Drug-Induced Thrombocytopenia: Mechanisms and Laboratory Diagnostics

Abstract

Thrombocytopenia is a condition characterized by a decreased number of platelets in peripheral blood, which can be caused by a myriad of both congenital and acquired disorders. Drug-induced thrombocytopenia (DIT) deserves a special focus since its cumulative incidence can be as high as 10 cases per million population per year, with a prevalence of approximately 25% in critically ill patients. This condition is usually suspected following identification of an acute and severe decrease in platelet count, with values usually < 50 ×109/L, thus potentially exposing patients to an increased risk of developing spontaneous hemorrhages. Conversely, however, some drug-related thrombocytopenias are instead (and perhaps counterintuitively) associated with increased thrombosis risk. Although a vast number of drugs have been implicated in DIT, the underlying pathogenetic mechanisms are essentially bifold, encompassing reduced platelet production due to bone marrow suppression (thus insufficient maturation or inefficient expansion of megakaryocytes, impaired release of platelets, or accelerated platelet apoptosis) or accelerated clearance of platelets from the circulation. This second form of DIT can be sustained by nonimmune, immune-mediated, or autoimmune mechanisms. An early and accurate diagnosis of DIT, which is crucial for reversing an otherwise unfavorable clinical outcome, is essentially based on the complete blood cell count, blood smear analysis, and performance of specific functional or immunochemical tests aimed at demonstrating the presence of antiplatelet antibodies.

Mediterranean Diet Maintained Platelet Count within a Healthy Range and Decreased Thrombocytopenia-Related Mortality Risk: A Randomized Controlled Trial

“…Of the 4381 PREDIMED participants with blood count available, we excluded 28 individuals without baseline data on MedDiet adherence or intake of alcohol, folate, and iron. To exclusively determine the effects on platelet levels of the dietary intervention, we also excluded those participants with any condition potentially related to alterations in platelet count at any point of the study [15,18], including the following: (1) any cancer of the immune system (17 individuals); (2) an autoimmune disease (28 individuals, determined as the use of immunosuppressant medications); (3) alcohol abuse (26 individuals, determined as a cumulative average of alcohol intake throughout the study of ≥4 drinks/day in men or ≥3 drinks/day in women); (4) viral infections (9 participants, determined as the use of oral antiviral medication); and (5) users of medications associated with platelet count alterations (10 users of heparins, 31 users of certain anticonvulsants (carbamazepine, phenytoin, and valproate), 32 users of L-dopa, 8 users of certain antibiotics (sulfamethoxazole, sulfa antibiotics, and vancomycin), and 3 fluconazole users). No participants with health outcomes related to altered platelet count (aplastic anemia, myelodysplastic syndromes, paroxysmal nocturnal hemoglobinuria, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation syndrome, hemolytic uremic syndrome, Wiskott-Aldrich syndrome, May-Hegglin anomaly, etc.)…”

Acute Levetiracetam-Induced Thrombocytopenia in an Anticoagulated Immunocompetent Patient

“…Drug-induced thrombocytopenia is a well-recognized clinical phenomenon in hospitalized patients which can occur through several mechanisms including direct bone marrow suppression, toxicity, or immunemediated platelet destruction through the production of anti-platelet antibodies [1,[7][8][9]13]. LEV, which is a widely used and well-tolerated antiseizure medication, has been rarely associated with this phenomenon, which can be potentially life-threatening in anticoagulated patients due to the potential risk of bleeding as in the index patient [1,[7][8][9][10][11][12].…”

Adalimumab-Induced Thrombocytopenia in a Patient With Hidradenitis Suppurativa

“…Flow cytometry, enzyme immunoassays (EIAs), glycoprotein (GP)-specific assays, platelet suspension immunofluorescence test, and antiglobulin-based assays are some of the methods that are used for the detection of drug-dependent antibodies. However, false-negative results may be seen due to the low sensitivity of some of these diagnostic methods for some antibodies [ 2 ]. Moreover, these tests may not be readily available in all instances [ 15 ].…”