Abstract
Abstract 3160
Poster Board III-97
The major challenges in acquired bleeding disorders are accurate assessment of bleeding risk and subsequent effective correction of the haemostatic imbalance without increasing the risk of thrombotic complications. The response to Fresh Frozen Plasma (FFP) is extremely variable when used in acquired bleeding disorders. The administration of higher doses of FFP is more effective (Chowdhury et al., Br J Haematology. 2004 Apr; 125(1):69-73), but is limited by the potential risk of fluid overload. In addition, as with the use of all blood products, the risk of transmitting infection and concerns regarding allergic reactions, anaphylaxis and transfusion-related lung injury remain. With the increasing availability of prothrombin complex concentrates (PCCs), it has become possible to give a defined dose of factor II, VII, IX, X and proteins C & S in a small volume. Its efficacy has been well described in patients requiring warfarin reversal, but the indication for its use in other acquired bleeding disorders is less clear and data published on the subject is very limited. Concerns remain regarding the thrombotic risk associated with its use and, as a plasma-derived product, there is also the potential of transmitting blood borne infections. Here we present our two-year experience of the use of PCCs in a wide range of acquired coagulopathies. We collected retrospective data on a total of 200 (n=200) administration events, which we subdivided as follows: (1) Warfarin reversal (n=54), (2) Gastrointestinal bleeding on the background of coagulopathy secondary to chronic liver disease (n=62), (3) Liver transplantation complicated by massive blood loss or renal impairment requiring volume restriction (n=31), (4) Massive haemorrhage (n=10), (5) Coagulopathy due to underlying malignancy (n=10), (6) Correction of coagulopathy prior to procedures (n=20), (7) Miscellaneous (n=13). Dosing of PCCs was decided based on weight of patient, severity of acquired coagulopathy, rate of blood loss and underlying pathology. If required the PCCs were administered in conjunction with fibrinogen concentrate, blood products (packed red cells, platelets, FFP, cryoprecipitate) and antifibrinolytic agents such as aprotinin or tranexamic acid. Our PCC dosing regime of 20 -30 units/kg usually led to an improvement in prothrombin time (PT) and international normalised ratio (INR) in all the above listed clinical settings. No excessive blood loss was noted during the procedures for which PCCs were given. In addition, we did not see a significant increase in thrombotic complications in our cohort of patients, but these findings have to be confirmed in larger studies. At our institution, patients requiring warfarin reversal with an INR >4.0 receive a universal dose of 30u/kg of PCCs based on a previous study (Gatt et al., J. Thrombosis and Haemostasis. 2009 Jul; 7(7); 1123-7), which demonstrated that sufficient thrombin generation is achieved with this dose and the retrospective analysis of our clinical data supports this. In patients with acute and chronic liver failure, the capacity to generate thrombin is probably not significantly impaired in steady state despite a prolonged PT and INR (Gatt et al., Blood, vol.112, No. 11, abstract 1826). However, these patients are more vulnerable to disturbances caused by major blood loss requiring large volume transfusion. We found that administration of PCC in this setting led to improvement of prothrombin time/INR and clinical outcome. We were able to correlate these findings to improvement in the thromboelastogram curves in patients undergoing liver transplant. We conclude that use of PCCs and their dosing must be tailored to the clinical setting. Administration of PCCs can be considered when rapid correction of clotting factors to haemostatic levels is required and/or if there is a significant restriction to volume that can be safely transfused. A comprehensive approach to the management of acquired coagulopathies should also include the addition of FFP, cryoprecipitate, fibrinogen concentrate, antifibrinolytics and recombinant factor VIIa. The correlation between bleeding tendency and standard coagulation tests remains unclear and has to be further investigated to help with future changes of clinical practice.
Disclosures
No relevant conflicts of interest to declare.
Catastrophe at menarche
