Subdural Hematomas in Pulmonary Arterial Hypertension Patients Treated with Protacyclin Analogs

Abstract

Prostacyclin analogs therapy has been associated with development of thrombocytopenia. Little is known whether this treatment increases the risk of intracranial hemorrhage in pulmonary artery hypertension (PAH) patients. We queried the Cleveland Clinic billing database to identify cases of nontraumatic sudural hematoma (SDH) in patients with PAH. We identified those individuals who were receiving prostacyclin analogs therapy at the time of the neurological event and assessed whether these patients were also taking antiplatelet or anticoagulation therapies. We identified three cases of nontraumatic SDH in 856-patient-year of prostacylin analog treatment. All patients were women, had low normal platelet counts or thrombocytopenia, and were concomitantly receiving anticoagulation therapy in the appropriate therapeutic anticoagulation range. All three patients were managed conservatively and had no neurologic sequelae. Nontraumatic acute subdural hematoma is a rare event in patients with PAH treated with prostacyclin analogs. All affected patients were concomitantly receiving anticoagulation therapy.

Prostacyclin Analogues Inhibit Platelet Reactivity, Extracellular Vesicle Release and Thrombus Formation in Patients with Pulmonary Arterial Hypertension

“…In line with previous studies, we showed that prostacyclin analogues inhibit platelet reactivity and decrease platelet EV release. Additionally, we showed that impaired platelet function is associated with impaired thrombus formation, explaining the pathophysiological mechanisms underlying increased risk of bleeding in patients treated with prostacyclin analogues [ 40 , 41 ]. We observed that two patients who did not achieve clotting in the whole blood perfusion systems subsequently experienced bleeding.…”

Non-traumatic Acute Subdural Hematoma in a Patient With Scleroderma Complicated by Pulmonary Arterial Hypertension: A Case Report

“…Our patient's platelet count on presentation of her SDH was 245 x 10*9/L, making thrombocytopenia an unlikely cause for hemorrhage. While rare, there have been several cases of non-traumatic SDH described in PAH patients, mainly occurring in patients receiving epoprostenol while on anticoagulation with vitamin K antagonists independent of INR value [6][7][8]. Interestingly, CTD-PAH patients in the Henkens et al study were also noted to have a significantly higher rate of major bleeding than other PAH sub-groups.…”

A case report of pulmonary arterial hypertension in pregnancy and complications of anticoagulation therapy

“…Louis et al reported that one patient had a low normal platelet count, a condition in which the platelet levels decreased after continuous intravenous treprostinil administration for approximately 7 months. [ 17 ] Wang and Chen also reported a case of treprostinil-induced thrombocytopenia, for which the platelet counts were directly related to the rate of intravenous treprostinil administration. [ 18 ] We have not yet seen studies about the pathogenesis of thrombocytopenia caused by treprostinil treatment.…”