PubMed · 13780944
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C VERMYLEN, M VERSTRAETE. 1961-08-15. [Some new data on antithrombin V].. https://pubmed.ncbi.nlm.nih.gov/13780944/
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CONTEXT: Important advances have been made in our understanding of severe sepsis. Outcome can be improved by targeted interventions, including early and appropriate antibiotic therapy and goal-directed resuscitation, and might be further improved by selective decontamination of the digestive tract, tight control of glucose, and possibly by giving corticosteroids to selected patients. Drugs that target specific steps in the septic cascade include cytokine inhibitors, anti-endotoxins, and the three naturally occurring anticoagulants. Only one of these trials, which assessed the efficacy of activated protein C, reported significant improvements in outcome. Translation of these results into practice has been hampered by high drug costs, and by apparent discrepancies between interim results and final outcomes in two of the trials with natural anticoagulants. STARTING POINT: Recently, Steven Opal and colleagues (Crit Care Med 2004; 32: 332-41) reported a randomised trial with platelet-activating-factor acetylhydrolase to suppress the inflammatory response in septic patients. No effects on outcome were observed (mortality 24% with placebo vs 25% with the intervention). By contrast, Jose Garnacho-Montero and colleagues, in a cohort study (Crit Care Med 2003; 31: 2742-51), saw large mortality reductions with initially appropriate choice of antibiotics in septic patients (19.8% reduction overall and 43.4% in patients with septic shock). These benefits were higher than those even in the most successful trial with an antisepsis agents, underscoring the importance of basic measures in severe sepsis. WHERE NEXT? Initial management in severe sepsis should include early goal-directed fluid resuscitation, appropriate antibiotic treatment, and surgical-site control. Intensive-care units should be run by specialists, with adequate medical and nursing staffing. Tight regulation of glucose, selective decontamination of the digestive tract, and moderate-dose corticosteroids in selected cases should be considered. Expensive new drugs, such as activated protein C, might further improve outcome, but should be considered only when organisational aspects and supportive care have been optimised.
OBJECTIVE: To describe the evidence assessing the use of anti-thrombin III (AT-III) in the management of toxicity associated with hematopoietic stem-cell transplantation (HSCT)-conditioning regimens. DATA SOURCES: Clinical literature was accessed through conference proceedings, EMBASE, the Cochrane database, and MEDLINE (1966-December 2003). STUDY SELECTION AND DATA EXTRACTION: Case reports, small case series, case-control and cohort studies, and randomized controlled trials of AT-III in HSCT were evaluated. Publications examining AT-III use in the non-HSCT setting were also explored. Key search terms included AT-III, transplantation, and veno-occlusive disease (VOD). DATA SYNTHESIS: Severe VOD and ensuing multiple organ dysfunction is associated with high mortality in HSCT. A low AT-III level has been shown to correlate with the development of organ dysfunction. Phase II trials, case series, and one small, randomized, placebo-controlled study suggest a benefit when AT-III therapy is instituted early in the course of VOD/multiple organ dysfunction syndrome. In all of these reports, AT-III use was devoid of adverse events. CONCLUSIONS: Although further studies are needed to ascertain the optimal target level, method, and duration of administration, AT-III is still a viable alternative for the treatment of severe VOD and ensuing multiple organ dysfunction.
OBJECTIVE: The aim of this study was to clarify the effect of hypoxia on the physiologic inhibition system of coagulation including protein S, protein C, and antithrombin III and to study their effect on thromboembolic accidents of hypoxic newborns. DESIGN: Clinical study including ten hypoxic-ischemic neonates and ten normal neonates as a control group. DATA SOURCES: MEDLINE, pediatric textbooks, neonatal intensive care unit, Department of Paediatrics, Faculty of Medicine, Cairo University. RESULTS: The results of this study revealed a marked decrease in the level of the physiologic inhibition system of coagulation including antithrombin III, protein C, and protein S in 100% of the hypoxic-ischemic neonates compared with the control group (p <.001) before the occurrence of thromboembolic complications. Fifty percent of the hypoxic-ischemic neonates developed disseminated intravascular coagulation and died, 40% developed necrotizing enterocolitis and rectal bleeding, 20% developed hematuria, 30% developed hematemesis, 20% developed intracranial hemorrhage, and 100% had convulsions. CONCLUSIONS: In this study, we evaluated the effect of asphyxia on the physiologic inhibition system of coagulation in neonates. Care providers should suspect hypoxia resulting from any obstructed labor and perform the necessary laboratory investigations for coagulation, including antithrombin III, protein C, and protein S levels, to help prevent thromboembolic accidents in asphyxiated neonates, including disseminated intravascular coagulation, necrotizing enterocolitis, and intracranial hemorrhage. Based on the development of antithrombin III and protein C concentrates, which are commercially available, require minimal monitoring, and have very few side effects, the time is ripe for evaluation of optimal treatment for thromboembolic accidents after neonatal asphyxia. This could be even more important if successful neuroprotectant strategies are also developed.