Chalayer Emilie, Tardy-Poncet Brigitte, Karlin Lionel, Chapelle Céline, Montmartin Aurélie, Piot Michèle, Guyotat Denis, Collet Philippe, Lecompte Thomas, Tardy Bernard
Centre d'Investigation Clinique Inserm CIC 1408 CHU de Saint-Etienne Saint-Etienne France.
INSERM U1059, Equipe DVH Université J Monnet Saint-Etienne France.
Res Pract Thromb Haemost. 2018 Dec 13;3(1):89-98. doi: 10.1002/rth2.12161. eCollection 2019 Jan.
Multiple myeloma (MM) is associated with a high risk of thrombosis, particularly during the first months of treatment including immunomodulatory drugs (IMiDs). There is no consensus on prevention of thromboembolic risk in patients with de novo MM, and identification of patients requiring anticoagulant thromboprophylaxis remains challenging. Evaluating coagulability by an in vitro thrombin generation (TG) test might be a way of identifying such patients.
To determine whether TG assessment could reveal an increase in coagulability during the first three chemotherapy cycles.
This prospective and longitudinal observational study included patients newly diagnosed with MM. TG was determined in platelet-rich and platelet-poor plasma using calibrated automated thrombography with a low tissue factor (TF) concentration.
Seventy-one patients were enrolled, allowing TG analysis during 213 chemotherapy cycles. TG remained unchanged throughout follow-up irrespective of treatment regimen, but values determined before cycles 2 and 3 were significantly higher in patients receiving iMiDs-containing regimens. No association was found between TG and its changes and thrombosis occurrence during follow-up: venous thrombosis in eight patients; no cardiovascular event. A significantly (87%) lower risk of venous thrombosis was observed in patients receiving prophylaxis with a low-molecular-weight heparin (LMWH; OR: 0.13 (95% CI: 0.02-0.76). Neither bortezomib- nor dexamethasone-containing regimens were associated with thrombotic risk. Changes in TG, as studied, were not associated with thrombotic events.
The only factor associated with a reduction in early thrombotic risk was prophylaxis with LMWH. The issue of how to identify patients requiring prophylactic anticoagulation remains unresolved.
多发性骨髓瘤（MM）与血栓形成的高风险相关，尤其是在包括免疫调节药物（IMiDs）的治疗的最初几个月。对于初发性MM患者血栓栓塞风险的预防尚无共识，识别需要抗凝血栓预防的患者仍然具有挑战性。通过体外凝血酶生成（TG）试验评估凝血能力可能是识别此类患者的一种方法。
确定TG评估是否能揭示前三个化疗周期中凝血能力的增加。
这项前瞻性纵向观察性研究纳入了新诊断为MM的患者。使用低组织因子（TF）浓度的校准自动血栓成像法在富血小板血浆和贫血小板血浆中测定TG。
纳入71例患者，可在213个化疗周期中进行TG分析。无论治疗方案如何，随访期间TG保持不变，但在接受含IMiDs方案的患者中，第2和第3周期之前测定的值显著更高。未发现TG及其变化与随访期间血栓形成的发生之间存在关联：8例患者发生静脉血栓形成；无心血管事件。接受低分子量肝素（LMWH）预防的患者静脉血栓形成风险显著降低（87%）；比值比：0.13（95%置信区间：0.02-0.76）。含硼替佐米或地塞米松的方案均与血栓形成风险无关。所研究的TG变化与血栓形成事件无关。
与早期血栓形成风险降低相关的唯一因素是LMWH预防。如何识别需要预防性抗凝的患者这一问题仍未解决。
