Disseminated intravascular coagulation following Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor

Disseminated intravascular coagulation (DIC) was produced by an infusion of a prothrombin activator (Echis carinatus venom; 30 minutes; 0.5 NIH thrombin equivalent U/kg) in mongrel dogs (Echis group, n = 7). Fibrinogen declined to below measurable levels (less than 25 mg/dl), and fibrin-fibrinogen degradation products appeared (53 +/- 8 micrograms/ml) at end venom infusion in the Echis group. These alterations were not seen when an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine-L-chloromethyl ketone (PPACK) (57 nmol/kg/min for 120 minutes), was given alone (PPACK group, n = 5) or in association with venom (Echis + PPACK group, n = 5). Factor II activity (1% +/- 1%) in the Echis and Echis + PPACK groups was significantly below the PPACK (55% +/- 9%) and the control (79% +/- 2%) levels at 120 minutes. In contrast, factor VIII coagulant (factor VIII:C) activity in the Echis group (1% +/- 1%) remained significantly below that in the Echis + PPACK (68% +/- 8%), PPACK (78% +/- 10%), and control (91% +/- 9%) groups at this interval. No change in factors X (91% +/- 7% to 81% +/- 7%, P not significant) and VII (64% +/- 10% to 48% +/- 11%, P not significant) activities were observed. Hemolysis was observed only in the Echis group, whereas thrombocytopenia and leukopenia were noted in both the Echis and the Echis + PPACK groups. These data show that large amounts of E. carinatus venom produce rapid DIC in vivo, because of the activation of prothrombin. In contrast, the decline in factor VIII:C activity appeared to be the result of the liberated thrombin. PPACK antagonized all of the venom-released thrombin without any major deleterious clotting abnormalities. This inhibitor appears to prevent thrombin-mediated DIC in vivo. In contrast, heparin was found to be an unreliable antagonist of the venom-released thrombin in vitro. PPACK also inhibited the marked hemolysis usually observed after venom. In addition, we found that the esterolytic (N-benzoyl-L-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide HCL) activity of E. carinatus venom degrades fibrinogen in vitro.     

Management of disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC) is a complex condition in which diffuse clotting and profuse hemorrhaging occur simultaneously. It is a serious, often fatal, condition that is estimated to occur in approximately 10% of all patients diagnosed with cancer. No single laboratory test is available that is absolutely diagnostic for DIC; however, several laboratory results, combined with certain clinical findings, will support the diagnosis. Despite the lack of a standardized protocol for clinical management, aggressive medical and nursing care can play a prominent role in the clinical outcome of the patient with DIC.     

弥散性血管内凝血诊断指南

<正>弥散性血管内凝血(disseminated intravascular coagulation,DIC)的诊断应包括临床和实验室资料(C级,水平Ⅳ)。国际血栓与止血委员会(ISTH)的DIC评分系统提供了客观的DIC诊断与治疗标准,该评分系统与临床和预后有关(C级,水平Ⅳ)。     

急性白血病与弥散性血管内凝血

目的分析急性白血病（AL）患者弥散性血管内凝血（DIC）的发生情况，凝血功能改变及其临床意义。方法对67例AL患者、25例AL完全缓解（CR）患者、20例健康体检者进行凝血常规、D-二聚体等检测。结果根据ISTH修订标准，15例AL患者合并DIC，发生率为22．4％，AML与ALL的DIC发生率AML-M3之间无统计学差异（P〉0．05），AML-M3与non-AML-M3的DIC的发生率之间有统计学差异（P〈0．05）。DIC组PT、APTT、TT较对照组、CR组及non-DIC组均明显延长（P〈0．01），而FIB则降低（P〈0．05）。结论AL尤其AML-M3患者容易合并DIC，观察患者凝血功能改变以及出血表现可有助于尽早发现DIC并指导临床预防及治疗，从而有利于改善AL合并DIC患者的临床预后。     

妊娠期高血压疾病与弥散性血管内凝血

妊娠期高血压疾病是妊娠期特有的疾病，也是产科常见的、严重威胁母儿安全的并发症。我国发病率为9．4％，国外报道为7％-12％。近年来的研究表明，妊娠期高血压疾病的发生与血管内皮细胞损伤及血管细胞因子的合成及障碍有关。其病理基础是全身小动脉痉挛，造成微小血管狭窄，血管壁渗透性增加。血液浓缩。此外，妊娠期高血压疾病患者的凝血因子活性多数增高，凝血功能亢进。上述病理生理变化，形成了妊娠期高血压疾病患者易发生弥散性血管内凝血（disseminated intravascular coagulation，DIC）的病理基础。     

Pathogenesis and treatment of disseminated intravascular coagulation in the septic patient

The incidence of sepsis and complications stemming from septicemia has remained constant in recent years despite improved levels of monitoring and care. Disseminated intravascular coagulation (DIC), a syndrome that occurs frequently in septic patients, is associated with increased mortality. Organ dysfunction is also a common sequela that is strongly correlated with DIC. Cytokines released early in the course of sepsis stimulate a procoagulant state that causes development of intravascular fibrin deposition. In a later stage of DIC, bleeding may occur in parallel because of consumption of clotting factors and inhibitors. Therapeutic strategies to attenuate or reverse these conditions have focused on multiple stages of the molecular cascade of events, including preventing cytokine induction, inhibiting coagulation processes, and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC associated with severe sepsis. Studies of other novel therapeutic avenues are still ongoing. Future efforts may be directed at combining 2 or more agents to achieve prompt and successful reversal of DIC. Copyright © 2002 by W.B. Saunders Company     

危重病患者并发弥散性血管内凝血的诊治

目的探讨危重病患者并发弥散性血管内凝血(DIC)的最早临床线索及有效治疗措施。方法对本科2002年1月至2004年12月危重病患者并发DIC的最早临床线索及治疗措施进行回顾性分析和总结。结果本组26例,治愈11例,死亡10例,自动出院5例。结论危重病患者DIC发生率高,死亡率高,ICU医生对DIC一定要保持高度警惕,及早发现线索,及时抓住线索,及时诊断,及时综合治疗,才能提高对危重病患者的抢救成功率。     

Heparin treatment in thrombin-induced disseminated intravascular coagulation in the baboon

BACKGROUND AND METHODS: We postulated that low-dose heparin (10 IU/kg.hr) administered as a continuous iv infusion may prevent or ameliorate the induction of thrombin-induced disseminated intravascular coagulation in baboons under general anesthesia. In a nonrandomized experiment lasting 8 hrs, animals were divided into three groups: 11 received thrombin only (group A); ten were pretreated with heparin before thrombin administration (group B); and 15 received heparin 2 hrs after disseminated intravascular coagulation was induced with thrombin (group C). All animals were monitored hemodynamically and coagulation tests were performed hourly. Tests included the following: one-stage prothrombin ratio; activated partial thromboplastin time; fibrinogen and fibrin degradation products; thrombin time; plasma fibrinogen level; antithrombin III and activated clotting time. After the acute phase of the experiment, the animals were observed for 6 days and a postmortem examination was performed on a survivor of each group. RESULTS: Six (55%) group A animals died within 6 days, while there were no deaths in group B and one animal (7%) died in group C. In group C, the administration of heparin could not normalize the clotting profile, but the mortality rate was significantly less than in group A. The prophylactic administration of heparin in group B prevented the induction of disseminated intravascular coagulation. The postmortem findings were of interest, but no statistically valid conclusions could be made, as only one autopsy was done for each group. However, the results suggest that heparin pretreatment may protect against lung edema and liver necrosis. CONCLUSIONS: The results suggest that heparin, in a dose of 10 IU/kg.hr iv, could possibly be safely used in patients at high risk of developing disseminated intravascular coagulation and in those patients with established disseminated intravascular coagulation.