Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro

Abstract

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.

Transient, Profound Thrombocytopenia in a Premature Infant: Is this a Ranitidine‐Induced Immune Reaction?

“…It can therefore be difficult to implicate a specific drug on clinical grounds because patients may be treated with several drugs at the time of thrombocytopenia or may have an underlying condition, such as septicaemia, which may be com-plicated by thrombocytopenia. 16 Having excluded other possible causes, this case has raised the possibility that premature infants may be capable of ranitidine-induced immune reactions under certain circumstances. Together with recent data from animal and human studies, surveillance of haematologic and immunologic changes in similar cases may extend our understanding of the immunology of premature infants.…”

“…On the other hand, platelet counts of <10 x 10 9 /L at thrombocytopenic nadir have been reported in a series of cases of drug-induced immune reactions associated with quinine, quinidine, gold, ampicillin, cimetidine and some sulfonamides. 16 In drug-induced allergic reactions, after initial exposure to a drug, potentially allergic individuals exhibit a latent period before the onset of hypersensitivity reactions. During this latent period (10-20 days), the drug or drug metabolite-protein complex stimulates antibody formation or T-effector cells.…”

Immune Thrombocytopenia Due to Tranilast (Rizaben®): Detection of Drug‐dependent Platelet‐associated IgG

“…The diagnosis of drug-induced thrombocytope nia is made clinically, based on the relation ship between the onset of thrombocytope nia and the administration of a drug, which is followed by a rapid recovery of platelet count after ceasing the medication. Provocaiton tests are often harmful, and various in vitro tests have been proposed to detect causative drugs (6,7). In order to detect drug-dependent platelet antibody, the antiglobulin consumption assay and the platelet adhesion immunofluorescence test are employed using platelets from healthy donors and the patient's serum (8,9).…”

Increased Platelet Destruction in Infancy and Childhood

“…217 Such methods are preferable to those that measure platelet-bound antibody, since the former can be performed in the presence or absence of the suspected drug. However, Kelton et al 128 have used a combination of PAIgG and S-PBIgG determinations to demonstrate the increased binding of IgG to platelets, both in vivo and in vitro, in patients with drug-induced thrombocytopenia.…”