Comprehensive Analyses of Coagulation Parameters in Patients with Vascular Anomalies.

BACKGROUND: Vascular anomalies comprise a diverse group of rare diseases with altered blood flow and are often associated with coagulation disorders. The most common example is a localized intravascular coagulopathy in venous malformations leading to elevated D-dimers. In severe cases, this may progress to a disseminated intravascular coagulopathy with subsequent consumption of fibrinogen and thrombocytes predisposing to serious bleeding. A separate coagulopathy is the Kasabach-Merritt phenomenon in kaposiform hemangioendothelioma characterized by platelet trapping leading to thrombocytopenia and eventually consumptive coagulopathy. Our previous work showed impaired von Willebrand factor and platelet aggregometry due to abnormal blood flow, i.e., in ventricular assist devices or extracorporeal membrane oxygenation. With altered blood flow also present in vascular anomalies, we hypothesized that, in particular, the von Willebrand factor parameters and the platelet function may be similarly impacted. METHODS: We prospectively recruited 73 patients with different vascular anomaly entities and analyzed their coagulation parameters. RESULTS: Acquired von Willebrand syndrome was observed in both of our patients with Kasabach-Merritt phenomenon. In six out of nine patients with complex lymphatic anomalies, both the vWF antigen and activity were upregulated. Platelet aggregometry was impaired in both patients with Kasabach-Merritt phenomenon and in seven out of eight patients with an arteriovenous malformation. CONCLUSIONS: The analysis of coagulation parameters in our patients with vascular anomalies advanced our understanding of the underlying pathophysiologies of the observed coagulopathies. This may lead to new treatment options for the, in part, life-threatening bleeding risks in these patients in the future.

Fulminant Bacillus cereus food poisoning with fatal multi-organ failure.

This case represents a rare fulminant course of fried-rice associated food poisoning in an immunocompetent person due to pre-formed exotoxin produced by Bacillus cereus, with severe manifestations of sepsis, including multi-organ (hepatic, renal, cardiac, respiratory and neurological) failure, shock, metabolic acidosis, rhabdomyolysis and coagulopathy. Despite maximal supportive measures (continuous renal replacement therapy, plasmapheresis, N-acetylcysteine infusion and blood products, and broad-spectrum antimicrobials) and input from a multidisciplinary team (consisting of infectious diseases, intensive care, gastroenterology, surgery, toxicology, immunology and haematology), mortality resulted. This case is the first to use whole genome sequencing techniques to confirm the toxigenic potential of B. cereus It has important implications for food preparation and storage, particularly given its occurrence in home isolation during the COVID-19 pandemic.

Commonalities Between COVID-19 and Radiation Injury.

As the multi-systemic components of COVID-19 emerge, parallel etiologies can be drawn between SARS-CoV-2 infection and radiation injuries. While some SARS-CoV-2-infected individuals present as asymptomatic, others exhibit mild symptoms that may include fever, cough, chills, and unusual symptoms like loss of taste and smell and reddening in the extremities (e.g., "COVID toes," suggestive of microvessel damage). Still others alarm healthcare providers with extreme and rapid onset of high-risk indicators of mortality that include acute respiratory distress syndrome (ARDS), multi-organ hypercoagulation, hypoxia and cardiovascular damage. Researchers are quickly refocusing their science to address this enigmatic virus that seems to unveil itself in new ways without discrimination. As investigators begin to identify early markers of disease, identification of common threads with other pathologies may provide some clues. Interestingly, years of research in the field of radiation biology documents the complex multiorgan nature of another disease state that occurs after exposure to high doses of radiation: the acute radiation syndrome (ARS). Inflammation is a key common player in COVID-19 and ARS, and drives the multi-system damage that dramatically alters biological homeostasis. Both conditions initiate a cytokine storm, with similar pro-inflammatory molecules increased and other anti-inflammatory molecules decreased. These changes manifest in a variety of ways, with a demonstrably higher health impact in patients having underlying medical conditions. The potentially dramatic human impact of ARS has guided the science that has identified many biomarkers of radiation exposure, established medical management strategies for ARS, and led to the development of medical countermeasures for use in the event of a radiation public health emergency. These efforts can now be leveraged to help elucidate mechanisms of action of COVID-19 injuries. Furthermore, this intersection between COVID-19 and ARS may point to approaches that could accelerate the discovery of treatments for both.

Coagulopatía por SARS-CoV-2 / SARS-COV-2 COAGULOPATHY

En diciembre de 2019 se descubrió un nuevo coronavirus, asociado a pacientes que sufrían un cuadro de neumonía en Hubei provincia de China, desde ese momento se estudia las características del virus, como también de la patología que produce. En los pacientes graves, se observó un estado proinflamatorio y procoagulante que provocó la disfunción multiorgánica, y, en muchos de ellos, la muerte. El objetivo de este trabajo consiste en describir la fisiopatología de la coagulopatía que esta infección, sorprendentemente, provoca. Es importante remarcar la relación que existe entre los estados inflamatorios y la cascada de la coagulación, cuyas disfunciones ocurren en situaciones de gravedad, como es la sepsis. El SARS-CoV-2 entrara a la célula mediante el receptor de la enzima convertidora de angiotensinógeno. En los estadios avanzados o críticos de la enfermedad, el estímulo hiperinflamatorio y el ambiente protrombótico provocarán un daño multiorgánico. El enfoque de los pacientes en estadios avanzados o críticos debe ser de soporte vital, junto a una terapia anticoagulante completa

In December 2019, a new coronavirus, SARS-CoV-2, was discovered in patients suffering from pneumonia. In critically ill patients, a proinflammatory and procoagulant state was observed: this led to multiorgan dysfunction, and, in many patients, to death. The objective of this work is to describe the pathophysiology of coagulopathy that this infection, surprisingly, causes. It is important to highlight the cross-talk between inflammation and coagulation in serious situations, such as sepsis. SARS-CoV-2 will enter the cell via the angiotensinogen converting enzyme receptor. In the advanced or critical stages of the disease, the hyperinflammatory stimulus and the prothrombotic environment will cause multi-organ damage. The approach of patients in advanced or critical stages should be life support, together with full anticoagulant therapy.

Endothelial dysfunction contributes to COVID-19-associated vascular inflammation and coagulopathy.

Great attention has been paid to endothelial dysfunction (ED) in coronavirus disease 2019 (COVID-19). There is growing evidence to suggest that the angiotensin converting enzyme 2 receptor (ACE2 receptor) is expressed on endothelial cells (ECs) in the lung, heart, kidney, and intestine, particularly in systemic vessels (small and large arteries, veins, venules, and capillaries). Upon viral infection of ECs by severe acute respiratory syndrome coronarvirus 2 (SARS-CoV-2), ECs become activated and dysfunctional. As a result of endothelial activation and ED, the levels of pro-inflammatory cytokines (interleukin -1, interleukin-6 (IL-6), and tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1), von Willebrand factor (vWF) antigen, vWF activity, and factor VIII are elevated. Higher levels of acute phase reactants (IL-6, C-reactive protein, and D-dimer) are also associated with SARS-CoV-2 infection. Therefore, it is reasonable to assume that ED contributes to COVID-19-associated vascular inflammation, particularly endotheliitis, in the lung, heart, and kidney, as well as COVID-19-associated coagulopathy, particularly pulmonary fibrinous microthrombi in the alveolar capillaries. Here we present an update on ED-relevant vasculopathy in COVID-19. Further research for ED in COVID-19 patients is warranted to understand therapeutic opportunities.

The clinical course of COVID in pregnancy.

The 2019 novel coronavirus disease (COVID-19) pandemic poses unique challenges to the medical community as the optimal treatment has not been determined and is often at the discretion of institutional guidelines. Pregnancy has previously been described as a high-risk state in the context of infectious diseases, given a particular susceptibility to pathogens and adverse outcomes. Although ongoing studies have provided insight on the course of this disease in the adult population, the implications of COVID-19 on pregnancy remains an understudied area. The objective of this study is to review the literature and describe clinical presentations among pregnant women afflicted with COVID-19.

Current Overview on Hypercoagulability in COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought many unique pathologies, such as coagulopathy, prompting a desperate need for effective management. COVID-19-associated coagulopathy (CAC) can cause various thromboembolic complications, especially in critically ill patients. The pathogenesis is likely due to endothelial injury, immobilization, and an increase in circulating prothrombotic factors. Data on treatment are limited, although prophylactic anticoagulation is advised in all hospitalized patients. Herein, we have comprehensively reviewed the current literature available on CAC and highlight the pathogenesis, clinical features, and management of CAC.

Hypothermic circulatory arrest induced coagulopathy: rotational thromboelastometry analysis.

OBJECTIVES: Hypothermic circulatory arrest (HCA) has been considered to cause coagulopathy during cardiac surgery. However, coagulopathy associated with HCA has not been understood clearly in details. The objective of this study is to analyze the details of coagulopathy related to HCA in cardiac surgery by using rotational thromboelastometry (ROTEM). METHODS: We retrospectively analyzed 38 patients who underwent elective cardiac surgery (HCA group = 12, non-HCA group = 26) in our hospital. Blood samples were collected before and after cardiopulmonary bypass (CPB). Standard laboratory tests (SLTs) and ROTEM were performed. We performed four ROTEM assays (EXTEM, INTEM, HEPTEM and FIBTEM) and analyzed the following ROTEM parameters: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF) and maximum clot elasticity (MCE). The amount of perioperative bleeding, intraoperative transfusion and perioperative data were compared between the HCA and non-HCA group. RESULTS: Operation time and hemostatic time were significantly longer in the HCA group, whereas CPB time had no difference between the groups. The amount of perioperative bleeding and intraoperative transfusion were much higher in the HCA group. SLTs showed no difference between the groups both after anesthesia induction and after protamine reversal. In ROTEM analysis, MCE contributed by platelet was reduced in the HCA group, whereas MCE contributed by fibrinogen had no difference. CONCLUSION: Our study confirmed that the amount of perioperative bleeding and intraoperative transfusion were significantly higher in the HCA group. ROTEM analysis would indicate that clot firmness contributed by platelet component is reduced by HCA in cardiac surgery.

Digital Ischemia in COVID-19 Patients: Case Report.

As coronavirus 2019 (COVID-19) continues to cause an immense burden on the global health care systems, it is crucial to understand the breadth of this disease process. Recent reports identified hypercoagulability in a subset of critically ill patients and extremity ischemia in an even smaller cohort. Because abnormal coagulation parameters and extremity ischemia have been shown to correlate with poor disease prognosis, understanding how to treat these patients is crucial. To better describe the identification and management of this phenomenon, we present 2 cases of critically ill patients with COVID-19 who developed fingertip ischemia while in the intensive care unit.

Multi-Modal Characterization of the Coagulopathy Associated With Extracorporeal Membrane Oxygenation.

OBJECTIVES: Extracorporeal membrane oxygenation is used to stabilize severe cardiocirculatory and/or respiratory failure. However, extracorporeal membrane oxygenation is associated with a coagulopathy characterized by thromboembolic and hemorrhagic complications. This study aimed to characterize the pathomechanism of the extracorporeal membrane oxygenation-associated coagulopathy and identify options to optimize its monitoring and therapy. DESIGN: Prospective observational clinical trial. SETTING: ICU of a university hospital. PATIENTS: Patients treated with venovenous extracorporeal membrane oxygenation (n = 10) due to acute respiratory distress syndrome and patients treated with venoarterial extracorporeal membrane oxygenation (n = 8) due to cardiocirculatory failure. One patient per group (venovenous extracorporeal membrane oxygenation or venoarterial extracorporeal membrane oxygenation) had surgery before extracorporeal membrane oxygenation. INTERVENTIONS: Blood was sampled before, and 1, 24, and 48 hours after extracorporeal membrane oxygenation implantation. Point-of-care tests (thrombelastometry/platelet aggregometry), conventional coagulation tests, whole blood counts, and platelet flow cytometry were performed. MEASUREMENTS AND MAIN RESULTS: Even before extracorporeal membrane oxygenation, plasmatic coagulation and platelet aggregation were impaired due to systemic inflammation, liver failure, anticoagulants (heparins, phenprocoumon, apixaban), and antiplatelet medication. During extracorporeal membrane oxygenation, hemodilution and contact of blood components with artificial surfaces and shear stress inside extracorporeal membrane oxygenation additionally contributed to coagulation and platelet defects. Fibrinogen levels, fibrin polymerization, platelet activation, and microparticle release were increased in venovenous extracorporeal membrane oxygenation compared to venoarterial extracorporeal membrane oxygenation patients. Point-of-care results were available faster than conventional analyses. Bleeding requiring blood product application occurred in three of 10 venovenous extracorporeal membrane oxygenation patients and in four of eight venoarterial extracorporeal membrane oxygenation patients. No thrombotic events were observed. In-hospital mortality was 30% for venovenous extracorporeal membrane oxygenation and 37.5% for venoarterial extracorporeal membrane oxygenation patients. CONCLUSIONS: The extracorporeal membrane oxygenation-associated coagulopathy is a multifactorial and quickly developing syndrome. It is characterized by individual changes of coagulation parameters and platelets and is aggravated by anticoagulants. The underlying factors of the extracorporeal membrane oxygenation-associated coagulopathy differ between venovenous extracorporeal membrane oxygenation and venoarterial extracorporeal membrane oxygenation patients and are best diagnosed by a combination of point-of-care and conventional coagulation and platelet analyses. Therapy protocols for treating extracorporeal membrane oxygenation-associated coagulopathy should be further validated in large-scale prospective clinical investigations.

Coagulation Disorders in Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and severe condition that can lead patients to the intensive care unit. HLH diagnosis may be challenging, as it relies on sets of aspecific criteria. Several organ dysfunctions have been described during HLH, including hemostasis impairment found in more than half of the patients. The most frequently reported anomaly is a decrease in the fibrinogen level, which has been associated with higher mortality rates. Coagulation impairment study in patients with HLH represents an interesting field of research, as little is known about the mechanism leading to hypofibrinogenemia.

Effect of tranexamic acid administration on acute traumatic coagulopathy in rats with polytrauma and hemorrhage.

Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA's various sites and modes of action may further improve patient outcomes.

[Systemic coagulopathic distress syndrome in surgery: concept, pathogenesis, prophylaxis]. / Ponyatie sistemnogo koagulopaticheskogo distress-sindroma v khirurgii, ego patogenez i printsipy profilaktiki.

OBJECTIVE: The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. MATERIAL AND METHODS: The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. RESULTS: In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.

Female platelets have distinct functional activity compared with male platelets: Implications in transfusion practice and treatment of trauma-induced coagulopathy.

BACKGROUND: Females are hypercoagulable and have survival benefit in trauma-induced coagulopathy (TIC). The mechanism for this sex-specific hypercoagulability is unknown. Platelets and platelet function are central in providing hemostatic potential and are the largest contributor to clot strength. Ligands (adenosine diphosphate [ADP] and platelet-activating factor [PAF]) bind distinct platelet receptors to potentiate activation and aggregation. We hypothesize that female platelets have a differential response to ADP and PAF, resulting in greater aggregation and activation compared to males, and that estradiol pretreatment of male or female platelets enhances this activity. METHODS: Platelets were collected from healthy volunteers: premenopausal/postmenopausal females (≤54 years, >54 years) and similarly aged males. Platelet aggregometry and flow cytometry (fibrinogen binding capacity) were examined. After treatment with ADP or PAF, platelet aggregation was assessed with Chronolog and activation assessed by CD41 receptor surface expression using flow cytometry. Aggregation and activation were again assessed after platelet pretreatment with estradiol. RESULTS: Healthy volunteers included 12 premenopausal and 13 postmenopausal females and 18 similarly aged males. Female platelets (combined premenopausal and postmenopausal) had increased aggregation with ADP stimulation, as compared to male platelets. Male and female platelets had differential fibrinogen receptor expression, with female platelets (combined premenopausal and postmenopausal) demonstrating robust activation with ADP versus male platelets with PAF. In the presence of estradiol incubation, male platelets' activation with PAF approximated that of females (combined premenopausal and postmenopausal) and activation with PAF was enhanced in both male and female platelets. CONCLUSION: Male and female platelets have differential response to stimuli, suggesting sex-dependent signaling and cellular activation. Female platelets have both increased aggregation and activation potential, and estradiol pretreatment feminizes male platelets to approximate female platelet activation with PAF. These findings offer potential explanation for sex-based differences in hemostatic potential in TIC and question whether donor sex of transfused platelets should be considered in resuscitation. Estradiol may also serve as a novel therapeutic adjunct in TIC.

Research progress on the pathogenesis of CTEPH.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an established long-term complication of pulmonary thromboembolism (PTE). However, studies have shown that many patients with a definitive CTEPH diagnosis have no history of symptomatic PTE, suggesting that PTE is not the only cause of CTEPH. Despite extensive progress in research on pulmonary hypertension in recent years, due to a lack of relevant studies on the pathophysiology of CTEPH, implementing pulmonary endarterectomy (PEA) in patients has many challenges, and the prognosis of patients with CTEPH is still not optimistic. Therefore, revealing the pathogenesis of CTEPH would be of great significance for understanding the occurrence and development of CTEPH, developing relevant drug treatment studies and formulating intervention strategies, and may provide new preventive measures. This article summarizes the current research progress in CTEPH pathogenesis from the perspective of risk factors related to medical history, abnormal coagulation and fibrinolytic mechanisms, inflammatory mechanisms, genetic susceptibility factors, angiogenesis, in situ thrombosis, vascular remodeling, and other aspects.

The impact of prehospital administration of freeze-dried plasma on casualty outcome.

BACKGROUND: Hemorrhage is the most common preventable cause of death in both civilian and military trauma. There is no consensus regarding the appropriate fluid resuscitation protocol. Plasma, as a resuscitative fluid, has substantial benefits as a volume expander, owing to its relatively high oncotic pressure and its positive effect on trauma-induced coagulopathy by replenishing the lost coagulation factors, rather than diluting the casualty's remaining factors. The Israel Defense Force Medical Corps decided to use freeze-dried plasma (FDP) as the fluid of choice for casualties in hemorrhagic shock in the prehospital setting. The aim of our study is to compare the differences of coagulation, perfusion measurements, resource utilization, and outcome between casualties receiving FDP to casualties who did not receive FDP in the prehospital setting. METHODS: This is a retrospective matched cohort study based on two groups of casualties (those treated with FDP vs. those without FDP treatment). The control group was compiled in three steps of precision for age, sex, mechanism of injury and maximum level of severity for each nine injured body regions. Data were collected from the IDF Trauma Registry and The National Israel Trauma Registry. RESULTS: The study group comprised 48 casualties receiving FDP and 48 controls with no differences in demographic, evacuation time, and injury characteristics. The FDP group demonstrated a lower level of hemoglobin (12.7 gr/dzl) (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.10-8.80), lower level of international normalized ratio (1.1) (OR, 3.09; 95% CI, 1.04-9.14), and lower level of platelets (230 × 109/L) (OR, 3.06; 95% CI, 1.16-8.06). No other differences were found between the two groups. CONCLUSION: The use of FDP in the prehospital setting has logistic benefits and a positive effect on coagulation profile, with no other significant effects. Future studies need to be performed on larger groups to verify trends or nullify our hypotheses. LEVEL OF EVIDENCE: Therapeutic, level IV.

Dynamic coagulability after injury: Is delaying venous thromboembolism chemoprophylaxis worth the wait?

BACKGROUND: Severely injured patients often progress from early hypocoagulable to normal and eventually hypercoagulable states, developing increased risk for venous thromboembolism (VTE). Prophylactic anticoagulation can decrease this risk, but its initiation is frequently delayed for extended periods due to concerns for bleeding. To facilitate timely introduction of VTE chemoprophylaxis, we characterized the transition from hypo- to hypercoagulability and hypothesized that trauma-induced coagulopathy resolves within 24 hours after injury. METHODS: Serial blood samples were collected prospectively from critically injured patients for 120 hours after arrival at an urban Level I trauma center. Extrinsic thromboelastometry maximum clot firmness was used to classify patients as hypocoagulable (HYPO, <49 mm), normocoagulable (NORM, 49-71 mm), or hypercoagulable (HYPER, >71 mm) at each time point. Changes in coagulability over hospital course, VTE occurrence, and timing of prophylaxis initiation were analyzed. RESULTS: 898 patients (median Injury Severity Score, 13; mortality, 12%; VTE, 8%) were enrolled. Upon arrival, 3% were HYPO (90% NORM, 7% HYPER), which increased to 9% at 6 hours before down-trending. Ninety-seven percent were NORM by 24 hours, and 53% were HYPER at 120 hours. Median maximum clot firmness began in the NORM range, up-trended gradually, and entered the HYPER range at 120 hours. Patients with traumatic brain injury (TBI) followed a similar course and were not more HYPO at any time point than those without TBI. Failure to initiate prophylaxis by 72 hours was predicted by TBI and associated with VTE development (27% vs 16%, p < 0.05). CONCLUSIONS: Regardless of injury pattern, trauma-induced coagulopathy largely resolves within 24 hours, after which hypercoagulability becomes increasingly more prevalent. Deferring initiation of chemoprophylaxis, which is often biased toward patients with intracranial injuries, is associated with VTE development. LEVEL OF EVIDENCE: Prognostic study, level III; Therapeutic, level IV.