PubMed · 12607613
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C J Randall. 2002-12-07. Wars on warfarin.. https://pubmed.ncbi.nlm.nih.gov/12607613/
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Platelet factor 4 (PF4) is a heparin-binding protein which exhibits anti-heparin activities through the inhibition of antithrombin (AT)-dependent reactions with the serine proteases thrombin and factor Xa. PF4 also neutralizes heparan sulfate (HS), a glycosaminoglycan (GAG) present on the surface of endothelial cells, thereby possibly modulating an anticoagulant response. Previous models of PF4 mechanism did not distinguish whether PF4 causes steric hindrance of AT binding to fXa or of AT binding to the surface of the GAG chain. To shed light on the mechanism of PF4, studies of HS/heparin-catalyzed fXa inactivation by AT were undertaken. The results were consistent with PF4 directly interfering with AT binding to fXa rather than AT binding to the GAG chain, since PF4 did not prevent the heparin-dependent increase in AT intrinsic fluorescence. In fact, PF4 mechanism was competitive with respect to AT and non-competitive with respect to fXa, suggesting inhibition of important regulatory/catalytic interactions of fXa with the polysaccharide. Altogether, the results suggested a model by which PF4 bound to proximal (but distinct) sites to AT, resulting in steric interference of fXa binding to both polysaccharide and AT. It is proposed that PF4 inhibited the sequence of events recapitulated in the template mechanism describing heparin-dependent inhibition of fXa.
OBJECTIVE: To update evidence-based guidelines for the treatment of proximal femoral fractures published in the Journal in 1999. DATA SOURCES: Systematic literature search of MEDLINE, CINAHL and EMBASE from January 1996 to September 2001 and the Cochrane Database of Systematic Reviews (most recent issue searched - Issue 2, 2002). STUDY SELECTION: Randomised controlled trials and meta-analyses of all aspects of acute-care hospital treatment and rehabilitation of proximal femoral fractures among subjects aged 50 years and over with proximal femoral fractures not associated with metastatic disease or multiple trauma. DATA EXTRACTION: All studies were read independently by two reviewers. Reviewers recorded individual study results, and an assessment of study quality and treatment conclusions according to Cochrane Collaboration protocols. If necessary, a third review was performed to reach consensus. RESULTS: 93 new studies were identified and 82 met our inclusion criteria. Recommendations for thromboprophylaxis, anaesthesia, surgical fixation of fractures and nutritional status have been altered to incorporate new evidence. Recommendations have been added regarding postoperative blood transfusion, the management of subtrochanteric fractures, and the type of surgical swabs which should be used. CONCLUSIONS: Although there have been few significant changes to the previous recommendations, updating the guidelines has required substantial effort. The common clinical problem of hip fracture should be treated according to the most up-to-date evidence to achieve the best possible outcomes and optimal utilisation of limited resources. Guideline updates also require resourcing.
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