Chapter 120: Acquired Qualitative Platelet Disorders

SUMMARY

Acquired qualitative platelet disorders are frequent causes of abnormal platelet function measured in vitro, although by themselves, they are usually associated with little or clinically less significant bleeding. However, there are important exceptions. Nevertheless, their major clinical impact becomes apparent in the additional presence of thrombocytopenia or additional acquired or congenital disorders of hemostasis. Acquired disorders of platelet function can be conveniently classified into those that result from drugs, hematologic diseases, and systemic disorders. Drugs are the most frequent cause of acquired qualitative platelet dysfunction. Aspirin is the most notable drug in this regard because of its frequent use, its irreversible effect on platelet prostaglandin (PG) synthesis, and its documented effect on hemostatic competency, although this effect is minimal in normal individuals. Other nonsteroidal antiinflammatory drugs reversibly inhibit platelet PG synthesis and usually have little effect on hemostasis. The antiplatelet effects of a number of drugs have proven useful in preventing arterial thrombosis, but as would be anticipated, excessive bleeding can be a complication of their use. In addition to aspirin, these drugs include the P2Y₁₂ adenosine diphosphate receptor antagonists (eg. clopidogrel, prasugrel and ticagrelor), an inhibitor of the PAR1 thrombin receptor (vorapaxar), and drugs that specifically inhibit adhesive ligand binding to platelet integrin α_IIbβ₃ (glycoprotein IIb/IIIa) (eg. abciximab, eptifibatide, and tirofiban). Other drugs used to treat thrombosis, such as heparin and fibrinolytic agents, may also impair platelet function in vitro and ex vivo, but the clinical significance of these observations is uncertain. High doses of the β-lactam antibiotics can impair platelet function in vitro, whereas clinically significant bleeding is unusual in the absence of a coexisting hemostatic defect. Similarly, a number of miscellaneous drugs, including a variety of psychotropic, chemotherapeutic, and anesthetic agents, as well as a number of foods and food additives, can affect platelet function in vitro but do not appear to be of clinical significance by themselves. Hematologic diseases associated with abnormal platelet function include marrow processes in which platelets may be intrinsically abnormal such as the myeloproliferative neoplasms, leukemias, and myelodysplastic syndromes; dysproteinemias in which monoclonal immunoglobulins can impair platelet function; and acquired forms of von Willebrand disease. Of the systemic diseases, renal failure is most prominently associated with abnormal platelet function because of the retention in the circulation of platelet inhibitory compounds. Platelet function may also be abnormal in the presence of antiplatelet antibodies, after cardiopulmonary bypass, and in association with liver disease or disseminated intravascular coagulation.

Acronyms and Abbreviations

ADP, adenosine diphosphate; BCNU, bis-chloroethylnitrosourea; BTK, Bruton tyrosine kinase; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; COX, cyclooxygenase; coxibs, COX inhibitors; CYP, cytochrome P; DDAVP, desmopressin or 1-desamino-8-D-arginine vasopressin; DIC, disseminated intravascular coagulation; EPO, erythropoietin; GP, glycoprotein; Ig, immunoglobulin; ITP, immune thrombocytopenia; KGD, lysine-glycine-aspartic acid tripeptide; NO, nitric oxide; NSAID, nonsteroidal antiinflammatory drug; PAR, protease-activated receptor; PCI, percutaneous coronary intervention; PG, prostaglandin; PGI₂, prostacyclin; PKC, protein kinase C; RGD, arginine-glycine-aspartic acid tripeptide; SLE, ...