Thrombosis in Myeloproliferative Neoplasms: A Single Center Experience of Using Whole Blood Platelet Aggregation Studies for Risk Assessment and Thromboprophylaxis
Clinical and Applied Thrombosis/Hemostasis
Thromboembolic complications are the most common causes of morbidity and mortality in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPN); and prevention of these complications remains a significant clinical challenge. Effective thromboprophylaxis in MPN patients generally requires use of anti-platelet therapy, commonly aspirin; however, there are no standardized or universally accepted guidelines regarding the dose of aspirin. This study evaluates the usefulness of whole blood platelet aggregation (WBPA) studies to identify patients at risk for thrombosis and to achieve safe and effective long term thromboprophylaxis. One hundred and thirty-two consecutive patients were enrolled into this study. WBPA studies were performed at diagnosis in 125 patients to identify those with platelet hyperactivity (deemed to be at risk for thrombosis) and repeated 4 weeks after commencement of anti-platelet therapy to ascertain the efficacy. In patients with incomplete drug effect, treatment was revised and the study repeated until optimum effect was achieved. Results of the WBPA studies and anti-platelet therapy requirements were correlated with the underlying driver mutations and various international prognostic score of thrombosis for essential thrombocythemia (IPSET- Thrombosis) sub-groups. WBPA studies showed varying degrees of platelet hyper-activity in 115 patients. Based on these results, the patients were commenced on anti-platelet therapy comprising aspirin (dose ranging from 100mg twice or thrice weekly to 400mg daily) and clopidogrel (75mg daily) alone or in combination with aspirin or odorless garlic. None of the patients developed thrombosis during the follow up period ranging from 1-23 years (median 8yrs), while on the prescribed, individualized anti-platelet therapy. No significant differences were noted in terms of aspirin dose requirements between the JAK-2 positive and CALR or MPL positive patients, and, among the four IPSET-Thrombosis sub-groups. Patients with normal (9) or hypo (1) – activity were not given any anti-platelet therapy at diagnosis. Conclusion: Routine use of WBPA studies enables safe and effective risk-adapted thromboprophylaxis in MPN patients, irrespective of the underlying driver mutation and their risk predicted by the IPSET- thrombosis criteria.
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