Thrombin Generation Kinetics are Predictive of Rapid Transfusion in Trauma Patients Meeting Critical Administration Threshold

Abstract

We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24 h after injury, independent of international normalized ratio (INR). Methods: In a prospective cohort study, trauma patients were enrolled over a 4.5-year period and serial blood samples collected at various time points. We retrospectively stratified pts into three categories: CATþ, CATÀ but receiving some pRBC Tx, receiving no Tx within the first 24 h. Blood collected prior to Tx was analyzed for thrombin generation parameters and prothrombin time (PT)/INR. Results: A total of 484 trauma pts were analyzed: injury severity score ¼ 13 [7,22], age ¼ 48 [28, 64] years, and 73% male. Fifty pts met criteria for CATþ, 64 pts CATÀ, and 370 received no Tx. Risk factors for meeting CATþ: decreased arrival systolic blood pressure (OR 2.82 [2.17, 3.67]), increased INR (OR 2.09, [1.66, 2.62]) and decreased time to peak OR 2. 27 [1.74, 2.95]). These variables remained independently associated with increased risk of requiring Tx in a multivariable logistic model, after adjusting for sex and trauma type. Conclusions: Pts in hemorrhagic shock, who meet CATþ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.

Thrombin Generation Following Severe Trauma: Mechanisms, Modulators, and Implications for Hemostasis and Thrombosis

“…Past work has shown that even minor injuries result in increases in thrombin generation, thus more extensive tissue injury likely excites a greater response from the coagulation system, leading to rapid exhaustion (11). Further, recent data from MacArthur et al (49) describe a patient population at higher risk for achieving the critical administration threshold (defined as > 3 units of red blood cells transfused in an hour) that demonstrate a combination of low peak thrombin levels with accelerated ttPeak. These data are indicative of a consumptive phenotype as despite rapid initiation of coagulation, maximal thrombin production is not achieved.…”

Exploring the utility of a novel point‐of‐care whole blood thrombin generation assay following trauma: A pilot study

“…Our pilot study shows that in trauma patients, the plasma and whole blood thrombin generation assays significantly correlate. A larger cohort is needed to assess if the novel whole blood thrombin generation assay is comparable to the plasma‐based assay in predicting VTE and hemorrhagic complications, as we have shown previously in our laboratory 25 …”

“…Trauma patients were compared with 13 healthy volunteers, who had a median age of 35 2539 and were 61.5% female (Table 1). All of the female controls were premenopausal and 3 of 8 (37.5%) were on the Nexplanon (etonogestrel 68 mg) hormonal contraceptive implant at the time of sample collection.…”

“…Our pilot study shows that in trauma patients, the plasma and whole blood thrombin generation assays significantly correlate. A larger cohort is needed to assess if the novel whole blood thrombin generation assay is comparable to the plasma-based assay in predicting VTE and hemorrhagic complications, as we have shown previously in our laboratory 25. ACK N OWLED G M ENTSFunding Sources: This project was supported by R38HL150086 Stimulating Access to Research in Residency (TAM) from the National Heart, Lung, and Blood Institute, R01 GM 126086-03 (MSP) from the National Institute of General Medical Sciences, 1 UL1 RR024150 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), the NIH Roadmap for Medical Research and by Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences.…”

What's New in Shock, March 2021?

“…MacArthur et al (5) stratified trauma patients from a prospective cohort study to assess thrombin generation kinetics into those who required more than three units of packed red blood cells (PRBC), those who received some PRBCs but less than three, and those who received no PRBCs. They found that accelerated thrombin generation was heavily associated with the need for transfusion.…”