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.

Early hypocoagulable state in traumatic brain injury patients: incidence, predisposing factors, and outcomes in a retrospective cohort study.

Coagulopathy development in traumatic brain injury (TBI) is among the significant complications that can negatively affect the clinical course and outcome of TBI patients. Timely identification of this complication is of utmost importance in the acute clinical setting. We reviewed TBI patients admitted to our trauma center from 2015 to 2021. Demographic data, mechanism of injury, findings on admission, imaging studies, procedures during hospitalization, and functional outcomes were gathered. INR with a cutoff of 1.3, platelet count less than 100 × 109/L, or partial thromboplastin time greater than 40s were utilized as the markers of coagulopathy. A total of 4002 patients were included. Coagulopathy occurred in 38.1% of the patients. Age of the patients (Odds Ratio (OR) = 0.993, 95% Confidence Interval (CI) = 0.986-0.999, p = 0.028), systolic blood pressure (OR = 0.993, 95% CI = 0.989-0.998, p = 0.005), fibrinogen level (OR = 0.998, 95% CI = 0.996-0.999, p < 0.001), and hemoglobin level (OR = 0.886, 95% CI = 0.839-0.936, p < 0.001) were independently associated with coagulopathy. Furthermore, coagulopathy was independently associated with higher mortality rates and longer ICU stays. Coagulopathy had the most substantial effect on mortality of TBI patients (OR = 2.6, 95% CI = 2.1-3.3, p < 0.001), compared to other admission clinical characteristics independently associated with mortality such as fixed pupillary light reflex (OR = 1.8, 95% CI = 1.5-2.4, p < 0.001), GCS (OR = 0.91, 95% CI = 0.88-0.94, p < 0.001), and hemoglobin level (OR = 0.93, 95% CI = 0.88-0.98, p = 0.004). Early coagulopathy in TBI patients can lead to higher mortality rates. Future studies are needed to prove that early detection and correction of coagulopathy and modifiable risk factors may help improve outcomes of TBI patients.

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.

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.

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.

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.

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.

Albumin in Advanced Liver Diseases: The Good and Bad of a Drug!

Human serum albumin is the most abundant plasma protein, and it regulates diverse body functions. In patients with advanced and decompensated cirrhosis, serum albumin levels are low because of a reduction in the hepatocyte mass due to disease per se and multiple therapeutic interventions. Because of their oncotic and nononcotic properties, administration of human albumin solutions (HAS) have been found to be beneficial in patients undergoing large-volume paracentesis or who have hepatorenal syndrome or spontaneous bacterial peritonitis. Albumin also improves the functionality of the immune cells and mitigates the severity and risk of infections in advanced cirrhosis. Its long-term administration can modify the course of decompensated cirrhosis patients by reducing the onset of new complications, improving the quality of life, and probably providing survival benefits. There is, however, a need to rationalize the dose, duration, and frequency of albumin therapy in different liver diseases and stages of cirrhosis. In patients with acute-on-chronic liver failure, potentially toxic oxidized isoforms of albumin increase substantially, especially human nonmercaptalbumin and 2, and nitrosoalbumin. The role of administration of HAS in such patients is unclear. Determining whether removal of the pathological and dysfunctional albumin forms in these patients by "albumin dialysis" is helpful, requires additional studies. Use of albumin is not without adverse events. These mainly include allergic and transfusion reactions, volume overload, antibody formation and coagulation derangements. Considering their cost, limited availability, need for a health care setting for their administration, and potential adverse effects, judicious use of HAS in liver diseases is advocated. There is a need for new albumin molecules and economic alternatives in hepatologic practice.

Coagulopathy, Bleeding Events, and Outcome According to Rotational Thromboelastometry in Patients With Acute Liver Injury/Failure.

BACKGROUND AND AIMS: Patients with acute liver injury or failure (ALI/ALF) experience bleeding complications uncommonly despite an abnormal hemostatic profile. Rotational thromboelastometry (ROTEM), which assesses clot formation in whole blood, was used to determine the nature of abnormal hemostasis and whether it contributes to bleeding events, illness severity, or survival. APPROACH AND RESULTS: A total of 200 patients were recruited from sites of the ALF Study Group. Blood collected daily for up to 5 days was analyzed using ROTEM delta devices. Consistent with standard laboratory evidence of hypocoagulability (median international normalized ratio = 2.9 and platelet count = 144 × 109 /L), patients frequently exhibited ROTEM parameters outside the normal range (73% and 62% had abnormalities in clot formation from extrinsic and intrinsic clotting cascades, respectively); however, measures of clot stability were generally normal. Eighteen patients (9%) experienced bleeding events, in whom clot initiation, assembly, and firmness were more severely deranged than patients without bleeding. Abnormal ROTEM parameters were more frequently observed in patients with non-acetaminophen ALI/ALF than those with acetaminophen ALI/ALF (clot initiation [P < 0.001], assembly [P = 0.02], firmness at 10 minutes [P = 0.05], and maximal firmness [P = 0.06]). Patients with more severe systemic complications (high-grade hepatic encephalopathy and need for renal replacement therapy) also had a higher incidence of abnormal ROTEM parameters. Finally, more hypocoagulable ROTEM parameters (clot initiation (P = 0.005), stiffness at 10 minutes (P = 0.05), and maximal stiffness by fibrin assembly (P = 0.004)) were observed in patients who died or underwent liver transplantation than those who survived with their native liver. CONCLUSIONS: In patients with ALI/ALF, abnormal ROTEM parameters are frequent and proportional to disease severity. Whether the increased bleeding risk associated with abnormal ROTEM indicates hemostatic failure or is a proxy for disease severity requires additional study.

Safety of Laparoscopic Appendectomy in the Setting of Coagulopathy: An ACS-NSQIP Study.

INTRODUCTION: Patients with coagulopathy requiring emergent appendectomy constitute a challenging patient population. It is unclear whether laparoscopic appendectomy (LA) is as safe as open appendectomy (OA) in these patients. METHODS: We queried the ACS-NSQIP database for adults with coagulopathy undergoing emergent appendectomy from 2014 to 2017. Demographic characteristics and operative outcomes were compared between the two groups. Propensity weighting for LA versus OA was estimated using augmented inverse probability of treatment weights (AIPW). RESULTS: A total of 137,429 patients were included, of which 7049 (5%) had coagulopathy. In patients with coagulopathy, LA was the most common approach (89%). After AIPW, there was no difference in the adjusted risk of either postoperative transfusion or 30-day reoperation between OA and LA. LA was associated with reduced operative time (56 versus 75 min), length of stay (3.5 versus 7.0 d), and surgical site infection rate (6% versus 13%) compared to OA. CONCLUSIONS: Patients with coagulopathy represent a significant proportion of those undergoing an appendectomy. The majority of patients with coagulopathy who require appendectomy undergo LA, and this approach appears to be safe with regard to transfusion requirement and reoperation.

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.

Mechanisms of immunothrombosis in COVID-19.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2. Over the past year, COVID-19 has posed a significant threat to global health. Although the infection is associated with mild symptoms in many patients, a significant proportion of patients develop a prothrombotic state due to a combination of alterations in coagulation and immune cell function. The purpose of this review is to discuss the pathophysiological characteristics of COVID-19 that contribute to the immunothrombosis. RECENT FINDINGS: Endotheliopathy during COVID-19 results in increased multimeric von Willebrand factor release and the potential for increased platelet adhesion to the endothelium. In addition, decreased anticoagulant proteins on the surface of endothelial cells further alters the hemostatic balance. Soluble coagulation markers are also markedly dysregulated, including plasminogen activator inhibitor-1 and tissue factor, leading to COVID-19 induced coagulopathy. Platelet hyperreactivity results in increased platelet-neutrophil and -monocyte aggregates further exacerbating the coagulopathy observed during COVID-19. Finally, the COVID-19-induced cytokine storm primes neutrophils to release neutrophil extracellular traps, which trap platelets and prothrombotic proteins contributing to pulmonary thrombotic complications. SUMMARY: Immunothrombosis significantly contributes to the pathophysiology of COVID-19. Understanding the mechanisms behind COVID-19-induced coagulopathy will lead to future therapies for patients.

An Outbreak of Synthetic Cannabinoid-Associated Coagulopathy in Illinois.

BACKGROUND: In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant. METHODS: We reviewed physician-reported data from patients admitted to Saint Francis Medical Center in Peoria, Illinois, between March 28 and April 21, 2018, and included in a case series adult patients who met the criteria used to diagnose synthetic cannabinoid-associated coagulopathy. A confirmatory anticoagulant poisoning panel was ordered at the discretion of the treating physician. RESULTS: A total of 34 patients were identified as having synthetic cannabinoid-associated coagulopathy during 45 hospitalizations. Confirmatory anticoagulant testing was performed in 15 of the 34 patients, and superwarfarin poisoning was confirmed in the 15 patients tested. Anticoagulant tests were positive for brodifacoum in 15 patients (100%), difenacoum in 5 (33%), bromadiolone in 2 (13%), and warfarin in 1 (7%). Common symptoms at presentation included gross hematuria in 19 patients (56%) and abdominal pain in 16 (47%). Computed tomography was performed to evaluate abdominal pain and revealed renal abnormalities in 12 patients. Vitamin K1 (phytonadione) was administered orally in all 34 patients and was also administered intravenously in 23 (68%). Red-cell transfusion was performed in 5 patients (15%), and fresh-frozen plasma infusion in 19 (56%). Four-factor prothrombin complex concentrate was used in 1 patient. One patient died from complications of spontaneous intracranial hemorrhage. CONCLUSIONS: Our data indicate that superwarfarin adulterants of synthetic cannabinoids can lead to clinically significant coagulopathy. In our series, in most of the cases in which the patient presented with bleeding diathesis, symptoms were controlled with the use of vitamin K1 replacement therapy. The specific synthetic cannabinoid compounds are not known.

Direct oral anticoagulant use and risk of severe COVID-19.

BACKGROUND: Hypercoagulability and thromboembolism are prominent features of severe COVID-19, and ongoing anticoagulant use might be protective. METHODS: We conducted a nationwide register-based cohort study in Sweden, February through May, 2020, to assess whether ongoing direct oral anticoagulant (DOAC) use was associated with reduced risk of hospital admission for laboratory-confirmed COVID-19, or a composite of intensive care unit (ICU) admission or death due to laboratory-confirmed COVID-19. RESULTS: DOAC use (n = 103 703) was not associated with reduced risk of hospital admission for COVID-19 (adjusted hazard ratio [aHR] [95% confidence interval] 1.00 [0.75-1.33] vs. nonuse atrial fibrillation comparator [n = 36 875]; and aHR 0.94 [0.80-1.10] vs. nonuse cardiovascular disease comparator [n = 355 699]), or ICU admission or death due to COVID-19 (aHRs 0.76 [0.51-1.12], and 0.90 [0.71-1.15], respectively). CONCLUSION: Ongoing DOAC use was not associated with reduced risk of severe COVID-19, indicating that prognosis would not be modified by early outpatient DOAC initiation.

Acute thrombotic manifestations of coronavirus disease 2019 infection: Experience at a large New York City health care system.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel coronavirus that has typically resulted in upper respiratory symptoms. However, we have encountered acute arterial and venous thrombotic events after COVID-19 infection. Managing acute thrombotic events from the novel virus has presented unprecedented challenges during the COVID-19 pandemic. In our study, we have highlighted the unique treatment required for these patients and discussed the role of anticoagulation for patients diagnosed with COVID-19. METHODS: The data from 21 patients with laboratory-confirmed COVID-19 disease and acute venous or arterial thrombosis were collected. The demographics, comorbidities, home medications, laboratory markers, and outcomes were analyzed. The primary postoperative outcome of interest was mortality, and the secondary outcomes were primary patency and morbidity. To assess for significance, a univariate analysis was performed using the Pearson χ2 and Fisher exact tests for categorical variables and the Student t test for continuous variables. RESULTS: A total of 21 patients with acute thrombotic events met our inclusion and exclusion criteria. Most cases were acute arterial events (76.2%), with the remainder venous cases (23.8%). The average age for all patients was 64.6 years, and 52.4% were male. The most prevalent comorbidity in the group was hypertension (81.0%). Several markers were markedly abnormal in both arterial and venous cases, including an elevated neutrophil/lymphocyte ratio (8.8) and D-dimer level (4.9 µg/mL). Operative intervention included percutaneous angiography in 25.00% of patients and open surgical embolectomy in 23.8%. Most of the patients who had undergone arterial intervention had developed a postoperative complication (53.9%) compared with a 0% complication rate after venous interventions. Acute kidney injury on admission was a factor in 75.0% of those who died vs 18.2% in the survivors (P = .04). CONCLUSIONS: We have described our experience in the epicenter of the pandemic of 21 patients who had experienced major thrombotic events from infection with COVID-19. The findings from our cohort have highlighted the need for increased awareness of the vascular manifestations of COVID-19 and the important role of anticoagulation for these patients. More data are urgently needed to optimize treatment and prevent further vascular complications of COVID-19 infections.

Trends, characteristics, and outcomes of placenta accreta spectrum: a national study in the United States.

BACKGROUND: Although an infrequent occurrence, the placenta can adhere abnormally to the gravid uterus leading to significantly high maternal morbidity and mortality during cesarean delivery. Contemporary national statistics related to a morbidly adherent placenta, referred to as placenta accreta spectrum, are needed. OBJECTIVE: This study aimed to examine national trends, characteristics, and perioperative outcomes of women who underwent cesarean delivery for placenta accreta spectrum in the United States. STUDY DESIGN: This is a population-based retrospective, observational study querying the National Inpatient Sample. The study cohort included women who underwent cesarean delivery from October 2015 to December 2017 and had a diagnosis of placenta accreta spectrum. The main outcome measures were patient characteristics and surgical outcomes related to placenta accreta spectrum assessed by the generalized estimating equation on multivariable analysis. The temporal trend of placenta accreta spectrum was also assessed by linear segmented regression with log transformation. RESULTS: Of 2,727,477 cases who underwent cesarean delivery during the study period, 8030 (0.29%) had the diagnosis of placenta accreta spectrum. Placenta accreta was the most common diagnosis (n=6205, 0.23%), followed by percreta (n=1060, 0.04%) and increta (n=765, 0.03%). The number of placenta accreta spectrum cases increased by 2.1% every quarter year from 0.27% to 0.32% (P=.004). On multivariable analysis, (1) patient demographics (older age, tobacco use, recent diagnosis, higher comorbidity, and use of assisted reproductive technology), (2) pregnancy characteristics (placenta previa, previous cesarean delivery, breech presentation, and grand multiparity), and (3) hospital factors (urban teaching center and large bed capacity hospital) represented the independent characteristics related to placenta accreta spectrum (all, P<.05). The median gestational age at cesarean delivery was 36 weeks for placenta accreta and 34 weeks for both placenta increta and percreta vs 39 weeks for non-placenta accreta spectrum cases (P<.001). On multivariable analysis, cesarean delivery complicated by placenta accreta spectrum was associated with increased risk of any surgical morbidities (78.3% vs 10.6%), Centers for Disease Control and Prevention-defined severe maternal morbidity (60.3% vs 3.1%), hemorrhage (54.1% vs 3.9%), coagulopathy (5.3% vs 0.3%), shock (5.0% vs 0.1%), urinary tract injury (8.3% vs 0.2%), and death (0.25% vs 0.01%) compared with cesarean delivery without placenta accreta spectrum. When further analyzed by subtype, cesarean delivery for placenta increta and percreta was associated with higher likelihood of hysterectomy (0.4% for non-placenta accreta spectrum, 45.8% for accreta, 82.4% for increta, 78.3% for percreta; P<.001) and urinary tract injury (0.2% for non-placenta accreta spectrum, 5.2% for accreta, 11.8% for increta, 24.5% for percreta; P<.001). Moreover, women in the placenta increta and percreta groups had markedly increased risks of surgical mortality compared with those without placenta accreta spectrum (increta, odds ratio, 19.9; and percreta, odds ratio, 32.1). CONCLUSION: Patient characteristics and outcomes differ across the placenta accreta spectrum subtypes, and women with placenta increta and percreta have considerably high surgical morbidity and mortality risks. Notably, 1 in 313 women undergoing cesarean delivery had a diagnosis of placenta accreta spectrum by the end of 2017, and the incidence seems to be higher than reported in previous studies.

Is the "Death Triad" a Casualty of Modern Damage Control Resuscitation.

BACKGROUND: Principles of damage control laparotomy (DCL) focus on early surgical control of hemorrhage and contamination in addition to damage control resuscitation (DCR) to combat the significant mortality associated with the "death triad" of hypothermia, acidosis, and coagulopathy. We hypothesized that DCL patients managed with DCR would have lower mortality from the death triad than historical studies. METHODS: A 5-y retrospective chart review of all consecutive adult trauma patients presenting to a Level I trauma center who underwent DCL was conducted. Parameters associated with the death triad were evaluated on admission and 24 h after the presentation. Kaplan Meier survival plots were used to compare the components of the death triad. Univariate and multivariate analyses were performed. RESULTS: A total of 149 adult patients were identified. The overall incidence of death triad was 20.8% (n = 31/149). 24-h mortality for all patients was 5.4% (n = 8/149). Kaplan Meier plots showed that 24-h mortality was significantly increased if 3/3 components of the death triad were present (P < 0.05). At 24-h after admission, mortality occurred in 16.6% (n = 5/30) of patients with the death triad. CONCLUSIONS: This study confirms that the 24-h mortality of trauma patients increased with the addition of all three death triad components. The death triad predicted death in 16.6% of patients treated with DCL and DCR at 24 h. Results suggest that the death triad might not be as applicable in the modern era of DCL in combination with DCR. Other factors contributing to in-hospital mortality need to be further elucidated.

Injury Severity, Arrival Physiology, Coagulopathy, and Outcomes Among the Youngest Trauma Patients.

BACKGROUND: Although physiologic differences exist between younger and older children, pediatric trauma analyses are weighted toward older patients. Trauma-induced coagulopathy, determined by rapid thrombelastography (rTEG), is a predictor of outcome in trauma patients, but the significance of rTEG values among very young trauma patients remains unknown. Our objective was to identify the prehospital or physiologic factors, including rTEG values, that were associated with mortality in trauma patients younger than 5 y old. MATERIALS AND METHODS: Patients younger than 5 y old that met the highest-level trauma activation criteria at an academic children's hospital from 2010-2016 were included. Data regarding demographics, pre-hospital management, laboratory values, injury severity, and outcome were queried. Univariate and multivariate analyses were performed comparing survivors and non-survivors. RESULTS: A total of 356 patients were included. 60% were male, and the median age was 3 y (IQR 1-4). Overall mortality was 13% (n = 45); brain injury (91%) and hemorrhage (9%) were the causes of death. Compared to survivors, rTEG values in nonsurvivors showed longer activated clotting time and slower speed of clot formation. Clot strength was also decreased in nonsurvivors. On stepwise regression modeling, rTEG values were not significant predictors of mortality. Admission base deficit, arrival temperature, and head injury severity were identified as independent predictors of mortality. CONCLUSIONS: While rTEG identified coagulopathy in trauma patients < 5 y old, it was not an independent predictor of mortality. Our findings suggest that trauma providers should pay close attention to admission base deficit, arrival temperature, and head injury severity when managing the youngest trauma patients.

Children and young adults hospitalized for severe COVID-19 exhibit thrombotic coagulopathy.

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children's hospital in the Bronx, New York, between March 1 and May 31, 2020. D-Dimer was > 0.5 µg/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-dimer > 5 µg/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (P = 0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis; however, no patients developed VTE on low-molecular-weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications, suggesting thrombotic coagulopathy. More data are needed to guide thromboprophylaxis in this age group.

Severe Rare Bleeding Disorders: A Single-center Experience.

Although rare bleeding disorders (RBDs) are not common diseases, they are important for life-threatening bleedings and prophylaxis approaches, especially in severe forms. In this retrospective study, the authors have analyzed data from children with severe RBDs who were examined at the center over a period of 10 years to describe the distribution, clinical features, treatment patterns, and outcome of severe RBDs in patients. Data from all children (age under 18 y) with RBDs who were examined in the center between 2005 and 2015 were retrospectively reviewed. In total, 12 patients were included in the study. Four of the cases had factor (F) VII (33.3%), 6 had FX (50%), 1 had FXIII (8.3%), and 1 had fibrinogen deficiency (8.3%). Of the 12 children with severe RBDs, 8 (67%) experienced at least 1 major bleeding. Prophylaxis was applied to 10 patients. In conclusion, RBDs are more common in our country because of the high parental consanguinity rates. So, it is necessary to raise public awareness about the risks of consanguineous marriages and increase access to genetic counseling and testing facilities. Delayed diagnosis and lack of adequate prophylactic replacement therapy are the most important risk factors that increase life-threatening bleeding.