Imbalance between ADAMTS13 and VWF Activities Might Identify Thrombotic of Bleeding Events in Essential Thrombocythemia (ET): Results from a Cohort of 72 Cases.

Background. Patients with Essential Thrombocythemia (ET) may have thrombotic and bleeding complications with increased morbidity and mortality. Age, previous history of thrombosis, elevated white cell counts and JAK2 allele burden are considered risk factors for both arterial (ATE) and venous (VTE) thrombosis while elevated platelet counts and qualitative defects of the von Willebrand factor (VWF) are associated with bleeds. ADAMTS13 regulates the pro-thrombotic activities of the VWF: reduced levels of ADAMTS13 or VWF activities expose patients to increased risk of thrombosis or bleeds. Aims: to evaluate whether or not the reduced activities of ADAMTS13/VWF were associated with thrombotic/bleeding complications, 72 patients with ET diagnosed according to WHO criteria at the Hematology Center of the L. Sacco University Hospital of Milan have been observed prospectively during a 36-month follow-up. Methods: Patients were exposed to all the diagnostic tests required for ET diagnosis and signed an informed consent for these ADAMTS13/VWF evaluations. VWF (VWF:RCo, VWF:Ag) activities and FVIII were measured in citrated plasma by the automatic ACL-TOP systems using commercially available reagent kits while ADAMTS-13 by TECHNOZYM activity ELISA. Statistical analyses among the cases with or without complications were performed with SPSS. Results: the cohort of ET patients was positive for JAK2(59%)/MPL(5%)/CALR(12%) with negative mutations in 17 cases. 3 different groups were found in this cohort: A)NOCOMPL=39/72(54.2%);B)ATE/VTE=22/72(30.5%);C)BLEEDS=11/72(15.2). The following clinical-lab data [median(range) according to these A/B/C groups are: M-F=11-28/5-17/3-8; Age=68(17-88)/73(33-89)/64(38-80);Plt-counts(/uL)=566(430-780)/559(398-551)/704(478 -1342);VWF:ACT(U/dL)=98(76-238)/163(86-282)/63(27-92); ADAMTS13(U/dL)=86(56-144)/45(31-105)/85(49/152);VWF:ACT/Ag:ratio=0.85(0.7-1.4)/0.75(0.6-1.2)/0.65(0.2/0.8); ADAMTS13/VWF:ACTratio=0.74(0.41-1.8)/0.54(0.25/1.2)/0.76(0.5-2.5). Liver and/or spleen enlargement was found in 23/72(32%) of all A/B/C patients but did not correlate with complications. A total of 30 ATE/VTE and 18 major/minor bleeds were observed in these 22 and 11 ET with complications while 6 patients had both VTE and BLEEDS during follow-up. Reduced levels of ADAMTS13 and of VWF activities correlated with the observed thrombotic and bleeding event. Conclusion: In a well characterized cohort of ET patients we could find that reduced levels of ADAMTS13 and VWF activities can be associated with their thrombotic and bleeding complications. These assays might be useful during the clinical follow-up to identify patient at risk for these complications.