Gugliotta L, D'Angelo A, Mattioli Belmonte M, Viganò-D'Angelo S, Colombo G, Catani L, Gianni L, Lauria F, Tura S
Istituto di Ematologia L.eA.Seràgnoli, University of Bologna, Italy.
Br J Haematol. 1990 Apr;74(4):465-70. doi: 10.1111/j.1365-2141.1990.tb06336.x.
To evaluate the occurrence of hypercoagulability during treatment with L-asparaginase (L-ase), thrombin-antithrombin complex (TAT) and D-dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. L-ase alone (20,000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to L-ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second L-ase infusion. Increased levels of TAT (P less than 0.05) and D-dimer (P less than 0.01) were observed prior to L-ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with L-ase alone, further elevation of TAT (P less than 0.05) and persistence of increased D-dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of D-dimer levels occurred during L-ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by L-ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to L-ase treatment remains to be determined.
为评估左旋门冬酰胺酶（L-ase）治疗期间高凝状态的发生情况，对15例近期完成阿糖胞苷和甲氨蝶呤化疗周期的成人急性淋巴细胞白血病或淋巴细胞淋巴瘤患者连续测定血浆凝血酶-抗凝血酶复合物（TAT）和D-二聚体水平。前8例患者（A组）仅接受静脉注射L-ase（20000 U/m²，隔日1次，共10天）；后7例患者（B组）除L-ase外，从第2次L-ase输注开始隔日静脉推注抗凝血酶浓缩物（2000 U），共6次。在使用L-ase之前观察到TAT水平升高（P<0.05）和D-二聚体水平升高（P<0.01），这可能与既往化疗继发的炎症和细胞溶解有关。在仅接受L-ase治疗的患者中，观察到TAT进一步升高（P<0.05）且D-二聚体持续升高，同时蛋白C、蛋白S和抗凝血酶III的抗凝活性显著降低。与之不同的是，在接受抗凝血酶III补充治疗的患者中，TAT没有升高，且在L-ase治疗期间D-二聚体水平恢复正常。在这些患者中，整个治疗过程中血浆抗凝血酶III活性平均维持在高于正常水平70%。抗凝血酶III补充治疗对纤维蛋白原、因子IX、蛋白C和蛋白S的下降速率没有影响，这表明高凝状态与L-ase治疗诱导的凝血因子和抑制剂减少几乎没有关联。抗凝血酶III浓缩物在预防接受L-ase治疗患者血栓栓塞并发症方面的有效性仍有待确定。
