Thrombocytopenia quinidine-induced

Quinidine Quinidine, molecular formula C20H24N2O2, is a stereoisomer of quinine found in Cinchona bark. Chemically, it is known as (2-ethenyl-4-azabicyclo[2.2.2]oct-5-yl)-(6-methoxyquinolin-4-yl)-methanol, or 6 -methoxycinchonan-9-ol. It is used as a Class 1 anti-arrhythmic agent. Intravenous injection of quinidine is also used in the treatment of P. falciparum malaria. Among the adverse effects, quinidine induces thrombocytopenia (low platelet counts) and may lead to thrombocytic purpurea. 

Saleh MN, Dhodaphar N, Allen K, LoBuglio AF. Quinidine-induced immune thrombocytopenia. Henry Ford Hosp Med J 1989 37(l) 28-32. 

Redell MA, Moore BR, Fass L. Use of i.v. immune globulin for presumed quinidine-induced thrombocytopenia. Clin Pharm 1989 8(2) 89. 

Chong BH, Bemdt MC, Koutts J, et al. Quinidine-induced thrombocytopenia and leukopenia Demonstration and characterization of distinct antiplatelets and antileukocyte antibodies. Blood 1983 62 1218-1223. 

Christie DJ, Aster RH (1982) Drag-antibody-platelet interaction in quinine- and quinidine-induced thrombocytopenia. J Clin Invest 70 989-998... 

Lewis IP, Austen KF (1964) Fatal systemic anaphylaxis in man. N Engl J Med 270 597 Libman LJ, Goldsmith KLG (1972) Quinidine-induced thrombocytopenia. Proc R Soc Med 65 590... 

Many drugs, especially quinidine and heparin, induce antibodies leading to thrombocytopenia. In most cases the antibodies are drug-dependent however, there are many examples in which the antibodies are autoimmune in nature [42], even for drugs, such as quinidine that are classically associated with drug-dependent antibodies [43], Gold therapy, in particular, is associated with autoimmune-thrombocytopenia [44],... 

Hypersensitivity or idiosyncrasy to quinidine or other cinchona derivatives manifested by thrombocytopenia, skin eruption or febrile reactions myasthenia gravis history of thrombocytopenic purpura associated with quinidine administration digitalis intoxication manifested by arrhythmias or AV conduction disorders complete heart block left bundle branch block or other severe intraventricular conduction defects exhibiting marked QRS widening or bizarre complexes complete AV block with an AV nodal or idioventricular pacemaker aberrant ectopic impulses and abnormal rhythms due to escape mechanisms history of drug-induced torsade de pointes history of long QT syndrome. 

The use of quinidine and quinine should be avoided in patients who previously showed evidence of quini-dine-induced thrombocytopenia. 

Various hypersusceptibility reactions have been attributed to quinidine, including fever, skin rashes, various types of hematological abnormalities (particularly thrombocytopenia), hepatitis, asthma, and anaphylactic shock. Quinidine has rarely been reported to cause a lupus-like syndrome. Tumor inducing effects have not been reported. 

The third mechanism described for drug-induced thrombocytopenia is the innocent bystander-type immune response. The most commonly implicated drug is quinidine, and the drug-induced thrombocytopenia is frequently related to higher doses of the drug. Quinidine may also form a hapten with the platelet membrane to produce thrombocytopenia. ... 

Noncardiac Diarrhea is the most common adverse effect during quinidine therapy, occurring in 30-50% of patients, usually within the first several days of quinidine therapy but sometimes later. Diarrhea-induced hypokalemia may potentiate the risk of torsades de pointes due to quinidine. A number of immunological reactions can occur during quinidine therapy. The most common is thrombocytopenia, which can be severe but resolves rapidly with drug discontinuation. Hepatitis, bone marrow depression, and lupus syndrome occur rarely. None of these effects is related to elevated plasma quinidine concentrations. Quinidine also can produce cinchonism, a syndrome that includes headache and tinnitus. In contrast to other adverse responses to quinidine therapy cinchonism usually is related to elevated plasma quinidine concentrations and can be managed by dose reduction. 

Christie DJ, Mullen PC, Aster RH (1985) Fab-mediated binding of drug-dependent antibodies to platelets in quinidine- and quinine-induced thrombocytopenia. J Clin Invest 75 310-314 Cunha PD, Lord RS, Johnson ST, Wilker PR, Aster RH, Bougie DW (2000) Immune hemolytic anemia caused by sensitivity to a metabolite of etodolac, a nonsteroidal anti-inflammatory drag. Transfusion 40 663-668... 

Thrombocytopenia is a well-recognized hypersensitivity reaction, inducible by quinidine, but only about 50 cases have been reported (Robinson 1978). Hemolytic anemia is even more rare one well-documented case was reported by Freedman et al. (1956) and one case of agranulocytosis with marrow depression was reported by Barzel (1967). 

Purpuric lesions are evident in patients with thrombocytopenia induced by both quinidine and methyldopa, but papular rashes, particularly on the legs, are seen more commonly in patients taking methyldopa. 

Stibophen is not a cardiovascular drug, but the proposed mechanism by which stibophen induces anemia would also fit the data generated by Freedman et al. (1956) for quinidine anemia and be compatible with Shulman s passive bystander hypothesis for drug-induced thrombocytopenia (Shulman 1958). The essential feature of the mechanism is the formation of a drug-antibody complex which passively adheres to red cells. Complement is fixed by the complex and the cells are lysed as a result. 

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