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.

中文翻译：

---

骨髓增生性肿瘤中的血栓形成：使用全血血小板聚集研究进行风险评估和血栓预防的单一中心经验

血栓栓塞并发症是费城染色体阴性骨髓增生性肿瘤 (MPN) 患者发病和死亡的最常见原因；预防这些并发症仍然是一项重大的临床挑战。MPN 患者的有效血栓预防通常需要使用抗血小板治疗，通常是阿司匹林；然而，没有关于阿司匹林剂量的标准化或普遍接受的指南。本研究评估了全血血小板聚集 (WBPA) 研究在识别有血栓形成风险的患者和实现安全有效的长期血栓预防方面的有用性。一百三十二名连续患者参加了这项研究。WBPA 研究在 125 名患者诊断时进行，以确定血小板过度活跃（被认为有血栓形成风险）的患者，并在开始抗血小板治疗 4 周后重复进行以确定疗效。在药物作用不完全的患者中，修改治疗并重复研究直至达到最佳效果。WBPA 研究的结果和抗血小板治疗要求与潜在的驱动突变和原发性血小板增多症（IPSET-血栓形成）亚组的各种国际血栓形成预后评分相关。WBPA 研究显示 115 名患者出现不同程度的血小板过度活跃。基于这些结果，患者开始接受抗血小板治疗，包括阿司匹林（剂量范围从 100mg 每周两次或三次到每天 400mg）和氯吡格雷（每天 75mg）单独或与阿司匹林或无味大蒜联合使用。在 1-23 年（中位 8 年）的随访期间，没有患者出现血栓形成，同时接受了处方的个体化抗血小板治疗。在 JAK-2 阳性和 CALR 或 MPL 阳性患者之间以及在四个 IPSET-血栓形成亚组之间，阿司匹林剂量要求没有显着差异。正常 (9) 或低 (1) – 活动的患者在诊断时未接受任何抗血小板治疗。在接受处方的个体化抗血小板治疗时。在 JAK-2 阳性和 CALR 或 MPL 阳性患者之间以及在四个 IPSET-血栓形成亚组之间，阿司匹林剂量要求没有显着差异。正常 (9) 或低 (1) – 活动的患者在诊断时未接受任何抗血小板治疗。在接受处方的个体化抗血小板治疗时。在 JAK-2 阳性和 CALR 或 MPL 阳性患者之间以及在四个 IPSET-血栓形成亚组之间，阿司匹林剂量要求没有显着差异。正常 (9) 或低 (1) – 活动的患者在诊断时未接受任何抗血小板治疗。

结论

WBPA 研究的常规使用能够在 MPN 患者中实现安全有效的风险适应血栓预防，无论潜在的驱动突变及其由 IPSET 血栓形成标准预测的风险如何。