Hyperprolactinemia in Patients on Antipsychotic Drugs Causes ADP-Stimulated Platelet Activation That Might Explain the Increased Risk for Venous Thromboembolism: Pilot Study

Abstract

Recently, an increased risk of venous thromboembolism in patients on antipsychotic drugs has been reported, but the molecular etiology is still unknown. Most antipsychotic drugs act as dopamine antagonists, and some of them cause hyperprolactinemia. Hyperprolactinemia has recently been found to cause increased platelet activation via potentiating ADP effects on human platelets. We assessed prolactin values as well as ADP-stimulated and thrombin receptor activator 6-stimulated expression of the platelet activation marker P-selectin in 20 consecutive patients under therapy with antipsychotic drugs. We detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in patients on antipsychotic drugs, revealing a significant higher platelet stimulation in hyperprolactinemic patients on antipsychotic drugs than in normoprolactinemic controls. Therefore, hyperprolactinemia might be the yet unknown acquired risk factor in patients on antipsychotic drugs explaining the increased risk for venous thromboembolism in these patients.

Massive Pulmonary Thromboembolism Demonstrated at Necropsy in Japanese Psychiatric Patients Treated With Neuroleptics Including Atypical Antipsychotics

“…Wallaschofski et al suggest that hyperprolactinemia is an important novel risk factor for PTE in patients on antipsychotic drugs and that the thrombogenic effect is mediated through enhanced platelet reactivity. 17 This adverse effect is also seen in male patients, but is more marked in female patients. 18 Unfortunately, we did not examine the prolactin concentrations in the present study and we wish to further investigate the hormonal effects in cases of PTE associated with antipsychotic drugs.…”

Risk of venous thromboembolism due to antipsychotic drug therapy

“…Prolactin has been reported as a potent platelet aggregation co-activator [91,92] and hyperprolactinemia is a well-known adverse reaction of antipsychotics [90,92]. Moreover, increased plasma levels of prolactin correlated with activation of platelets in users of antipsychotic in one study [90].…”

“…Hyperprolactinemia has recently been suggested as a plausible underlying mechanism for VTE in users of antipsychotics [90]. Prolactin has been reported as a potent platelet aggregation co-activator [91,92] and hyperprolactinemia is a well-known adverse reaction of antipsychotics [90,92].…”

Prolactin Levels, Endothelial Dysfunction, and the Risk of Cardiovascular Events and Mortality in Patients with CKD

“…For example, prolactin elevations occur in essential hypertension (10) and during the acute phase of coronary syndromes, ischemic strokes, transient ischemic attacks (11)(12)(13), and preeclampsia (14,15), playing a causative role in the heart failure that accompanies postpartum cardiomyopathy (16). Prolactin levels predicted major cardiovascular events in men with erectile dysfunction (17), and increased expression of prolactin receptors was found in advanced human atherosclerotic plaques (18).…”