Bussel J B, Steinherz P G, Miller D R, Hilgartner M W
Am J Hematol. 1984 Jan;16(1):83-90. doi: 10.1002/ajh.2830160111.
An 8-month-old male with acute monoblastic leukemia died during induction chemotherapy of severe bleeding refractory to repeated infusions of platelets and clotting factors. A heparin effect was suggested by prothrombin time (PT) of 26 seconds, partial thromboplastin time (PTT) of 94 seconds, thrombin time 240 seconds, and reptilase time 18.4 seconds, with a fibrinogen of 88 mg/dl. Both plasma mixed with the patient's urine and the patient's plasma had their thrombin times corrected toward normal by both PF4 and protamine. Synergism of the anticoagulant with antithrombin III was demonstrated not only by enhanced inhibition of thrombin but also by an increased rate of formation of thrombin--antithrombin III complexes in the presence of the anticoagulant, which was eliminated by preincubation with heparinase. Since the anticoagulant activity was not found in the blasts themselves, it is presumed that the anticoagulant is heparin/heparan liberated from the endothelial lining by products of the cell destruction secondary to chemotherapy.
一名8个月大的急性单核细胞白血病男性患儿,在诱导化疗期间死于严重出血,尽管反复输注血小板和凝血因子仍难以控制。凝血酶原时间(PT)为26秒,部分凝血活酶时间(PTT)为94秒,凝血酶时间为240秒,爬虫酶时间为18.4秒,纤维蛋白原为88mg/dl,提示存在肝素样作用。患者尿液与血浆混合后以及患者血浆的凝血酶时间,通过PF4和鱼精蛋白均能校正至正常。抗凝剂与抗凝血酶III的协同作用不仅表现为对凝血酶抑制作用增强,还表现为在有抗凝剂存在时凝血酶 - 抗凝血酶III复合物形成速率增加,而肝素酶预孵育可消除这种作用。由于在原始细胞本身未发现抗凝活性,推测该抗凝剂是化疗继发细胞破坏产物从内皮表面释放的肝素/类肝素。