Preclinical evaluation of point‐of‐care prothrombin time as a biomarker test to guide prothrombin replacement therapy in coagulopathic bleeding

Abstract

Summary Essentials Prediction of bleeding risk in trauma patients is difficult.We evaluated a test which measures prothrombin time/ability of blood to clot.We showed the prothrombin time test reflected prothrombin concentration in blood.The test could be used in trauma patients to identify those in need of prothrombin replacement. BackgroundHemorrhage is still a common cause of death in trauma. Central lab measured prothrombin time (lab PT) is predictive of low prothrombin concentration and clinical outcome in trauma patients, however, treatment guidance is limited by slow turnaround times. Here, we have preclinically evaluated the potential of a point‐of‐care prothrombin time test (POC PT) as a faster alternative to identify patients with low prothrombin concentration.MethodsHuman whole blood was serially diluted and prothrombin time measured by POC PT (CoaguChek XS Pro, Roche) and lab PT. Recombinant human prothrombin (MEDI8111) was added to human whole blood with or without depletion of prothrombin by pretreatment with prothrombin neutralizing antibodies.ResultsThere was no observable difference in the sensitivity of either test to dilution at blood volumes of 60‐100%. At blood volumes of ≤55% (equivalent to 47 mg/L prothrombin), PT sharply increased, with greater dilutional sensitivity observed in the POC test. Both tests were insensitive to prothrombin up to 194 mg/L added MEDI8111 (equivalent to 328 mg/L prothrombin versus endogenous concentration of 129 mg/L). Depletion of endogenous prothrombin inversely correlated with an increase in PT which returned to baseline following addition of 97 mg/L MEDI8111 or above. Both assays correlated well above 48.5 mg/L added MEDI8111 (65.9 mg/L prothrombin).ConclusionsOur data supports that POC PT tests, such as the CoaguChek XS Pro, are fit for purpose to confirm a coagulopathic threshold for prothrombin and provide a fast, simple, and mobile method to guide MEDI8111 therapy in bleeding trauma patients.

Microfluidic Simulation and Optimization of Blood Coagulation Factors and Anticoagulants in Polymethyl Methacrylate Microchannels

“…Table 1 shows the comparison between the point of care We have calculated the prothrombin time and compared the values with those found in past studies [26][27][28][29]. Table 1 shows the comparison between the point of care (POC) and lab PT results from the literature [30] and the simulated PT results and different blood volumes (40-100%). The simulated PT and POC PT are similar, and when the volume of the blood is low, both the POC PT and simulated PT are high.…”

“…When the volume of the blood increases the PT time is shorter. When the volume is 100%, the simulated PT time is 12.3 s and the lab POC PT result is 12 s. (POC) and lab PT results from the literature [30] and the simulated PT results and different blood volumes (40-100%). The simulated PT and POC PT are similar, and when the volume of the blood is low, both the POC PT and simulated PT are high.…”

Prothrombin Complex Concentrates in Post-traumatic Hemorrhage: A Review

“…[32][33][34][35] Furthermore, TXA is usually given empirically because there are suspicion about the accuracy of diagnostic workup to address hyperfibrinolysis in victims of trauma. 36 CRASH-2 trial (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage), pointed out that management of bleeding trauma cases with TXA leads to a more favorable outcome. In combat casualties, empiric use of TXA showed the greatest benefit observed in patients who subsequently required a massive transfusion.…”