,000
• Viral Hepatitis 1/10,000
• Hemolytic transfusion rxn Fatal: 1/500,000
• Immunosuppression: Unknown
• HIV infection 1/500,000
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22. Packed Red Blood Cells
• 1 unit= 300ml
• Increment/ unit: HCT: 3% Hb1/g/dl
• Shelf life of 42 days
• Frozen in glycerol+up to 10 years for
rare blood types and unusual Ab
profiles
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23. Special RBC’s
• Leukocyte-reduced= 108 WBCs prevent
FNHTR
• Leukocyte-depleted= 106 WBCs prevent
alloimmunization and CMV
transmission
• Washed: plasma proteins removed to
prevent allergic reaction
• Irradiated: lymphocytes unable to
divide, prevents GVHD
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24. Hebert et. al, NEJM, Feb 1999
• A multicenter randomized, controlled
clinical trial of transfusion requirements
in critical care
• Designed to compare a restrictive vs. a
liberal strategy for blood transfusions in
critically ill patients
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25. Methods: Hebert et. al
• 838 patients with euvolemia after initial
treatment who had hemoglobin
concentrations < 9.0g/dl within 72 hours
of admission were enrolled
• 418 pts: Restrictive arm: transfused for
hb<7.0
• 420 pts: Liberal arm: transfused for Hb<
10.0
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26. Exclusion Criteria
• Age <16
• Inability to receive blood products
• Active blood loss at time of enrollment
• Chronic anemia: hb< 9.0 in preceding
month
• Routine cardiac surgery patients
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27. Study population
• 6451 were assessed for eligibility
• Consent rate was 41%
• No significant differences were noted
between the two groups
• Average apache score was 21(hospital
mortality of 40% for nonoperative
patients or 29% for post-op pts)
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28. Success of treatment
Restrictive Group Liberal
Group
Average 8.5+0.7 10.7+0.7
Hemoglobin
Noncompliance 1.4% 4.3%
>48hrs
# of transfusions 2.6+ 4.1 5.6+ 5.3
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29. Outcome Measures
Restrictive Liberal group
group
Rate of death at 30 18.7% 23.3
days
Mortality rates 22.2% 28.1
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30. Complications while in ICU
restrictive liberal P value
cardiac 13.2% 21.0% <0.01
MI 0.7% 2.9% 0.02
Pulm edema 5.3% 10.7% <0.01
ARDS 7.7% 11.4% 0.06
Septic shock 9.8% 6.9% 0.13
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31. Survival curve
• Survival curve was significantly
improved in the following subgroups:
– Apache<20
– Age<55
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32. Conclusions
• A restrictive approach to blood
transfusions is as least as effective if
not more effective than a more liberal
approach
• This is especially true in a healthier,
younger population
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33. Thrombocytopenia
• Defined as a subnormal amount of
platelets in the circulating blood
• Pathophysiology is less well defined
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34. Thrombocytopenia:
Differential Diagnosis
• Pseudothrombocytopenia
• Dilutional Thrombocytopenia
• Decreased Platelet production
• Increased Platelet Destruction
• Altered Distribution of Platelets
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35. Pseudothrombocytopenia
• Considered in patients without evidence
of petechiae or ecchymoses
• Most commonly caused by platelet
clumping
– Happens most frequently with EDTA
– Associated with autoantibodies
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36. Dilutional Thrombocytopenia
• Large quantities of PRBC’s to treat
massive hemmorhage
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37. Decreased Platelet Production
• Fanconi’s anemia
• Paroxysmal Nocturnal Hemoglobinuria
• Viral infections: rubella, CMV, EBV,HIV
• Nutritional Deficiencies: B12, Folate, Fe
• Aplastic Anemia
• Drugs: thiazides, estrogen, chemotherapy
• Toxins: alcohol, cocaine
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38. Increased Destruction
• Most common cause of thrombocytopenia
• Leads to stimulation of thrombopoiesis and
thus an increase in the number, size and rate
of maturation of the precursor
megakaryocytes
• Increased consumption with intravascular
thrombi or damaged endothelial surfaces
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39. Increased Destruction (Cont.)
• ITP
• HIV associated ITP
• Drugs: heparin, gold, quinidine,lasix,
cephalosporins, pcn, H2 blockers
• DIC
• TTP
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40. Altered Distribution of Platelets
• Circulating platelet count decreases,
but the total platelet count is normal
– Hypersplenism
– Leukemia
– Lymphoma
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41. Prophylactic Versus Therapeutic
Platelet Transfusions
• Platelet transfusions for active bleeding
much more common on surgical and
cardiology services
• Prophylactic transfusions most common
on hem/onc services
• 10 x 109/L has become the standard
clinical practice on hem/onc services
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42. Factors affecting a patients
response to platelet transfusion
• Clinical situation: Fever, sepsis,
splenomegaly, Bleeding, DIC
• Patient: alloimunization, underlying
disease, drugs (IVIG, Ampho B)
• Length of time platelets stored
• 15% of patients who require multiple
transfusions become refractory
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43. Strategies to improve response to
platelet transfusions
• Treat underlying condition
• Transfuse ABO identical platelets
• Transfuse platelets <48 hrs in storage
• Increase platelet dose
• Select compatible donor
– Cross match
– HLA match
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44. Platelet Transfusions
Reactions
• Febrile nonhemolytic transfusion:
caused by patients leucocytes reacting
against donor leukocytes
• Allergic reactions
• Bacterial contamination: most common
blood product with bacterial
contamination
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45. BIKHA