Heparin-induced thrombocytopenia associated with thrombotic microangiopathy

Summary

Some cases of thrombotic microangiopathy (TMA) are refractory to plasma exchange therapy (PE) with persistence or recurrence of thrombocytopenia. We report two patients suffering from TMA of different aetiologies (associated with disseminated malignancy, typical haemolytic uraemic syndrome) with recurrent or persistent thrombocytopenia despite adequate therapy including PE. Since both patients were exposed to unfractionated heparin, heparin-induced thrombocytopenia (HIT) was suspected as a cause. Pretest probabilities for HIT were intermediate. ELISA for PF4/heparin antibodies was strongly positive in both cases, and HIT was confirmed by heparin-induced platelet activation assay. Anticoagulation with lepirudin was initiated, with subsequent rapid increase of the platelet count.

TMA might represent a predisposition for HIT. This could be due to TMA-related platelet activation with increased PF4 release. In TMA patients exposed to heparin and with refractory or rapidly recurrent thrombocytopenia HIT should always be considered as a possible cause.

Zusammenfassung

Bei einem Teil der Patienten mit thrombotischen Mikroangiopathien (TMA) kommt es trotz adäquater Therapie einschliesslich Plasmaaustauschs (PE) zur Persistenz oder zum Wiederauftreten der Thrombozytopenie. Wir berichten über zwei Patienten mit TMA (bei disseminiertem Tumorleiden, typisches hämolytisch-urämisches Syndrom), bei denen ein solcher Verlauf zu beobachten war. Beide hatten unfraktioniertes Heparin erhalten. Wir vermuteten daher eine Heparin-induzierte Thrombozytopenie (HIT) und errechneten eine intermediäre Vortestwahrscheinlichkeit für diese. Im ELISA waren Antikörper gegen PF4/Heparin nachzuweisen. Das Vorliegen einer HIT wurde mittels eines funktionellen Tests bestätigt (Heparin-induzierte Plättchenaktivierung). Nachfolgend war unter Therapie mit Lepirudin eine rasche Normalisierung der Thrombozytenzahl zu verzeichnen.

Wir vermuten, dass TMA das Auftreten einer HIT begünstigen, möglicherweise infolge einer TMA-bedingt gesteigerten Plättchenaktivierung und konsekutiv vermehrten PF4-Freisetzung. Persistiert oder rezidiviert eine Thrombozytopenie bei heparinexponierten Patienten mit TMA, so sollte eine HIT als mögliche Ursache stets bedacht werden.

Keywords

Thrombotic microangiopathy - TMA - thrombocytopenia - heparin - heparin-induced thrombocytopenia - HIT

Schlüsselwörter

Thrombotische Mikroangiopathie - TMA - Thrombozytopenie - Heparin - Heparin-induzierte Thrombozytopenie - HIT

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