Background Previous investigators have demonstrated that postinjury thrombocytosis is associated with an increase in thromboembolic (TE) risk. Increased rates of thrombocytosis have been found ...specifically in patients after splenectomy for trauma. We hypothesized that patients undergoing splenectomy (1) would demonstrate a more hypercoagulable profile during their hospital stay and (2) that this hypercoagulable state would be associated with increased TE events. Methods This was a 14-month, prospective, observational trial evaluating serial rapid thrombelastography (rTEG) at 3 American College of Surgeons−verified, level 1 trauma centers. Inclusion criteria were highest-level trauma activation and arrival within 6 hours of injury. Exclusion criteria were <18 years of age, incarcerated, and burns>20% total body surface area. Serial rTEG (activated clotting time, k-time, α-angle, MA, lysis) and traditional coagulation testing (prothrombin time, partial thromboplastin time, fibrinogen and platelet count) were obtained at admission and then at 3, 6, 12, 24, 48, 72, 96, and 120 hours. Thromboembolic complications were defined as the development of deep-vein thrombosis, pulmonary embolism, acute myocardial infarction, or ischemic stroke during hospitalization. Patients were stratified into splenectomy versus nonsplenectomy cohorts. Univariate analysis was then conducted followed by longitudinal analysis using generalized estimating equations to evaluate the effects of time, splenectomy, and group-time interactions on changes in rTEG and traditional coagulation testing. We used an adjusted generalized estimating equation model to control for age, sex, ISS, admission blood pressure, base deficit, and hemoglobin. Results A total of 1,242 patients were enrolled; 795 had serial rTEG data. Of these, 605 had serial values >24 hours and made up the study population. Splenectomy patients were younger, more hypotensive, and in shock on arrival. Although there was no difference in 24-hour or 30-day mortality, splenectomy patients were more likely to develop TE events. Using the GEE model, we found that α-angle and MA in splenectomy patients were lesser (more hypocoagulable) within the first 6 hours; however, they became substantially greater (more hypercoagulable) at 48, 72, 96, and 120 hours; all P < .05. In addition, platelet counts were greater in the splenectomy group beginning at 72 hours and continuing through 120 hours; P < .05. Conclusion This multicenter, prospective study demonstrates that patients undergoing splenectomy have a more hypercoagulable state than other trauma patients. This hypercoagulable state (identified by greater α-angle and mA values) begins at approximately 48 hours after injury and continues through at least day 5. Moreover, this hypercoagulable state is associated with increased risk of TE complications.
COVID-19 disease progression can be accompanied by a “cytokine storm” that leads to secondary sequelae such as acute respiratory distress syndrome. Several inflammatory cytokines have been associated ...with COVID-19 disease progression, but have high daily intra-individual variability. In contrast, we have shown that the inflammatory biomarker γ' fibrinogen (GPF) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. The aims of the study were to measure GPF in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression. COVID-19 patients were retrospectively enrolled between 3/16/2020 and 8/1/2020. GPF was measured using a commercial ELISA. We found that COVID-19 patients can develop extraordinarily high levels of GPF. Our results showed that ten out of the eighteen patients with COVID-19 had the highest levels of GPF ever recorded. The previous highest GPF level of 80.3 mg/dL was found in a study of 10,601 participants in the ARIC study. GPF levels were significantly associated with the need for ECMO and mortality. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients.
•We found that COVID-19 patients can develop extraordinarily high levels of GPF.•We found the highest level of GPF ever measured, 260 mg/dL, in a COVID-19 patient.•These findings suggest that GPF could be used as an inflammatory biomarker.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable technique for management of noncompressible torso hemorrhage. The major limitation of the current unilobed fully ...occlusive REBOA catheters is below-the-balloon ischemia-reperfusion complications. We hypothesized that partial aortic occlusion with a novel bilobed partial (p)REBOA-PRO would result in the need for less intraaortic balloon adjustments to maintain a distal goal perfusion pressure as compared with currently available unilobed ER-REBOA.
Anesthetized (40-50 kg) swine randomized to control (no intervention), ER-REBOA, or pREBOA-PRO underwent supraceliac aortic injury. The REBOA groups underwent catheter placement into zone 1 with initial balloon inflation to full occlusion for 10 minutes followed by gradual deflation to achieve and subsequently maintain half of the baseline below-the-balloon mean arterial pressure (MAP). Physiologic data and blood samples were collected at baseline and then hourly. At 4 hours, the animals were euthanized, total blood loss and urine output were recorded, and tissue samples were collected.
Baseline physiologic data and basic laboratories were similar between groups. Compared with control, interventions similarly prolonged survival from a median of 18 minutes to over 240 minutes with comparable mortality trends. Blood loss was similar between partial ER-REBOA (41%) and pREBOA-PRO (51%). Partial pREBOA-PRO required a significantly lower number of intraaortic balloon adjustments (10 ER-REBOA vs. 3 pREBOA-PRO, p < 0.05) to maintain the target below-the-balloon MAP. The partial ER-REBOA group developed significantly increased hypercapnia, fibrin clot formation on TEG, liver inflammation, and IL-10 expression compared with pREBOA-PRO.
In this highly lethal aortic injury model, use of bilobed pREBOA-PRO for a 4-hour partial aortic occlusion was logistically superior to unilobed ER-REBOA. It required less intraaortic balloon adjustments to maintain target MAP and resulted in less inflammation.
Abstract Background Conventional thrombelastography has been in use for over 6 decades and provides a functional assay of coagulation. Rapid thrombelastography was developed to provide more rapid ...comprehensive analysis of coagulation status in an emergency setting. The purpose of this study was to determine the correlation of rapid thrombelastographic values with conventional thrombelastographic values in trauma patients. Methods We performed a prospective study on trauma patients at a university level 1 trauma center. Conventional thrombelastography and rapid thrombelastography were performed on 190 consecutive major trauma patients upon admission between 2010 and 2012. Conventional thrombelastographic and rapid thrombelastographic parameters were analyzed using bivariate analysis with Pearson correlation. Group comparisons were performed using the Mann-Whitney U test. Results Patients were predominantly male (71.6%, P < .05) with a median Injury Severity Score of 17 (range 10 to 29) and a median age of 43 years (range 29 to 53 years). There were significantly more patients with blunt trauma than penetrating trauma (72% vs 28%, P < .05). There was a strong correlation between the rapid thrombelastographic and conventional thrombelastographic maximal amplitude value, which represents platelet function ( r = .80). There was a moderate correlation between the G (overall clot strength, r = .70), k (speed of clot formation, r = .66), and α-angle ( r = .38), which reflects the degree of fibrin cross-linking. Lysis at 30 minutes correlated poorly ( r = .19). Conclusions Overall, there is a strong correlation between rapid thrombelastography and conventional thrombelastography in terms of overall clot strength and platelet function. There is a moderate correlation in assessing the degree of fibrin cross-linking and a poor correlation in evaluating thrombolysis. These correlations should be considered when evaluating coagulation status using rapid thrombelastography.
Abstract Background The International Normalized Ratio (INR) is commonly used to guide therapy after hepatectomy. We hypothesized that the use of thrombelastography (TEG) would demonstrate a ...decreased incidence of hypocoagulability in this patient population. Methods Seventy-eight patients were prospectively enrolled before undergoing hepatectomy. INR, TEG, and coagulation factors were drawn before incision, postoperatively, and on postoperative days 1, 3, and 5. Results Patients demonstrated an elevated INR at all postoperative time points. However, TEG demonstrated a decreased R value postoperatively, with subsequent normalization. Other TEG measurements were equivalent to preoperative values. All procoagulant factors save factor VIII decreased postoperatively, with a simultaneous decrease in protein C. Conclusions TEG demonstrated a brief hypercoagulable state after major hepatectomy, with coagulation subsequently normalizing. The INR significantly overestimates hypocoagulability after hepatectomy and these data call into question current practices using the INR to guide therapy in this patient population.
Abstract Background It was hypothesized that splenectomy following trauma results in hypercoagulability. Methods A prospective, nonrandomized, single-center study was performed to evaluate ...coagulation parameters in trauma patients with splenic injury. Results Patients with splenectomy (n = 30) and nonoperative management (n = 50) were enrolled. Splenectomy patients were older, had higher Injury Severity Scores, and had longer intensive care unit and hospital stays ( P < .05). Splenectomy patients had significantly increased white blood cell counts and platelet counts at baseline and follow-up ( P < .01). Fibrinogen was initially elevated in both groups and remained elevated in the splenectomy group ( P < .05). Tissue plasminogen activator, plasminogen activator inhibitor–1, and activated partial thromboplastin time were higher in splenectomy patients only at baseline ( P < .05). Baseline thromboelastography showed faster fibrin cross-linking and enhanced fibrinolysis following splenectomy ( P < .05). Only clot strength was greater at follow-up in the splenectomy group ( P < .01). Deep venous thrombosis developed in 7% of splenectomy patients and no control patients ( P = .03). Conclusions A significant difference in deep venous thrombosis formation was noted, and coagulation assays indicated persistent hypercoagulability following splenectomy for trauma.
The incidence of deep venous thrombosis (DVT) remains high in general surgery and trauma patients despite widespread prophylaxis with enoxaparin. A recent study demonstrated decreased incidence of ...DVT if patients on enoxaparin had a change in R time (ΔR) of greater than 1 minute when heparinase-activated thromboelastography (TEG) was compared with normal TEG. We hypothesized that using ΔR-guided dosing would result in decreased DVT rates.
A prospective, randomized controlled trial was performed at a Level 1 trauma center. Both trauma and general surgery patients were included. Upon enrollment, demographic data including age, sex, body mass index, and Acute Physiology and Chronic Health Evaluation II score were obtained. Enrolled patients were randomized to standard (30 mg twice a day) or TEG-guided dosing. Dose-adjusted patients underwent daily enoxaparin titration to achieve an ΔR of 1 minute to 2 minutes. Venous thromboembolism screening was performed per institutional protocol. Antithrombin III (AT-III) and anti-Xa levels were drawn at peak enoxaparin concentrations.
A total of 87 patients were enrolled. There was no difference in demographic data between the groups. No pulmonary emboli were identified. The control group had a DVT rate of 16%, while the experimental group had a rate of 14% (p = nonsignificant). The experimental group's median enoxaparin dosage, 50 mg twice a day, was significantly higher than that of the control (p < 0.01). TEG ΔR was not different between the control and experimental groups. Beginning at Day 3, anti-Xa levels were higher in the experimental group (p < 0.05). There was no difference in AT-III activity between the two groups; 67% of the patients demonstrated AT-III deficiency.
TEG adjusted enoxaparin dosing led to significant increases in anti-Xa activity, which did not correlate with a decreased DVT rate. Failure to reduce the DVT rate and increase ΔR despite increased dosing and increased anti-Xa activity is consistent with the high rate of AT-III deficiency detected in this study cohort. These data suggest that the future of DVT prevention may not lie in the optimization of low molecular weight heparin therapy but rather in compounds that increase antithrombin directly or operate independently of the AT-III pathway.
Therapeutic study, level III.
The management of severe traumatic brain injury (TBI) frequently involves invasive intracranial monitoring or cranial surgery. In our institution, intracranial procedures are often deferred until an ...international normalized ratio (INR) of less than 1.4 is achieved. There is no evidence that a moderately elevated INR is associated with increased risk of bleeding in patients undergoing neurosurgical intervention (NI). Thrombelastography (TEG) provides a functional assessment of clotting and has been shown to better predict clinically relevant coagulopathy compared with INR. We hypothesized that in patients with TBI, an elevated INR would result in increased time to NI and would not be associated with coagulation abnormalities based on TEG.
A secondary analysis of prospectively collected data was performed in trauma patients with intracranial hemorrhage that underwent NI (defined as cranial surgery or intracranial pressure monitoring) within 24 hours of arrival. Time from admission to NI was recorded. TEG and routine coagulation assays were obtained at admission. Patients were considered hypocoagulable based on INR if their admission INR was greater than 1.4 (high INR). Manufacturer-specified values were used to determine hypocoagulability for each TEG variable.
Sixty-one patients (median head Abbreviated Injury Scale AIS score, 5) met entry criteria, of whom 16% had high INR. Demographic, physiologic, and injury scoring data were similar between groups. The median time to NI was longer in patients with high INR (358 minutes vs. 184 minutes, p = 0.027). High-INR patients were transfused more plasma than patients with an INR of 1.4 or less (2 U vs. 0 U, p = 0.01). There was no association between an elevated INR and hypocoagulability based on TEG.
TBI patients with an admission INR of greater than 1.4 had a longer time to NI. The use of plasma transfusion to decrease the INR may have contributed to this delay. A moderately elevated INR was not associated with coagulation abnormalities based on TEG. Routine plasma transfusion to correct a moderately elevated INR before NI should be reexamined.
Diagnostic study, level III.
To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients.
Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening ...storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown.
We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined.
Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 1-4; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2).
Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.
Abstract Background Prothrombin time-international normalized ratio (PT-INR) is widely utilized to guide plasma therapy and initiation of thromboprophylaxis after a hepatectomy. Thrombelastography ...(TEG) monitors shear elasticity, which is sensitive to cellular and plasma components in blood, allowing for functional assessment of the life of the clot. The objective of this study was to prospectively compare PT-INR and TEG in liver resection patients. Methods Forty patients were enrolled before undergoing an elective hepatectomy. Patients underwent a liver resection utilizing a low central venous pressure (CVP) anaesthetic technique and intermittent Pringle manoeuver. PT-INR and TEG were drawn prior to incision, post-operatively, and post-operative days 1, 3 and 5. Results All post-operative PT-INR values increased significantly when compared with pre-operative PT-INR ( P < 0.01). The time of onset to clot ( R -value) decreased significantly at the post-operative time point ( P = 0.04), consistent with a relative hypercoagulability. Subsequent R -values were not different compared with the pre-operative R -value. The strength of the clot (maximum amplitude, MA) was unchanged when comparing pre- and post-operative time points. Discussion In spite of an elevation in PT-INR, patients undergoing a liver resection demonstrated a brief hypercoagulable state, followed by normal coagulation function based on TEG. These data call into question the practice of utilizing PT-INR to guide plasma transfusion and timing of prophylactic anticoagulation after a liver resection.
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