Boys Joshua A, Medaugh Christine J, Hassouna Houria I
Department of Medicine, Division of Thrombosis, College of Human Medicine, Michigan State University B-214 Clinical Center East Lansing, MI 48824 USA.
Cases J. 2009 Aug 24;2:7024. doi: 10.4076/1757-1626-2-7024.
Venous thromboembolism is a multifactorial disease defined by multiple interactions between genetic and environmental components. It is managed by oral anticoagulation with warfarin sodium (Coumadin), a drug that targets the vitamin K epoxide reductase to prevent the recycling of vitamin K epoxide to the reduced form of vitamin K. The reduced form of vitamin K is an essential cofactor in the formation of active clotting factors II, VII, IX, X and regulatory factors protein C, and cofactor protein S through gamma-glutamyl carboxylation. The duration of Coumadin treatment, three to six months or life-long, should be based on the individual risk for recurrent deep vein thrombosis and on the associated increased risk for bleeding complications.
A previously healthy 50-year-old white male developed a deep vein thrombosis consequent to surgical placement of a titanium rod to correct a fracture of the femur and he was maintained for over a year on daily oral doses of Coumadin 9 mg and aspirin 325 mg. When he began to bruise spontaneously with multiple large hematomas appearing without provocation, he requested that his primary care physician reconsider the anticoagulation. Because of his age, sex, and the possibility of an inherited or acquired anticoagulant protein deficiency he was maintained on Coumadin and a thrombophilia work up was ordered. Test results were interpreted as deficiencies in both protein C and protein S and he was instructed that life-long therapy with Coumadin was necessary. Is this a correct evaluation by his primary care physician?
This case illustrates that Coumadin, a vitamin K agonist, was exerting a therapeutically acceptable negative influence on plasma activity levels of vitamin K-dependent protein C and protein S. Relying on the outcome of a thrombophilia work-up for a decision to maintain or cease Coumadin treatment of patients at risk for recurrent deep vein thrombosis has pitfalls that can be avoided. The use of real-time B-mode venous ultrasonography to verify complete restoration of venous flow before ceasing Coumadin treatment is not always considered in the long-term management of a patient with a first thrombosis, despite the well documented significant risk of deep vein thrombosis recurrence associated with an unresolved thrombosis.
静脉血栓栓塞是一种多因素疾病，由遗传和环境因素之间的多种相互作用所定义。它通过口服华法林钠（香豆素）进行治疗，该药物作用于维生素K环氧还原酶，以阻止维生素K环氧再循环为还原形式的维生素K。还原形式的维生素K是通过γ-谷氨酰羧化作用形成活性凝血因子II、VII、IX、X以及调节因子蛋白C和辅因子蛋白S的必需辅因子。华法林治疗的持续时间，即三到六个月或终身治疗，应基于个体复发性深静脉血栓形成的风险以及出血并发症相关的风险增加情况。
一名此前健康的50岁白人男性因手术植入钛棒矫正股骨骨折而发生深静脉血栓形成，他每日口服9毫克华法林和325毫克阿司匹林，持续治疗了一年多。当他开始自发出现瘀伤，且毫无诱因地出现多个大血肿时，他要求其初级保健医生重新考虑抗凝治疗。鉴于他的年龄、性别以及存在遗传性或获得性抗凝蛋白缺乏的可能性，他继续服用华法林，并被安排进行血栓形成倾向检查。检查结果被解读为蛋白C和蛋白S均缺乏，他被告知需要终身服用华法林治疗。他的初级保健医生的这种评估正确吗？
该病例表明，作为维生素K激动剂的华法林，正在对维生素K依赖的蛋白C和蛋白S的血浆活性水平产生治疗上可接受的负面影响。依靠血栓形成倾向检查的结果来决定维持或停止对有复发性深静脉血栓形成风险的患者进行华法林治疗存在一些可以避免的陷阱。在首次发生血栓形成的患者的长期管理中，尽管有充分记录表明未解决的血栓形成与深静脉血栓形成复发的显著风险相关，但在停止华法林治疗前使用实时B型静脉超声检查来验证静脉血流是否完全恢复的情况并不总是被考虑到。
