Quinine thrombocytopenia with

Bougie DW, Birenbaum J, Rasmussen M, Poncz M, Aster RH. (2008) Quinine-dependent, platelet-reactive monoclonals mimic antibodies found in patients with quinine-induced immune thrombocytopenia. Blood 113 1105-1111. 

In one patient with AIDS with severe but reversible thrombocytopenia after intravenous pentamidine, the serum during the acute phase contained antiplatelet antibodies that reacted with glycoprotein Ilb/IIIa, similar to the reactions observed with quinine-induced thrombocytopenia (SEDA-18, 292). This suggests that even aerosol treatment or environmental exposure will need to be avoided in such patients. 

Isolated thrombocytopenia after the use of quinine for malaria or leg cramps has been described in isolated cases. The FDA s Center for Drug Evaluation and Research received 141 reports of isolated thrombocytopenia in association with quinine from 1974 to December 2000 (18). After elimination of cases that were confounded by acute or chronic disease or concomitant drug therapy, 64 reports of quinine-associated thrombocytopenia were analysed. Thrombocytopenia occurred soon after the start of therapy (median 7 days) and was often severe (hospitalization reported in 55 of the 64 cases). 

Renal damage accompanies acute hemolysis due to quinine. Renal insufficiency in cases of quinine poisoning is probably due to circulatory collapse. Allergic reactions underlie at least some cases. The picture can be complex, with the renal insufficiency coming in association with cortical necrosis, thrombocytopenia, intravascular coagulation, and deposition of fibrin. 

Quinine can cause a variety of immune-mediated syndromes, most commonly isolated thrombocytopenia, but rarely microangiopathic hemoljdic anemia with thrombocytopenia and acute renal insufficiency (hemolytic-uremic syndrome). Two reports of immune-mediated syndromes following the use of quinine for leg cramps have helped to provide an immunopathological explanation for the diversity of such presentations (29,30). 

Brinker AD, Beitz J. Spontaneous reports of thrombocytopenia in association with quinine chnical attributes and timing related to regulatory action. Am J Hematol 2002 70(4) 313-17. 

Quinine is contraindicated in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, optic neuritis, tinnitus, or a history of blackwater fever and thrombocytopenia purpura. The symptoms of overdosage are tinnitus, dizziness, skin rash, and GI disturbance (intestinal cramping). With higher doses, cardiovascular and CNS effects may occur, including headache, fever, vomiting, apprehension, confusion, and convulsions. 

Garratty G, Amdt P, Prince HE, Shulman lA (1993) The effect of methyldopa and procainamide on suppressor cell activity in relation to red cell autoantibody production. Br J Haematol 84 310-315 Gottschall JL, Elliot W, Lianos E, McFarland JG, Wolfmeyer K, Aster RH (1991) Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome a new clinical entity. Blood 77 306-310... 

The unambiguous demonstration, in presumptive allergic reactions, of immunochemical specificity determined by drug-derived haptenic structures, is absent in the majority of cases, with the exception of some instances of contact allergic dermatitis induced by antifungal agents applied topically. In this chapter immunochemical specificity is discussed also in relation to the antibodies responsible for quinine-induced thrombocytopenia and levamisole-induced anti-leucocyte antibodies in agranulocytosis. 

Quinine (Fig. 9) is probably the oldest effective therapeutic agent for the prophylaxis and therapy of Plasmodium infections and, although now largely superseded for routine use, it is of considerable value in the treatment of chloroquine-resistant P. falciparum, for which it is used in combination with other antimalarials. The main side effects of quinine therapy comprise a syndrome of classical cinchonism, i.e., tinnitus, vision defects, nausea, headache and gastrointestinal effects, but im-munologically the much rarer complication, drug-induced thrombocytopenia is of more interest. 

The pathogenesis of thrombocytopenia will become clearer when the mechanism of production of autoimmune disease is discussed. Only a few salient points are mentioned here. A number of drugs, among them allylisopropylacetyl carbamide (Sedormid), quinine, quinidine, are known to autosensitize platelets. In affected patients, the combination of platelet, drugs, and serum leads to thrombocytopenia a large number of patients with idiopathic thrombocytopenia have antiplatelet antibodies in their blood. If the blood of such patients is injected to normal individuals, thrombocytopenia occurs. 

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