Prothrombin complex concentrate versus placebo, no intervention, or other interventions in critically bleeding patients associated with oral anticoagulant administration: a protocol for a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

Abstract

BackgroundAcute critical bleeding is one of the most feared complications during treatment with oral anticoagulating agents. As more patients undergo treatment with anticoagulating agents, critically bleeding episodes in patients with vitamin K antagonists, thrombin inhibitor, or factor Xa inhibitor-inducted coagulopathy will be encountered frequently by physicians. Hence, an effective treatment capable of reversing the iatrogenic coagulopathy in the acute setting is needed. In randomised clinical trials and observational studies, prothrombin complex concentrate has been reported to be superior to other acute interventions, and many guidelines recommend prothrombin complex concentrate in treatment of critically bleeding patients. The aim of this systematic review is to synthesise the evidence of the effects of prothrombin complex concentrate compared with placebo, no intervention, or other treatment options in critically bleeding patients treated with oral anticoagulants.Methods/designA comprehensive search for relevant published literature will be undertaken in Cochrane Central Register of Controlled Trials, MEDLINE, Embase, WHO International Clinical Trials Registry Platform, Science Citation Index, regulatory databases, and trial registers. We will include randomised clinical trials comparing prothrombin complex concentrate versus placebo, no intervention, or other interventions in critically bleeding patients with oral anticoagulant-induced coagulopathy. Data extraction and risk of bias assessment will be handled by two independent review authors. Meta-analysis will be performed as recommended by Cochrane Handbook for Systematic Reviews of Interventions, bias will be assessed with domains, and trial sequential analysis will be conducted to control random errors. Certainty will be assessed by GRADE.DiscussionAs critical bleeding in patients treated with oral anticoagulants is an increasing problem, an up-to-date systematic review evaluating the benefits and harms of prothrombin complex concentrate is urgently needed. It is the hope that this review will be able to guide best practice in treatment and clinical research of these critically bleeding patients.Systematic review registration PROSPERO CRD42018084371 Electronic supplementary materialThe online version of this article (10.1186/s13643-018-0838-y) contains supplementary material, which is available to authorized users.

Noteworthy Literature in 2018 for Cardiovascular Anesthesiologists and Intensivists

“…The area under the receiver operating characteristic curve of RFR for detection of AKI was 0.83 (95% confidence interval [CI] = 0.70 to 0.96); and using an RFR cutoff of 15 mL/min/1.73 m 2 has 67% sensitivity and 94% specificity for prediction of postoperative AKI. Patients with preoperative RFR ≤15 mL/min/1.73 m 2 were 11.8 times more likely to experience AKI than those who had RFR >15 mL/min/1.73 m 2 .…”

“…Until recently, the only options to reverse the effects of this drug class has been the administration of plasma or factor concentrates. 2 In May of 2018, the Food and Drug Administration (FDA) approved intravenous (IV) andexanet alfa (Andexxa, Portola Pharmaceuticals, San Francisco, CA), a first-in-class, recombinant, modified factor Xa protein, for the reversal of the anticoagulant effects of rivaroxaban and apixaban, in patients with life-threatening or uncontrolled bleeding. 3 Andexanet alfa acts as a decoy and binds to factor Xa inhibitors, thus neutralizing their anticoagulant effects.…”

“…Until recently, the only options to reverse the effects of this drug class has been the administration of plasma or factor concentrates. 2…”

Decision-Making Process for the Management of Acute Stroke in Patients on Oral Anticoagulant: From Guidelines to Clinical Routine

“…Non-specific Anticoagulation Reversal Fresh frozen plasma (FFP) has been widely used for many years, but its use is limited in routine practise by blood type matching, maximal acceptable or possible complications related to fluid overload, so its use has been supplanted by prothrombin complex concentrates (PCCs), particularly in situations involving critical bleeding (17,18). Four-factor PCC consists of vitamin Kdependent coagulation factors (II, VII, IX, and X) with a final overall clotting factor concentration that is approximately 25 times higher than in normal plasma (19).…”

“…Four-factor PCC consists of vitamin K-dependent coagulation factors (II, VII, IX, and X) with a final overall clotting factor concentration that is approximately 25 times higher than in normal plasma ( 19 ). Several studies have shown that PCCs act more quickly and effectively than FFP in terms of correcting the INR of patients on VKA ( 16 , 18 ). The effect of PCC on NOAC-associated ICH is less clear.…”