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Review
. 2020 Jun 30;12(7):1746.
doi: 10.3390/cancers12071746.

Essential Thrombocythemia and Acquired von Willebrand Syndrome: The Shadowlands between Thrombosis and Bleeding

Hassan Awada  1 , Maria Teresa Voso  2   3 , Paola Guglielmelli  4 , Carmelo Gurnari  1   2
Affiliations
Review

Essential Thrombocythemia and Acquired von Willebrand Syndrome: The Shadowlands between Thrombosis and Bleeding

Hassan Awada et al. Cancers (Basel). .

Abstract

Over the past decade, new insights have emerged on the pathophysiology of essential thrombocythemia (ET), its clinical management, and associated thrombohemostatic disturbances. Here, we review the latest diagnostic and risk stratification modalities of ET and its therapeutics. Moreover, we discuss the clinical evidence-based benefits, deriving from major clinical trials, of using cytoreductive therapy and antiplatelet agents to lower the risk of fatal vascular events. Also, we focus on the condition of extreme thrombocytosis (>1000 × 109/L) and bleeding risk, the development and pathogenesis of acquired von Willebrand syndrome, and the clinical approach to this paradoxical scenario in ET.

Keywords: acquired von Willebrand syndrome; cytoreductive therapy; essential thrombocythemia; excessive thrombocytosis.

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Conflict of interest statement

The authors have no conflicts to disclose.

Figures

Figure 1
Figure 1
Bleeding mechanisms in patients with essential thrombocythemia. Patients with ET are prone to bleeding from AVWS or due to the use of antiplatelet/anticoagulant drugs. (A) illustrates the disease mediated mechanism in setting of excessive thrombocytosis which may cause AVWS due to in vivo absorption of VWF multimers. (B) describes iatrogenically induced bleeding risk in ET. Aspirin suppresses the production of thromboxane and prostaglandins by inactivating cyclooxygenase enzymes 1 and 2 (COX1/2) and thus impairing platelets aggregation. Vitamin K antagonist (used in selected patients with ET with active or prior thrombosis) have an intrinsic bleeding risk because of their narrow therapeutic window. Finally, excessive thrombocytosis may cause AVWS due to in vivo absorption of VWF multimers. COX1/2, cyclooxygenase enzymes type 1 and 2; VWF, von Willebrand factor.
Figure 2
Figure 2
Approach to aspirin use in essential thrombocythemia with extreme thrombocytosis. The algorithm explains how to approach extreme thrombocytosis (platelet count > 1000–1500 × 109/L) in essential thrombocythemia. It illustrates the investigational steps required for testing acquired von Willebrand syndrome in accordance with aspirin use, in a timely manner. ET, essential thrombocythemia; AVWS, acquired von Willebrand syndrome; HMW, high molecular weight; VWF:RCoA, von Willebrand factor ristocetin cofactor activity; ASA, aspirin.
See this image and copyright information in PMC

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