Yağci Münci, Sucak Gülsan Türköz, Haznedar Rauf
Gazi Medical School Division of Hematology, Ankara, Turkey.
Am J Hematol. 2003 Dec;74(4):231-7. doi: 10.1002/ajh.10433.
The incidence of thromboembolic events is high as a result of disease, disease-related complications, and therapy in multiple myeloma (MM). In patients with hematologic tumors, impaired fibrinolysis may be present and may contribute to the development of thrombotic complications. Therefore, we designed a study to investigate fibrinolytic activity in MM. We compared plasma levels of interleukin (IL)-6, C-reactive protein (CRP), IL-1beta, IL-11, tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor-1 (PAI-1) activity, and global fibrinolytic capacity (GFC) in patients with MM (n = 66) and in control subjects (n = 18). The prevalence of venous thromboembolism was 4.5%, with a median follow-up period of 7 months in our myeloma group. Results are given as mean (median, range). Plasma levels of IL-6 (8.27 +/- 0.74 [9.65, 0.90-13.32] pg/mL versus 2.64 +/- 0.66 [1.80, 0.10-11.86] pg/mL, P < 0.001), CRP (45.57 +/- 9.92 [21.00, 1.34-330.00] mg/L versus 1.96 +/- 0.50 [1.05, 0.19-8.03] mg/L, P < 0.001), PAI-1 (7.40 +/- 0.67 [5.57, 2.40-31.80] IU/mL versus 4.73 +/- 0.65 [3.60, 2.32-11.00] IU/mL, P < 0.01), GFC score (1.90 +/- 0.02 [2, 1-3] versus 2.50 +/- 0.14 [3, 1-3], P < 0.001) were increased compared with controls. In patients with MM, the level of IL-6 was positively correlated with CRP (r = 0.66, P < 0.001), IL-1beta (r = 0.29, P < 0.05), and PAI-1 (r = 0.35, P < 0.01) and negatively correlated with GFC (r = -0.37, P < 0.01). CRP level was positively correlated with plasma PAI-1 level (r = 0.40, P < 0.01) and negatively correlated with GFC (r = -0.44, P < 0.001). A significant negative correlation between PAI-1 level and GFC (r = -0.75, P < 0.001) was also detected. IL-1beta levels were negatively correlated with tPA level (r = -0.26, P < 0.05). These results suggest that patients with myeloma have a decreased fibrinolytic activity mainly because of increased PAI-1 activity. In MM, increased PAI-1 activity seems to be related with elevated IL-6 level. MM should be considered as a hypercoagulable state as a result of both increased procoagulant activity and decreased fibrinolytic activity. Achieving a plateau by means of conventional chemotherapies does not improve the decreased fibrinolytic activity.
由于疾病、疾病相关并发症以及多发性骨髓瘤（MM）治疗的原因，血栓栓塞事件的发生率很高。在血液系统肿瘤患者中，可能存在纤维蛋白溶解功能受损，这可能促使血栓形成并发症的发生。因此，我们设计了一项研究来调查MM患者的纤维蛋白溶解活性。我们比较了MM患者（n = 66）和对照组（n = 18）的白细胞介素（IL）-6、C反应蛋白（CRP）、IL-1β、IL-11、组织型纤溶酶原激活剂（tPA）活性、纤溶酶原激活剂抑制剂-1（PAI-1）活性以及整体纤维蛋白溶解能力（GFC）的血浆水平。在我们的骨髓瘤组中，静脉血栓栓塞的发生率为4.5%，中位随访期为7个月。结果以平均值（中位数，范围）表示。与对照组相比，MM患者血浆IL-6水平（8.27±0.74 [9.65，0.90 - 13.32] pg/mL对2.64±0.66 [1.80，0.10 - 11.86] pg/mL，P < 0.001）、CRP水平（45.57±9.92 [21.00，1.34 - 330.00] mg/L对1.96±0.50 [1.05，0.19 - 8.03] mg/L，P < 0.001）、PAI-1水平（7.40±0.67 [5.57，2.40 - 31.80] IU/mL对4.73±0.65 [3.60，2.32 - 11.00] IU/mL，P < 0.01）、GFC评分（1.90±0.02 [2，1 - 3]对2.50±0.14 [3，1 - 3]，P < 0.001）均升高。在MM患者中，IL-6水平与CRP（r = 0.66，P < 0.001）、IL-1β（r = 0.29，P < 0.05）和PAI-1（r = 0.35，P < 0.01）呈正相关，与GFC呈负相关（r = -0.37，P < 0.01）。CRP水平与血浆PAI-1水平呈正相关（r = 0.40，P < 0.01），与GFC呈负相关（r = -0.44，P < 0.001）。还检测到PAI-1水平与GFC之间存在显著负相关（r = -0.75，P < 0.001）。IL-1β水平与tPA水平呈负相关（r = -0.26，P < 0.05）。这些结果表明，骨髓瘤患者的纤维蛋白溶解活性降低主要是由于PAI-1活性增加。在MM中，PAI-1活性增加似乎与IL-6水平升高有关。由于促凝活性增加和纤维蛋白溶解活性降低，MM应被视为一种高凝状态。通过传统化疗达到平台期并不能改善降低的纤维蛋白溶解活性。
