OBJECTIVE: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients.
METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn\'t develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings.
RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770).
CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.

UNASSIGNED: Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor with a high risk of mortality. Few studies with large samples of KHE have been reported. KHE may develop into the Kasabach-Merritt phenomenon (KMP), which is characterized by thrombocytopenia and consumptive coagulopathy. The features of severe symptomatic anemia and life-threatening low platelets make the management of KHE associated with KMP challenging.
UNASSIGNED: The aim of this study was to examine the clinical characteristics of patients with KHE and discuss the treatment experience for different risk groups of KHE.
UNASSIGNED: Through a retrospective review of 70 patients diagnosed with KHE between 2017 and 2022 in our center, we classify lesions into three clinicopathological stages based on the tumor involving depth, and divided the severity of KHE into three levels by estimating clinicopathological stages and severity of thrombocytopenia. Treatments of different severity groups were estimated with sufficient data.
UNASSIGNED: In our cohort, 27% were neonates, and KHE lesion occurred at birth in 84% of patients. There was a slight male predominance (32 girls and 38 boys). Common clinical characteristics included associated coagulation disorder (100%), locally aggressive cutaneous blue-purple mass (89%), thrombocytopenia (78%), and local pain or joint dysfunction (20%). The lower extremities were the dominant location (35%), followed by the trunk (29%), the maxillofacial region and neck (24%), and the upper extremities (10%). Of the total cohort, 78% developed KMP; the median age at which thrombocytopenia occurred was 27.8 days. The median platelet count of patients who were associated with KMP was 24,000/µL in our cohort. Ninety-two percent of patients were given surgery treatment and 89% of these patients were given high-dose methylprednisolone (5-6 mg/kg daily) before surgery. In 55 patients with KMP, 36% were sensitive to high-dose corticosteroid therapy. Patients from the low-risk group (eight cases) underwent operation, all of whom recovered without recurrence after a maximum follow-up of 5 years. Out of 26 patients from the high-risk group, 25 underwent surgery treatment, with 1 case undergoing secondary surgery after recurrence and 1 case taking sirolimus. Out of 36 cases from the extremely high-risk group, 32 underwent surgery (including 2 cases who underwent external carotid artery ligation and catheterization), 3 of whom underwent secondary operation after recurrence, and the remaining 4 cases took medicine. The mean length of having sirolimus was 21 months; two cases stopped taking sirolimus due to severe pneumonia. Two cases died at 1 and 3 months after discharge.
UNASSIGNED: Our study describes the largest assessment of high-risk patients with KHE who have undergone an operation to date, with 5 years of follow-up to track recovery, which provides invaluable knowledge for the future treatment of patients with KHE and KMP from different risk groups: Early surgical intervention may be the most definitive treatment option for most patients with KHE; multimodality treatment is the best choice for the extremely high-risk group.

Anti-beta-2 glycoprotein I antibodies are an important player in hypercoagulable states, including those that lead to antiphospholipid syndrome. Traditionally, assays have only detected IgG and IgM isotypes of this antibody. However, newer assays also detect the IgA isotype. The problem lies in the largely unknown significance of this IgA isotype. This paper describes a middle-aged male who presented with hypertensive emergency and was later found to have IgA anti-beta-2 glycoprotein I antibodies. He was treated with multiple anti-hypertensives, aspirin, and statin therapy. In addition to the case, we discuss the implications of this IgA isotype and how it may relate to antiphospholipid syndrome, despite not currently being included in the laboratory diagnostic criteria for the disease.

BACKGROUND: Coronavirus 2019 symptoms include coagulopathy and thromboembolic risk. Using one parameter to diagnose coagulopathy has little predictive value.
OBJECTIVE: This study will examine if D-dimer and APTT testing can predict COVID-19 severity and aid triage and manage patients.
METHODS: 214 COVID-19 patients were enrolled and classified into two categories based on their respiratory manifestations; mild (126 cases) and severe (88 cases). Patient data regarding age, gender, D-Dimer level, and APTT level were collected. When both D-Dimer and APTT levels were abnormal, in this study, the patient was considered to have a coagulation disorder. Indicators of coagulation in the COVID-19 patients were collected and compared between the two groups. Chi-square (χ2) tests were used to determine the significant differences between coagulation disorders in the two groups.
RESULTS: Our findings showed that patients with coagulopathies were more likely to belong to the severe group. Within the two groups of patients, the rate of coagulation disorders was as follows: mild = 8.8 % within coagulation disorders, 4.8% within the two Groups; severe = 91.2 % within coagulation disorders, 77.8 % within the two Groups. There was a statistically significant relationship between coagulation disorder and severe COVID-19 patients compared to mild patients (p < 0.05).
CONCLUSIONS: Coagulation disorders are more likely to occur in severe COVID-19 patients. D-Dimer and APTT tests are significant indicators for predicting COVID-19 severity. Our research found an abnormal pattern of coagulation disorders and COVID-19 severity that should be considered in the COVID-19 treatment protocol.

UNASSIGNED: Hyperthermia and multiple organ dysfunction syndrome (MODS) are the main characteristics of heatstroke and COVID-19. Differentiating between these illnesses is crucial during a summer COVID-19 pandemic, but cases of heatstroke comorbid with COVID-19 are rarely reported.
UNASSIGNED: We report the first case of heatstroke comorbid with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in a 52-year-old male. After receiving intravenous antibiotics, organ protection measures, and treatment for coagulation disorders, his fever and coma resolved. However, he developed dyspnea and cerebral hemorrhage after several days. This patient experienced a multi-pathogen pulmonary infection and an intractable coagulopathy that ultimately resulted in MODS and death.
UNASSIGNED: The combination of heatstroke and SARS-CoV-2 infection exacerbated inflammation, immune abnormalities, and coagulation disorders. The interaction between inflammation and coagulation disturbances contributed to the underlying mechanism in this case, highlighting the importance of early anti-infection, treatment for coagulopathy, immune regulation, and organ protection as crucial interventions.

OBJECTIVE: Inherited bleeding disorders may cause heavy menstrual bleeding in women, impacting quality of life and impairing daily and social activities. The levonorgestrel-releasing intrauterine system is a potential treatment for these women, which might reduce menstrual blood loss.
METHODS: We performed a systematic review and single-arm meta-analysis to examine the levonorgestrel-releasing intrauterine system in women with inherited bleeding disorders and heavy menstrual bleeding.
RESULTS: A systematic search on PubMed, Embase and Cochrane yielded 583 results, of which six observational studies (n = 156) met inclusion criteria. Levonorgestrel-releasing intrauterine system use in patients with inherited bleeding disorders and heavy menstrual bleeding was associated with amenorrhea in 60% of patients and a significant increase of 1.40 g/dL in hemoglobin and of 19.75 ng/mL in ferritin levels when comparing post- and pre-treatment levels. The post-treatment mean hemoglobin was 13.32 g/dL and the mean ferritin was 43.22 ng/dL. The rate of intrauterine device expulsion or removal due to mal position was low (13%), as was the need for intrauterine device removal due to lack of efficacy (14%).
CONCLUSIONS: The levonorgestrel-releasing intrauterine system may improve bleeding patterns and quality of life in patients with inherited bleeding disorders and heavy menstrual bleeding.
CONCLUSIONS: Women with inherited bleeding disorders could benefit from levonorgestrel-releasing intrauterine system, so its use should be an option for this women.

Congenital prothrombin deficiency is a rare hemorrhagic disorder, frequent in areas with high degrees of consanguinity as it is autosomal recessive in nature. Clinical manifestations are highly variable, ranging from mild episodes of bleeding to severe hemorrhages. Here, we report a child with isolated prothrombin deficiency who presented with a history of pain and soreness in the prepuce associated with bleeding. Laboratory evaluation showed an altered coagulation profile with a prothrombin activity level of 29.8%, indicative of factor-II deficiency. This case highlights the importance of coagulation screening in all patients before even minor invasive procedures and the role of a detailed coagulation profile in confirming a diagnosis in the case of abnormal screening tests.

BACKGROUND: Acute pancreatitis (AP) is a potentially lethal acute disease highly involved in coagulation disorders. Pyroptosis has been reported to exacerbate coagulation disorders, yet this implication has not been illustrated completely in AP.
METHODS: RNA sequencing data of peripheral blood of AP patients were downloaded from the Gene Expression Omnibus database. Gene set variation analysis and single sample gene set enrichment analysis were used to calculate the enrichment score of coagulation-related signatures and pyroptosis. Spearman and Pearson correlation analysis was used for correlation analysis. Peripheral blood samples and related clinical parameters were collected from patients with AP and healthy individuals. A severe AP (SAP) model of mice was established using caerulein and lipopolysaccharide. Enzyme-linked immunosorbent assay, chemiluminescence immunoassay and immunohistochemical analysis were employed to detect the level of coagulation indicators and pyroptosis markers in serum and pancreas tissues. Additionally, we evaluated the effect of pyroptosis inhibition and NLRC4 silence on the function of human umbilical vein endothelial cells (HUVECs).
RESULTS: Coagulation disorders were significantly positively correlated to the severity of AP, and they could be a predictor for AP severity. Further analyses indicated that six genes-DOCK9, GATA3, FCER1G, NLRC4, C1QB and C1QC-may be involved in coagulation disorders of AP. Among them, NLRC4 was positively related to pyroptosis that had a positive association with most coagulation-related signatures. Data from patients showed that NLRC4 and other pyroptosis markers, including IL-1β, IL-18, caspase1 and GSDMD, were significant correlation to AP severity. In addition, NLRC4 was positively associated with coagulation indicators in AP patients. Data from mice showed that NLRC4 was increased in the pancreas tissues of SAP mice. Treatment with a pyroptosis inhibitor effectively alleviated SAP and coagulation disorders in mice. Finally, inhibiting pyroptosis or silencing NLRC4 could relieve endothelial dysfunction in HUVECs.
CONCLUSIONS: NLRC4-mediated pyroptosis damages the function of endothelial cells and thereby exacerbates coagulation disorders of AP. Inhibiting pyroptosis could improve coagulation function and alleviate AP.

Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased IL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients.

OBJECTIVE: Tonsillectomy is a common surgery performed for indications such as chronic tonsilitis, tonsil hypertrophy and obsructive sleep apnea. Although posttonsillectomy bleeding (PTB) is rare and can be controlled with simple interventions in many patients, it is one of the most feared complications of tonsillectomy surgery. In our study, we investigated the effects of changes in hemogram and coagulation values and seasonal effects on PTB.
METHODS: Pediatric and adult patients who underwent tonsillectomy with cold knife method between August 2020 and August 2023 in our clinic were retrospectively reviewed. Demographic data, hemogram and coagulation values of the patients in the control and study groups were recorded and the differences between the two groups in terms of these parameters were evaluated.
RESULTS: Our study included 991 patients aged 1-51 years. The rate of PTB was calculated as 2.82%. No patient with primary PTB was found. The duration of bleeding development was 7.03 days. Age, WBC and neutrophil values were statistically significantly higher in the study group. There were no significant differences between two groups in terms of gender, season and other hemogram and coagulation parameters.
CONCLUSIONS: Age, high WBC and neutrophil levels were determined as possible risk factors for PTB. Seasonal and gender distribution, aPTT and INR values were similar in the two groups. In order to prevent and predict bleeding, detailed infection investigation should be performed and the risk of bleeding should be considered to increase with increasing age.