Table 1.

The Derriford protocols for using PCC in patients with severe bleeding associated with warfarin and cardiac reversal

Indication	Details
Cardiac surgery	There have been some limited data from a few sources regarding the benefit of using Beriplex (a PCC) within the context of life-threatening bleeding associated with cardiothoracic surgery. Much of these data in the UK are provided by the Cardiothoracic Unit of Southampton General Hospital. Investigators there have used Beriplex in more than 100 patients, both paediatric and adult, with very good effect, particularly when there are volume concerns and in the paediatric population.
	They have experienced no episodes of thrombosis when using one to two vials Beriplex P/N 500 only. 2.
	1. Beriplex should only to be given after administration of sufficient recognized blood products (FFP, platelets or cryoprecipitate) but with limited effect on bleeding in spite of documented continued coagulopathy based on laboratory data
	2. This should usually occur within the context of TEG data being unable to demonstrate clear abnormalities
	3. The maximum Beriplex usage should be two vials of P/N 500. The suggestion is to give a single vial initially, followed by a second vial if bleeding is obviously continuing. This respects the prothrombotic nature of Beriplex
	4. There should be adequate fibrinogen to produce a reasonable clot. Therefore, fibrinogen levels should be monitored and kept above 1.0 g/l if possible
	5. Note that Beriplex is held in blood transfusion and should only be administered after consultation with consultant haematologist
Anticoagulant (warfarin) reversal	In patients with life-threatening bleeding on warfarin (or other oral vitamin K antagonists), rapid reversal of anticoagulation is indicated if the thrombotic risks of complete reversal are relatively less than the risk of continuing bleeding. If the bleeding risk is greater, then Beriplex may be used for reversal on the understanding that this product is itself prothrombotic. This policy is endorsed by guidelines on oral anticoagulation [20]. Beriplex P/N 250 contains clotting factors II (200 to 480 IU), VII (100 to 250 IU), IX (200 to 310 IU) and X (220 to 600 IU), as well as protein C (150 to 450 IU) and protein S (130 to 260 IU)[13,32]. Beriplex P/N 500 contains approximately double these values of vitamin K dependent clotting factors. The 250/500 values relate to the factor IX content. In the majority of patients, FFP is not recommended because it does not completely reverse the anticoagulation effect of warfarin when it is given in quantities according to guidelines; calculated volumes would be clinically excessive [12]. FFP also requires slow thawing, which will delay reversal.
	The majority of fatal, anticoagulant-related bleeds are intracranial, in which the volume of bleeds is double [33], tend to enlarge more rapidly [34] and are associated with twice the mortality compared with intracranial bleeds in those not taking anticoagulants [33]. In order to maintain reversal, intravenous vitamin K is indicated, producing 70% correction of INR at 8 hours [33]. This dual approach is safe, with rapid replacement of clotting factors and few documented thromboses[12,13]. If possible, a repeat coagulation screen should be performed before surgery, and further doses of Beriplex should be avoided, respecting its thrombotic potential.
	There may be concerns related to the continuing anticoagulation of patients (particularly those with heart valves) after control of the bleeding episode. Advice should be sought from haematologists or cardiologists.
	Guideline for correction of Warfarin-associated life-threatening bleeding:
	Immediate:
	1. Beriplex P/N. Dose (INR): 25 IU/kg (2.0 to 3.9), 35 IU/kg (4.0 to 6.0) and 50 IU/kg (>6.0). For instance, eight vials of Beriplex P/N 500 for an 80 kg patient with INR >6.0. Beriplex to be given by slow intravenous injection over 10 to 15 minutes
	2. Vitamin K intravenous 2 to 5 mg
	Later:
	Consider repeating vitamin K administration 24 hours later, in those patients previously severely over-anticoagulated. An INR will help guide this decision together with clinical assessment

FFP, fresh frozen plasma; INR, International Normalized Ratio; PCC, prothrombin complex concentrate; TEG, thromboelastography.