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11..blood transfusion anemia thrombocyt


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11..blood transfusion anemia thrombocyt

  1. 1. Anemia, Thrombocytopenia,& Blood Transfusions Dr. Rafi Ahmed Ghori FCPS Professor MedicineLiaquat University of Medical & Health Sciences, Jamshoro Rafi BIKHA
  2. 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. 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. 4. Symptoms of Anemia• Nonspecific and reflect tissue hypoxia: – Fatigue – Dyspnea on exertion – Palpatations – Headache – Confusion, decreased mental acuity – Skin pallor Rafi BIKHA
  5. 5. History and Physical in Anemia• Duration and onset of symptoms• Change in stool habits: Stool Guaiacs in all• Splenomegaly?• Jaundiced? Rafi BIKHA
  6. 6. Components of Oxygen Delivery• Hemoglobin in red cells• Respiration (Hemoglobin levels increase in hypoxic conditions)• Circulation (rate increases with anemia) Rafi BIKHA
  7. 7. Classification of Anemia Kinetic classification• Hypoproliferative• Ineffective Erythropoiesis• Hemolysis• Bleeding Morphologic classification• Microcytic• Macrocytic• Normocytic Rafi BIKHA
  8. 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. 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. 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. 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. 12. AnemiaLow Retic count & Normal High Retic count & HighBili/LDH Bili/LDHHypoproliferative Anemia Hemolytic AnemiaLow Retic count & High High Retic count & normalBili/LDH Bili/LDHIneffective Erythropoiesis Blood Loss Rafi BIKHA
  13. 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. 14. Lab Evaluation of Hypoproliferative Anemias Fe TIBC FerritinFe Deficiency low High(>300) lowAnemia of low low Normal toChronic Dx highAplastic anemia High Extremely Normal to high high Rafi BIKHA
  15. 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. 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. 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. 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. 19. Bleeding• Labs directed at site of bleeding and clinical situation Rafi BIKHA
  20. 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. 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. 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. 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. 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. 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. 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. 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. 28. Success of treatment Restrictive Group Liberal GroupAverage 8.5+0.7 10.7+0.7HemoglobinNoncompliance 1.4% 4.3%>48hrs# of transfusions 2.6+ 4.1 5.6+ 5.3 Rafi BIKHA
  29. 29. Outcome Measures Restrictive Liberal group groupRate of death at 30 18.7% 23.3daysMortality rates 22.2% 28.1 Rafi BIKHA
  30. 30. Complications while in ICU restrictive liberal P valuecardiac 13.2% 21.0% <0.01MI 0.7% 2.9% 0.02Pulm edema 5.3% 10.7% <0.01ARDS 7.7% 11.4% 0.06Septic shock 9.8% 6.9% 0.13 Rafi BIKHA
  31. 31. Survival curve• Survival curve was significantly improved in the following subgroups: – Apache<20 – Age<55 Rafi BIKHA
  32. 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. 33. Thrombocytopenia• Defined as a subnormal amount of platelets in the circulating blood• Pathophysiology is less well defined Rafi BIKHA
  34. 34. Thrombocytopenia: Differential Diagnosis• Pseudothrombocytopenia• Dilutional Thrombocytopenia• Decreased Platelet production• Increased Platelet Destruction• Altered Distribution of Platelets Rafi BIKHA
  35. 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. 36. Dilutional Thrombocytopenia• Large quantities of PRBC’s to treat massive hemmorhage Rafi BIKHA
  37. 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. 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. 39. Increased Destruction (Cont.)• ITP• HIV associated ITP• Drugs: heparin, gold, quinidine,lasix, cephalosporins, pcn, H2 blockers• DIC• TTP Rafi BIKHA
  40. 40. Altered Distribution of Platelets• Circulating platelet count decreases, but the total platelet count is normal – Hypersplenism – Leukemia – Lymphoma Rafi BIKHA
  41. 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. 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. 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. 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. 45. BIKHA