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Objectives: Cell counts have a significant impact on the complex mechanism of thrombosis in patients with essential thrombocythemia (ET). We recently demonstrated a considerable impact of white blood cell (WBC) counts on thrombotic risk in patients with optimized platelet counts by analysing a large anagrelide registry. In contrast, the current analysis of the registry aimed to estimate the influence of platelet counts on thrombotic risk in patients with optimized WBC counts., Methods: Cox regression analysis and Kaplan-Meier plot were applied on all patients in the registry with optimized WBC counts., Results: By using the calculated cut-off of 593 G/L for platelets, Cox regression analysis revealed a clear influence of elevated platelet counts on the occurrence of a major thrombotic event (P < .001). A Kaplan-Meier plot revealed a markedly shorter time to a major thrombotic event for patients with platelet counts above the cut-off (P < .001)., Conclusions: The data show clear impact of platelet lowering on the thrombotic risk in ET patients with normal WBC counts. Therefore, selective platelet lowering with anagrelide appears sufficient for thrombotic risk reduction in WHO-diagnosed ET patients lacking leukocytosis., (© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Patients with myeloproliferative neoplasms (MPN) are at an increased risk of thrombotic events even during antiplatelet therapy with aspirin. In the current study, we sought to investigate the association of the platelet count with the inhibitory potential of antiplatelet therapy in MPN. We determined arachidonic acid (AA)- and adenosine diphosphate (ADP)-inducible platelet reactivity by multiple electrode aggregometry in 93 patients with essential thrombocythemia, polycythemia vera or primary myelofibrosis. In patients without aspirin therapy (n = 44), the platelet count did not correlate with platelet aggregation. In aspirin-treated patients (n = 49), we observed a moderate correlation of residual AA-inducible platelet aggregation with the platelet count (r = 0.49; P < 0.001). Further, patients with high on-treatment residual platelet reactivity to AA (HRPR AA) had a significantly higher platelet count than patients without HRPR AA (547 × 10 9 /L [340 - 644 × 10 9 /L] vs 358 × 10 9 /L [242 - 501 × 10 9 /L], P = 0.01). Receiver-operating characteristic curve analysis revealed a platelet count of ≥317 × 10 9 /L as best threshold to distinguish between patients without and with HRPR AA (area under the curve: 0.73). After adding the direct ADP P2Y 12 inhibitor cangrelor to blood samples from all 93 patients in vitro, residual ADP-inducible platelet reactivity correlated weakly with the platelet count (r = 0.26, P = 0.01), but the platelet count did not differ significantly between patients with and without HRPR ADP (396 × 10 9 /L [316 - 644 × 10 9 /L] vs 340 × 10 9 /L [241 - 489 × 10 9 /L]; P = 0.2). In conclusion, our findings suggest that the extent of platelet inhibition by aspirin in patients with MPN at least in part depends on their individual platelet count., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Although guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high-risk essential thrombocythemia (ET), retrospective studies could not prove a correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms., Methods: This study considers the Austrian cohort of a European registry regarding the platelet-lowering therapeutic anagrelide. Influence of platelet and white blood cell (WBC) counts on thrombotic risk was assessed., Results: Using the calculated cutoffs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on the occurrence of major thrombotic events. The time to a major thrombotic event was shortest (P < 0.001) and the frequency related to 100 patient-years was highest (P = <0.001) when both platelet and WBC counts ranged above the calculated cutoffs., Conclusion: Our data add evidence to the impact of platelet and WBC counts on thrombosis in ET. We suspect a particular interaction between platelets and WBC which might be based on a biological interplay depending on particular cell counts., (© 2016 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.)

Objective: There is strong evidence that certain thrombophilic single nucleotide polymorphisms (SNPs) account for an increased risk of thrombosis. The additive impact of inherited thrombotic risk factors to a certain disease- immanent thrombotic risk is vastly unknown. Therefore, we aimed to investigate the influence of three novel, preselected SNPs on the risk of thrombosis in patients diagnosed with myeloproliferative neoplasm (MPN)., Method: In 167 patients with a diagnosis of essential thrombocythemia (ET) or prefibrotic primary myelofibrosis (PMF) thrombophilic SNPs in the genes of factor VII (F7), nitric oxide synthase 3 (NOS3) and FcɣRIIa (FCGR2A) were determined. Subsequently, the polymorphic variants were correlated with the incidence of major thrombosis after diagnosis., Results: Decanucleotide insertion polymorphism of F7 emerged as an independent, significant risk factor for total thrombosis and arterial thrombosis in particular in the whole group of patients (P = 0.0007) as well as in the separate analysis of patients with ET (P = 0.0002)., Conclusion: Our results illustrate that the risk of thrombosis in MPN is significantly multiplied by inherited thrombophilic SNPs. This result points to the importance of a combined consideration of the inherited and the acquired hypercoagulable state in patients with MPN. Larger studies are needed to confirm and extend these important findings., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We aimed to determine risk factors for thrombotic events in early/prefibrotic myelofibrosis diagnosed according to the World Health Organization criteria. Multivariate Cox regression analysis was calculated on a total number of 264 patients derived from an international database. After a median follow-up of 6.28 years, 42 (15.9%) patients experienced arterial (n = 31) or venous thrombosis (n = 11). A higher leukocyte count correlated with an increased risk for total thrombosis and in particular, with an increased risk for arterial thrombosis (P = 0.005, HR 1.15 and P = 0.047, HR 1.12, respectively). A platelet count above 870 × 10⁹/L was associated with a lower risk for total thrombosis and also for venous thrombosis (P = 0.022, HR 0.44 and P = 0.027, HR 0.19). Moreover, a lower hemoglobin level was associated with an increased risk for venous thrombosis (P = 0.007, HR 0.59). Our data indicate that leukocytosis is a prominent risk factor for thrombosis in early/prefibrotic MF., (Copyright © 2012 Wiley Periodicals, Inc.)

The effect of interferon alpha (IFN) on myeloproliferation and vascular complications was studied in 32 patients (17 female, 15 male; median age 60.5 yr) with polycythemia vera (PV). IFN therapy was initiated at a median time of 19 months after diagnosis. Ten patients were pretreated with chemotherapy in addition to phlebotomy. IFN dose was 12 megaU/wk during the first year, 9 megaU/wk during the second year and 12 megaU/wk thereafter. During IFN alpha treatment hematocrit level was 45.7% and remained at this level after the second year of treatment, compared to 46.5% before IFN. The frequency of phlebotomy before IFN was 0.49/month and dropped to 0.19/month (p <0.0005) during the first year of IFN treatment. IFN normalized high platelet and leukocyte counts in a majority of patients. The incidence of deep venous thromboses was 3.6%/yr before IFN alpha and 1.8%/yr during the first year of treatment. IFN-induced side-effects were mainly flu-like symptoms, fever, fatigue and arthralgia. In conclusion, IFN allowed the reduction of the dose of chemotherapy and decreased the need of phlebotomy. Despite improvement of hematological parameters, it is still uncertain whether IFN alpha can improve clinical symptoms in PV.