PATHOPHYSIOLOGY OF THROMBOCYTOPENIA AND RESULTANT CLINICAL INDICATIONS FOR PLATELET TRANSFUSION

Careful evaluation of platelet survival data in normal individuals and patients with thrombocytopeniasecondary to marrow aplasia has demonstrated that platelets are lost from circulation by two mechanisms a fixed fraction of platelets, amounting to approxi mately 7,100 platelets/ul/day, are lost randomly while the remaining platelets are removed by senescent mechanisms. At platelet counts of <100,000/ul, platelet survival becomes progressively shorter as the fixed platelet loss becomes a proportionately greater fraction of the circulating platelets. Thus, there is a direct relationship between platelet count and platelet survival in thrombocytopenic patients. Therefore, when judging the effectiveness of platelet therapy in thrombocytopenic patients, the influence of platelet count on platelet survival must be considered. As yet, there have been no studies to determine if there are ways to interrupt this fixed platelet loss? whether such therapy might improve platelet support in thrombocyotpenic patients by prolonging platelet survival? or, alternatively, whether such therapy might enhance the bleeding risk if random platelet removal is related to physiologic platelet-endothelial cell interactions.Besides taking into account the effect of thrombocytopenia on the expected response to platelet transfusions, the risk of alloimmunization with platelet transfusion therapy requires a careful assessment of the indications for platelet transfusions for each patient.Based on 51Cr-labeled stool blood loss measurements, we have determined that the bleeding risk is minimal at platelet counts above 10,000 platelets/ul.Only when the platelet count falls to a lower level of 5,000/ul is GI bleeding significantly increased. However, there are certain medications that may enhance the bleeding risk and require platelet transfusions to be given at higher platelet counts.In those patients who are thrombocytopenic, not because of failure of marrow platelet production, but rather because of accelerated platelet removal, indications for platelet transfusions must be adjusted to meet the particular problem. For example, for patients with autoimmune thrombocytopenic purpura, platelet transfusions are rarely indicated (one exception being intracerebral bleeding) because of the rapid rate of platelet removal and because the patients are usually releasing young hyperfunctional platelets from the bone marrow reducing the hemorrhagic risk at any given platelet count. In some patients with consumptive coagulopathies, even though platelet removal is rapid, platelets may have to be provided until specific therapy resolves the underlying disease process causing the platelet consumption. For these patients, increased levels of fibrinogen/fibrin degregation products, as well as various medications they maybe receiving, may produce platelet dysfunction necessitating platelet transfusions at higher platelet levels. Finally, massive transfusion patients may develop a dilution thrombocytopenia requiring platelet transfusions.