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

INTRODUCTION: 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: CAT+, CAT- 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 = 13 [7,22], age = 48 [28, 64] years, and 73% male. Fifty pts met criteria for CAT+, 64 pts CAT-, and 370 received no Tx. Risk factors for meeting CAT+: 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 CAT+ 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.

Urinary extracellular vesicle-associated MCP-1 and NGAL derived from specific nephron segments differ between calcium oxalate stone formers and controls.

Randall's plaque (RP; subepithelial calcification) appears to be an important precursor of kidney stone disease. However, RP cannot be noninvasively detected. The present study investigated candidate biomarkers associated with extracellular vesicles (EVs) in the urine of calcium stone formers (CSFs) with low (<5% papillary surface area) and high (≥5% papillary surface area) percentages of RP and a group of nonstone formers. RPs were quantitated via videotaping and image processing in consecutive CSFs undergoing percutaneous surgery for stone removal. Urinary EVs derived from cells of different nephron segments of CSFs (n = 64) and nonstone formers (n = 40) were quantified in biobanked cell-free urine by standardized and validated digital flow cytometer using fluorophore-conjugated antibodies. Overall, the number of EVs carrying surface monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL) were significantly lower in CSFs compared with nonstone former controls (P < 0.05) but did not differ statistically between CSFs with low and high RPs. The number of EVs associated with osteopontin did not differ between any groups. Thus, EVs carrying MCP-1 and NGAL may directly or indirectly contribute to stone pathogenesis as evidenced by the lower of these populations of EVs in stone formers compared with nonstone formers. Validation of EV-associated MCP-1 and NGAL as noninvasive biomarkers of kidney stone pathogenesis in larger populations is warranted.

Thrombin generation and procoagulant microparticle profiles after acute trauma: A prospective cohort study.

OBJECTIVE: The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma. METHODS: Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/µL) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]). RESULTS: Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7% male; 95% with blunt mechanism; mortality, 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/µL plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible "hypercoagulable state" (lag time ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible "hypocoagulable state" (lag time ≥ 18.6, peak height ≤ 17.8, and ttPeak ≥ 29.45) were not reached until 1 day to 3 days. CONCLUSION: Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Transfusion of stored red blood cells in trauma patients is not associated with increased procoagulant microparticles.

BACKGROUND: We set out to determine the effects of transfusing stored red blood cells (RBCs) on the levels of procoagulant microparticles (MPs) in the blood of trauma patients. METHODS: Blood was drawn and processed to platelet poor plasma for MP analysis for 409 injured patients seen in the trauma bay from February 2011 to January 2013. Blood from 27 noninjured volunteers was also analyzed. Quantification of total procoagulant MP (per microliter plasma) using a direct plasma analysis via flow cytometry was performed. Demographic data, Injury Severity Score (ISS), overall mortality, and units of transfused packed RBCs were collected. Data are presented as median (interquartile range [IQR]). Transfusion groups were assessed using t test or Wilcoxon rank-sum test as appropriate. The α level was set as 0.05 for statistical significance. RESULTS: Median ISS was 12 (IQR, 5-19), 12% were transfused, median age was 48 years (IQR, 29-62 years), 68% were male, and overall mortality was 3%. Median units transfused were 3 (IQR, 2-5). The median number of all procoagulant MP was greater in trauma patients (median 758; IQR, 405-1,627) when compared with our control subjects (median, 232; IQR, 125-372; p < 0.0001). This difference remained significant after adjusting for age and sex (p < 0.0001). In 39 patients who had MP levels measured before transfusion with RBC, the procoagulant MP levels did not change after transfusion (p = 0.07). Patients transfused with RBCs that were 14 days or older did not have increased procoagulant MP levels when compared with those that received RBCs that were younger than 14 days (p = 0.5).This was also true for those who received RBCs that were 28 days or older when compared with those that received RBCs that were younger than 28 days (p = 0.84). CONCLUSION: Procoagulant MP is significantly greater in trauma patients as compared with volunteers, even after adjusting for age and sex. We did not observe any change in the levels of procoagulant MPs after transfusion of stored RBCs. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.