Fresh Frozen Plasma Transfusion Ameliorates INR and aPTT but Does Not Increase Thrombomodulin-Corrected Thrombin Generation in Patients with Cirrhosis

Introduction: In vitro studies have shown that transfusion of fresh frozen plasma (FFP) has limited efficacy in correcting coagulopathy in cirrhosis. This study aims to assess the effect of FFP transfusion on endogenous thrombin potential (ETP) in patients with cirrhosis with abnormal coagulation test results. Methods: Using a stringent protocol for control of pre-analytic variables, blood samples were collected before and up to 8 hours after FFP transfusion. All samples were tested for INR, aPTT and ETP. The ETP assay was performed in platelet-poor plasma, using an automated fluorometer (CAT, Netherlands), using the technique developed by Hemker and modified by Tripodi. ETP was defined as the area under ROC curve and results were expressed as the ratio of ETP with thrombomodulin addition to ETP without (used to mimic in vivo conditions when patients are transfused). Results: 42 patients were included (male n=28; Child-B n= 11; Child-C n=31). Patients underwent FFP transfusion prior to high-risk invasive procedures (n=25), for treatment of bleeding (n=10) or for both reasons (n=6). The mean dose of FFP was 11.3 ml/kg (95% CI 9.16 - 20.46). After transfusion, INR decreased from 2.6±1,4 to 2.09±0.5 (p<0.0001) and aPTT from 1.47±0.5 to 1.27±0.26 (p<0.0001). At baseline, normal or above normal values of ETP ratio (³0.66) were found in 37 (88%) patients, and mean values remained largely unchanged after FFP transfusion (0.75±0.22; median 0.82 before to 0.76±0.16; median 0.81 after transfusion; p=0.56). The results for INR, aPTT and ETP are shown in figure 1. During the one-week follow-up period, 4 patients (9,5%) had acute reactions to transfusion, including fluid overload and allergic reactions. Of the 31 patients that underwent invasive procedures, four had severe bleeding. Discussion: FFP transfusion at standard doses ameliorated INR and aPTT, but did not increase thrombin generation corrected by thrombomodulin. That might be explained by the fact the former tests detect only 5% of the amount of thrombin generated. Besides, they are performed without the addition of thrombomodulin, an endothelial protein with anticoagulant effects, to which patients with cirrhosis have shown to be resistant. Patients were exposed to the risks of transfusions, without a clear benefit in the improvement in thrombin generation and decreasing the risk of bleeding. Our results call into question the common use of INR and aPTT for guiding the transfusion policy of FFP when treating coagulopathy in cirrhosis.

Figure 1: Results showing comparison before and after FFP transfusion

for (A) INR, (B) aPTT and (C) ETP ratio with and without thrombomodulin.