Dager William E, Andersen Judith, Nutescu Edith
Department of Pharmacy, University of California-Davis Medical Center, and University of California-Davis School of Medicine, Sacramento, California, USA.
Pharmacotherapy. 2004 Jul;24(7 Pt 2):88S-94S. doi: 10.1592/phco.24.10.88s.36122.
Multiple options for anticoagulation therapy are now available, placing an additional responsibility on health care workers for choosing the optimal therapy for each patient. The heparins carry a risk of heparin-induced thrombocytopenia (HIT), an immune-mediated reaction to heparin that may lead to pulmonary embolism and death. Fondaparinux, a new, synthetic pentasaccharide, binds to antithrombin III and potentiates antithrombin III's inhibition of factor Xa. Fondaparinux does not bind to platelet factor 4 and thus is theoretically unable to cause immunoallergic HIT. Unlike low-molecular-weight heparins, fondaparinux does not cross-react in vitro with sera from patients with clinical cases of HIT. These findings suggest that fondaparinux would not lead to formation of HIT antibodies and would not provoke clinical thrombosis in patients who had HIT antibodies because of previous exposure to heparins. To date, no cases of immunoallergic HIT have been associated with fondaparinux use in clinical trials. Anecdotal evidence suggests that fondaparinux eventually may prove to be valuable for preventing and treating thrombosis in patients with HIT. The effect of anticoagulants on wound healing is another consideration when choosing a thromboprophylactic strategy after major surgery. There is evidence that thrombin plays a role in wound healing, but fondaparinux is too small to enable antithrombin III to inhibit thrombin. Thus, fondaparinux may be less likely than a low-molecular-weight heparin to interfere with wound healing.
目前有多种抗凝治疗方案可供选择,这就给医护人员增添了为每位患者选择最佳治疗方案的额外责任。肝素存在肝素诱导的血小板减少症(HIT)的风险,这是一种对肝素的免疫介导反应,可能导致肺栓塞和死亡。磺达肝癸钠是一种新型合成五糖,它与抗凝血酶III结合并增强抗凝血酶III对Xa因子的抑制作用。磺达肝癸钠不与血小板因子4结合,因此理论上不会引起免疫过敏性HIT。与低分子肝素不同,磺达肝癸钠在体外不与HIT临床病例患者的血清发生交叉反应。这些发现表明,磺达肝癸钠不会导致HIT抗体的形成,也不会在因先前接触肝素而产生HIT抗体的患者中引发临床血栓形成。迄今为止,在临床试验中尚未有与使用磺达肝癸钠相关的免疫过敏性HIT病例。轶事证据表明,磺达肝癸钠最终可能被证明对预防和治疗HIT患者的血栓形成具有重要价值。在选择大手术后的血栓预防策略时,抗凝剂对伤口愈合的影响是另一个需要考虑的因素。有证据表明凝血酶在伤口愈合中起作用,但磺达肝癸钠太小,无法使抗凝血酶III抑制凝血酶。因此,磺达肝癸钠比低分子肝素更不容易干扰伤口愈合。