1. Anemia,
Thrombocytopenia,
& Blood Transfusions
Dr. Rafi Ahmed Ghori
FCPS
Professor Medicine
Liaquat University of Medical & Health Sciences,
Jamshoro
Rafi
BIKHA

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
Rafi
BIKHA

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)
Rafi
BIKHA

4. Symptoms of Anemia
• Nonspecific and reflect tissue
hypoxia:
– Fatigue
– Dyspnea on exertion
– Palpatations
– Headache
– Confusion, decreased mental acuity
– Skin pallor
Rafi
BIKHA

5. History and Physical in Anemia
• Duration and onset of symptoms
• Change in stool habits: Stool
Guaiacs in all
• Splenomegaly?
• Jaundiced?
Rafi
BIKHA

6. Components of
Oxygen Delivery
• Hemoglobin in red cells
• Respiration (Hemoglobin levels
increase in hypoxic conditions)
• Circulation (rate increases with
anemia)
Rafi
BIKHA

7. Classification of Anemia
Kinetic classification
• Hypoproliferative
• Ineffective Erythropoiesis
• Hemolysis
• Bleeding
Morphologic classification
• Microcytic
• Macrocytic
• Normocytic
Rafi
BIKHA

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)
Rafi
BIKHA

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
Rafi
BIKHA

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)
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

16. Ineffective Erythropoiesis
• B12 and Folate Deficiency
– Macrocytosis
– Decreased serum levels
– Elevated homocysteine level
• Myelodysplastic Syndromes
– Qualitative abnormalities of platlets/wbc
– Bone marrow
Rafi
BIKHA

17. Hemolysis
• Thalassemia
– Microcytosis
– RBC count elevated
– Family history
• Microangiopathy
– Smear with schistocytes and RBC
fragments
– HUS/TTP vs. DIC vs. Mechanical Valve
Rafi
BIKHA

18. Hemolysis (cont.)
• Autoimmune (warm hemolysis)
– Spherocytes
– + Coomb’s test
• Autoimmune (cold Hemolysis)
– Polychromasia and reticulocytosis
– Intravascular hemolysis
– + cold agglutinins
– Hemoglobinuria/hemosiderinuria
Rafi
BIKHA

19. Bleeding
• Labs directed at site of bleeding and
clinical situation
Rafi
BIKHA

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?
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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)
Rafi
BIKHA

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
Rafi
BIKHA

29. Outcome Measures
Restrictive Liberal group
group
Rate of death at 30 18.7% 23.3
days
Mortality rates 22.2% 28.1
Rafi
BIKHA

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
Rafi
BIKHA

31. Survival curve
• Survival curve was significantly
improved in the following subgroups:
– Apache<20
– Age<55
Rafi
BIKHA

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
Rafi
BIKHA

33. Thrombocytopenia
• Defined as a subnormal amount of
platelets in the circulating blood
• Pathophysiology is less well defined
Rafi
BIKHA

34. Thrombocytopenia:
Differential Diagnosis
• Pseudothrombocytopenia
• Dilutional Thrombocytopenia
• Decreased Platelet production
• Increased Platelet Destruction
• Altered Distribution of Platelets
Rafi
BIKHA

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
Rafi
BIKHA

36. Dilutional Thrombocytopenia
• Large quantities of PRBC’s to treat
massive hemmorhage
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

39. Increased Destruction (Cont.)
• ITP
• HIV associated ITP
• Drugs: heparin, gold, quinidine,lasix,
cephalosporins, pcn, H2 blockers
• DIC
• TTP
Rafi
BIKHA

40. Altered Distribution of Platelets
• Circulating platelet count decreases,
but the total platelet count is normal
– Hypersplenism
– Leukemia
– Lymphoma
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

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
Rafi
BIKHA

45. BIKHA