Development of a Drum Tower Severity Scoring (DTSS) system for pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome

Background and aims There has been no reliable severity system based on the prognosis to guide therapeutic strategies for patients with pyrrolizidine alkaloid (PA)-induced hepatic sinusoidal obstruction syndrome (HSOS). We aimed to create a novel Drum Tower Severity Scoring (DTSS) system for these patients to guide therapy. Methods 172 Patients with PA-HSOS who received supportive care and anticoagulation therapy in Nanjing Drum Tower Hospital from January 2008 to December 2020 were enrolled and analyzed retrospectively. These patients were randomized into a training or validation set in a 3:1 ratio. Next, we established and validated the newly developed DTSS system. Results Analysis identified a predictive formula: logit (P) = 0.004 × aspartate aminotransferase (AST, U/L) + 0.019 × total bilirubin (TB, μmol/L) − 0.571 × fibrinogen (FIB, g/L) − 0.093 × peak portal vein velocity (PVV, cm/s) + 1.122. Next, we quantified the above variables to establish the DTSS system. For the training set, the area under the ROC curve (AUC) (n = 127) was 0.787 [95% confidence interval (CI) 0.706–0.868; p < 0.001]. With a lower cut-off value of 6.5, the sensitivity and negative predictive value for predicting no response to supportive care and anticoagulation therapy were 94.7% and 88.0%, respectively. When applying a high cut-off value of 10.5, the specificity was 92.9% and the positive predictive value was 78.3%. For the validation set, the system performed stable with an AUC of 0.808. Conclusions The DTSS system can predict the outcome of supportive care and anticoagulation in PA-HSOS patients with satisfactory accuracy by evaluating severity, and may have potential significance for guiding therapy.

Biological Role of Vitamin K—With Particular Emphasis on Cardiovascular and Renal Aspects

Vitamin K (VK) plays many important functions in the body. The most important of them include the contribution in calcium homeostasis and anticoagulation. Vascular calcification (VC) is one of the most important mechanisms of renal pathology. The most potent inhibitor of this process—matrix Gla protein (MGP) is VK-dependent. Chronic kidney disease (CKD) patients, both non-dialysed and hemodialysed, often have VK deficiency. Elevated uncarboxylated matrix Gla protein (ucMGP) levels indirectly reflected VK deficiency and are associated with a higher risk of cardiovascular events in these patients. It has been suggested that VK intake may reduce the VC and related cardiovascular risk. Vitamin K intake has been suggested to reduce VC and the associated cardiovascular risk. The role and possibility of VK supplementation as well as the impact of anticoagulation therapy on VK deficiency in CKD patients is discussed.

Clinical and laboratory testing of oral anticoagulation therapy vitamin k antagonists at the emergency department of Hanoi Heart Hospital

Background: The most commonly used oral anticoagulant is acenocoumarol with the brand name is Sintrom and recently, warfarin with the brand name is Coumadin has begun to be used. Anticoagulation with vitamin K antagonists faces two main obstacles: the narrow therapeutic range and the effectiveness of the drug varies by many factors. Objective: " Current status of coagulation disorders in the treatment of anticoagulants with vitamin K antagonists. Understanding some factors affecting the goal of anticoagulant treatment". Method: Cross-sectional, retrospective, descriptive analysis of drug use and influencing factors of patients diagnosed with coagulopathy admitted to the emergency department at Hanoi Heart Hospital from April 2020 to August 2021. Results: There were 675 patients admitted to the hospital with blood clotting disorders. The average age is 60,17±10,13, the youngest is 30, the oldest is 90; 63 patients, accounting for 9.42%, need to be hospitalized for inpatient treatment; There are 108 patients, accounting for 16%, with bleeding and 18 patients, accounting for 2.7%, with thromboembolism or valve obstruction. Conclusion: Coagulation disorders during treatment with vitamin K antagonist anticoagulants is a common condition in the emergency department. However, the complication rate is not high. There are many factors that affect the patient's treatment goals and the drug use is a fairly common factor.

Clinical Efficacy of Conventional Heparin Anticoagulation Combined with Apixaban in the Treatment of Patients with Cerebral Venous Thrombosis and Its Effect on Serum D-Dimer and FIB Expression

Objective. The aim of this study was to explore the clinical efficacy of conventional heparin anticoagulation in combination with apixaban in the treatment of patients with cerebral venous thrombosis (CVT) and its influence on serum D-dimer (D-D) and fibrinogen (FIB). Methods. One hundred and fifty-seven consecutive CVT patients admitted to our hospital from January 1, 2006, to December 31, 2013, were allocated into two groups according to the different treatment methods, of which 95 cases received standard anticoagulation therapy (standard group (SG)) and the remaining 62 cases were given apixaban therapy (research group (RG)). The curative effects and the changes of coagulation function during the treatment, as well as the incidence of adverse reactions, were analyzed in the two groups. The changes of D-D and FIB levels before treatment and at days 1, 4, and 7 posttreatment were detected. Results. In treatment efficacy, RG was superior to SG. No evident difference was observed in the incidence of adverse events or coagulation function between the two groups. At day 1 posttreatment, D-D level was increased largely in both SG and RG, but the increase was much more significant in RG. However, D-D level was decreased gradually with time in both groups, and the reduction was more notable in RG. The FIB level in SG declined gradually with time after treatment and was higher than that in RG at the same time point. In RG, FIB was decreased gradually at day 1 and day 4 posttreatment, and its level at day 7 posttreatment showed no difference compared with that at day 4 posttreatment. Spearman’s analysis identified that the higher the D-D level or the lower the FIB level at day 1 posttreatment was, the better the treatment efficacy was. After seven-day treatment, the lower the level of D-D and FIB was, the better the therapeutic effect was. Logistic analysis indicated that age, time of diagnosis, deep vein thrombosis (DVT), Glasgow Coma Scale (GCS) score, infection, Apixaban, D-D, and FIB all independently affect the treatment effect of patients. Conclusions. The combined use of Apixaban with heparin is high-performing and safe in the treatment of CVT. The changes of D-D and FIB levels during the treatment are strongly linked to the therapeutic effect, which can be used as plausible evaluation indexes for the efficacy of CVT.

Survival Benefit of Anticoagulation Therapy in End Stage Kidney Disease Patients with Atrial Fibrillation: A Single Center Retrospective Study

Background and Objectives: Although the need for anticoagulation to prevent thromboembolism is increasing and non-vitamin K antagonist oral anticoagulants (NOACs) have been tried, there is still controversy about the efficacy of anticoagulation in patients with dialysis. Materials and Methods: We retrospectively analyzed the risk and benefit of anticoagulation in dialysis patients with atrial fibrillation (AF). We retrospectively analyzed all data of 89 patients who received dialysis therapy and were diagnosed with AF. Among them, 27 received anticoagulation (11 warfarin and 16 apixaban 2.5 mg twice a day), while 62 received no anticoagulation. Results: In multivariate Cox regression analysis, compared to no anticoagulation treatment, anticoagulation treatment was associated with a low incidence of all-cause mortality (hazard ratios (HR) 0.36; 95% confidence interval (CI) 0.15–0.88). Compared to no anticoagulation treatment, more anticoagulation treatment patients experienced severe bleeding (HR 4.67; 95% CI 1.26–17.25) and any bleeding (HR 2.79; 95% CI 1.01–7.74). Compared to no anticoagulation, warfarin treatment patients were associated with a low incidence of all-cause mortality (HR 0.26; 95% CI 0.09–0.81) and a high incidence of severe bleeding (HR 4.85; 95% CI 1.12–21.10). All-cause mortality and bleeding were not significantly different between no anticoagulation and apixaban treatment patients. Conclusions: In dialysis patients with AF, anticoagulation therapy is associated with an increased incidence of severe bleeding, but anticoagulation therapy is associated with a low incidence of all-cause mortality. Individualized anticoagulation therapy with careful bleeding monitoring is needed in dialysis patients with AF.

Anticoagulation Practice in Patients with Cancer-Associated Thrombosis: Insights from GeCAT, a German Prospective Registry Study

Introduction: Cancer-associated venous thrombosis (CAT) is a common and serious complication of active malignancies, increasing in frequency during systemic treatment and radiotherapy. Due to a high risk of recurrence and bleeding, the administration of anticoagulants for initial treatment and secondary prevention of CAT is challenging. We conducted a prospective registry study of patients with acute CAT to evaluate the way treatment is given to these patients in routine practice. Methods: From May 2015 to May 2017, all consecutive patients with acute venous thromboembolism (VTE) admitted to specialty or emergency departments of the participating hospitals in Berlin, Germany, were entered in the registry. Patients with cancer underwent extensive baseline evaluation including the type and location of thrombosis and use of anticoagulant therapy. Follow-up assessments were made at discharge and by telephone interviews at 3 and 6 months. Results: A total of 382 patients with acute CAT were enrolled in the study, representing 24.5% of all patients with thrombosis. 70.4% of CAT patients had deep vein thromboses (DVT), 48.2% had pulmonary embolism (PE), and 18.6% had concurrent PE and DVT. A significant proportion of VTE (27%) were asymptomatic and were diagnosed only incidentally. At baseline, 97.9% of the patients received anticoagulant therapy, predominantly with low-molecular-weight heparin (LMWH) (n=334, 87.4%). Direct oral anticoagulants (DOACs) were given to 5.8% of patients, and vitamin K antagonists (VKAs) were rarely used (<2% of patients). Changes in the prescription of antithrombotic agents were seen at discharge from hospital and during follow-up. Overall, the use of LMWH declined during follow-up, while the proportion of patients treated with DOACs increased to 32.4% at 6 months. At baseline, the most frequently used LMWH were enoxaparin and nadroparin, but many patients were switched to once daily tinzaparin prior to discharge. Initially and after discharge the majority of patients were treated by oncologists. Overall, 263 (68.8%) and 222 (58,1%) patients were still alive and could be contacted at 3 and 6 months of follow-up, respectively. Of these, 84.0% and 71.6% were still on anticoagulant therapy (58.6% and 36.5% on LMWH). Conclusion: In accordance with the guidelines, the majority of CAT patients received anticoagulation therapy for the recommended minimum duration of 3-6 months. LMWH remained the preferred option throughout the study, demonstrating good patient adherence. In deviation from guideline recommendations and available study results during the study period, more than a quarter of CAT patients were treated with DOACs. Only recently, DOACs have been established as another option for anticoagulation in CAT patients.

Anticoagulation Changes Following Major and Clinically Relevant Nonmajor Bleeding Events in Non-valvular Atrial Fibrillation Patients

Background Bleeding events are common complications of oral anticoagulant drugs, including both warfarin and the direct oral anticoagulants (DOACs). Some patients have their anticoagulant changed or discontinued after experiencing a bleeding event, while others continue the same treatment. Differences in anticoagulation management between warfarin- and DOAC-treated patients following a bleeding event are unknown. Methods Patients with non-valvular atrial fibrillation from six anticoagulation clinics taking warfarin or DOAC therapy who experienced an International Society of Thrombosis and Haemostasis (ISTH)-defined major or clinically relevant non-major (CRNM) bleeding event were identified between 2016 and 2020. The primary outcome was management of the anticoagulant following bleeding (discontinuation, change in drug class, and restarting of same drug class). DOAC- and warfarin-treated patients were propensity matched based on the individual elements of the CHA2DS2-VASc and HAS-BLED scores as well as the severity of the bleeding event. Results Of the 509 patients on warfarin therapy and 246 on DOAC therapy who experienced a major or CRNM bleeding event, the majority of patients continued anticoagulation therapy. The majority of warfarin (231, 62.6%) and DOAC patients (201, 81.7%) restarted their previous anticoagulation. Conclusion Following a bleeding event, most patients restarted anticoagulation therapy, most often with the same type of anticoagulant that they previously had been taking.