Acute thrombocytopenic purpura in relation to the use of drugs

Abstract

The relation of acute thrombocytopenic purpura (TP) to the use of drugs was investigated in a case-control study conducted in eastern Massachusetts, Rhode Island, and the Philadelphia region; 62 cases over the age of 16 years with acute onset and with a rapid recovery were compared with 2,625 hospital controls. After control for confounding by multiple logistic regression, use of the following drugs in the week before the onset of symptoms was significantly associated: trimethoprim/sulfamethoxazole (relative risk [RR] estimate, 124), quinidine/quinine (101), dipyridamole (14), sulfonylureas (4.8), and salicylates (2.6). The overall annual incidence of acute TP was estimated to be 18 cases per million population. The excess risks for the associated drugs were estimated to be 38 cases per million users of trimethoprim/sulfamethoxazole per week, 26 per million for quinidine/quinine, 3.9 per million for dipyridamole, 1.2 per million for sulfonylureas, and 0.4 per million for salicylates. Associations with sulfonamides, quinidine/quinine, sulfonylureas, and salicylates have been previously reported, but the present study has provided the first quantitative measures of the risk. The association with dipyridamole was unexpected. In general, despite large RRs, the incidence rates attributable to the drugs at issue (excess risks) were low, suggesting that TP is not an important consideration in the use of the various drugs.

Use of an active surveillance system by the FDA to observe patterns of quinine sulfate use and adverse hematologic outcomes in CMS Medicare data

“…Our estimate is consistent with that provided by a case-control study, which provides an attributable risk of quinine-quinidine induced thrombocytopenia of 26 cases of every 1 million users. 13 Notably, the relative risk of quinine associated thrombocytopenias in our analysis using diltiazem as a comparator is significant. Incidence rate ratios comparing quinine with diltiazem were 4.2 overall for ITP and 3.4 for the first 30 days of exposure.…”

Thrombocytopenia as an adverse effect of complementary and alternative medicines, herbal remedies, nutritional supplements, foods, and beverages*

“…Because only few reports were identified and because interpretation of the reports was often difficult, a concise summary of each patient report is presented in Tables 3-7. Articles reporting thrombocytopenia associated with quinine-containing beverages were identified but not included in the Tables because quinine is well recognized as one of the most common causes of drug-induced isolated thrombocytopenia (8,9). In addition to the 27 articles included in the Tables, six articles were identified that described seven patients with thrombocytopenia associated with quinine-containing beverages (16)(17)(18)(19)(20)(21).…”

“…The ISI Web of Knowledge interface was used to search the [1] Current Contents Connect and [2] Web of Science databases; the OvidSP interface was used to search the [3] Allied and Complementary Medicine (AMED), [4] Cochrane Database of Systematic Reviews, [5] EMBASE, [6] International Pharmaceutical Abstracts, and [7] MEDLINE databases. Reports were also sought from the [8] Natural Medicines Comprehensive Database, [9] FDA MedWatch Database, [10] International Bibliographic Information on Dietary Supplements Database (IBIDS), and [11] the Health and Wellness Resource Center. The websites for these databases are provided in the legend of Table 1.…”

“…(i) The absence of well-documented reports clearly describing an association of thrombocytopenia with these substances may lead to lack of suspicion of a possible association. The recognition of quinine-containing beverages as a cause of isolated thrombocytopenia (16)(17)(18)(19)(20)(21) is an exception and may only occur because of familiarity with quinine as one of the most common causes of drug-induced thrombocytopenia (8,9). (ii) When clinicians ask their patients about the medicines they are taking, they often do not explicitly ask about complementary ⁄ alternative medicines, herbal remedies, and nutritional supplements.…”

“…With the exception of quinine-containing beverages, thrombocytopenia caused by nutritional supplements, foods, and beverages is rarely reported. Patients with thrombocytopenia associated with quinine-containing beverages may have been recognized because quinine is among the most common causes of drug-induced thrombocytopenia (8,9).…”