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Archived Comments for: Recombinant activated factor VII as an adjunctive therapy for bleeding control in severe trauma patients with coagulopathy: subgroup analysis from two randomized trials

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  1. "Coagulopathy" or co-administration of blood products and response to rFVIIa?

    Richard Pugh, Department of Critical Care, University Hospital Aintree, Liverpool, UK

    8 February 2007

    This is a very interesting paper. It is the authors' conclusion that the sub-group of patients, from the only RCT to date evaluating rFVIIa efficacy in trauma [1], who are "coagulopathic" derive particular benefit from rFVIIa for traumatic haemorrhage.

    The benefit that patients receive (whether trauma is penetrating or blunt) among the coagulopathic group following treatment with rFVIIa, in terms of reduction in blood transfusion, is even more dramatic than previously published (reduction in RBC transfusion 3.5 units in this group, compared with 2.6 units among coagulopathic and non-coagulopathic patients who had sustained blunt trauma [1]. This is consistent with the authors’ conclusions that bleeding associated with coagulopathy is particularly responsive to rFVIIa.

    However, I would like to see data regarding the total number of units transfused to “coagulopathic” and “non-coagulopathic” patients following rFVIIa or placebo administration. Interestingly, “coagulopathic” patients treated with placebo seem to be less likely to require massive transfusion in this study than the group of all patients (coagulopathic and non-coagulopathic) treated with placebo in the original study [1]. Oddly, this would suggest that “coagulopathy” confers greater haemostatic benefit.

    Arguably, the definition of “coagulopathy” used in this study, which is: ongoing bleeding that required the use of transfusion of FFP and RBC at a ratio of 1 or more units of FFP for every 4 units of RBC, and/ or the use of FFP with whole blood, and/or transfusion of platelets, and/or the transfusion of cryoprecipitate, is not robust, particularly since this was an international study which enrolled patients from multiple centres, with a probability of differing transfusion practices. As the authors point out, definitions of coagulopathy more usually refer to laboratory measures, and in particular to the prothrombin and partial thromboplastin times. Prothrombin time (PT) and activated partial thromboplastin time (APTT) greater than 1.8 times normal are associated with reduction in coagulation factor to less than 20% normal, and with diffuse microvascular bleeding in massively transfused patients [2].

    An alternative interpretation of the data is that co-administration of FFP, platelets and cryoprecipitate improve the response to rFVIIa of patients with traumatic haemorrhage. For example, it would seem that a significant proportion of “non-coagulopathic” patients did not receive any FFP prior to trial enrolment (mean 95 ml). This seems to be reflected in the baseline characteristics of the “coagulopathic” and “non-coagulopathic” patients; PT and APTT are more prolonged, and platelet count and fibrinogen levels are lower in “non-coagulopathic” patients.

    A prolonged prothrombin time (>17.6 s) was found to be an independent predictor of failure to respond to rFVIIa for traumatic haemorrhage [3]. A previous small study of patients treated with rFVIIa for traumatic haemorrhage found that survival was improved by correction of coagulation measures with blood products prior to rFVIIa administration [4].

    I would suggest that this paper might offer evidence to support the co-administration of blood products in an attempt to correct traumatic coagulopathy prior to rFVIIa administration. This is consistent with recent European recommendations: “rFVIIa is not a first-line treatment for bleeding… for rFVIIa to promote coagulation, sufficient levels of platelets and fibrinogen are required…rFVIIa should be considered only if first-line treatment with a combination of blood products and surgical approaches fails to control bleeding” [5].

    1. Boffard KD, Riou B, Warren P, et al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. J Trauma 2005; 59: 8-18

    2. Ciavarella D, Reed RL, Counts RB, et al. Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient. Br J Haematol 1987; 67: 365-8

    3. Stein DM, Dutton RP, O’Connor J, et al. Determinants of futility of administration of recombinant factor VIIa in trauma. J Trauma 2005; 59: 609-15

    4. Mayo A, Misgav M, Kluger Y, et al. Recombinant activated factor VII: addition to replacement therapy in acute, uncontrolled and life-threatening bleeding. Vox Sang 2004; 87: 34-40

    5. Vincent JL, Rossaint R, Riou B, et al. Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding – a European perspective. Crit Care 2006; 10: R120

    Competing interests

    None declared