Coagulopathic Trauma Patients Research Articles

Point-of-care, goal-directed management of bleeding in trauma patients.

The purpose of this review is to consider the clinical value of point-of-care (POC) testing in coagulopathic trauma patients with traumatic brain injury (TBI) and trauma-induced coagulopathy (TIC). Patients suffering from severe TBI or TIC are at risk of developing pronounced haemostatic disorders. Standard coagulation tests (SCTs) are insufficient to reflect the complexity of these coagulopathies. Recent evidence has shown that viscoelastic tests (VETs) identify haemostatic disorders more rapidly and in more detail than SCTs. Moreover, VET results can guide coagulation therapy, allowing individualised treatment, which decreases transfusion requirements. However, the impact of VET on mortality remains uncertain. In contrast to VETs, the clinical impact of POC platelet function testing is still unproven. POC SCTs are not able to characterise the complexity of trauma-associated coagulopathy. VETs provide a rapid estimation of underlying haemostatic disorders, thereby providing guidance for haemostatic therapy, which impacts allogenic blood transfusion requirements. The value of POC platelet function testing to identify platelet dysfunction and guide platelet transfusion is still uncertain.

3-Factor Versus 4-Factor PCC in Coagulopathy of Trauma: Four is Better Than Three.

Coagulopathy of trauma (COT) is common and highly lethal. Prothrombin complex concentrate (PCC) has been advocated for correction of COT. However, the difference in efficacy between three-factor PCC (3-PCC) versus four-factor PCC (4-PCC) remains unclear. The aim of our study was to compare efficacy of 3-PCC versus 4-PCC in COT. Five-year (2013-2017) review of coagulopathic trauma patients at our Level-I trauma center who received 3- or 4-PCC. Patients were divided into two groups (4-PCC and 3-PCC) and matched in 1:1 ratio using propensity-score-matching for demographics, injury parameters, admission vitals, and hematological parameters. Primary outcomes were time to correction of international normalized ratio (INR), blood products transfusion, thromboembolic complications, and mortality. Secondary outcomes were hospital-length of stay (LOS), intensive care unit (ICU)-LOS, cost of therapy, and total hospital cost. Six hundred fifty-seven patients met inclusion criteria of whom 250 patients (4-PCC:125; 3-PCC:125) were matched. The mean age was 50 ± 19.4 y, 64% were male, and median-injury severity score was 24[15-33]. 4-PCC was associated with accelerated correction of INR (365 vs. 428 min, P = 0.01), decrease in red blood cells (7 units vs. 10 units, P = 0.04) and FFP (6 units vs. 8 units, P = 0.03) transfused. There was no difference in platelet transfusion, thromboembolic complications, mortality, hospital, and ICU-LOS. 4-PCC was associated with higher cost of PCC therapy, and lower cost of transfusion. There was no difference regarding the total hospital cost between the two groups. Compared with 3-factor PCC, the use of 4-factor PCC is associated with a rapid reversal of INR and reduction in transfusion requirement without increasing the overall hospital cost or the risk of thromboembolic events. 4-PCC may be preferred as an adjunct for the resuscitation of coagulopathic trauma patients.

Diagnostic performance of prothrombin time point-of-care to detect acute traumatic coagulopathy on admission: experience of 522 cases in trauma center.

Early identification of acute traumatic coagulopathy is a key challenge during initial management to determine whether to initiate early hemostatic support. We assessed the performance of prothrombin time (PT) at point-of-care in trauma patients to detect moderate and severe coagulopathy on admission. All admitted consecutive trauma patients were analyzed retrospectively between April 2014 and July 2015. PT was measured on admission with both a PT point-of-care device (PTr-CGK) and a standard coagulation test (PTr-STD). The results for PTr-CGK and PTr-STD were compared using analysis of agreement, precision, and accuracy. The diagnostic performance of PTr-CGK to predict coagulopathy was established by analysis of receiver operating characteristic curves. The predictive performance of different thresholds and risk factors for misclassification were also studied. Over a 16-month period, 522 patients were included. PTr-CGK estimated PTr-STD with a bias of 0.00 (95% confidence interval [CI], -0.48 to 0.50) and a precision of 0.25. The optimal threshold was 1.4 to predict severe coagulopathy (sensitivity 81% [95% CI, 68%-94%], negative predictive value 98% [95% CI, 97%-99%]), and 1.2 for moderate coagulopathy (sensitivity 80% [95% CI, 72%-88%], negative predictive value 94% [95% CI, 91%-96%]). A low PTr-CGK in the presence of severity criteria (Injury Severity Score ≥ 16, Trauma Associated Severe Hemorrhage score ≥ 12, hemoglobin level<7 g/dL, fibrinogen level<2 g/L, base deficit ≥ 6 mmol/L) was strongly associated with a false-negative risk. The PT point-of-care device is reliable and accurate for the early identification of coagulopathic trauma patients.

Thrombelastography early amplitudes in bleeding and coagulopathic trauma patients: Results from a multicenter study.

Early amplitudes in the viscoelastic hemostatic assays, thrombelastography (TEG) and rotation thromboelastometry (ROTEM), provide fast results, which is critical in the resuscitation of bleeding patients. This study investigated associations between TEG early amplitudes and standard TEG variables in a large multicenter cohort of moderately to severely injured trauma patients admitted at three North European Level I Trauma Centers. Prospective observational study of 404 trauma patients with clinical suspicion of severe injury from London, UK, Copenhagen, Denmark and Oslo, Norway. Biochemistry and clinical data including outcome and TEG parameters were recorded upon arrival. Kaolin TEG, Rapid TEG, and TEG functional fibrinogen curves were extracted, and early amplitudes A5 and A10 (amplitude at 5 and 10 minutes) were registered. Patients were stratified according to international normalized ratio of 1.2 or less or greater than 1.2, as well as transfusion requirements (nontransfused, 1-9 red blood cell units and ≥10 red blood cell units in 12 hours). In total, 404 patients were included, median Injury Severity Score was 13. There were strong positive correlations between A5/A10 and maximum amplitude in all investigated assays. All TEG values except rTEG maximum amplitude and kTEG maximum amplitude correlated significantly with mortality in transfused patients. Time from initiation of assay to A5 and A10 were lowest for rapid TEG and TEG functional fibrinogen compared with kaolin TEG. Rapid TEG A5 reduced time to result with greater than 50% compared with rapid TEG maximum amplitude. We found strong associations between TEG early amplitudes A5/A10 and maximum amplitude in rapid TEG, kaolin TEG, and TEG functional fibrinogen across trauma patients with coagulopathy and massive transfusion requirements. Introducing the use of early amplitudes can reduce time to diagnosis of coagulopathy and may be used in TEG monitoring of trauma patient. Further randomized controlled trials evaluating the role of TEG in guiding hemostatic resuscitation are warranted. Prognostic study, level III.

Gerinnungsmanagement bei Polytrauma mit Hilfe viskoelastischer Tests

Exsanguination represents the most common and potentially preventable cause of death in major trauma patients. Rapid surgical intervention coupled with an early and aggressive hemostatic therapy not only results in survival benefits of coagulopathic trauma patients, but also reduces the incidence of complications and costs. Standard coagulation tests are not suitable to adequately characterize the complexity of trauma-induced coagulopathy (TIC). This fact has led to a renaissance of viscoelastic tests, such as rotational thromboelastometry (ROTEM®) and thrombelastography (TEG®), which can be used as point-of-care monitors. In some trauma centers treatment algorithms have been developed, where hemostatic therapy is based on viscoelastic test results. Shock and tissue trauma activate profibrinolytic pathways which in turn result in premature dissolution of formed clots. Tranexamic acid rapidly and inexpensively blocks hyperfibrinolysis. ROTEM®/TEG® measurements revealed that diminished clot strength is associated with an increased bleeding tendency. Depending on the underlying cause, administration of fibrinogen concentrate and/or platelet concentrate administration improves clot firmness. Thrombin generation is initially less compromised and can be improved by the administration of plasma, prothrombin complex concentrate, or with restrictiveness by recombinant activated factorVII.

Coagulopathy In Trauma Patients Is Accompanied By Oxidation Of a Methionine Residue In The αC Domain Of Fibrinogen and Abnormal Fibrin Polymerization

IntroductionThe concentration of clottable fibrinogen in plasma decreases rapidly after severe traumatic injury and resuscitation, a reduction associated with both greater transfusion requirements and mortality. Fibrinogen is very sensitive to oxidative modification by oxidants generated during ischemia and inflammation, including hypochlorous acid and peroxynitrite, which both can oxidize methionine to methionine sulfoxide. Here, we investigated the potential of this mechanism to contribute to the coagulopathy of trauma. MethodsWe obtained plasma, clinical data, and outcomes from a biorepository of trauma patients presenting to the Emergency Department of a local Level I trauma center. Subjects with plasma INR ≥1.3 were defined as being coagulopathic while those with INR<1.3 were used as non-coagulpathic controls. We precipitated fibrinogen from plasma with glycine and tested it for the presence of methionine sulfoxide using tandem mass spectrometry. We also tested for defects in fibrin polymerization using thrombin time, reptilase time, and fibrinogen activity/antigenic ratio and correlated these changes with the presence of methionine sulfoxide in fibrinogen. The effects of selectively oxidizing certain methionine residues on fibrinogen structure and polymerization were then simulated using molecular dynamics. ResultsTrauma patients who were coagulopathic (N=31) required more blood products in the first 24 hours of care compared to non-coagulopathic subjects (N=30) (mean PRBC: 3.9 vs. 0.5 units, p < 0.001; mean plasma transfused: 3.2 vs. 0.2 units, p < 0.001; and mean platelets transfused: 0.8 vs. 0.2 units, p=0.008) and were more likely to die (29% vs. 10% mortality, ChiSqr Likelihood Ratio p=0.056). Methionine sulfoxide was selectively increased in coagulopathic trauma patients at position 476 in the alpha C domain compared to controls [mean(SEM) 1.8(0.1)% vs. 2.5(0.1)%, p=0.003] and this low-level of oxidation was confirmed to be associated with an increasing reptilase time in vitro. Mean thrombin time (16 vs. 17.8 sec, p = 0.01) and reptilase times (18.2 vs. 23.7 sec, p<0.001) were prolonged in coagulopathic subjects and the fibrinogen activity/antigen ratio, standardized to albumin content to adjust for hemodilution, tended to be higher in coagulopathic patients (1.3 vs. 1.6, p = 0.06). Percent M476alpha oxidation was associated with increased INR (R=0.5, p=0.016), lower clottable fibrinogen concentration (R=-0.546, p=0.009), increased thrombin time (R=0.4, p=0.04), and increased reptilase time (R=0.5, p=0.01). Using multivariate regression, M476alpha oxidation remained significantly associated with reptilase time (M476alpha p=0.035) after adjusting for D-dimer concentration, fibrinogen concentration, and volume of plasma transfused at the time of measurement (whole model R2=0.77, p=0.003). When M476alpha oxidation was introduced into a human fibrinogen alpha C domain homology model, thermodynamic fluctuations were reduced, favoring a more-open configuration for beta sheet-hairpins that are hypothesized to play a role in fibrin monomer lateral aggregation by their dimerization and oligomerization via beta-hairpin swapping. ConclusionsThe level of oxidation of methionine residues in fibrinogen was increased in coagulopathic trauma patients presenting to the Emergency Department. Even at low levels, this modification was associated with altered fibrin polymerization suggesting that it may contribute mechanistically to coagulopathy by altering fibrin alpha C domain dimerization during the lateral aggregation of fibrin monomer. Disclosures:White:Stasys Medical Corp: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Vidacare Corp: Honoraria; NIH: Research Funding; Coulter Foundation: Research Funding; Washington State Life Sciences Discovery Fund: Research Funding.

The utility of recombinant factor VIIa as a last resort in trauma

IntroductionThe use of recombinant factor VII (rFVIIa) as a last resort for the management of coagulopathy when there is severe metabolic acidosis during large bleedings in trauma might be deemed inappropriate. The objective of this study was to identify critical degrees of acidosis and associated factors at which rFVIIa might be considered of no utility.MethodsAll massively transfused (≥ 8 units of red blood cells within 12 hours) trauma patients from Jan 2000 to Nov 2006. Demographic, baseline physiologic and rFVIIa dosage data were collected. Rate of red blood cell transfusion in the first 6 hours of hospitalization (RBC/hr) was calculated and used as a surrogate for bleeding. Last resort use of rFVIIa was defined by a pH≤ 7.02 based on ROC analysis for survival. In-hospital mortality was analyzed in last resort and non-last resort groups. Univariate analysis was performed to assess for differences between groups and identify factors associates with no utility of rFVIIa.Results71 patients who received rFVIIa were analyzed. The pH> 7.02 had 100% sensitivity for the identification of potential survivors. All 11 coagulopathic, severely acidotic (pH ≤ 7.02) patients with high rates of bleeding (4RBC/hr) died despite administration of rFVIIa. The financial cost of administering rFVIIa as a last resort to these 11 severely acidotic and coagulophatic cases was $75,162 (CA).ConclusionsOur study found no utility of rFVIIa in treating severely acidotic, coagulopathic trauma patients with high rates of bleeding; and thus restrictions should be set on its usage in these circumstances.

Temporal changes in ROTEM®-measured coagulability of citrated blood samples from coagulopathic trauma patients

BackgroundRotational thromboelastometry (ROTEM®) relies on citrated blood samples, which are regarded as biologically stable for up to 4h after venepuncture. However, this recommendation is based on data from normal volunteers. The aim of this study was to evaluate possible temporal changes in the coagulability of blood samples from coagulopathic trauma patients. Patients and methodsThis is a prospective series of 10 coagulopathic (maximum clot firmness, MCF<40mm) trauma patients. ROTEM® EXTEM (tissue factor activated) and FIBTEM (tissue factor activated, cytochalasin D inhibited) analyses were performed on samples obtained on admission, and after approximately 60min of storage in an incubator, at 37°C. ResultsThere were statistically significant differences between the median EXTEM MCF (22mm vs 54mm, p<0.001) and α angle (30.5 vs 59.5°, p=0.004) of the analyses performed immediately after sampling, and 51min (median) subsequently, but not coagulation time (CT, p=0.133), clot formation time (p=0.0625) or maximum lysis (ML, p=0.154). There were also no differences in median FIBTEM MCF (p=1.00) or CT (p=0.877) between the immediate and delayed analyses. ConclusionsRepeated ROTEM® EXTEM analysis of citrated samples from coagulopathic trauma patients shows a spontaneous improvement in coagulability with time. The absence of parallel changes on FIBTEM analysis suggests that this effect may be due to a change in platelet function.

A High Fresh Frozen Plasma: Packed Red Blood Cell Transfusion Ratio Decreases Mortality in All Massively Transfused Trauma Patients Regardless of Admission International Normalized Ratio

Coagulopathy is present in 25% to 38% of trauma patients on arrival to the hospital, and these patients are four times more likely to die than trauma patients without coagulopathy. Recently, a high ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBCs) has been shown to decrease mortality in massively transfused trauma patients. Therefore, we hypothesized that patients with elevated International Normalized Ratio (INR) on arrival to the hospital may benefit more from transfusion with a high ratio of FFP:PRBC than those with a lower INR. Retrospective multicenter cohort study of 437 massively transfused trauma patients was conducted to determine whether the effect of the ratio of FFP:PRBC on death at 24 hours is modified by a patient's admission INR on arrival to the hospital. Contingency tables and logistic regression were used. Trauma patients who arrived to the hospital with an elevated INR had a greater risk of death than those with a lower INR. However, as the ratio of FFP:PRBC transfused increased, mortality decreased similarly between the INR quartiles. The mortality benefit from a high FFP:PRBC ratio is similar for all massively transfused trauma patients. This is contrary to the current belief that only coagulopathic trauma patients benefit from a high FFP:PRBC ratio. Furthermore, it is unnecessary to determine whether INR is elevated before transfusing a high FFP:PRBC ratio. Future studies are needed to determine the mechanism by which a high FFP:PRBC ratio decreases mortality in all massively transfused trauma patients.

453: The Efficacy of Factor VIIa in Emergency Department Patients With Warfarin Use and Traumatic Intracranial Hemorrhage

The use of recombinant activated factor VII (rFVIIa) is gaining popularity in coagulopathic trauma patients. Its utility in patients on warfarin with traumatic intracranial hemorrhage (tICH) is unclear. The objective of this study was to compare outcomes in emergency department patients with pre-injury warfarin use and tICH who did and did not receive rFVIIa for reversal of their coagulopathy.

Low-dose recombinant factor VIIa for trauma patients with coagulopathy

Coagulopathy in injured patients is common and is generally treated with fresh frozen plasma (FFP). Response can be variable, thus complete correction may take hours and require large volumes of fluids. High-dose recombinant factor VIIa (FVIIa, Novoseven, Novo Nordisk, Bagsvaerd, Denmark) has been used off-label to treat severe coagulopathy following trauma. Expense has limited use. Recently, we began administering low dose FVIIa (1.2mg) to patients with mild to moderate coagulopathy after trauma, hypothetising that it would be effective and safe. We retrospectively reviewed consecutive patients who received a low dose of 1.2mg of FVIIa over a 2-year period. Factor VIIa is administered after approval by a gatekeeper at the discretion of the treating physician. Demographics, injury and laboratory data were abstracted as were indications for use, source of coagulopathy, effectiveness, and complications. A two-tailed paired t-test was used to determine significant changes in coagulation parameters and blood product utilisation. Eighty-one patients received 84 low doses of FVIIa. The mean age of the patients was 51 (+/-22) with a mean ISS of 29 (+/-11). Seventy-three per cent were male and 67% had a traumatic brain injury (TBI) as their primary injury. The aetiology of the coagulopathy in the study population included; TBI (40%), warfarin use (22%), and cirrhosis (13%). Mean prothrombin time (PT) fell from 17.0 s (+/-3.2) to 10.6s (+/-1.4) (p<0.0001). All patients had a good clinical response with no bleeding complications. Utilisation of packed red blood cells and fresh frozen plasma were significantly less in the 24h after FVIIa administration as compared to the 24h prior. Subsequent thromboembolic events were observed in 12 of the 81 patients (15%) and included; cerebrovascular accident (CVA) (6), mesenteric thrombosis (2), myocardial infarction (MI) (1), pulmonary embolism/deep venous thrombosis (PE/DVT) (2), and atrial thrombus (1). Only four of these events were thought to be related to the FVIIa administration, with two of the four contributing to a lethal outcome. Low dose FVIIa rapidly and effectively treats mild to moderate coagulopathy following injury. This low dose (1.2mg) FVIIa is the smallest available unit dose. It costs approximately the same as 8 units of plasma and may be cost-effective in patients who require high volume factor administration. Low dose FVIIa may be effective in coagulopathic trauma patients who are not in shock but require rapid normalisation of clotting function.

Thromboembolic Complications Associated With Factor VIIa Administration

Factor VIIa (FVIIa) is given to promote hemostasis in coagulopathic trauma patients at high risk for death. FVIIa is associated with thromboembolic complications, but the incidence is not known, nor is which patients are at risk. We examined our experience with FVIIa to better understand this issue. Medical records of patients who received FVIIa from 2001 to 2006 were reviewed for evidence of thromboembolic events, including ischemic cardiovascular accident, myocardial ischemia or infarct, mesenteric infarct, peripheral arterial thromboembolism, deep venous thrombosis, or pulmonary embolus. Indication for FVIIa dosing, timing of complication, and clinical outcome were recorded. Each event was assessed by a panel of experienced clinicians to determine the contribution of FVIIa to the event and to patient outcome. Two hundred eighty-five medical records were reviewed. Twenty-seven patients (9.4%) had thromboembolic complications after administration of FVIIa. Nine events were thought to be highly related to FVIIa, and 10 of 14 deaths were, in part, caused by the thrombotic complication. Eighteen of the events, including all cardiovascular accidents and most cases of mesenteric ischemia, were attributed to a combination of FVIIa and a definable, high-energy vascular injury. FVIIa is a potent procoagulant, with the potential for adverse thromboembolic events in susceptible patients. Our experience suggests that caution should be exercised in administration of FVIIa to patients with arterial injuries. Injured mesenteric and cerebral vessels may be especially susceptible to thrombosis.

The Use of Fresh Whole Blood in Massive Transfusion

Most indications for whole blood transfusion are now well managed exclusively with blood component therapy, yet the use of fresh whole blood for resuscitating combat casualties has persisted in the U.S. military. Published descriptions of whole blood use in military and civilian settings were compared with use of whole blood at the 31st Combat Support Hospital (31st CSH) stationed in Baghdad in 2004-2005. Concerns about logistics, safety, and relative efficacy of whole blood versus component therapy have argued against the use of whole blood in most settings. However, military physicians have observed some distinct advantages in fresh warm whole blood over component therapy during the massive resuscitation of acidotic, hypothermic, and coagulopathic trauma patients. In this critical role, fresh whole blood was eventually incorporated as an adjunct into a novel whole-blood-based massive transfusion protocol. Under extreme and austere circumstances, the risk:benefit ratio of whole blood transfusion favors its use. Fresh whole blood may, at times, be advantageous even when conventional component therapy is available.

Recombinant activated factor VII as an adjunctive therapy for bleeding control in severe trauma patients with coagulopathy: subgroup analysis from two randomized trials

IntroductionWe conducted a post-hoc analysis on the effect of recombinant factor VIIa (rFVIIa) on coagulopathic patients from two randomized, placebo-controlled, double-blind trials of rFVIIa as an adjunctive therapy for bleeding in patients with severe trauma.MethodsBlunt and penetrating trauma patients were randomly assigned to rFVIIa (200 + 100 + 100 μg/kg) at 0, 1, and 3 hours after transfusion of 8 units of red blood cells (RBCs) or to placebo. Subjects were monitored for 48 hours post-dosing and followed for 30 days. Coagulopathy was retrospectively defined as transfusion of fresh frozen plasma (FFP) (>1 unit of FFP per 4 units of RBCs), FFP in addition to whole blood, and transfusion of platelets and/or cryoprecipitate.ResultsSixty rFVIIa-treated and 76 placebo subjects were retrospectively identified as being coagulopathic. No significant differences were noted in baseline characteristics. The rFVIIa-treated coagulopathic subgroup consumed significantly less blood product: RBC transfusion decreased by 2.6 units for the whole study population (P = 0.02) and by 3.5 units among patients surviving more than 48 hours (P < 0.001). Transfusion of FFP (1,400 versus 660 ml, P < 0.01), platelet (300 versus 100 ml, P = 0.01), and massive transfusions (29% versus 6%, P < 0.01) also dropped significantly. rFVIIa reduced multi-organ failure and/or acute respiratory distress syndrome in the coagulopathic patients (3% versus 20%, P = 0.004), whereas thromboembolic events were equally present in both groups (3% versus 4%, P = 1.00).ConclusionCoagulopathic trauma patients appear to derive particular benefit from early adjunctive rFVIIa therapy.

Coagulopathy in the trauma patient

Homeostasis represents a delicate balance between hemostatic and fibrinolytic processes. This balance permits arrest of hemorrhage after mild injury but prevents thrombosis from occurring under normal circumstances. Trauma disturbs the equilibrium between hemostatic and fibrinolytic processes, frequently producing either a hypocoagulable state or a hypercoagulable state depending on the severity of injury, degree of hemorrhage, and the nature of the resuscitation. The purpose of this review is to describe the epidemiology and pathophysiology of coagulopathy after trauma and to discuss novel methods of treating it. Published reports during the past year focus on the pathophysiology of coagulopathy after trauma and novel methods of treatment. Individual effects of hypothermia and acidosis on clotting factors and platelet function have been described. The effects of varying resuscitation fluids on coagulopathy have also been described as well as the course of coagulopathy over time. Recombinant factor VIIa has emerged as a popular therapy for traumatic coagulopathy although a prospective randomized trial has yet to be published. The efficacy of several new dressings for the local control of hemorrhage has been reported. Changes in coagulation following trauma are characterized by a complex series of events that may result in either a hypocoagulable or a hypercoagulable state. Routinely analyzed coagulation parameters do not adequately describe this state and they are deficient for guiding its therapy. Several promising new agents are available for treating hemorrhage in coagulopathic trauma patients that should result in improved survival.

Factor VIIa for Correction of Traumatic Coagulopathy

Activated factor VIIa (FVIIa) was developed to treat hemophiliacs with high-titer antibodies to factor VIII. FVIIa initiates thrombin formation by binding with exposed tissue factor. Anecdotal reports have described the utility of FVIIa in correcting coagulopathy from trauma, but no large series exists. We present our experience with 81 coagulopathic trauma patients treated using FVIIa in years 2001-2003, compared with "control" patients matched from the trauma registry from the same time period. Use of FVIIa was restricted to active hemorrhage with clinical coagulopathy. We recorded the cause of coagulopathy, dose of FVIIa administered, effect on clinical coagulation, pertinent laboratory values, length of stay, number and type of blood products administered, and patient outcome. For the same time period we also examined outcomes in coagulopathic patients who did not receive FVIIa. Causes of coagulopathy were diverse, and included acute traumatic hemorrhage (46 patients), traumatic brain injury (20), warfarin use (9), congenital Factor VII deficiency (2), and other acquired hematologic defects (4). Coagulopathy was reversed in 61/81 cases (75%), with an associated reduction in PT from 19.6 to 10.8 (p=0.000018). 34 patients (42%) survived to hospital discharge (20/46 traumatic hemorrhage, 5/20 TBI, 4/9 on warfarin, 2/2 factor deficient, 3/4 other). Patients died from irreversible shock, multiple organ system failure, or traumatic brain injury. FVIIa patients had a higher mortality than coagulopathic controls matched by specific anatomic injuries, admission lactate value, and predicted probability of survival. Only a group identified by all three characteristics had a similar mortality to the FVIIa cohort, but the number of patients that could be matched this way was too small to be meaningful. FVIIa therapy lead to an immediate reduction in coagulopathic hemorrhage in most cases, accompanied by a significant improvement in laboratory measures. Application of FVIIa as a therapy of last resort makes the identification of equivalent control patients difficult. Use of FVIIa should be considered for any patient with coagulopathic hemorrhage in which surgically-accessible bleeding has been controlled. Prospective trials of FVIIa in patients with traumatic coagulopathy are strongly indicated, and should focus on appropriate patient selection and the dose and timing of therapy.

Modified Rapid Deployment Hemostat Bandage Terminates Bleeding in Coagulopathic Patients with Severe Visceral Injuries

We recently reported that a new dressing, the Modified Rapid Deployment Hemostat (MRDH) controlled bleeding in hypothermic coagulopathic swine after traumatic liver avulsion. The purpose of this study was to evaluate the MRDH in coagulopathic trauma patients undergoing abbreviated laparotomy. A prospective, observational clinical trial of the MRDH dressing was performed at our Level One Trauma Center in patients with high-grade visceral injuries with coagulopathy who failed conventional therapy and required packing. Attending surgeons graded the injury and the adequacy of hemostasis following application of the dressing. Patients were followed until discharge or death. Ten patients were enrolled: nine severe hepatic injuries, and one major abdominal vascular injury. All patients were hypothermic, acidotic, and clinically coagulopathic. Intraoperative hemostasis was immediately obtained after MRDH placement in all cases except one. There was one death. The Modified Rapid Deployment Hemostat terminates bleeding from severe visceral injuries in coagulopathic patients undergoing abbreviated laparotomy.

Intraoperative detection of traumatic coagulopathy using the activated coagulation time.

Traumatic coagulopathy manifests as a hypocoagulable state associated with hypothermia, acidosis, and coagulation factor dilution. The diagnosis must be made clinically because traditional coagulation tests are neither sensitive nor specific and take too long to be used for intraoperative monitoring. We hypothesized that the activated coagulation time (ACT) would reflect the global coagulation status of traumatized patients and would become elevated as coagulation reserves become exhausted. A prospective protocol was used to study 31 victims of major trauma who underwent immediate surgical Intervention. Victims of major head trauma were excluded and patients were selected at random over an 8-month period. At least two serial intraoperative blood samples were obtained at 15-min intervals via indwelling arterial catheters. A Hemochron model 801 coagulation monitor was used to measure the ACT. Of the 31 patients studied, 7 became clinically coagulopathic and 24 did not. The ACT measurements of coagulopathic and noncoagulopathic trauma patients were significantly different by multiple statistical comparisons. Both groups differed from normal, nontraumatized patients. The coagulopathic trauma patients had significantly elevated values when compared with other trauma patients or to normal values. We conclude that a low ACT reflects the initial hypercoagulability associated with major trauma and an elevated ACT is an objective indicator that the coagulation system reserve is near exhaustion. An elevated ACT may represent an indication for considering damage control maneuvers or more aggressive resuscitation.

Recombinant Activated Factor VII for Adjunctive Hemorrhage Control in Trauma*

SUMMARY Background: Recombinant activated factor VII (rFVIIa) was approved for treatment of hemorrhages in patients with hemophilia who develop inhibitors to factors VIII or IX. Conditions with increased thromboembolic risk, including trauma with or without disseminated intravascular coagulation, were considered a contraindication for the drug. The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. Therefore, use of the drug in trauma patients suffering uncontrolled hemorrhage appears to be rational. Methods: Seven massively bleeding, multitransfused (median, 40 units [range, 25–49 units] of packed cells), coagulopathic trauma patients were treated with rFVIIa (median, 120 μg/kg [range, 120–212 μg/kg]) after failure of conventional measures to achieve hemostasis. Results: Administration of rFVIIa resulted in cessation of the diffuse bleed, with significant decrease of blood requirements to 2 units (range, 1–2 units) of packed cells (p &lt; 0.05); shortening of prothrombin time and activated partial thromboplastin time from 24 seconds (range, 20–31.8 seconds) to 10.1 seconds (range, 8–12 seconds) (p &lt; 0.005) and 79 seconds (range, 46–110 seconds) to 41 seconds (range, 28–46 seconds) (p &lt; 0.05), respectively; and an increase of FVII level from 0.7 IU/mL (range,0.7‐0.92 IU/mL) to 23.7 IU/mL (range, 18–44 IU/mL) (p &lt; 0.05). Three of the seven patients died of reasons other than bleeding or thromboembolism. Conclusion: The results of this report suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure, in addition to surgical hemostatic techniques, and provides the motivation for controlled animal and clinical trials.

Recombinant activated factor VII for adjunctive hemorrhage control in trauma.

Recombinant activated factor VII (rFVIIa) was approved for treatment of hemorrhages in patients with hemophilia who develop inhibitors to factors VIII or IX. Conditions with increased thromboembolic risk, including trauma with or without disseminated intravascular coagulation, were considered a contraindication for the drug. The mechanism of action of rFVIIa suggests enhancement of hemostasis limited to the site of injury without systemic activation of the coagulation cascade. Therefore, use of the drug in trauma patients suffering uncontrolled hemorrhage appears to be rational. Seven massively bleeding, multitransfused (median, 40 units [range, 25-49 units] of packed cells), coagulopathic trauma patients were treated with rFVIIa (median, 120 microg/kg [range, 120-212 microg/kg]) after failure of conventional measures to achieve hemostasis. Administration of rFVIIa resulted in cessation of the diffuse bleed, with significant decrease of blood requirements to 2 units (range, 1-2 units) of packed cells (p < 0.05); shortening of prothrombin time and activated partial thromboplastin time from 24 seconds (range, 20-31.8 seconds) to 10.1 seconds (range, 8-12 seconds) (p < 0.005) and 79 seconds (range, 46-110 seconds) to 41 seconds (range, 28-46 seconds) (p < 0.05), respectively; and an increase of FVII level from 0.7 IU/mL (range, 0.7-0.92 IU/mL) to 23.7 IU/mL (range, 18-44 IU/mL) (p < 0.05). Three of the seven patients died of reasons other than bleeding or thromboembolism. The results of this report suggest that in trauma patients rFVIIa may play a role as an adjunctive hemostatic measure, in addition to surgical hemostatic techniques, and provides the motivation for controlled animal and clinical trials.