Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Blood Adv. 2023 Nov 28;7(22):7056-7066. doi: 10.1182/bloodadvances.2023011379.
Thrombosis and bleeding are significant contributors to morbidity and mortality in patients with hematological cancer, and the impact of altered fibrinolysis on bleeding and thrombosis risk is poorly understood. In this prospective cohort study, we investigated the dynamics of fibrinolysis in patients with hematological cancer. Fibrinolysis was investigated before treatment and 3 months after treatment initiation. A dynamic clot formation and lysis assay was performed beyond the measurement of plasminogen activator inhibitor 1, tissue- and urokinase-type plasminogen activators (tPA and uPA), plasmin-antiplasmin complexes (PAP), α-2-antiplasmin activity, and plasminogen activity. Clot initiation, clot propagation, and clot strength were assessed using rotational thromboelastometry. A total of 79 patients were enrolled. Patients with lymphoma displayed impaired fibrinolysis with prolonged 50% clot lysis time compared with healthy controls (P = .048). They also displayed decreased clot strength at follow-up compared with at diagnosis (P = .001). A patient with amyloid light-chain amyloidosis having overt bleeding at diagnosis displayed hyperfibrinolysis, indicated by a reduced 50% clot lysis time, α-2-antiplasmin activity, and plasminogen activity, and elevated tPA and uPA. A patient with acute promyelocytic leukemia also displayed marked hyperfibrinolysis with very high PAP, indicating extreme plasmin generation, and clot formation was not measurable, probably because of the extremely fast fibrinolysis. Fibrinolysis returned to normal after treatment in both patients. In conclusion, patients with lymphoma showed signs of impaired fibrinolysis and increased clot strength, whereas hyperfibrinolysis was seen in patients with acute promyelocytic leukemia and light-chain amyloidosis. Thus, investigating fibrinolysis in patients with hematological cancer could have diagnostic value.
血栓形成和出血是导致血液病患者发病率和死亡率升高的重要因素，而纤溶改变对出血和血栓形成风险的影响尚未被充分认识。在这项前瞻性队列研究中，我们研究了血液病患者纤溶的动态变化。在治疗前和治疗开始后 3 个月进行纤溶研究。除了测量纤溶酶原激活物抑制剂 1、组织型和尿激酶型纤溶酶原激活物（tPA 和 uPA）、纤溶酶-抗纤溶酶复合物（PAP）、α-2-抗纤溶酶活性和纤溶酶原活性外，还进行了动态血凝块形成和溶解测定。使用旋转血栓弹性测定法评估血凝块的起始、传播和强度。共纳入 79 例患者。与健康对照组相比，淋巴瘤患者的纤溶功能受损，50%血凝块溶解时间延长（P =.048）。与诊断时相比，他们在随访时的血凝块强度也降低（P =.001）。一位诊断时明显出血的轻链淀粉样变性患者表现出高纤溶状态，表现为 50%血凝块溶解时间、α-2-抗纤溶酶活性和纤溶酶原活性降低，以及 tPA 和 uPA 升高。一位急性早幼粒细胞白血病患者也表现出明显的高纤溶状态，具有非常高的 PAP，表明极端的纤溶酶生成，且由于纤溶速度极快，无法测量血凝块形成。两位患者在治疗后纤溶均恢复正常。总之，淋巴瘤患者表现出纤溶受损和血凝块强度增加的迹象，而急性早幼粒细胞白血病和轻链淀粉样变性患者则表现出高纤溶状态。因此，研究血液病患者的纤溶功能可能具有诊断价值。
