Do we need antiplatelet therapy in thrombocytosis? Contra

Summary

Thrombocytosis is a frequent laboratory finding but not a diagnosis. Therefore, elevated platelet counts (>450 × 10⁹/l) require careful diagnostic work-up to differentiate between reactive thrombocytosis (RT), caused by various conditions, and essential thrombocythemia (ET), a myeloproliferative neoplasm (MPN). In either setting, aspirin is widely used in clinical practice. However, RT (even at platelet counts >1000 × 10⁹/l) has never been shown to cause thrombosis or bleeding due to acquired von Willebrand factor defects in association with high platelet counts. Identification of reactive conditions and appropriate therapy of the underlying disorder are most relevant. By contrast to RT, ET and related MPN can be associated with thrombosis and/or hemorrhage. Current recommendations suggest the use of low-dose aspirin in all patients with ET unless contraindicated. However, the strength of this recommendation is weak, i. e. evidence level IIb grade B. A potential benefit of aspirin used for primary thromboprophylaxis in ET is mostly derived from the ECLAP study in polycythemia vera (PV). However, translating study results from PV to ET appears to be highly questionable and may be biased. In the absence of robust data regarding the benefit-risk balance of aspirin in ET, it appears reasonable (1) to stratify patients according to their individual thrombotic and bleeding risk, (2) to restrict the use of aspirin to high-risk categories and patients with microcirculatory disturbances, (3) to test for pharmacological efficacy (COX-1 inhibition; measurement of TXB₂), and (4) to modify the aspirin dosing regimen (twice instead of once daily) if required.

Zusammenfassung

Thrombozytose ist ein häufiger Laborbefund, aber keine Diagnose. Erhöhte Thrombozytenwerte (>450 × 10⁹/l) erfordern daher eine Differenzierung zwischen reaktiver Thrombozytose (RT) bei verschiedenen Erkrankungen und essenzieller Thrombozythämie (ET), einer myeloproliferativen Neoplasie (MPN). In beiden Fällen wird Aspirin breit eingesetzt. Allerdings wurde nie belegt, dass eine RT (selbst bei Thrombozytenwerten >1000 × 10⁹/l) Thrombosen oder Blutungen als Folge eines erworbenen von-Willebrand-Syndroms bei ausgeprägter Thrombozytose hervorruft. Bei RT bleiben Nachweis auslösender Ursachen und Behandlung der Grunderkrankung maß-geblich. Im Gegensatz dazu treten bei ET und anderen MPN Thrombosen und/oder Blutungen auf. Sofern keine Kontraindikation besteht, wird derzeit bei allen Patienten mit ET eine niedrig dosierte Aspirin-Behandlung empfohlen. Die Beweislage hierfür ist aber schwach (Evidenzklasse IIb Grad B). Ein möglicher Nutzen von Aspirin zur antithrombotischen Primärprophylaxe bei ET wird hauptsächlich aus der ECLAP-Studie bei Polycythaemia vera (PV) abgeleitet. Eine Übertragung der PV-Studienergebnisse auf ET-Patienten erscheint jedoch äußerst fragwürdig, da potenziell irrtumsbelastet. Auf Grund fehlender verlässlicher Daten zur Nutzen-Risiko-Bewertung von Aspirin bei ET wird vorgeschlagen, 1) die Patienten entsprechend ihrem individuellen Thrombose- und Blutungsrisiko zu stratifizieren, 2) eine Aspirin-Behandlung auf die Hochrisikogruppe und Patienten mit akuten Mikrozirkulationsstörungen zu beschränken, 3) die pharmakologische Wirksamkeit von Aspirin zu prüfen (COX-1-Hemmung; TXB₂-Spiegel-Bestimmung) und 4) das Aspirin-Dosierungsintervall (2-mal statt 1-mal tgl.) gegebenenfalls zu anzupassen.

Keywords

Reactive thrombocytosis - essential thrombocythemia - von Willebrand factor - bleeding - thrombosis - aspirin - personalized medicine

Schlüsselwörter

Reaktive Thrombozytose - essenzielle Thrombozythämie - von-Willebrand-Faktor - Blutungen - Thrombosen - individualisierte Medizin

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