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Introduction
The use of oral anticoagulation treatment is increasing [1, 2–3]. A major concern when administering oral anticoagulants to patients is the risk of critical bleeding and especially the risk of intracranial haemorrhage. Until 2008, the only option for oral anticoagulation treatment was vitamin K antagonists (VKA) [4]. During the last two decades, direct oral anticoagulants (DOACs) have replaced VKA as first-line therapy within several indications, e.g. non-valvular atrial fibrillation [1, 3, 5]. Even if DOACs are used increasingly, the use of the older drug-class of VKA is not expected to be phased out within the foreseeable future due to a number of unique indications (e.g. prosthetic heart valves) necessitating its use [3, 4, 5–6].
Randomised clinical trials have indicated that the incidence of critical bleeding events is generally lower among patients taking DOAC compared with VKA [7, 8], but the absolute risk of critical bleeding in individuals treated with DOAC is still far from neglectable with an estimated event rate of 2 to 4 events per 100 person years [9, 10, 11, 12–13]. As the number of patients being prescribed anticoagulation treatment increases [1, 2, 3–4], clinically beneficial methods for swift reversal of anticoagulation treatment seem essential for patient safety.
Prothrombin complex concentrate (PCC) is a concentrate of coagulation factors II, IX, and X (3-factor PCC) or II, VII, IX, and X (4-factor PCC) [14]. The concentration of coagulation factors in PCC is approximately 25 times greater than in human plasma [14]. In addition, activated PCC containing enhanced levels of activated coagulation factors has been developed [15]. Guidelines from European and American medical societies [16, 17, 18–19] recommend using PCC to reverse the effect of VKA based on data from randomised clinical trials [20, 21–22]. Guidelines [16, 17, 18–19, 23, 24] and expert opinions [25, 26] also recommend PCC to reverse the anticoagulating effect of DOAC, if specific antidotes cannot be procured. We conducted an extensive systematic review of randomised clinical trials assessing the effect of PCC versus placebo, no treatment, or other treatment strategies in patients with critical bleeding events while undergoing treatment with VKA or DOAC.
Methods
This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines (PRISMA) [27] and the Cochrane...