Background-Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established. Methods and Results-MEDLINE, EMBASE, and Cochrane databases (2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (ϭ0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0 -3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0 -1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42-1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00 -9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52-8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04 -2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27-4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non-vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses. Conclusions-Vitamin K antagonist-treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging. (Circulation. 2012;126:1630-1639.)Key Words: anticoagulants Ⅲ bridging Ⅲ heparin Ⅲ periprocedural Ⅲ thromboembolism Ⅲ warfarin V itamin K antagonists (VKAs) such as warfarin are commonly used long term for the prevention of arterial thromboembolic events such as stroke and systemic embolism in patients with atrial fibrillation or mechanical heart valves and recurrent venous thromboembolic events. Approximately 10% of patients receiving long-term warfarin may require interruption of therapy for invasive procedures or surgery, and it is estimated that Ͼ250 000 patients on long-term warfarin undergo periprocedural assessment in North America each year. 1 There is concern that periprocedural interruption of warfarin may increase the risk of thromboembolic events, whereas continuation of warfarin in the periprocedural period will increase the risk of bleeding. 2 Periprocedural bridging anticoagulation with short-acting parenteral agents such as unfractionated heparin or lowmolecular-weight heparin (LMWH) has been increasingly used in the past decade with the aim ...

Clp ATPases are a unique group of ATP-dependent chaperones supporting targeted protein unfolding and degradation in concert with their respective proteases. ClpX is a representative member of these ATPases; it consists of two domains, a zinc-binding domain (ZBD) that forms dimers and a AAA ؉ ATP-binding domain that arranges into a hexamer. Analysis of the binding preferences of these two domains in ClpX revealed that both domains preferentially bind to hydrophobic residues but have different sequence preferences, with the AAA ؉ domain preferentially recognizing a wider range of specific sequences than ZBD. As part of this analysis, the binding site of the ClpX dimeric cofactor, SspB 2, on ZBD in ClpX was determined by NMR and mutational analysis. The SspB C terminus was found to interact with a hydrophobic patch on the surface of ZBD. The affinity of SspB 2 toward ZBD2 and the geometry of the SspB 2-ZBD2 complex were investigated by using the newly developed quantitative optical biosensor method of dual polarization interferometry. The data suggest a model for the interaction between SspB 2 and the ClpX hexamer.

Altered oxygen affinity variant hemoglobins (Hbs) are caused by mutations of the globin genes.Changes in Hb oxygen affinity shift the oxygen dissociation curve, and can be identified by abnormal p50 measurements of patient red blood cells. Variants are categorized as either low oxygen affinity (high p50) or high oxygen affinity (low p50). Accurate diagnosis requires recognition of typical clinical and laboratory findings. In this case-based review, we present two patients with altered oxygen affinity variants, illustrating barriers to prompt and accurate diagnosis, and issues in management. We then review pathophysiology, diagnostic tests, clinical features, and management strategies.