von Tempelhoff G F, Niemann F, Schneider D M, Kirkpatrick C J, Hommel G, Heilmann L
Department of Obstetrics and Gynecology, City Hospital Ruesselsheim, Germany.
Thromb Res. 1998 Apr 15;90(2):73-82. doi: 10.1016/s0049-3848(98)00022-x.
The use of platinum based chemotherapy in ovarian malignancy and other cancer types is known to be associated with deep vein thrombosis. In a prospective study of 47 patients with ovarian cancer of International Federation of Gynecology and Obstetrics stage Ib-IV, serial rheological parameters were determined (plasma viscosity, red blood cell aggregation under conditions of stasis and low shear) in addition to hemoglobin, hematocrit, leukocytes, platelets, and fibrinogen. At the same time the incidence of deep vein thrombosis was recorded before, during six cycles of first line cisplatinum/epirubicin/cyclophosphamide chemotherapy, and 2 months thereafter (two-months check-up). Only six patients with previous deep vein thrombosis concomitantly received thrombosis prophylaxis once with 3000 anti Xa Units/day subcutaneously low molecular weight heparin (Certoparin, NOVARTIS) throughout chemotherapy. Before each cycle of chemotherapy impedance plethysmography was used for deep vein thrombosis screening and when this was suspected on the basis of physical examination or a pathological result of impedance plethysmography, ascending venography of both legs was performed. During chemotherapy, the venographically proven deep vein thrombosis incidence was 10.6%; (95% CI: 3.5-23.1) with no differences in occurrence between FIGO stages. Before operation mean plasma viscosity was higher in patients who developed deep vein thrombosis postoperatively (n = 5; 1.46 +/- 0.2 mPas) and during chemotherapy (n = 5; 1.49 +/- 0.1 mPas) as compared to those without deep vein thrombosis (1.38 +/- 0.2 mPas; p = 0.04). Postoperatively (before chemotherapy) none of the rheological variables were significantly different in patients with versus those without deep vein thrombosis during chemotherapy. Leukocyte and platelet counts decreased significantly during chemotherapy until the two-months check-up after chemotherapy while red blood cell aggregation (stasis & low shear), hemoglobin, and hematocrit showed a continuous but nonsignificant increase. The mean plasma viscosity, instead, declined into the normal range after the 4th cycle of chemotherapy (1.33 +/- 0.1 mPas) in patients without thrombosis. In contrast, mean plasma viscosity was increased to 1.48 +/- 0.1 mPas at the time of deep vein thrombosis diagnosis during chemotherapy. In the ovarian cancer patients of this study, the development of deep vein thrombosis postoperatively and during chemotherapy was associated with a hematocrit-independent increase in blood viscosity characterized by a high plasma viscosity and normal or low hematocrit, which was present before primary surgery as well as at the time of deep vein thrombosis diagnosis.
已知在卵巢恶性肿瘤和其他癌症类型中使用铂类化疗与深静脉血栓形成有关。在一项对国际妇产科联盟（FIGO）Ib-IV期的47例卵巢癌患者的前瞻性研究中，除了测定血红蛋白、血细胞比容、白细胞、血小板和纤维蛋白原外，还测定了一系列流变学参数（血浆粘度、血液淤滞和低切变条件下的红细胞聚集）。同时记录在一线顺铂/表柔比星/环磷酰胺化疗的六个周期之前、期间以及之后2个月（两个月检查）深静脉血栓形成的发生率。只有6例既往有深静脉血栓形成的患者在整个化疗期间每天皮下注射一次3000抗Xa单位的低分子量肝素（Certoparin，诺华公司）进行血栓预防。在每个化疗周期前，使用阻抗体积描记法进行深静脉血栓筛查，当根据体格检查或阻抗体积描记法的病理结果怀疑有深静脉血栓时，对双腿进行上行静脉造影。化疗期间，静脉造影证实的深静脉血栓形成发生率为10.6%；（95%可信区间：3.5-23.1），FIGO各期之间发生率无差异。与无深静脉血栓形成的患者相比，术后（n = 5；1.46±0.2 mPas）和化疗期间（n = 5；1.49±0.1 mPas）发生深静脉血栓形成的患者术前平均血浆粘度更高（1.38±0.2 mPas；p = 0.04）。术后（化疗前），化疗期间有或无深静脉血栓形成的患者，流变学变量均无显著差异。化疗期间白细胞和血小板计数显著下降，直至化疗后两个月检查时，而红细胞聚集（血液淤滞和低切变）、血红蛋白和血细胞比容呈持续但不显著的升高。相反，无血栓形成的患者在化疗第4周期后平均血浆粘度降至正常范围（1.33±0.1 mPas）。相比之下，化疗期间深静脉血栓形成诊断时平均血浆粘度升高至1.48±0.1 mPas。在本研究的卵巢癌患者中，术后和化疗期间深静脉血栓形成的发生与血细胞比容无关的血液粘度增加有关，其特征为血浆粘度高，血细胞比容正常或低，这在初次手术前以及深静脉血栓形成诊断时均存在。
