Cause Of Coagulopathy Research Articles

Traumatic brain injury: Advances in coagulopathy (Review).

Trauma is a prevalent cause of coagulopathy, with traumatic brain injury (TBI) accompanied by coagulation disorders particularly linked to adverse outcomes. TBI is distinguished by minimal bleeding volume and unique injury sites, which precipitate complex coagulation disturbances. Historically, research into trauma-induced coagulopathy has primarily concentrated on the molecular biology and pathophysiology of endogenous anticoagulation and inflammation. Nonetheless, recognizing that cells are the fundamental units of structure and function in all living organisms, the present review aimed to distill our understanding of coagulopathy post-TBI by elucidating the intricate cellular mechanisms involving endothelial cells, neutrophils and platelets. Additionally, this study evaluates the strengths and weaknesses of various diagnostic tools and discusses the characteristics of pharmacological treatments and potential therapies for patients with TBI and coagulation disorders. The aim of this review is to amalgamate recent updates in mechanistic research and innovative diagnostic and therapeutic methodologies, thereby fostering the progression of precision medicine within this specialized domain.

A mysterious hematochezia in an adolescent boy: atypical presentation of childhood systemic lupus erythematosus

Thrombosis is a well-known entity in presence of antiphospholipid antibody (APLA) associated with systemic lupus erythematosus (SLE) as a hematological complication. Bleeding manifestations instead of thrombosis is hardly found in literature in presence of APLA seromarkers in SLE. Since these can range from minor bleeding like epistaxis to major life-threatening intracranial bleeding, early diagnosis and prompt treatment is essential to manage such condition. We report a 12 years old boy with no significant past history presented with hematochezia and epistaxis along with pallor requiring blood transfusion. Hematological investigations were normal except for elevated PT, aPTT and INR. Common causes of coagulopathy were ruled out. Upon suspecting systemic diseases, the investigations were carried out which revealed ANA 4+ along with high titre of dsDNA, low C3 and C4 complement and positive anti-β2 glycoprotein, anticardiolipin antibody and lupus anticoagulant. Diagnosis of SLE was made according to ACR-EULAR criteria with no renal involvement. Immunological basis was considered for coagulopathy in this child. He was started on oral prednisolone, hydroxychloroquine and methotrexate. He is now under close monitoring of the coagulation profile for titration of steroid dose. We want to create awareness about the uncommon hematological manifestation of SLE presenting as bleeding diathesis instead of thrombosis through this case report and that can be life threatening too if not treated promptly. A high index of suspicion and careful follow-up may help in preventing adverse outcome of the disease.

Basic Principles of Rotational Thromboelastometry (ROTEM®) and the Role of ROTEM-Guided Fibrinogen Replacement Therapy in the Management of Coagulopathies.

Rotational thromboelastometry (ROTEM) is a viscoelastic method, which provides a graphical and numerical representation of induced hemostasis in whole blood samples. Its ability to quickly assess the state of hemostasis is used in the management of bleeding from a variety of causes. The separate activation of particular parts of hemocoagulation in INTEM, EXTEM, and FIBTEM tests allows for a more comprehensive and faster evaluation of the missing component of hemostasis followed by targeted therapy. One of the most common cause of coagulopathy is trauma-induced coagulopathy. Fibrinogen replacement therapy by ROTEM allows for the use of a standard dosage of fibrinogen, which has been shown to be successful in preventing dilutional coagulopathy following colloid and crystalloid replacement and excessive amount of allogeneic blood transfusions. The best reflection of fibrinogen activity is observed in the FIBTEM assay, where fibrinogen replacement therapy is recommended at an MCF (maximum clot firmness) of FIBTEM < 10 mm and FIBTEM A10 < 7 mm. ROTEM also plays an important role in the diagnostic and management of inherited fibrinogen disorders. These can be manifested by bleeding complications, where changes in the MCF parameter are the most useful tool for assessing the effectiveness of fibrinogen replacement therapy. ROTEM-guided bleeding management algorithms effectively reduce the number of transfusions, healthcare costs, and complications, leading to the improvement of patient safety and overall health.

Common Coagulopathies Associated With COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) outbreak, which first appeared in the Chinese province of Hubei city of Wuhan, has been spreading internationally since December 2019. The World Health Organization (WHO) declared the coronavirus illness from 2019 to be a pandemic on March 11, 2020. Patients hospitalised with severe coronavirus or comorbid conditions (like cardiovascular disease and obesity) are linked to a worse prognosis. The rise in D-dimer and its relationship to prognosis are the most often documented aberrations in coagulation/fibrinolysis in COVID-19. However, the D-dimer assessment's utility is not limitless. Since the coagulation/fibrinolytic state might occasionally change over a short period of time, routine exams are also advantageous in understanding the relevance of the inquiry. Both thrombotic and hemorrhagic diseases should be taken into consideration, despite the fact that the pathophysiology of disseminated intravascular coagulation (DIC) linked with coronavirus disease 19 differs significantly from that of septic disseminated intravascular coagulation. Coagulation as well as fibrinolysis indicators are used to make the diagnosis of COVID-19 thrombosis, which encompasses both macro- and micro-thrombosis. Compared to bacterial-sepsis-associated coagulopathy/DIC, COVID-19 has a lower prevalence of prolonged prothrombin time, activated partial thromboplastin time, and decreased antithrombin activity. However, the causes of coagulopathy remain poorly understood. Hypoxia, endothelial injury, dysregulated immunological responses mediated by inflammatory cytokines, and lymphocyte cell death are thought to be implicated. While blood loss tends to be rare, it is uncertain if COVID-19 suffers from thrombosis or whether the current recommendations for regular venous thromboembolic dose are appropriate. It is important to decide on the COVID-19 therapy phases. Antiviral therapy, cytokine storm therapy, and thrombosis therapy are the steps. Future advancements are predicted, such as a therapy that combines heparin and nafamostat.

Wasp-stung rat model translationally expresses the coagulopathy manifestations of human wasp patients.

Two over 80 wasp stings male victims appeared severe abnormal coagulation were consecutively examined by thromboelastography (TEG) guided with heparinase during hospitalization. However, the cause of coagulopathy remains unsolved. Rats were applied to establish a wasp-stung animal model highly resembled the manifestations of wasp-stung patients. According body surface area conversion, Sprague-Dawley rats were stung based on wasp sting numbers (0, 4, 8, 12 stings; n = 6 each) with various exposure times (0, 1, 3, 6 h) to determine the simulation of coagulopathy. The blood R, K values, and angle degree of wasp-stung rats were measured by TEG. The TEG profiles of stung rats were found to be concomitant with that of wasp-stung patients. Data showed that the endogenous heparinization of rats was time-dependent. Compared to the TEG profile of eight stings given rat, the coagulation time of 2mm clot formation at 3 h (R value) was longer than that at 0 h. The coagulation time was prolonged with increasing sting numbers when compared to the various stings at 1, 3, and 6 h exposed. Interestingly, there was observed the peak coagulation at 3 h of eight stings. The Ck-standard and Ck-heparinase at 3 h after 8 stings given were R: 9.6-4.4 min; K: 3.8-1.8 min; angle degree: 49.8-68.0, respectively. The original data of R, K values and angle degree in two wasp-stung victims were 11.7-13.6 min, 4.3-5.5 min, and 41.2-32.8° in CK-standard, respectively; whereas those of the CK-heparinase groups were 5.6-6.7 min, 2.4-2.5 min, and 59.5-58.8°, correspondingly. Conclusively, this massive wasp-stung animal model can be applied to the investigations of pathogenesis and provides a clinical strategy or guideline for clinical intervention.

Potential clinical benefits of warfarin in end-stage cancers: A retrospective analysis.

Coagulopathy and thromboembolism are common comorbidities in cancer, and anticoagulants, such as warfarin, are needed in specific situations. This study aimed to determine the clinical relevance of prothrombin time (PT) monitoring and the clinical usefulness of warfarin in patients with malignancy. We retrospectively investigated patients with PT lower than 10% treated in our hospital between April 2006 and March 2013. Cases of false coagulopathy, including those due to technical errors during blood sampling, were excluded. The cause of coagulopathy was determined or estimated by physicians. This study included 338 cases comprising 155 females and 183 males with a median age was 68 (0-97) years. Among them, 89 (26.3%) had cancer, and 163 (48.2%) received warfarin at a median dose of 2.23 (0.5-8.0) mg/day. PT prolongation caused by warfarin overdose and malignancy exacerbation were observed in 75 (22.2%) and 64 (18.9%) patients, respectively. The leading reasons for warfarin administration were arterial fibrillation, chronic heart failure, and deep vein thrombosis. Univariate analysis revealed that the overall survival was higher in the warfarin and nononcology groups than in the nonwarfarin and oncology groups (both p < 0.001). In multivariate analysis, survival was significantly decreased in older adults (p = 0.049), those with malignancy (p < 0.001), and those without warfarin therapy (p < 0.001). Early mortality (within 3 days after PT prolongation) was observed in 65 patients and was mostly related to emergent diseases (36.9%, 24/65) and end-stage malignancy (32.3%, 21/65). Patients with malignancy may experience subclinical PT prolongation upon disease progression. Warfarin treatment mitigates panic PT values in patients with malignancy. Conversely, those not treated with warfarin have poor survival, suggesting that coagulopathy without warfarin treatment can lead to death. Warfarin enhances hemostatic conditions, thereby preventing malignancy-related lethal hemorrhagic or thromboembolic events.

Prevalence and Characteristics of Hepatic Hemangioma Associated with Coagulopathy and Its Predictive Risk Factors.

Background: Knowledge of the relationships between hepatic hemangiomas and coagulopathy and the risk factors for hemangiomas is lacking. The aim of this study was to investigate the prevalence and characteristics of hepatic hemangiomas associated with coagulopathy, elucidate the causes of coagulopathy, and identify the predictive factors for hemangioma-related complications. Methods: In 281 consecutive patients with hepatic hemangiomas, we performed ultrasonography and conducted serum laboratory tests for liver function and six coagulation factors, i.e., platelets, as well as five coagulation fibrinolytic markers (prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), d-dimer, and fibrin and fibrinogen degradation products (FDP)) as indicators of coagulation disorder. Results: Among 281 patients, 56 (19.9%) had abnormal coagulation factors. Abnormal values of d-dimer were most frequently found among the six coagulation factors. The number of abnormal coagulation factors was significantly correlated with tumor size, M2BPGi, and HDL cholesterol, among which tumor size was the most significant independent predictor of the number of abnormal coagulation factors. Conclusions: The prevalence of hepatic hemangiomas associated with coagulopathy was relatively high and became more frequent with increases in tumor size. Predictive factors of hemangioma-related complications were found to be a tumor size of >5 cm in diameter and coagulopathy, especially the elevation of d-dimer.

Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients

Systemic inflammation and coagulopathy are characteristic hallmarks of COVID19. “COVID coagulopathy” manifests mainly as a prothrombotic state affecting both large and small blood vessels, and presenting as arterial, venous, and microangiopathic thrombotic events with von Willebrand factor (VWF) and soluble thrombomodulin increased in hospitalized patients. The causes of coagulopathy are poorly understood. Aim: To investigate the relationship between von Willebrand factor (VWF) biomarkers, intravascular hemolysis, coagulation, and organ damage in COVID19 patients and to study their association with disease severity and mortality. Methods: 181 hospitalized adult COVID19 patients were randomly selected with a balanced distribution of survivors and non-survivors during the period of March 26th 2020 to May 5th 2020. The medical records and laboratory values were reviewed. Statistical analysis was performed using R studio V.3.6.2. Results: Patients who died (n=90) had significantly lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, elevated lactate dehydrogenase levels, increased schistocyte/RBC fragment counts, and elevated VWF antigen and activity levels compared to patients discharged alive (n=91). In 31 patients, we measured several of these biomarkers on two or more occasions. The trending of ADAMTS13 activity illustrated that it is not steady throughout the hospitalization course. ADAMTS13 activity levels tended to improve and/or reach normal levels in patients that survived, yet ADAMTS13 activity levels worsened in most patients that died. Likewise, the VWF antigen and activity levels tended to decrease in patients that survived whereas tended to increase well above the normal range (2-3 folds) in patients that died. D-Dimer levels trended downwards in survivors, sometimes to levels less than 1 µg/ml, yet tended to increase in patients who died. Given the relationship between ADAMTS13 activity and mortality, we wanted to determine a cut-point of initial ADAMTS13 activity (within 72 hours from admission) to predict mortality. 102 patients in our cohort had an ADAMTS13 activity measurement within this timeframe. We determined that this optimal cut-point of initial ADAMTS13 activity was 43% using Youden’s J statistic. Only 30% of patients who had an ADAMTS13 activity level of less than 43% on admission survived, yet 60% of patients survived who had an ADAMTS13 activity level of greater than 43% on admission. Conclusions: COVID-19 may present with low ADAMTS13 activity in a subset of hospitalized patients. Presence of schistocytes/RBC fragment and elevated D-dimer levels on admission may warrant a work-up for ADAMTS13 activity and VWF antigen and activity levels. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of treatments aimed at prevention and/or amelioration of microangiopathy in COVID-19.

Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection.

BackgroundSARS-CoV-2 infection is associated with thrombotic and microvascular complications. The cause of coagulopathy in the disease is incompletely understood.MethodsA single-center cross-sectional study including 66 adult COVID-19 patients (40 moderate, 26 severe disease), and 9 controls, performed between 04/2020 and 10/2020. Markers of coagulation, endothelial cell function [angiopoietin-1,-2, P-selectin, von Willebrand Factor Antigen (WF:Ag), von Willebrand Factor Ristocetin Cofactor, ADAMTS13, thrombomodulin, soluble Endothelial cell Protein C Receptor (sEPCR), Tissue Factor Pathway Inhibitor], neutrophil activation (elastase, citrullinated histones) and fibrinolysis (tissue-type plasminogen activator, plasminogen activator inhibitor-1) were evaluated using ELISA. Tissue Factor (TF) was estimated by antithrombin-FVIIa complex (AT/FVIIa) and microparticles-TF (MP-TF). We correlated each marker and determined its association with severity. Expression of pulmonary TF, thrombomodulin and EPCR was determined by immunohistochemistry in 9 autopsies.FindingsComorbidities were frequent in both groups, with older age associated with severe disease. All patients were on prophylactic anticoagulants. Three patients (4.5%) developed pulmonary embolism. Mortality was 7.5%. Patients presented with mild alterations in the coagulogram (compensated state). Biomarkers of endothelial cell, neutrophil activation and fibrinolysis were elevated in severe vs moderate disease; AT/FVIIa and MP-TF levels were higher in severe patients. Logistic regression revealed an association of D-dimers, angiopoietin-1, vWF:Ag, thrombomodulin, white blood cells, absolute neutrophil count (ANC) and hemoglobin levels with severity, with ANC and vWF:Ag identified as independent factors. Notably, postmortem specimens demonstrated epithelial expression of TF in the lung of fatal COVID-19 cases with loss of thrombomodulin staining, implying in a shift towards a procoagulant state.InterpretationCoagulation dysregulation has multifactorial etiology in SARS-Cov-2 infection. Upregulation of pulmonary TF with loss of thrombomodulin emerge as a potential link to immunothrombosis, and therapeutic targets in the disease.FundingJohn Hopkins University School of Medicine.

Validation of the relationship between coagulopathy and localization of hydroxyethyl starch on the vascular endothelium in a rat hemodilution model

Various anticoagulant properties have been associated with hydroxyethyl starch (HES). However, the mechanism remains unclear and it has not been fully considered whether these properties are beyond the dilutional effect itself. The aim of this study was to reproduce the coagulopathy induced by HES and to test the hypothesis that the coagulopathy is caused by endothelial or glycocalyx damage due to localization of HES on the endothelium, which is caused by the high shear viscosity of dilutional blood. Using a rat model, we compared blood coagulability measured by Sonoclot, levels of endothelial and glycocalyx damage markers and coagulation factors, and blood shear viscosity when hemodilution was performed with physiological saline (PS), 6% HES 130/0.4 in PS, and 10% HES 200/0.5 in PS. We also evaluated the localization rates of fluorescently labeled HES on endothelium in the isolated aorta. HES decreased the fibrin gel formation rate more than did PS. HES was shown to cover the endothelium, possibly due to its high shear viscosity, and this mechanism potentially acted to protect, rather than damage, the endothelium and glycocalyx. However, this covering effect may be the cause of coagulopathy due to inhibition of von Willebrand factor secretion from the endothelium.

A rare presentation of an elderly patient with acute lymphocytic leukemia and platelet count of zero associated with ST-elevation myocardial infarction, pulmonary thromboembolism in the setting of SARS-CoV 2: a case report

BackgroundNovel coronavirus disease 2019 (COVID-19) is known to lead not only to severe acute respiratory syndrome, but also can result in thromboembolic events in both the venous and the arterial circulation by inducing coagulation disorders. The potential causes of coagulopathy are inflammation, platelet activation, endothelial dysfunction, and stasis. The thrombotic events including pulmonary embolism, deep venous thrombosis as well as intracatheter thrombosis are more likely to develop in patients infected with severe form of SARS-CoV-2 who are admitted to ICU. Furthermore, these events contribute to multi-organ failure.Case presentationHerein, we report a case of an immunocompromised COVID-19 elderly patient with acute lymphocytic leukemia who developed myocardial infarction with ST elevation in the setting of acute pulmonary thromboembolism in the presence of zero platelet count. Despite successful urgent coronary revascularization and platelet transfusion, the patient eventually died after failed resuscitation efforts.ConclusionPatients with COVID-19 infection are at a greater risk of developing cardiovascular complications, but their appropriate management can decrease the risk of fatal events. Coronary thrombosis associated with pulmonary thromboembolism in the setting of thrombocytopenia is a rare and a complex to manage condition. Significance of single antiplatelet agent in STEMI with thrombocytopenia merits further studies. According to expert opinions and literature reviews, we must avoid dual antiplatelet therapy in these patients and keep platelet transfusion as a standard therapy to avoid drastic bleeding complications.

Snake venom proteins and coagulopathy caused by snakebite

Snakebite affects around 3 or 4 million humans annually leading to more than 100,000 deaths. Coagulopathy is one of the significant causes of both morbidity and mortality in these patients. Accordingly, it is of utmost importance to diagnose and treat coagulation disorder due to bites; in addition, it is accompanied by various clinical aspects, such as pre-coagulation, fibrinogen coagulation time, fibrinolytic, platelet activation, anticoagulant, thrombotic, and bleeding. The main cause of coagulopathy caused by snakebite is the presence of compounds found in snake venom. These compounds are mostly proteins with enzymatic activity and high stability; moreover, they rapidly react with factors in the blood circulatory system and disrupt their correct functioning. Regarding the snake venom compounds, especially their proteins, it should be mentioned that different snakes' venoms have different proteins, which can have a role in coagulation or anticoagulation depending on its amount. The coagulant proteins are subclassified as clotting factor activators and thrombin-like enzymes. The anticoagulant proteins can prevent blood clotting leading to coagulopathy and include phospholipases A2, fibrinolytic, protein C activator, and L-amino acid oxidase (enzymatic anticoagulants) or C-type lectin-like proteins, three-finger toxins (TFTs), and proteinase inhibitors (nonenzymatic anticoagulants). All of these factors cause coagulopathy due to snake bites, which is a clinically important phenomenon and should be carefully examined; otherwise, it would be difficult to make the diagnosis and treatment process. If untreated, coagulopathy can develop quickly and lead to the patient's death.

Fibrinogen Concentrate Vs. Cryoprecipitate for Acquired Hypofibrinogenemia in Cardiac Surgery — the FIBRES Study

Introduction: Cardiac surgery involving cardiopulmonary bypass (CPB) is associated with coagulopathy and excessive bleeding. This often requires the transfusion of large volumes of allogeneic blood products and is linked to an increased risk of adverse outcomes. A primary cause of coagulopathy is acquired hypofibrinogenemia; when fibrinogen levels drop below 1.5-2 mg/L, fibrinogen supplementation is required to maintain hemostasis. The FIBrinogen REplenishment in Surgery (FIBRES) study aims to compare the standard intervention, cryoprecipitate, with a new highly purified, double virus-inactivated human fibrinogen concentrate.Methods: The FIBRES study (NCT03037424) is a pragmatic, multicenter, active-control, randomized, single-blinded, non-inferiority phase 3 trial in adult patients undergoing cardiac surgery with CPB. The study will enroll patients with clinically significant bleeding associated with acquired hypofibrinogenemia. Patients for whom fibrinogen supplementation is ordered within 24 hours of surgery will be randomized to receive fibrinogen concentrate (4 g; Fibryga; Octapharma) or cryoprecipitate (10 units; dose equivalent to 4 g fibrinogen concentrate) (Figure 1). All randomized patients will receive fibrinogen supplementation as clinically indicated. Owing to the emergency nature of the clinical setting, patient consent at the point of randomization will be waived, with written informed consent obtained within 24-48 hours thereafter. The primary outcome is total allogeneic blood products (red blood cells, plasma, platelets) administered within the first 24 hours of surgery. Secondary outcomes include blood product use within 7 days, incidence of major bleeding within 24 hours, fibrinogen levels, and adverse events (AEs) and serious AEs within 28 days. Enrolment of 1,200 patients will provide >90% power to demonstrate non-inferiority, assuming a 20% non-inferiority margin, ≥550 patients per group, and an approximate 10% drop-out rate. One pre-planned interim analysis will be conducted after data are available for 600 evaluable patients with the option to stop early for futility or overwhelming efficacy. The pragmatic design and treatment algorithm align with standard practice, aiding adherence and generalizability.Results: To date, 530 patients have been treated across 11 sites. An IDMEAC review of safety has been performed every 100 patients enrolled, with the recommendation to continue as planned each time. The study is expected to complete in late 2018, with results available in early 2019.Conclusions: The FIBRES study is the largest randomized study to date of fibrinogen concentrate versus cryoprecipitate in adult cardiac surgical patients, an under-studied yet high-risk population. Non-inferiority of the new fibrinogen concentrate would support its use for patients developing acquired hypofibrinogenemia during cardiac surgery. Results from the FIBRES study are likely to improve care for cardiac surgical patients experiencing significant bleeding. DisclosuresKarkouti:Octapharma US: Research Funding.

Indications, Efficacy and Complications of Kcentra Use in Reversing Coagulopathy

IntroductionDirect acting oral anticoagulants are rapidly replacing warfarin, the most commonly used anticoagulant for patients with atrial fibrillation, pulmonary embolism (PE) and deep vein thrombosis (DVT). However, there is limited data on the efficacy and adverse effects of the commercial Kcentra used in these patients. Kcentra, the only approved PCC in the USA, is FDA approved for urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA) therapy in adult patients with acute major bleeding or need for an urgent surgery/invasive procedure. In this study we examine the indications for administration of Kcentra, efficacy of the PCC in several coagulopathies, incidence of adverse events including ischemic stroke and DVT/ PE, and overall mortality.MethodsRetrospective analysis of inpatients at UPMC Presbyterian, Shadyside and Mercy, admitted between February 2016 and 2017 was done. A total of 213 patients, with history of stroke / DVT / PE who received Kcentra were grouped based on the cause of coagulopathy, sites of bleed (CNS or non-CNS) or the clinical setting of Kcentra administration. Definitions of the International Society on Thrombosis and Hemostasis (ISTH) / Scientific and Standardization Committee were used to assess the efficacy of management. Among the patients on Warfarin, only non-CNS and prophylactic administration group were included here as those with CNS bleeding were part of an earlier study. Adverse events measured were incidence of ischemic stroke and DVT/ PE during their hospital stay.ResultsThe 213 patients who received Kcentra included those on warfarin (40%), apixaban (21%), Rivaroxaban (23%), with the remaining 16% including patients with hepatic cirrhosis, disseminated intravascular coagulation and those with coagulopathy related to heparin/ fondaparinux or antiplatelets (ASA, clopidogrel). The study group included those with CNS bleeds (33%), non-CNS bleeds (37%) and those in the prophylactic, pre-operative setting (30%). The majority of the non-CNS bleeds were patients with gastrointestinal bleeding (45%), with the rest including the musculoskeletal (31%) and intra-abdominal / intra-thoracic (16%) bleeding. Mortality was highest in patients with cirrhosis (n = 15), DIC (n = 8), and on anti-platelet medications (n = 2) at 100%, followed by 60% in patients on heparin / fondaparinux (n = 5). The mortality was markedly lower (~13%) in patients on Coumadin, Apixaban and Rivaroxaban. 2 of the patients, previously on rivaroxaban, developed multiple CNS infarcts. Thromboembolic events were significantly higher (40%) in patients with cirrhosis, with moderate effect in the Rivaroxaban group (14.5%) when compared to coumadin (2.3%) and apixaban (0%).ConclusionsKcentra was used in several off-label clinical settings, with comparable mortality among the coumadin, rivaroxaban and apixaban groups and no identifiable benefit in the setting of cirrhosis, DIC or antiplatelet medications, but with an increased incidence of deep vein thrombosis and stroke. DisclosuresNo relevant conflicts of interest to declare.

HEPATITIS E AS A POSSIBLE CONTRIBUTOR TO INTRACRANIAL HEMORRHAGE

SESSION TITLE: Critical Care 6 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Hepatitis E has been previously been associated with idiopathic neurological dysfunction, as new information is being reported about the extrahepatic effects. Zhou et al. have found HEV in the CSF of patients with both acute and chronic infections. Shi et al. have also described positive and negative strand HEV RNA in the brain and spinal cord for up to 28 days post-infection. New reports are appearing constantly about the effects of HEV infections. Here we present a case of HEV possibly contributing to intracranial hemorrhage. CASE PRESENTATION: Our patient is 29-year-old female, 25 weeks pregnant by US, who was previously healthy except for a history of two first trimester spontaneous abortions. She was a native of Mexico, living in the United States for six years, with no recent travel or sick contacts. Patient presented with right-sided numbness, headache, and altered mental status. In the ED, CT head noted large intraparenchymal hemorrhage in the left parietal lobe with herniation. She had emergent decompressive craniotomy and was started on levetiracetam for seizure prophylaxis.CTA head, MRV, and cerebral angiogram found no evidence of AV malformation, venous sinus thrombosis, or occlusion. On day five she developed transaminitis, ALT 88 and AST 100, which were previously normal, and Levetiracetam was held out of concerns for drug-induced liver injury. ALT peaked at 503 and AST 289 by day 10. GGT was 13, total bilirubin 1.5, and alkaline phosphatase 116. Labs were negative for Hepatitis A, B, and C. Doppler of the liver showed normal hepatic anatomy, and negative for Budd-Chiari or SVC thrombus. Labs showed normal serum ceruloplasmin, negative Anti-SMA, and negative AMA, iron studies within normal limits. Alpha-1-antitrypsin was mildly elevated. She had no signs of HELLP syndrome. Patient was positive for Hepatitis E IgM, but IgG negative by immunologic studies. Hep E PCR RNA was found to be <1,300 IU/ml. Levetiracetam was resumed on day 15 due to partial seizure. LP was not performed due to concern for hemorrhage. Without specific treatment, her AST/ALT started decreasing by day 20. She continued to have right hemiparesis and hypoesthesia, but was discharged home with physical therapy. DISCUSSION: Our patient had extensive work up for spontaneous hemorrhage, but no specific cause was ever identified. While a limited number of cases report HEV as a cause of coagulopathy, hypercoagulable studies were essentially within normal limits for a pregnant woman; angiography failed to visualize any vascular deformity. CONCLUSIONS: We hypothesize that HEV contributed to her ICH due to HEV’s neurotropic tendencies. Reference #1: Zhou et. al, “Hepatitis E Virus Infects Neurons and Brains”, JID 2017:215, 1197 -1206. Reference #2: Cencic A, Chingwaru W. Hepatitis E Virus (HEV) – An Emerging Viral Pathogen: Springer Netherlands 2010. Reference #3: Shi et. al, “Evidence of Hepatitis E virus breaking the blood brain barrier and replicating in the central nervous system” Journal of Viral Hepatitis, 2016: 23, 930–939. DISCLOSURES: My spouse/partner as a Speaker/Speaker's Bureau relationship with Salix Please note: $1001 - $5000 Added 03/02/2018 by Ebtesam Islam, source=Web Response, value=Consulting fee No relevant relationships by Ximena Solis, source=Web Response

Use of prothrombin complex concentrate for management of coagulopathy after cardiac surgery: a propensity score matched comparison to plasma

BackgroundAn important cause of coagulopathy in cardiac surgery is impaired thrombin generation. While plasma is often used to correct this element of the coagulopathy, studies in vitro suggest that prothrombin complex concentrates (PCCs) might be more effective. Comparative data, however, are scant. MethodsWe compared the outcomes of those who received only plasma with those who received PCCs (with or without plasma) for management of coagulopathy in patients who underwent cardiac surgery with cardiopulmonary bypass at a single institution from 2012 to 2016. Propensity score matching was used to obtain between-group balance. Primary outcome was avoidance of perioperative red cell transfusions. Other outcomes were incidence of massive transfusion (more than nine red cell units), refractory bleeding (requiring factor VIIa), and adverse events. ResultsOf 6362 patients, 1151 (18.2%) received plasma without any PCCs, and 204 (3.2%) received PCCs, either with (n=125) or without plasma (n=79). Overall, patient risk-profile was higher in the PCCs group. In a well-balanced propensity score match that included 117 patients per group, the odds ratio (OR) for red cell avoidance was 2.4-fold [95% confidence interval (CI) 1.2–4.8] higher in the PCCs group. Massive transfusion (OR 0.58; 95% CI 0.33–1.0) and refractory bleeding (OR 0.49; 95% CI 0.24–1.03) incidences were almost significantly lower in the PCCs group. The adverse event profiles were similar. ConclusionsOur exploratory study suggests that the use of PCCs as part of a multifaceted coagulation management strategy may have blood-sparing effects. Their incorporation into clinical practice, however, must await determination of their risk-benefit profile via multicentre randomised trials.

Disseminated Intravascular Coagulopathy and Newly Diagnosed Ulcerative Colitis, a Rare but Serious Complication: A Case Report: 2017 Presidential Poster Award

Ulcerative colitis has various extraintestinal manifestations, including coagulation disorders, however the presence of disseminated intravascular coagulation (DIC) is rare. The current case depicts a patient in whom DIC arose secondary to damage of the endothelium of colonic blood vessels. A 19 year-old female was admitted with abdominal pain, nausea, emesis, and hematochezia. Abdominal CT scan suggested extensive colitis and colonoscopy confirmed Mayo grade 3 ulcerative pancolitis. The patient subsequently developed extensive thromboses, anemia, and purpura fulminans. Her laboratory evaluation was consistent with DIC. Because she failed to respond to corticosteroids and infliximab induction, total proctocolectomy with end-ileostomy was performed, which led to resolution of DIC. DIC involves mechanical and/or endothelial cell injury, and thus, intestinal vasculature may play a key role in thrombosis in IBD. IBD results in destructive inflammation of the GI tract, and chronic inflammation of endothelial cells and microvasculature of the GI tract precipitates physiologic and functional alterations in contrast to uninvolved intestine. The damaged microvasculature subsequently has decreased perfusion and stenosis, which may predispose patients to hypercoagulability [1]. In our patient, the underlying cause of coagulopathy was fulminant UC that was unresponsive to corticosteroid and biologic therapy. Ultimately, surgical intervention with total colectomy resulted in rapid improvement of DIC parameters. In conclusion, we report a rare case of an association of DIC and UC which can be managed with timely diagnosis and appropriate therapeutic management of the underlying condition.

Unusual Presentation of Diffuse Large B-Cell Lymphoma With Splenic Infarcts.

A 67-year-old man presented with a 3-day history of abdominal pain, fever, and significant weight loss over 2 months. Physical examination revealed left upper quadrant tenderness, hepatomegaly, splenomegaly, and bilateral pitting edema but peripheral lymphadenopathy was absent. Laboratory tests showed anemia, thrombocytopenia, elevated prothrombin time (PT), partial thromboplastin time (PTT), and increased lactate dehydrogenase (LDH). PTT was corrected completely in mixing study. Further workup for the cause of coagulopathy revealed decreased levels of all clotting factors except factor VIII and increase fibrinogen levels, which ruled out disseminated intravascular coagulation (DIC). Flow cytometry of peripheral blood was normal. Contrast-enhanced computed tomography (CECT) revealed splenomegaly with multiple splenic infarcts without any mediastinal or intraabdominal lymphadenopathy. Further investigations for infective endocarditis (blood cultures and transthoracic echocardiography) and autoimmune disorders (ANA, dsDNA, RA factors) were negative. The patient received treatment for sepsis empirically without any significant clinical improvement. The diagnosis remained unclear despite extensive workup and liver biopsy was conducted due to high suspicion of granulomatous diseases. However, the liver biopsy revealed high-grade diffuse large B-cell lymphoma (DLBCL). Unfortunately, patient died shortly after the diagnosis. Here we report a case of high-grade DLBCL with hepatosplenomegaly and splenic infarcts in the absence of any lymphadenopathy or focal lesions. This case highlights the fact that unusually lymphoma can present in the absence of lymphadenopathy or mass lesion mimicking autoimmune and granulomatous disorders. The diagnosis in these cases can only be made on histology, and hence the threshold for biopsy should be low in patients with unclear presentations and multiorgan involvement.

Ácido tranexámico en cirugía cardiaca. ¿Qué dosis es segura?

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with increased postoperative bleeding, blood product consumption, and the number of surgical re-explorations. Currently, of the 50% of transfused patients from cardiac surgery, 20% have significant bleeding, and 5% required reoperation for postoperative bleeding. This increased consumption of blood increases morbidity, mortality, hospital stay, and healthcare costs. The causes of coagulopathy after CPB are multifactorial: hemodilution, blood exposure to CPB circuits, destruction of platelets, and thrombin activation. The guidelines of the American and European scientific societies recommend the use of tranexamic acid (TA) to reduce perioperative bleeding in cardiac surgery. TA saves an average of 300ml of blood, with a relative reduction of 32% receiving transfusion. CS interventions with CPB carried out without using any antifibrinolytic drug is characterized by increased blood loss, increased reoperations for bleeding, and increased transfusion and blood products, when compared to other interventions where antifibrinolytic were used. The main problem with the use of TA lies in the many administration patterns and different doses,, which vary from one article to another. The aim of this article is to alert on the use of high doses of TA and its consequences according to the latest recommendations in the literature.

How do we manage cardiopulmonary bypass coagulopathy?

Patients who undergo cardiopulmonary bypass (CPB) are at risk for coagulopathy. Suboptimal turnaround time (TAT) of laboratory coagulation testing results in empiric administration of blood products to treat massive bleeding. We describe our initiative in establishing the coagulation-based hemotherapy (CBH) service, a clinical pathology consultation service that uses rapid TAT coagulation testing and provides comprehensive assessment of bleeding in patients undergoing CPB. A transfusion algorithm that treats the underlying cause of coagulopathy was developed. The coagulation testing menu includes all aspects of coagulopathy with close proximity of the laboratory to the operating room to allow for rapid test results. The hemotherapy pathologist monitors laboratory results at several stages in surgery and uses a comprehensive algorithm to monitor a patient's hemostasis. The optimal number and type of blood products are selected when the patient is taken off CPB. The CBH service was consulted for 44 ventricular assist device implants, 30 heart transplants, and 31 other cardiovascular surgeries from May 2012 through November 2013. The TAT for laboratory tests was 15 minutes for complete blood count, antithrombin, and coagulation panel and 30 minutes for VerifyNow and thromboelastography, in comparison to 45 to 60 minutes in normal settings. The transfusion algorithms were used with optimal administration of blood components with preliminary data suggestive of reduced blood product usage and better patient outcomes. We described the successful introduction of a novel pathology consultation service that uses a rapid TAT coagulation testing menu with transfusion algorithms for improved management of CPB patients.