Inactivated Four-Factor Prothrombin Complex Concentrate Dosing Practices for Reversal of Warfarin-Related Intracranial Hemorrhage.

BACKGROUND/OBJECTIVE: Inactivated four-factor prothrombin complex concentrate (I4F-PCC, Kcentra®) has become an important agent for the urgent or emergent reversal of bleeding associated with vitamin K antagonists such as warfarin. There is recognized inter-institutional variability with the use of I4F-PCC, especially as it relates to dosing practices. We sought to characterize variations in I4F-PCC dosing practices and their impact on patient outcomes and describe overall real-world clinical practice surrounding I4F-PCC utilization in the context of the management of warfarin-related intracranial hemorrhage (ICH). METHODS: This is a multicenter retrospective pragmatic registry study of adult patients admitted at a participating study site between January 1, 2014, and December 31, 2015, who received I4F-PCC for reversal of warfarin-related ICH. Practices around warfarin-related ICH reversal in context of I4F-PCC utilization are described, including repeat I4F-PCC dosing, adjunctive reversal agents, and dose rounding policies (i.e., rounding doses to nearest vial size vs preparing exact/unrounded doses). All research was approved by local human investigation committees at each institution. RESULTS: Seventeen institutions contributed data on 528 patients to this registry. These institutions were primarily urban centers (74%), located in the southeast USA (47%), with Level 1 Trauma designation (79%), and with Comprehensive Stroke Center designation (74%). Most patients included in the study had sustained a non-traumatic ICH (68%), had a median admission GCS of 14 (IQR 7-15), and were receiving warfarin for atrial fibrillation (57.4%). There was substantial time latency between baseline INR and I4F-PCC (median 2.4 h, IQR 1.4-4.5 h). Most patients received adjunctive reversal agents, including vitamin K (89.5%) and fresh frozen plasma (FFP) (31.9%). A smaller proportion (6.0%) of patients received repeat I4F-PCC dosing. The median ICU length of stay (LOS) was 3 days (IQR 2-7 days), median hospital LOS was 6 days (IQR 3-12 days), and overall mortality rate was 28.8%. For institutions rounding doses to the nearest vial size, the first post-I4F-PCC dose INR was statistically but not clinically significantly lower than for institutions without vial size dose rounding, with comparable degrees of INR reduction from baseline. No differences were observed between dose rounding cohorts in adverse effects, ICU or hospital LOS, modified Rankin score at discharge, or mortality rates. CONCLUSIONS: Most patients received single doses of I4F-PCC, with adjunctive reversal agents and rounding doses to vial size. The time difference from baseline INR to factor product administration is a potential opportunity for process improvement in the management of warfarin-related ICH.

Comparison of in vitro virulence factors of Campylobacter jejuni to in vivo lesion production.

Campylobacter jejuni is recognized as one of the most common agents of food-borne bacterial gastroenteritis in humans. Previous work has shown that C. jejuni isolates vary in their ability to invade and survive in laboratory grown cells. The correlation of these assays to actual lesion development in the hosts has not been determined. Therefore, this study aims to define the relationship between in vitro and in vivo assays for determining the virulence of C. jejuni isolates. Fifty-nine C. jejuni poultry isolates were analyzed in invasion and macrophage assays, and five isolates showing different invasion and survival abilities were examined for pathogenicity in the piglet model. All five isolates examined in the piglet model induced diarrhea without the presence of blood. Four of the five isolates produced microscopic lesions in piglets consisting of mucosal congestion, villous degeneration, and epithelial cell erosion. These studies imply that invasion or macrophage survival had little effect on the production of lesions typical of those noted in patients with campylobacteriosis. The most surprising finding was that isolates that produced a fluid exudate in piglets failed to invade epithelial cells. It is not known if the production of this fluid exudate is related to the production of a toxin(s) by C. jejuni. More work on the identification of the gene expressing this virulence factor is needed to confirm that this is indeed a putative toxin produced by C. jejuni.

Prophylaxis and treatment of venous thromboembolism in the critically ill.

Venous thromboembolism (VTE) is a frequent complication in critically ill patients and is associated with increased rates of morbidity and mortality. The use of thromboprophylaxis to reduce the risk of VTE in this patient population is the standard of care. This review will summarize the recommendations set forth in consensus guidelines for the prevention and treatment of VTE across subgroups within the critically ill patient population. In addition, the drug properties of the recommended pharmacologic agents for thromboprophylaxis will be highlighted including their pharmacokinetics, dosing and complications. The critical care practitioner may also encounter novel oral anticoagulants with increasing frequency. These agents will be briefly reviewed in terms of their approved and investigational indications and the clinical concerns related to their use will also be discussed.