IgM Inhibitors of the Contact Activation Phase of Coagulation in Chlorpromazine‐ Treated Patients

Abstract

In this report we have described three patients with chronic schizophrenia on long-term chlorpromazine therapy who developed asymptomatic IgM inhibitors of the intrinsic phase of blood coagulation. The anticoagulant resulted in decreased measurements of all of the plasma clotting factors in the intrinsic pathway (factors VIII, IX, XI, XII, Fletcher factor and Fitzgerald factor). Using crude coagulation reagents, the serum of these patients interfered with the clot promoting activity of contact product. To determine the relationship between drug therapy and these IgM inhibitors, we have studied nine additional schizophrenic patients on long-term chlorpromazine therapy. All nine chlorpromazine-treated patients had significantly increased levels of serum IgM and asymptomatic inhibitors of coagulation. We conclude that long-term high-dose chlorpromazine treatment of schizophrenic patients results in an increased concentration of IgM which has inhibitory activity in the contact phase of blood coagulation.

A new cryopathic syndrome.

“…Interaction of activated macrophages, complement, and immunoglobulins leads to destruction of T. gondii with release of Toxoplasma and cellular debris (6). This damaged cell debris may act as immunosuppressive products and stimulate suppressor T-lymphocytes (7), which block the reaction of responder T-lymphocytes (8). (B) Phospholipid glycoprotein complex from damaged cells activates factor VII and thus the extrinsic pathway of blood coagulation (9).…”

“…To demonstrate the specificity of the inhibitor, assays of factors V, VIII, IX, X, XI, and XII were performed on mixtures of normal plasma and dilutions of patient's plasma. Detection of an inhibitor of the contact phase of blood coagulation was according to Zucker et al 8 The inhibitory effect was quantified by comparing the clotting time of the patient's plasma with a dilution curve of contact factors. Neutralisa-tion of the circulating anticoagulant was performed using rabbit anti-human ,s chain and y chain antisera (Dako, Copenhagen).9…”

Drug-Induced Lupus Anticoagulants and Antiphospholipid Antibodies

“…One year later, Zucker et al [40] were the first to describe elevated serum IgM levels in chlorpromazine-induced LA (CPZILA). Additionally, they demonstrated that the IgM fraction was responsible for the LA activity.…”

“…Chlorpromazine is the most frequent culprit with over 300 cases reported [14,18,31,32,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. The first report of a phenothiazine-induced LA (PZILA) was published in 1977 by Canoso and Hutton [39].…”

Acquired Factor XI Inhibitor Presenting as Spontaneous Bilateral Subdural Hematoma in an Elderly Patient

“…AHA has been associated with malignancy, autoimmune disorders, pregnancy, multiple transfusions, or no apparent disease [3]. Inhibitors against other clotting factors are much rarer [1]; in particular those against FXI have been only anecdotally reported [4–12]. …”