Drug-Induced Thrombocytopenia
Section snippets
Clinical Features
Clinically, these patients present with moderate to severe thrombocytopenia (defined as a platelet count of less than 50 × 109/L) and spontaneous bleeding varying from simple ecchymoses, petechiae, and mucosal bleeding to life-threatening spontaneous intracranial hemorrhage. Exclusion of other causes of thrombocytopenia (such as congenital disorders and inflammatory processes), anamnestic analysis (such as a temporal relationship between the administration of the putative drug and the
Etiology
Hundreds of drugs have been implicated in the pathogenesis of DIT. DIT disorders can be a consequence of decreased platelet production or accelerated platelet destruction.
A decrease in platelet production is usually attributable to a generalized myelosuppression, a common and anticipated adverse effect of cytotoxic chemotherapy [12]. In addition, it has been reported that some chemotherapeutic agents can induce thrombocytopenia secondary to an immune-mediated mechanism [13], [14], [15], [16],
Mechanisms of Drug-Induced Immunologic Thrombocytopenia
DITP is a relatively common and sometimes serious clinical disorder characterized by drug-dependent antibodies (DDAbs) that bind to platelets and cause their destruction. Antibodies associated with DITP are unusual in that they typically bind to glycoproteins (GPs) on the cell membrane of the platelets only in the presence of the provocative drug [21], [22]. Hundreds of drugs have been implicated in its pathogenesis; among those, drugs most often associated with DITP are heparin, cinchona
Laboratory Diagnosis
The diagnosis of drug-induced thrombocytopenia is often empiric. In patients exposed only to a single drug, recovery after its discontinuation provides circumstantial evidence that the thrombocytopenia was caused by drug sensitivity [28], [44]. In vitro documentation of platelet-bound immunoglobulins, in the presence of the putative drug, provides direct evidence for the involvement of the tested drug in causing in vivo platelet destruction.
Many different methods have been used to detect the
Summary
DIT disorders can be a consequence of decreased platelet production (bone marrow suppression) or accelerated platelet destruction (especially immune-mediated destruction). Immune-mediated platelet consumption is associated with a large number of drugs leading to DITP in which platelet destruction is caused by immunoglobulins that recognize specific platelet membrane GPs only in the presence of the sensitizing drug noncovalently associated with a specific GP. In some instances, not only the drug
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2022, Toxicology and Applied PharmacologyCitation Excerpt :GRN may exert its effect by interfering with lineage-specific transcripts, growth factors, cytokines, or cell cycle proteins that regulate granulopoiesis (Cowland and Borregaard, 2016). Similar to a wide assortment of approved and investigative chemotherapeutic agents (Alfhili et al., 2021a; Visentin and Liu, 2007), platelets have also been identified as particularly susceptible to GRN action (Fig. 10H) which argues for careful consideration of GRN in cancer therapy. In conclusion, this study highlights the immunomodulatory properties of GRN in WB; a highly relevant, yet understudied model system, and presents a novel pro-eryptotic activity against mature erythrocytes.
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2021, Blood ReviewsCitation Excerpt :Numerous drugs have been reported to induce drug-induced immunologic thrombocytopenia as cinchona alkaloid derivatives, penicillin, sulfonamides, nonsteroidal anti-inflammatory drugs, anticonvulsants, antirheumatic, oral antidiabetic drugs, diuretics, rifampicin, and ranitidine. For a structured review of the pathophysiological mechanisms leading to drug-induced thrombocytopenia, we refer to the work of Visentin and Liu [44]. At last, increased splenic sequestration occurs in patients with severe liver cirrhosis [47].
Pediatric bleeding disorders
2021, Biochemical and Molecular Basis of Pediatric DiseaseAlcohol-induced thrombocytopenia: Current review
2020, AlcoholCitation Excerpt :Some drugs have a proven thrombocytogenic effect (PLT over 400,000–450,000/μL) on increasing the PLT (Frye & Thompson, 1993; Vo & Thompson, 2019). Almost any drug can change the number of platelets, and the pathological mechanism of drug-induced TP varies (George & Aster, 2009; Kenney & Stack, 2009; Sekhon & Roy, 2006; Visentin & Liu, 2007). Particular attention should be paid to TP caused by the drugs.
This work was supported in part by Grants HL-64704 from the National Heart, Lung, and Blood Institute.