Anemia, Thrombocytopenia, & Blood Transfusions

1. Anemia, Thrombocytopenia,& Blood Transfusions Joel Saltzman MD Hematology/Oncology Fellow Metro Health Medical Center

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

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)

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

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

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

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

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)

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

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)

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

12. Anemia

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

14. Lab Evaluation of Hypoproliferative Anemias

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

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

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

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

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

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?

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

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

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

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

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

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

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)

28. Restrictive Group Liberal Group Average Hemoglobin 8.5+0.7 10.7+0.7 Noncompliance >48hrs 1.4% 4.3% # of transfusions 2.6+ 4.1 5.6+ 5.3 Success of treatment

29. Outcome Measures

30. Complications while in ICU

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

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

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

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

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

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

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

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

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

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

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

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

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

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