BY RANJEET RAMAN

 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.

 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.

 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.

 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!!

 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+.

 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.

 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.

 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.

 ​ 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)

 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.

 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.

 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.

 These drugs are actually prodrugs that are metabolized to active metabolites.  Toxicities include severe neutropenia, bleeding, and thrombocytopenia.  Platelet GPIIb/IIIa antagonists (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.

 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.

 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.