Abnormal coagulation after hepatectomy in patients with normal preoperative coagulation function.

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.

Bleeding disorders in Saudi Arabia, causes and prevalence: a review.

As bleeding disorders are a worldwide health concern, Saudi Arabia is experiencing a notable prevalence of such disorders. Studying the frequency and cause of hemostatic disorders is the key to successful clinical interventions and instigating effective public policies that limit the spread of such disorders. The current review aims to highlight the major findings of the body of literature that has investigated the causes, prevalence, and major challenges associated with bleeding disorders in the country. The current review summarizes the major findings of different studies that have been conducted in Saudi Arabia regarding different bleeding disorders. Multiple causes and symptoms of bleeding disorders have been reported by different studies. Some studies investigated the genetic aspect of bleeding disorders and revealed specific mutations in coagulation factor genes influencing the symptoms of different bleeding disorders. Moreover, rare bleeding disorders such as Glanzmann thrombasthenia and Henoch-Schönlein purpura, have been reported in different regions of Saudi Arabia. Combining clinical presentations, genetic factors, and epidemiological data, the current review of the literature provides a comprehensive insight into bleeding disorders in the kingdom. This will help in advancing the diagnostic capabilities and genetic counseling enhancing management strategies and therapeutic interventions benefiting bleeding disorder patients and the kingdom.

Rare bleeding disorders: Real-world data from a Spanish tertiary hospital.

INTRODUCTION: Due to their low prevalence, rare bleeding disorders (RBDs) remain poorly characterized. AIM: To gain insight of RBDs through our clinical practice. METHODS: Retrospective study of the medical records of RBD patients followed up at the Central University Hospital of Asturias between January 2019 and December 2022. RESULTS: A total of 149 patients were included. Factor (F) VII (44 %) and FXI (40 %) deficiencies were the most common diagnosed coagulopathies. Most of the patients were asymptomatic (60.4 %) and the most frequent type of bleeding were mucocutaneous and after surgery. All replacement treatments were administered on demand and no patient was on a prophylaxis regimen. Currently available products were safe; allergic reactions after administration of plasma were the most frequent complication. Genetic analysis, carried out on 55 patients (37 %), showed that the most frequent mutations in RBDs are of missense type (71.9 %). We identified 11 different novel genetic alterations in affected genes. The c.802C > T (p.Arg268Cys) variant, previously described, was identified in 71 % (15 of 21) of the patients with FXI deficiency genotyped and none were related (probable founder effect). CONCLUSION: Our study on an unusual large single center cohort of RBD patients portrays location-dependent distinct genetic drives and clinical practice particularities.

Derivation of Coagulation Phenotypes and the Association with Prognosis in Traumatic Brain Injury: A Cluster Analysis of Nationwide Multicenter Study.

BACKGROUND: The pathogenesis and pathophysiology of traumatic coagulopathy during traumatic brain injury is not well understood, and the appropriate treatment strategy for this condition has not been established. This study aimed to evaluate the coagulation phenotypes and their effect on prognosis in patients with isolated traumatic brain injury. METHODS: In this multicenter cohort study, we retrospectively analyzed data from the Japan Neurotrauma Data Bank. Adults with isolated traumatic brain injury (head abbreviated injury scale > 2; abbreviated injury scale of any other trauma < 3) who were registered in the Japan Neurotrauma Data Bank were included in this study. The primary outcome was the association of coagulation phenotypes with in-hospital mortality. Coagulation phenotypes were derived using k-means clustering with coagulation markers, including prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), fibrinogen (FBG), and D-dimer (DD) on arrival at the hospital. Multivariable logistic regression analyses were conducted to calculate the adjusted odds ratios of coagulation phenotypes with their 95% confidence intervals (CIs) for in-hospital mortality. RESULTS: In total, 556 patients were enrolled and five coagulation phenotypes were identified. The median (interquartile range) score for the Glasgow Coma Scale was 6 (4-9). Cluster A (n = 129) had the closest to normal coagulation values; cluster B (n = 323) had a mild high DD phenotype; cluster C (n = 30) had a prolonged PT-INR phenotype with a higher frequency of antithrombotic medication in elderly patients than in younger patients; cluster D (n = 45) had a low amount of FBG, high DD, and prolonged APTT phenotype with a high incidence of skull fracture; and cluster E (n = 29) had a low amount of FBG and extremely high DD phenotype with high energy trauma and a high incidence of skull fracture. In the multivariable logistic regression analysis, the association of clusters B, C, D, and E with in-hospital mortality yielded the corresponding adjusted odds ratios of 2.17 (95% CI 1.22-3.86), 2.61 (95% CI 1.01-6.72), 10.0 (95% CI 4.00-25.2), and 24.1 (95% CI 7.12-81.3), respectively, relative to cluster A. CONCLUSIONS: This multicenter, observational study identified five different coagulation phenotypes of traumatic brain injury and showed associations of these phenotypes with in-hospital mortality.

A newly proposed heatstroke-induced coagulopathy score in patients with heat illness: A multicenter retrospective study in China.

PURPOSE: In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC. METHODS: This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0. RESULTS: The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis -DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decreased, D-dimer level rose, and prothrombin time and activated partial thromboplastin time prolonged (p < 0.05). CONCLUSIONS: The newly proposed HIC score may provide a valuable tool for early detection of HIC and prompt initiation of treatment.

Coagulation Disorders and Thrombotic Complications in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with multiple cardiovascular and noncardiovascular comorbidities and risk factors which increase the risk of thrombotic complications, such as atrial fibrillation, chronic kidney disease, arterial hypertension and type 2 diabetes mellitus. Subsequently, thromboembolic risk stratification in this population poses a great challenge. Since date from the large randomized clinical trials mostly include both patients with truly preserved EF, and those with heart failure with mildly reduced ejection fraction, there is an unmet need to characterize the patients with truly preserved EF. Considering the significant evidence gap in this area, we sought to describe the coagulation disorders and thrombotic complications in patients with HFpEF and discuss the specific thromboembolic risk factors in patients with HFpEF, with the goal to tailor risk stratification to an individual patient.

Blood coagulation, risk factors and associated complications in COVID-19 patients in Saudi Arabia: A retrospective cohort study.

A good understanding of the possible risk factors for coronavirus disease 19 (COVID-19) severity could help clinicians in identifying patients who need prioritized treatment to prevent disease progression and adverse outcomes. COVID-19-linked coagulopathy is one of the life-threatening severe acute respiratory syndrome coronavirus 2 infections. Growing evidence indicates a correlation between abnormal coagulation and increased risk of venous thromboembolism; in COVID-19-infected patients, yet a clear understanding of the role of coagulopathy in the severity of COVID-19 illness is still unresolved. This retrospective cohort study was thus undertaken to investigate the role of coagulation dysfunction with COVID-19 mortality/severity. Blood samples from 1000 hospitalized patients with COVID-19 pneumonia were collected. The study participants were both male and female in equal ratios with a mean age of 48.94. Patients were followed-up until discharge either for recovery or death. All biochemical investigations-complete blood count and coagulation profile including D-dimers, prothrombin time, partial prothrombin time, and international normalized ratio was performed in COVID-19 survivors and in non-survivors admitted in intensive care unit. In the survivor group, all coagulation parameters were within normal limits, and 8.7% had a low red blood count. The most common risk factors associated with COVID-19 patients were diabetes mellitus (2.8%), hypertension (10.8%), and heart disease (3%). In the non-survivor group, the coagulation parameters were above the normal range (prothrombin in 31.5%, PTT in 10.5%, international normalized ratio in 26.3%, D-dimer in 36.8%) with thrombocytopenia in 21.04% of patients. Other complications were pulmonary embolism in 21.05% and venous thromboembolism in 15.7% of non-survivors. A significant association was found between increased markers of coagulopathy and the severity of SARS-CoV2 infection. Furthermore, the severity of infection was observed to increase with risk factors such as age, heart disease, hypertension, and DM eventually affecting COVID-19 prognosis and mortality.

The prevalence and risk factors of coagulopathy in pediatric patients undergoing surgery for epilepsy.

OBJECTIVE: Hematological consequences of novel antiseizure medications (ASMs) or combined therapies are rarely reported, especially in pediatric patients undergoing surgery for epilepsy. This study aimed to assess the prevalence and risk factors of coagulation dysfunction in this population and evaluate their relationship with intra- and postoperative bleeding. METHODS: Three hundred ninety children who underwent surgery for epilepsy and 104 children without epilepsy who underwent nonepilepsy surgery at the authors' center were included in the study. The authors retrospectively collected and analyzed the following clinical data: sex, age, weight, course of epilepsy, antiseizure therapy, first laboratory data after admission, and transfusion-related data. RESULTS: ASMs were responsible for the higher incidence of coagulation dysfunction in pediatric epilepsy surgery patients. Low body weight (OR 0.95, 95% CI 0.92-0.98) and valproic acid (VPA) therapy (OR 5.13, 95% CI 3.25-8.22) were the most relevant factors leading to coagulation dysfunction. The most common hematological side effects of VPA were thrombocytopenia and hypofibrinogenemia, whereas low body weight was only associated with hypofibrinogenemia. Both VPA and low body weight increased the need for intra- or postoperative transfusion (p < 0.001). CONCLUSIONS: Pediatric epilepsy surgery patients often take multiple ASMs, resulting in an increased incidence of coagulopathy. VPA levels and low body weight were found to be the main influential factors associated with an increased risk of coagulation dysfunction. Platelet and fibrinogen levels were the main indices that were affected. Both VPA and low body weight were relevant to additional surgery-related transfusion, necessitating the need for increased awareness of preoperative coagulopathy before pediatric epilepsy surgery. Clinical trial registration no.: NCT05675254 (ClinicalTrials.gov).

Independent risk factors for COVID-19-associated coagulopathy.

OBJECTIVE: Past three years since the beginning of the outbreak, we have obtained satisfactory data on COVID-19. However, data on risk factors of COVID-19-associated coagulopathy (CAC) are extremely limited. Prediction of CAC might be a game changer since it is related to poor prognosis. Seeking independent risk factors for CAC was the main aim of the study. PATIENTS AND METHODS: 510 hospitalized COVID-19 patients were retrospectively screened. Forty-eight of them were excluded due to irrelevant D-dimer or ferritin elevation. The remaining patients were stratified into three groups as overt coagulopathy, significant pulmonary microthrombosis, and patients without coagulopathy. The overt coagulopathy group included cases with macrothrombosis or disseminated intravascular coagulation (DIC). The significant pulmonary microthrombosis group covered the cases that had clinical deterioration with simultaneous marked D-dimer elevation. The group of patients without coagulopathy included the asymptomatic patients with normal or elevated D-dimer levels. RESULTS: Overt coagulopathy developed in 3.2% and significant pulmonary microthrombosis in 10.1% of the patients. In the multivariate analysis, not receiving low molecular weight heparin (LMWH) (p=0.002), a level of D-dimer >15,000 U/ml (p=0.013) were associated with overt coagulopathy. In addition, levels of initial LDH >480 IU/L (p=0.022) and initial ferritin >1,000 ng/ml (p=0.036) were associated with significant pulmonary microthrombosis. Not receiving LMWH (p=0.001) was also associated with significant pulmonary microthrombosis, when multivariate analysis was performed by the parameters with a p-value <0.1 in the univariate analysis. Furthermore, all cases with DIC had Gram-negative bacterial sepsis. CONCLUSIONS: Not receiving LMWH, high levels of D-dimer, initial LDH, and initial ferritin are independent risk factors for CAC. DIC does not appear to develop based on COVID-19.

Blood Coagulation Disorders Among the Iranian Population: a Systematic Review.

BACKGROUND: Blood coagulation disorders are one of the causes of mortality. Therefore, the study of coagulation disorders is also important. This systematic review was conducted to investigate blood coagulation disorders in the Iranian population. METHODS: Searches in electronic databases such as Web of Science, PubMed, Scopus, SID, ProQuest, and Magiran from May 10, 1990 to May 10, 2019 were performed according to PRISMA guidelines. Cross-sectional, cohort, experimental, and case-control studies were included according to the inclusion criteria without gender and language restrictions. RESULTS: After screening and selection, 14 studies were selected for data extraction. Accordingly, the most common blood coagulation disorder in the south of Iran was a defect in FXIII (599 of 1,165). C.559T>C (27 of 189) and c.562T>C (20 of 189) mutations had the highest frequency. The most common FXIII polymorphism among the Iranian Azerbaijanis was Val34Leu (203 of 410). The second most common coagulation disorder was FV Leiden (396 of 1,165). Then, c.1691G>A (151 of 396) was the most common mutation. CONCLUSIONS: This study shows that the most critical coagulation disorder among the Iranian population is FXIII deficiency and the most common mutation is c.562T>C.

High prevalence of heavy menstrual bleeding in women with rare bleeding disorders in the Netherlands: retrospective data from the RBiN study.

BACKGROUND: Heavy menstrual bleeding (HMB) is associated with a reduced quality of life and limitations in social and physical functioning. Data on HMB in women with rare bleeding disorders (RBDs), including coagulation factor deficiencies and fibrinolytic disorders, are scarce. OBJECTIVES: To analyze the prevalence, severity, and treatment of HMB in Dutch women with an RBD. METHODS: The Rare Bleeding Disorders in the Netherlands (RBiN) study included 263 patients with an RBD from all 6 hemophilia treatment centers (October 2017-November 2019). In this analysis, data of 111 women aged ≥16 years were studied. According to the International Society on Thrombosis and Haemostasis bleeding assessment tool, HMB symptoms were scored from 0 (no/trivial) to 4 (severe symptoms requiring medical intervention). HMB was defined as a score ≥1. Age at RBD diagnosis was extracted from patient files. RESULTS: HMB was reported by 80% of women (89/111) and was more prevalent in women with a fibrinolytic disorder (33/35; 94%) than in women with a coagulation factor deficiency (56/76; 74%) (P = .011). Of the 89 women with HMB, 82% (n = 73) ever required treatment. Multiple treatment modalities were frequently used, both in severe and mild deficiencies. Hormonal treatment was mostly used (n = 64; 88%), while antifibrinolytics were prescribed less frequently (n = 18; 25%). In women with HMB since menarche (n = 61; 69%), median age at RBD diagnosis was 28 years (IQR, 14-41). CONCLUSION: HMB is common in women with RBDs. Women with mild deficiencies also frequently reported HMB. Only a minority of women were treated with hemostatic agents. A significant diagnostic delay was observed after the onset of HMB symptoms.

An outbreak of severe coagulopathy in northern Israel among users of illicit synthetic cannabinoids adulterated with brodifacoum.

INTRODUCTION: Adulteration of illicit drugs is a well-known phenomenon that may expose consumers to unexpected adverse effects. We report a large outbreak of severe coagulopathy in northern Israel during nine months in 2021-2022 among users of synthetic cannabinoids adulterated with a long-acting anticoagulant, brodifacoum. METHODS: We performed a retrospective cohort study based on data extracted from the Israeli National Poison Information Center database and from electronic medical patient records at three participating hospitals. Confiscated drug samples and blood samples obtained at admission in a subgroup of patients were tested for the presence of long-acting anticoagulants. RESULTS: We identified 98 patients affected by the outbreak. All patients had a prolonged international normalized ratio on admission, and in 69%, the blood was non-coagulating. For patients treated in the three participating centers (n = 72), the presenting complaint was overt bleeding in 79% of patients, most commonly in the urinary (53%) and gastrointestinal tracts (50%). The most severe complications were intracranial bleeding (4%), hemothorax (3%), pericardial bleeding (1%), and four patients died. Brodifacoum was detected in all available blood samples (median concentration 207 µg/L, interquartile range 112-349 µg/L, range 45-1,118 µg/L), and the drug samples contained both brodifacoum and the synthetic cannabinoid ADB-BUTINACA. All patients were treated with high-dose phytomenadione (vitamin K1) and additionally by packed red blood cell transfusions, fresh frozen plasma, and/or 4-factor prothrombin complex concentrate when indicated. The most frequent phytomenadione (vitamin K1) dose regimen was initially 20 mg intravenously every eight hours, and at discharge, 20 mg orally three times daily. CONCLUSIONS: Outbreaks of severe coagulopathies in users of synthetic cannabinoids adulterated with a long-acting anticoagulant continue to erupt in different regions of the world. Rapid recognition of an outbreak requires a high index of suspicion when confronting young, otherwise healthy subjects with otherwise unexplained severe coagulopathy.

Thromboembolic Disorder in COVID-19 Infection.

Coronavirus (COVID-19) is a global pandemic with over 600 million cases identified. In addition to extensive pulmonary complications of COVID-19, one feature unique to many patients with severe COVID-19 infections is coagulopathy with a rising prevalence of multi-systemic thromboembolic manifestations. Global data suggests a relationship between coagulopathy and mortality. In this review, we highlight multiple COVID-19 thromboembolic complications with emphasis on pathophysiology, clinical management, and radiological manifestations.

Postoperative coagulopathy among otherwise healthy pediatric patients undergoing open craniosynostosis repair: a retrospective study.

Significant blood loss and resultant transfusion may lead to coagulopathy. The need for routine transfusion of non-RBC blood products in healthy pediatric patients suffering significant, yet controlled, intra-operative blood loss is controversial. Open craniosynostosis surgery is often associated with significant intra-operative blood loss and transfusion, and routinely preformed on otherwise healthy pediatric patients. Therefore, we found it as a useful model for our study, which aimed to assess the need for routine transfusion of non-RBC blood products in healthy pediatric patients suffering significant intra-operative blood loss. We conducted a retrospective cohort study of otherwise healthy pediatric patients, undergoing open craniosynostosis surgery and transfused solely with packed red blood cells (pRBCs) in a single large-volume tertiary surgical center, between January 2010 and December 2021. Among 457 eligible patients, 34 (7.4%) developed significant postoperative coagulopathy. Median [IQR] intra-operative pRBC transfusion volume was 17.4 ml kg-1 [13.3, 23.1]. Patients who developed coagulopathy did not have higher postoperative pRBC transfusion rate (8.8% vs 3.8%, P = 0.16) or volume (median [IQR], 0 [0, 0] vs 0 [0, 0] ml, P = 0.15), nor higher hospital LOS (5 [4, 5] vs 5 [4, 5] days, P = 0.66). ICU LOS was 0.8 [0.7, 1] vs 0.7 [0.6, 0.8] days (P = 0.02), a difference of no clinical significance.  Conclusions: The incidence of significant coagulopathy after craniosynostosis surgery was low, and not associated with clinically important complications. In otherwise healthy pediatric patients, even significant intra-operative blood loss can be safely managed solely with intravenous fluids and pRBC transfusion. What is Known: • Significant intra-operative blood loss and resultant transfusion may lead to postoperative coagulopathy. • There are potential deleterious effects from both coagulopathy and administration of blood products. What is New: • Open craniosynostosis corrective surgery is a useful model for studying coagulopathy after significant intra-operative blood loss and transfusion in otherwise healthy children. • Under certain conditions, in otherwise healthy pediatric patients, even significant intra-operative blood loss can be safely treated with intravenous fluids and pRBC transfusion alone, with no clinically significant postoperative coagulopathy or its complications.

Comprehensive analysis of coagulation factor delivery strategies in a cohort of trauma patients.

PURPOSE: The 5th edition of The European recommendations for the management of major bleeding and coagulopathy following trauma leaves room for various coagulation factor administration strategies. The present study examines these strategies reporting prevalence and timing of administration, quantity dispensed, and transfusion ratios in French trauma centers and their compliance with recommendations alongside associated mortality data. METHODS: All adult patients, admitted directly to participating centers between 2011 and 2019, were extracted from a trauma registry. Two subpopulations were studied: severe hemorrhage (SH) and massive transfusion (MT) groups. RESULTS: A total of 19,396 patients were included, among whom 8.4% (1630) experienced SH and 3% (579) received MT. Within the first 24 hours, 10% received fresh frozen plasma (FFP), rising to 93% and 99% in the subgroups of patients experiencing SH and MT respectively. Only, 8% received fibrinogen concentrate (FC), increasing to 75% and 92% in subgroups SH and MT respectively. Co-administration of FFP and FC became the dominant strategy with 68% of patients at 6 h and 72% at 24 h in SH subgroup. In unadjusted data, mortality was systematically lower in groups that complied with recommendations, a lower mortality than expected was mostly observed in contrast to non-compliant subgroups. The per-patient compliance to studied recommendations was 21% and 22% in SH and MT subgroups. CONCLUSION: The main hemostatic strategy for major bleeding combined the administration of both FFP and FC, favoring an early additional supply of fibrinogen. Compliance with the recommendations was low in SH and MT subgroups.

Coagulation dysfunction of severe burn patients: A potential cause of death.

BACKGROUND: Research on coagulation dysfunction following burns is controversial. This study aimed to describe the coagulation changes in severe burn patients by examining coagulation parameters. METHODS: Patients with third-degree total body surface area (TBSA) burns of ≥30% were enrolled between 2017 and 2020. Platelet (PLT) count and coagulation indexes (including APTT, INR, FIB, DD, and AT Ⅲ) were measured at admission and once weekly for 8 weeks, and statistical analysis was performed. The patient medical profiles were reviewed to extract demographic and clinical data, including TBSA, third-degree TBSA, and inhalation injury. The total intravenous fluids and transfusions of crystalloids, fresh frozen plasma (FFP), and red blood cells (RBC) were calculated during the forty-eight-hour period. The number of sepsis cases was recorded. RESULTS: We enrolled 104 patients , and while the overall coagulation trend fluctuated, inflection points appeared around one week and demonstrated hypercoagulability. INR was significantly higher in the non-survival group than in the survivors' group from admission to three weeks after burn (all p<0.01). From post-injury week 1 to post-injury week 3, the APTT in the non-survival group was greater than in the survival group, but the non-survival group's PLT count was lower than that in the survival group (all p<0.05). At two and three weeks after burns, the FIB levels in the non-survival group were significantly lower than those of the survival group (both p<0.01). The prevalence of inhalation injury and the proportion of sepsis cases were significantly higher in the non-survival group than in the survival group ( p ＜ 0.05, p ＜ 0.001, respectively). At the time of death, APTT, INR, and FDP levels were significantly higher in the non-survival group in the survivor group, and FIB, ATIII, and PLT were significantly lower than in the survivor group (all p<0.01). On the day of death, nine of the 12 dead patients had disseminated intravascular coagulation (DIC). CONCLUSIONS: Coagulation dysfunction was most prominent in severe burn patients 1 week after injury and presented as hypercoagulability. Large-area burn injury, large amounts of fluid resuscitation, inhalation injury, and sepsis may all contribute to coagulation dysfunction, which can further develop into DIC and even death in severe burns patients.

Prothrombinex®-VF in chronic liver disease: Friend or foe?

OBJECTIVE: Management of coagulopathy in chronic liver disease (CLD) poses a challenge for critical care physicians. Prothrombinex®-VF is a low-volume product with rapid onset of action. Evidence for its efficacy and safety in CLD is limited and cases of acute intravascular coagulation and fibrinolysis (AICF) and/or disseminated intravascular coagulation (DIC) have been reported. Our objective was to evaluate the role of Prothrombinex®-VF in reversal of coagulopathy and the incidence AICF/DIC, thromboembolic events and mortality. METHODS: This was a retrospective, multi-centre study of Prothrombinex®-VF use in CLD across 11 hospitals over a 2-year period, excluding those on therapeutic anticoagulation. Patients were subclassified into acute on chronic liver failure (ACLF), acute decompensation (ADC) and compensated cirrhosis. Reversal of coagulopathy was defined as international normalised ratio (INR) <1.5× upper limit normal (ULN), prothrombin time <1.5× ULN, activated partial thromboplastin time <1.5× ULN and fibrinogen >1 g/L. Markers of AICF/DIC were recorded. RESULTS: Thirty CLD patients were included, and the median model for end-stage liver disease score was 23.5. Acute bleeding was the most common indication for Prothrombinex®-VF (60%). All had baseline coagulopathy and the majority did not achieve reversal. Key indicators of AICF/DIC were mainly observed in those with ACLF; bleeding from mucosa or lines (53%), worsening hypofibrinogenaemia (60%), worsening thrombocytopaenia (60%). The ADC and compensated cirrhosis groups were relatively unaffected. Incidence of venous thromboembolism was 6%. Overall mortality was 43% and 70% in ACLF. CONCLUSION: Prothrombinex®-VF did not lead to meaningful reversal of coagulopathy and should be used with caution in CLD. Patients with ACLF were more likely to develop AICF/DIC following Prothrombinex®-VF, although the association is uncertain. Further studies are needed to evaluate the safety and efficacy of Prothrombinex®-VF use in CLD.

BLOOD TYPE O IS A RISK FACTOR FOR HYPERFIBRINOLYSIS AND MASSIVE TRANSFUSION AFTER SEVERE INJURY.

ABSTRACT: Background: Blood type O is the most common blood type and has lower von Willebrand factor (vWF) levels (25%-35% lower than non-O blood types). von Willebrand factor is important for initiating platelet attachment and binding factor VIII. We hypothesized that patients with type O blood are at an increased risk of trauma-induced coagulopathy and bleeding post injury. Study Design: Adult trauma activations with known blood type at a level I trauma center with field systolic blood pressure < 90 mm Hg were studied retrospectively. The relationships of blood group O versus non-O to coagulation assays, massive transfusion (MT), ventilator-free days, and mortality were adjusted for confounders. Hyperfibrinolysis (HF) was defined as thromboelastogram of percent lysis in 30 min > 3%, and fibrinolysis shutdown was defined as percent lysis in 30 min < 0.9%. von Willebrand factor activity was quantified on 212 injured patients using a STAGO apparatus. Results: Overall, 268 patients met criteria. Type O patients were more likely to develop HF than non-type O blood patients (43% vs. 29%, P = 0.06) and had significantly lower vWF activity (222% vs. 249%, P = 0.01). After adjustment for New Injury Severity Score and blunt mechanism, type O had higher odds of HF (odds ratio, 1.94, 95% confidence interval, 1.09-3.47) and increased odds of MT (odds ratio, 3.02; 95% confidence interval, 1.22-7.49). Other outcomes were not significantly affected. Conclusion: Type O patients with hypotension had increased HF and MT post injury, and these were associated with lower vWF activity. These findings have implications for the monitoring of HF in patients receiving type O whole-blood transfusions post injury.

Analysis of Risk Factors of Coagulation Dysfunction and Hemorrhage in Newly Diagnosed Hyperleukocytic Acute Myeloma Leukemia.

Purpose: To explore whether and why abnormal coagulation function and hemorrhage can appear in patients with hyperleukocytic acute myeloid leukemia (HAML). Method: We retrospectively reviewed the charts of 724 acute myeloid leukemia (AML) patients admitted with a white blood cell count of >100 × 109/L between 2010 and 2019 in order to analyze the coagulation index of patients with HAML and explore the correlation of abnormal coagulation. Result: Prothrombin time (PT) was extended in group HAML compared with group non-HAML. Respiratory failure, intracranial hemorrhage, and infection were more common in the HAML group. Among the 76 HAML patients, there were 33 patients who had ≥3 abnormal items of coagulation index, and 51.5% of them had level 2 hemorrhage which was more than level 0 hemorrhage, and the difference is statistically significant (P < 0.01). Similarly, we can discover that 40.9% of patients with 2 abnormal items had level 2 hemorrhage in contrast to 0 abnormal items. The use of hydroxyurea had a significant effect on PT and D-dimer (DD). Survival analysis by the Kaplan-Meier method showed that there were statistically significant differences in white blood cell (WBC) count＞200 × 109//L and DD. Abnormal PT is associated with WBC count＞200 × 109//L, and abnormal activated partial thromboplastin time (APTT) is associated with HLA-DR mutation. Infection and respiratory failure were independent influencing factors for the coagulation of patients. Conclusion: DD had a marked effect on the survival rate. Infection and respiratory failure were independent influencing factors for the coagulation of patients.

Thrombosis and coagulopathy in COVID-19 patients rceiving ECMO: A narrative review of current literature.

Extracorporeal membrane oxygenation (ECMO) is an established part of the treatment algorithm for coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome. An intense inflammatory response may cause an imbalance in the coagulation cascade making both thrombosis and bleeding common and notable features of the clinical management of these patients. Large observational and retrospective studies provide a better understanding of the pathophysiology and management of bleeding and thrombosis in COVID-19 patients requiring ECMO. Clinically significant bleeding, including intracerebral hemorrhage, is an independent predictor of mortality, and thrombosis (particularly pulmonary embolism) is associated with mortality, especially if occurring with right ventricular dysfunction. The incidence of heparin-induced thrombocytopenia is higher than the general patient cohort with acute respiratory distress syndrome or other indications for ECMO. The use of laboratory parameters to predict bleeding or thrombosis has a limited role. In this review, the authors discuss the complex pathophysiology of bleeding and thrombosis observed in patients with COVID-19 during ECMO support, and their effects on outcomes.