Disseminated Intravascular Coagulation in Acute Promyelocytic Leukemia Patients: A Retrospective Analysis of Outcomes and Healthcare Burden in US Hospitals

Objective: Acute promyelocytic leukemia (APL) is associated with an elevated risk of developing disseminated intravascular coagulation (DIC). The purpose of this study was to assess the outcomes of hospitalizations related to DIC in APL and their impact on healthcare. Materials and Methods: This study entailed a cross-sectional and retrospective analysis of the US National Inpatient Sample database. We identified adults with APL and categorized them into groups of patients with and without DIC. Our focus areas included in-hospital mortality, length of stay, charges, and complications associated with DIC. Unadjusted odds ratios/coefficients were computed in univariate analysis, followed by adjusted odds ratios (aOR)/coefficients from multivariate analysis that accounted for confounding factors. Results: Our analysis revealed that APL patients with DIC had a substantially higher aOR for mortality (aOR: 6.68, 95% confidence interval [CI]: 4.76-9.37, p<0.001) and a prolonged length of stay (coefficient: 10.28 days, 95% CI: 8.48-12.09, p<0.001) accompanied by notably elevated total hospital charges (coefficient: $215,512 [95% CI: 177,368-253,656], p<0.001), thereby emphasizing the reality of extended medical care and economic burden. The presence of DIC was associated with increased odds of sepsis, vasopressor support, pneumonia, acute respiratory failure, intubation/mechanical ventilation, and acute kidney injury, reflecting heightened vulnerability to these complications. Patients with DIC demonstrated significantly higher odds ratios for major bleeding, intracranial hemorrhage, gastrointestinal bleeding, red blood cell transfusion, platelet transfusion, fresh frozen plasma transfusion, and cryoprecipitate transfusion, highlighting the pronounced hematological risks posed by DIC. Conclusion: This study has revealed the significant associations between DIC in APL and various outcomes, underscoring the clinical and economic implications of these conditions. The hematological risks further increase patients' vulnerability to bleeding events and the need for transfusions.

Consumptive coagulopathy in the ICU.

A consumptive coagulopathy describes a situation where there is a loss of hemostatic factors, which leads to an increased risk of bleeding. Some recent studies have used the term interchangeably with disseminated intravascular coagulation (DIC), but we have reverted to the older definition, which covers a broader range of issues where there is loss of hemostatic factors due to multiple causes, which includes systemic activation of coagulation as seen in DIC. Therefore, the term consumptive coagulopathy covers conditions from the hemostatic effects of major hemorrhage to the use of extracorporeal circuits to true DIC. We review the current understanding of the pathophysiology, diagnosis, and management of common consumptive coagulopathy in critical care patients, focusing on recent advances and controversies. Particular emphasis is given to DIC because it is a common and often life-threatening condition in critical care patients and is characterized by the simultaneous occurrence of widespread microvascular thrombosis and bleeding. Second, we focus on the effect of modern medical technology, such as extracorporeal membrane oxygenation, on hemostasis.

Varicella-associated disseminated intravascular coagulation secondary to Henoch-Schönlein purpura with renal and gastrointestinal system involvement in a child: A case report.

RATIONALE: Immunocompromised patients who developed varicella-zoster virus (VZV)-associated disseminated intravascular coagulation (DIC) previously included recipients of bone marrow, hematopoietic stem cell, or organ transplantations, patients with primary nephropathy receiving corticosteroid therapy, cancer patients receiving chemotherapy, and patients with human immune deficiency virus infection. The case reported here is novel because, to our knowledge, there has been no report of VZV-associated DIC after the onset of Henoch-Schönlein purpura (HSP). PURPOSE: To report the successful treatment of a novel pediatric case with VZV-associated DIC secondary to HSP. DIAGNOSIS AND INTERVENTION: An 8-year-old girl developed VZV-associated DIC 24 days after diagnosis of HSP with renal and gastrointestinal involvement. She was treated with methylprednisolone at a local hospital for 19 days, and suddenly developed fever starting from day 4 in our hospital. Her fever persisted with vesicular skin rashes on her back, strong abdominal and lower back pain, epistaxis, hematochezia, erosion and bleeding on her lips, in her mouth and at puncture sites on day 5. She was diagnosed with DIC with the laboratory evidence of dramatically decreased platelet count and fibrinogen, prolonged activated partial thromboplastin time and prothrombin time, and increased fibrin degradation products including d-dimers. She also developed multiple organ dysfunction syndrome. On day 7, the patient VZV nucleic acid result turned out to be positive. Methylprednisolone treatment was discontinued, and she was given a multi-modality therapy including medications of acyclovir and antibiotics, intravenous gamma-immunoglobulin, various blood product transfusions, continuous renal replacement therapy, plasma exchange, and administration of liver and gastrointestinal system protection drugs. OUTCOMES: The patient multi-organ function damage gradually recovered. After VZV control, the patient was treated with oral methylprednisolone again for HSP with nephritis. Urine analysis was normal 1 year later, and oral hormone was discontinued. No complication or relapse occurred during 2 years of follow-up. SIGNIFICANCE: This case report, for the first time, adds HSP treated with corticosteroids to the spectrum of clinical conditions that progressed to life-threatening secondary varicella-associated DIC. Early identification of varicella infection and DIC, combined with timely antiviral, immunoglobulin transfusion, plasma exchange, and other combined therapies are essential for saving patients' lives.

A 16-year-old man with leptospirosis and atypical disseminated intravascular coagulation: a case report.

BACKGROUND: Leptospirosis is known for its pulmonary form characterized by intra-alveolar hemorrhage, exhibiting a high mortality rate. Management by venous-venous extracorporeal membrane oxygenation has been reported in a small number of cases. CASE PRESENTATION: We report herein the case of a 16-year-old Caucasian male who was admitted with rapidly deteriorating respiratory and digestive complaints. He developed severe acute respiratory distress syndrome secondary to disseminated intravascular coagulation and intra-alveolar hemorrhage, requiring initiation of venous-venous extracorporeal membrane oxygenation. Initial infectious and immunological assessments were inconclusive, but repeat serology on the tenth day of admission confirmed a diagnosis of leptospirosis. The patient received multiple transfusions, and upon favorable response to treatment with corticosteroids and antibiotics, he was successfully weaned off venous-venous extracorporeal membrane oxygenation, which was discontinued after 12 days. CONCLUSION: Leptospirosis is a rare cause of severe acute respiratory failure following pulmonary hemorrhage. It is typically diagnosed by serology, with detectable IgM antibodies 5-7 days after the onset of symptoms. We report that early support with respiratory extracorporeal membrane oxygenation favors timely clearance of endobronchial clotting, parenchymal recovery, and prevention of ventilator-induced lung injury. Major hypofibrinogenemia, which did not seem to worsen during extracorporeal membrane oxygenation application, was managed by repeated transfusions. Further studies investigating the pathogenesis of this coagulopathy are required to further optimize the management of this rare and severe complication.

The impact of vascular endothelial glycocalyx on the pathogenesis and treatment of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a complex disorder characterized by widespread activation of blood clotting mechanisms throughout the body. Understanding the role of vascular endothelial glycocalyx in the pathogenesis and treatment of DIC is crucial for advancing our knowledge in this field. The vascular endothelial glycocalyx is a gel-like layer that coats the inner surface of blood vessels. It plays a significant role in maintaining vascular integrity, regulating fluid balance, and preventing excessive clotting. In the pathogenesis of DIC, the disruption of the vascular endothelial glycocalyx is a key factor. Pathological conditions trigger the activation of enzymes, including heparanase, hyaluronase, and matrix metalloproteinase. This activation leads to glycocalyx degradation, subsequently exposing endothelial cells to procoagulant stimuli. Additionally, the ANGPTs/Tie-2 signaling pathway plays a role in the imbalance between the synthesis and degradation of VEG, exacerbating endothelial dysfunction and DIC. Understanding the mechanisms behind glycocalyx degradation and its impact on DIC can provide valuable insights for the development of targeted therapies. Preservation of the glycocalyx integrity may help prevent the initiation and propagation of DIC. Strategies such as administration of exogenous glycocalyx components, anticoagulant agents, or Tie-2 antibody agents have shown promising results in experimental models. In conclusion, the vascular endothelial glycocalyx plays a crucial role in the pathogenesis and treatment of DIC. Further research in this field is warranted to unravel the complex interactions between the glycocalyx and DIC, ultimately leading to the development of novel therapies.

Mechanisms and management of the coagulopathy of trauma and sepsis: trauma-induced coagulopathy, sepsis-induced coagulopathy, and disseminated intravascular coagulation.

Disseminated intravascular coagulation can occur due to different causes but commonly following sepsis. Trauma-induced coagulopathy (TIC) occurs on hospital arrival in approximately 25% of seriously injured patients who initially presents with impaired hemostasis and a bleeding phenotype that can later progress to a prothrombotic phase. Following traumatic injury, ineffective hemostasis is driven by massive blood loss, tissue damage, and hyperfibrinolysis. This initial impaired hemostasis continues until surgical or other management strategies not only to stop the causes of hemorrhage but also progresses to a prothrombotic and hypofibrinolytic state, also termed fibrinolytic shutdown. Prothrombotic progression is also promoted by inflammatory mediator release, endothelial injury, and platelet dysregulation, which is commonly seen in sepsis with increased mortality. Unlike TIC, the early phase of sepsis is frequently complicated by multiorgan dysfunction described as sepsis-induced coagulopathy (SIC) that lacks a hemorrhagic phase. The phenotypes of SIC and TIC are different, especially in their initial presentations; however, patients who survive TIC may also develop subsequent infections and potentially sepsis and SIC. Although the pathophysiology of SIC and TIC are different, endothelial injury, dysregulated fibrinolysis, and coagulation abnormalities are common. Management includes treatment of the underlying cause, tissue injury vs infection is critical, and supportive therapies, such as hemostatic resuscitation and circulatory support are essential, and adjunct therapies are recommended in guidelines. Based on clinical studies and certain guidelines, additional therapies include tranexamic acid in the limited timing of initial traumatic injury and anticoagulants, such as antithrombin and recombinant thrombomodulin in disseminated intravascular coagulation.

Successful perioperative management with damage control surgery following cardiac arrest due to massive postpartum hemorrhage: A case report.

INTRODUCTION: Although declining, maternal mortality due to postpartum hemorrhage (PPH) remains significant. Here we report the case of a 31-year-old primipara patient admitted with cardiac arrest due to PPH. CASE PRESENTATION: Labor was induced at gestational week 39, and the infant was delivered rapidly. Cardiac arrest due to PPH occurred during the transfer to our hospital, and the patient underwent cardiopulmonary resuscitation upon arrival to the emergency room. On admission, her hemoglobin level was 0.7 g/dL and she was in hypovolemic shock. Resuscitation and hysterectomy were performed immediately, including damage control surgery and gauze packing, to control the diffuse oozing bleeding due to severe disseminated intravascular coagulation. Relaparotomy for hemostasis was subsequently performed because of a decrease in hemoglobin level and blood pressure, and gauze packing was reinserted with temporary abdominal closure. Two days later, the abdominal wall was closed after confirming the absence of bleeding and the patient recovered well without further intervention. CONCLUSION: A prompt and assertive intensive response through collaborative efforts, utilizing feasible damage control surgery, can elegantly salvage uncontrolled bleeding in PPH patients with disseminated intravascular coagulation.

International Survey of the Management of Disseminated Intravascular Coagulation Among Pediatric and Neonatal Health Care Practitioners.

The International Society of Thrombosis and Hemostasis (ISTH) provides objective disseminated intravascular coagulation (DIC) measurement through diagnostic criteria validated in adults. The applicability of these criteria in pediatric and neonatal DIC is controversial and unvalidated. Primary objective: to evaluate current practice in pediatric and neonatal DIC management among different specialties. Secondary objective: to understand the potential impact of developmental hemostasis on DIC laboratory evaluation. We performed a multicenter survey between January and September 2016. The questionnaire was distributed internationally through professional societies. In all, 211 responses were received, of which 160 were full responses and 51 were partial. Overall, 85% of respondents practiced in tertiary academic centers; 70% practiced in pediatric-only hospitals. The majority of respondents (42%) used their personal clinical experience in the management of DIC. Sixty percent of respondents treated DIC until the resolution of both clinical and laboratory parameters. Laboratory investigations were monitored in the majority of DIC cases without thrombosis or bleeding (80%); age-specific reference ranges for tests were lacking in 20% of pediatric-only hospitals and 35% of combined pediatric/adult hospitals. Adherence to standardized DIC guidelines was poor but varied by geographical location. This survey reveals variable practices among pediatricians in the management of DIC. Further studies are needed to validate the DIC diagnostic criteria in children.

Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation: What We Need to Know and How to Manage for Prolonged Casualty Care.

Coagulopathy can occur in trauma, and it can affect septic patients as a host tries to respond to infection. Sometimes, it can lead to disseminated intravascular coagulopathy (DIC) with a high potential for mortality. New research has delineated risk factors that include neutrophil extracellular traps and endothelial glycocalyx shedding. Managing DIC in septic patients focuses on first treating the underlying cause of sepsis. Further, the International Society on Thrombolysis and Haemostasis (ISTH) has DIC diagnostic criteria. "Sepsis-induced coagulopathy" (SIC) is a new category. Therapy of SIC focuses on treating the underlying infection and the ensuing coagulopathy. Most therapeutic approaches to SIC have focused on anticoagulant therapy. This review will discuss SIC and DIC and how they are relevant to prolonged casualty care (PCC).

Maternal Coagulation Disorders and Postpartum Hemorrhage.

Coagulation disorders are rare causes of postpartum hemorrhage. Disturbances in coagulation should be suspected in patients with a family history of coagulopathy, those with a personal history of heavy menstrual bleeding, and those with persistent bleeding despite correction of other causes. The coagulopathic conditions discussed include disseminated intravascular coagulation, platelet disorders, and disturbances of coagulation factors. These should not be overlooked in the evaluation of obstetric hemorrhage, as diagnosis and appropriate treatment may prevent severe maternal morbidity and mortality.

Disseminated Intravascular Coagulation Post Endovascular Aortic Repair.

BACKGROUND: Disseminated Intravascular Coagulation (DIC) after Endo-Vascular Aneurysm Repair (EVAR) is a highly uncommon clinical entity. With only a few case-reports available, its management strategy still remains enigmatic. OBJECTIVES: The purpose of this study was to retrieve, synthesize, and appraise all existing data for DIC after EVAR. MATERIALS AND METHODS: All published articles regarding DIC post-EVAR were identified from 3 major databases and analyzed. Clinical parameters, predisposing factors, along with mortality and morbidly were assessed. RESULTS: The total number of publications included in the review was 15 describing 17 cases. DIC presented with a broad spectrum of clinical manifestations, while the time of diagnosis varied significantly. Endoleak was the main causative factor, with an incidence reaching 71%. The mortality of DIC after EVAR reached 29%, regardless of the therapeutic approach chosen. DIC was treated effectively in 47% of the patients (8/17), with better outcomes among patients who received conservative therapy or among those who were submitted to endovascular interventions. CONCLUSIONS: DIC after EVAR, although rare, is a potentially lethal clinical condition which requires prompt diagnosis and urgent medical consideration. Treatment of endoleak may help in quick restoration of normal parameters.

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy.

Hematotoxicity is the most common long-term adverse event (AE) after chimeric antigen receptor T-cell (CAR T) therapy. However, patients who receive CAR T therapy in pivotal clinical trials are subjected to restrictive selection criteria, and this means that rare but fatal toxicities are underestimated. Here, we systematically analyzed CAR T-associated hematologic AE using the US Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC); the lower limit of the ROR and IC 95% confidence interval (CI) (ROR025 and IC025) exceeding one and zero was considered significant, respectively. Among the 105,087,611 reports in FAERS, 5,112 CAR T-related hematotoxicity reports were identified. We found 23 significant over-reporting hematologic AE (ROR025 >1) compared to the full database, of which hemophagocytic lymphohistiocytosis (HLH; n=136 [2.7%], ROR025 = 21.06), coagulopathy (n=128 [2.5%], ROR025 = 10.43), bone marrow failure (n=112 [2.2%], ROR025 = 4.88), disseminated intravascular coagulation (DIC; n=99 [1.9%], ROR025 = 9.64), and B-cell aplasia (n=98 [1.9%], ROR025 = 118.16, all IC025 > 0) were highly under-reported AE in clinical trials. Importantly, HLH and DIC led to mortality rates of 69.9% and 59.6%, respectively. Lastly, hematotoxicity-related mortality was 41.43%, and 22 death-related hematologic AE were identified using LASSO regression analysis. These findings could help clinicians in the early detection of those rarely reported but lethal hematologic AE, thus reducing the risk of severe toxicities for CAR T recipients.

Effectiveness of transarterial embolisation for intractable postpartum haemorrhage in a disseminated intravascular coagulation state, despite emergency hysterectomy.

PURPOSE: We evaluated the effectiveness of transarterial embolization (TAE) for intractable postpartum hemorrhage in patients with disseminated intravascular coagulation (DIC) despite emergency hysterectomy. MATERIALS AND METHODS: We retrospectively assessed TAE performed after emergency hysterectomy in 15 patients between July 2008 and January 2022. Underlying condition, technical success, clinical success, angiographic findings, laboratory findings, pregnancy-modified DIC score (The International Society on Thrombosis and Haemostasis), blood transfusion, ICU (Intensive care unit) admission day, hospital day, in-hospital mortality, and long-term sequelae were evaluated. RESULTS: All patients were diagnosed with DIC before embolization, with a 43.9 mean DIC score. All patients showed positive angiographic findings for active bleeding. Thirty-eight bleeding arteries were confirmed. The remnant uterine artery (n=25) was the most common focus of persistent bleeding, followed by the cervicovaginal artery (n=6), pudendal artery (n=3), obturator artery (n=2), vesical artery (n=1), and unspecified artery from the internal iliac artery (n=1). Technical and clinical success rates were 100% (15/15) and 93.3% (14/15), respectively. Mean nadir hemoglobin (Hb) level before embolization was 4.9 g/dL. All patients underwent massive transfusion before embolization (mean 33.2 packs of RBC). Postoperatively, a smaller amount of blood was transfused than before the procedure (mean 10.6 packs of RBC). Mean nadir Hb level after embolization was 8.2 g/dL. There was one instance each of in-hospital death, hypoxic brain damage, and ischemic acute kidney injury. CONCLUSION: Despite hysterectomy for postpartum bleeding, there could be multiple residual or uncontrolled bleeding foci, especially in case of DIC, for which TAE could be an effective treatment.

Lower Limb Necrosis Secondary to Purpura Fulminans: A Case Report.

Purpura fulminans is a rare and rapidly progressive septic process characterized by the development of hemorrhagic and ecchymotic lesions and skin necrosis. In this work, we report a case of a 52-year-old woman admitted to the Department of Emergency due to progressive purpura. The physical examination demonstrated a decreased skin temperature, unpalpable dorsalis pedis arteries, and ecchymoses covering both lower extremities. Laboratory tests indicated disseminated intravascular coagulation with prolonged activated partial thromboplastin time (APTT), low prothrombin time (PT), elevated d-dimer levels, and a low platelet count. A diagnosis of purpura fulminans was made, and steroids, therapeutic plasma exchange and empiric therapy, including antibiotic and anticoagulation therapy, were initiated immediately. Our treatment resulted in a good and sustained clinical response, as evidenced by the receding of blood blisters and the normalization of the patient's coagulation factors, but bilateral below-knee amputation was inevitable. Finally, the patient recovered well and was discharged home without any complications other than amputation.

The indicators for early blood transfusion in patients with placental abruption with intrauterine fetal death: a retrospective review.

BACKGROUND: Placental abruption (PA) with intrauterine fetal death (IUFD) is associated with a high risk of postpartum hemorrhage (PPH) resulting from severe disseminated intravascular coagulation (DIC). Therefore, blood products that are sufficient for coagulation factor replacement must be prepared, and delivery should occur at referral medical institutions that are equipped with sufficient blood products and emergency transfusion protocols. We retrospectively reviewed the records of patients with PA and IUFD (PA-IUFD) to identify possible factors that may indicate the need for early blood transfusion and investigated whether the Japanese scoring system for PPH can be applied in such cases. METHODS: We used a database of 16,058 pregnant patients who delivered at Yokohama City University Medical Center between January 2000 and February 2016. Thirty-three patients were diagnosed with PA-IUFD before delivery and categorized into two groups-blood transfusion and non-transfusion-to compare the maternal characteristics and pregnancy outcomes. RESULTS: In patients with PA-IUFD, the transfusion group exhibited significantly more blood loss; lower fibrinogen levels and platelet counts; higher levels of fibrin degradation products (FDP), D-dimer, and prothrombin time; and a tendency for tachycardia on admission, compared to the non-transfusion group. Many patients in the transfusion group had normal fibrinogen levels on admission but later displayed markedly decreased fibrinogen levels. The Japan Society of Obstetrics and Gynecology (JSOG) DIC score was significantly higher in the transfusion than in the non-transfusion group. CONCLUSIONS: In PA-IUFD, the fibrinogen level, platelet count, D-dimer, FDP, heart rate, and JSOG DIC score on admission may indicate the need for blood transfusion. However, even with normal fibrinogen levels on admission, continuous monitoring is indispensable for identifying progressive fibrinogen reductions in patients with PA-IUFD.

Amniotic fluid embolism - review and multicentric case analysis.

Amniotic fluid embolism (AFE) is a rare and often fatal obstetric complication, characterized by sudden cardiovascular collapse, dyspnea, seizures, mental alteration or coma and laboratory and clinically dia-gnosed disseminated intravascular coagulation (DIC). Patients reaction is typically biphasic with initial pulmonary hypertension and right ventricular failure, followed by left ventricular failure during or immediately right after labor. Early recognition of AFE is critical to a successful survival. Aggressive shock management is needed in collaboration with an anesthesiologist. Several aspects of the condition remain a controversy. This review critically examines, from the best available evidence, the current knowledge regarding the epidemiology, pathophysiology, dia-gnosis, and available treatment of AFE. This dia-gnosis still determines perinatal morbidity and mortality and potential permanent neurological symptoms for surviving patients.

Overt Disseminated Intravascular Coagulation with Severe Hypofibrinogenemia During Veno-Venous Extracorporeal Membrane Oxygenation.

Disseminated intravascular coagulation (DIC) is a life-threatening hematologic derangement characterized by dysregulated thrombin generation and excessive fibrinolysis. However, DIC is poorly characterized in the extracorporeal membrane oxygenation (ECMO) population, and the underlying mechanisms are not well understood. Several mechanisms contribute to DIC in ECMO, including consumption of coagulation factors, acquired von Willebrand's syndrome leading to thrombocytopenia, and hyperfibrinolysis. There are few case reports of DIC in adult ECMO patients. Most are in the context of venoarterial ECMO, which is typically used in the setting of cardiogenic shock and cardiac arrest. These disease states themselves are known to be associated with DIC, liver failure, impaired anticoagulant mechanisms, and increased fibrinolysis. We present an unusual case of a 74-year-old man who developed overt DIC during veno-venous (VV) ECMO. DIC resulted in clinical bleeding and severe hypofibrinogenemia requiring massive cryoprecipitate transfusion of 87 pooled units. When the patient was decannulated from ECMO, his platelet count and fibrinogen concentration improved within 24 hours, suggesting that ECMO was a proximate cause of his DIC.

Exploring the epidemiology of disseminated intravascular coagulation: protocol for the DANish Disseminated Intravascular Coagulation (DANDIC) Cohort Study.

INTRODUCTION: Since disseminated intravascular coagulation (DIC) was first described, it has been considered a serious disease of the coagulation system and a major challenge to clinicians. Currently, several important knowledge gaps remain. The DANish Disseminated Intravascular Coagulation (DANDIC) Cohort Study will aim to answer questions regarding the incidence and mortality of patients with DIC including time trends. The study will also identify prognostic factors that may guide personalised prevention and treatment. Furthermore, the study will describe treatment patterns and the safety and effectiveness of various treatment modalities. METHODS AND ANALYSIS: We will establish the DANDIC Cohort using data collected in daily clinical practice from the Central Denmark Region, which covers approximately 1.3 million residents. The study period will encompass 1 January 2011 through 1 July 2021. Potential DIC cases will be identified from the hospital laboratory database, based on coagulation biomarkers, and diagnoses will be adjudicated by medical experts. The dataset will be enriched with detailed clinical data from electronic medical charts on aetiologies, bleeding, microthrombus formation, organ failure, thrombosis, treatments and comorbidities. The dataset will also take advantage of in-hospital data with longitudinal information on laboratory records, transfusions, microbiology and treatments. It will be possible to merge this dataset with other unique Danish health registries with more than 10 years of virtually complete follow-up. The project will use state-of-the-art epidemiological and biostatistical methods. ETHICS AND DISSEMINATION: The project has been approved by the Danish Patient Safety Authority (31-1521-452), the Central Denmark Region (1-45-70-83-21), the Danish Data Protection Agency (1-16-02-258-21) and all the hospital chairs. Register-based studies require no ethical approval in Denmark. The results will be disseminated in international peer-reviewed journals.

Coagulopathy and Traumatic Brain Injury: Overview of New Diagnostic and Therapeutic Strategies.

Coagulopathy is a common sequela of traumatic brain injury. Consumptive coagulopathy and secondary hyperfibrinolysis are associated with hypercoagulability. In addition, fibrinolytic pathways are hyperactivated as a result of vascular endothelial cell damage in the injured brain. Coagulation and fibrinolytic parameters change dynamically to reflect these pathologies. Fibrinogen is consumed and degraded after injury, with fibrinogen concentrations at their lowest 3-6 h after injury. Hypercoagulability causes increased fibrinolytic activity, and plasma levels of D-dimer increase immediately after traumatic brain injury, reaching a maximum at 3 h. Owing to disseminated intravascular coagulation in the presence of fibrinolysis, the bleeding tendency is highest within the first 3 h after injury, and often a condition called "talk and deteriorate" occurs. In neurointensive care, it is necessary to measure coagulation and fibrinolytic parameters such as fibrinogen and D-dimer routinely to predict and prevent the development of coagulopathy and its negative outcomes. Currently, the only evidence-based treatment for traumatic brain injury with coagulopathy is tranexamic acid in the subset of patients with mild-to-moderate traumatic brain injury. Coagulation and fibrinolytic parameters should be closely monitored, and treatment should be considered on a patient-by-patient basis.