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TRANSFUSION MEDICINE—HEMATOLOGY {S1}

TRANSFUSION MEDICINE—HEMATOLOGY {S1}. BY RANJEET RAMAN. Almost all hemolytic transfusion reactions are caused by mislabeling and misadmini - stering ​ ​blood samples into the wrong patient !

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TRANSFUSION MEDICINE—HEMATOLOGY {S1}

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  1. TRANSFUSION MEDICINE—HEMATOLOGY {S1} BY RANJEET RAMAN

  2. Almost all hemolytic transfusion reactions are caused by mislabeling and misadmini- stering ​ ​blood samples into the wrong patient! • Components, not whole blood, are transfused. This avoids volume overload, concentrates the ​required component, and maximizes blood use. • ​RBC lose their 2,3DPG during storage, and accumulate metabolites.

  3. Platelets are collected by aphaeresis and administered for abnormal bleeding time, thrombocytopenia, ​and after invasive procedures or trauma. • ​HLA antibodies will destroy incompatible platelets, so platelets have to be matched like ​other tissues. • Irradiation is used to prevent graft-versus-host disease by destroying WBC.

  4. Immunohematology – ABO, Rh factor • ABO group is a molecular extension from the membrane. They are genetic polymorphisms. • Antibodies to ABO antigens are T-cell independent and occur spontaneously. They do not ​require an immune response. • ABO antigens are in very high concentration on RBC. ABO incompatibility is the most common ​cause of hemolytic transfusion reactions.

  5. Reciprocal arrangement: People who are Group A have anti-B antibodies!! These antibodies ​are high titer IgM antibodies and will cause hemolysis. They are formed because blood ​group antigens mimic antigens found in foods and bacteria. • ​O is the universal RBC donor, but AB is the universal plasma donor!!

  6. Rh is integral to the RBC membrane. Rh is also called the “D antigen.” • Rh+ babies born to mothers with anti-Rh antibodies will die of hemolysis. Rh antigen is ​extremely immunogenic. Incompatibility causes hemolytic transfusions reactions. • 85% of people are Rh+.

  7. Adverse effects of transfusion • 1. Acute hemolytic transfusion reactions. Usually caused by IgM, which will activate ​complement and bind foreign antigens. Can cause shock, DIC, but especially acute renal ​failure. Signs include free hemoglobin in urine/plasma, and a positive Coombs test.

  8. 2. Delayed hemolytic transfusion reactions. Slower destruction of transfused cells by ​alloantibodies. Usually involves extravascular RBC destruction in the RES. • 3. Allergic reactions. Often happens in patients with IgA deficiency, and may cause ​anaphylaxis. Can be prevented by using washed blood or IgA deficient blood.

  9. 4. Transfusion transmitted diseases. • ​HIV. Current risk is less than one per two million. • ​HepC. Current risk is less than one per two million. • ​CMV. • ​Bacteria. Current risk is one per two thousand. Major problem in platelet transfusions.

  10. ​HepA is NOT TRANSMITTED by infusions since there is no asymptomatic chronic stage. • Alternatives to Transfusion • 1. Predeposit autologous blood. • 2. Hematopoietic growth factors (erythropoietin for RBC, G-CSF for neutropenia, DDAVP for vWD)

  11. PHARMACOLOGY OF BLOOD –TARGETING PLATELETS

  12. All inhibitors of platelet function are used prophylactically and don’t affect formed thrombi. • Aspirin • ASA is an excellent drug that inhibits COX, and thus thromboxane A2 synthesis. Thromboxane ​is a potent inducer of platelet aggregation and a vasoconstrictor, so ASA is potent against ​platelet activation. • It permanently and covalently inhibits COX, so effect lasts until new platelets are formed.

  13. Dipyridamole • Increases cAMP inside platelets. This inhibits platelet aggregation. • Dipyridamole inhibits adenosine uptake (which normally activates adenylate cyclase), so this ​raises cAMP and platelets fail to aggregate. • Only works in combination with aspirin or warfarin.

  14. ADP antagonists – Thienopyridine, Ticlopidine, Clopidogrel Since ADP induces platelet aggregation, these drugs prevent thrombus formation. • ADP antagonists include Thienopyridine, Ticlopidine, and Clopidogrel. • These permanently and irreversibly bind the ADP receptor on platelets, which blocks release of ​alpha and dense granules. They also inhibit fibrinogen binding.

  15. These drugs are actually prodrugs that are metabolized to active metabolites. • Toxicities include severe neutropenia, bleeding, and thrombocytopenia. • Platelet GPIIb/IIIaantagonists (note: will not cause intracranial bleeding!!) 1. Abciximab is an antibody against GPIIb/IIIa, so fibrinogen can’t crosslink platelets. • ​Abciximab is cleared within minutes from the body.

  16. 2. Ebtifibatide is a peptide against GPIIb/IIIa. It mimics the AA sequence of fibrinogen that ​binds to IIb/IIIa, as well as the AA sequence that VWF uses to bind platelets. • ​Ebtifibatide blocks fibrinogen and vWF-mediated aggregation of platelets. • ​Unlike ASA and the ADP antagonists, Ebtifibatide has a short and reversible effect.

  17. 3. Tirofiban is a small molecule against GPIIb/IIIa. It reversibly blocks fibrinogen binding and ​like Ebtifibatide is rapidly cleared. • Erythropoietin • Erythropoietin binds the EPO receptor of RBC precursors, activating a Jak/Stat pathway. Stat5 ​becomes phosphorylated and acts as a nuclear transcription factor for RBC maturation genes. • ​This blocks apoptosis of erythroid precursor cells. • Erythropoietin actually increases the risk of thrombosis.

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