Efficacy and safety of prothrombin complex concentrate in patients treated with rivaroxaban or apixaban compared to warfarin presenting with major bleeding

This retrospective study investigated the efficacy and safety of prothrombin complex concentrates (PCCs) for management of major bleeding events (MBE) in 344 patients receiving the anticoagulants rivaroxaban, apixaban or warfarin during the period January 2016 to April 2018. Median (range) PCC dose was 2000 units (1000–4500). Intracranial haemorrhage (ICH) was the most common indication (137/344, 39·8%) for PCC use followed by gastrointestinal bleeding (93/344, 27%). ICH patients more frequently received rivaroxaban (62·5%) or apixaban (52·5%) compared to warfarin (34·5%), P = 0·002; and visceral bleeding patients received warfarin more frequently (24·2%) than rivaroxaban (5%) or apixaban (10%), P = 0·003. Median rivaroxaban and apixaban levels were 230 ng/ml (47–759) and 159 ng/ml (45–255). Median International Normalised Ratio pre- and post-PCC in patients on warfarin were 3·4 (1·9–15·4) and 1·2 (1·0–1·9). Blood products use was the same between groups. Thirty-day mortality and re-bleeding rates in patients with ICH were 35% (P = 0·50) and 18% (P = 0·90) with no differences between the groups. Thrombosis occurred in 4·1% patients within 30 days with no difference between groups. Two of 91 (2·2%) patients with ICH only (both on warfarin) had ischaemic strokes within 30 days post-PCC. In conclusion, there was no difference in the safety (thrombosis) or efficacy (30-day mortality, re-bleeding) in use of PCC for MBE in patients on warfarin, rivaroxaban or apixaban.     

Lupus anticoagulant associated with transient severe factor X deficiency: a report of two patients presenting with major bleeding complications

Acquired factor X (FX) deficiency is rare, but has been reported in diverse disease states, including systemic amyloidosis and respiratory infections. FX deficiency associated with lupus anticoagulant (LA) and a bleeding diathesis has not been previously reported. We report two patients both of whom presented with a severe bleeding diathesis after a preceding respiratory infection due to isolated FX deficiency associated with a LA. The FX deficiency and LA were transient. We conclude that patients with LA may rarely present with severe acquired FX deficiency. This may be another mechanism whereby patients with antiphospholipid antibodies present with bleeding complications.     

Effects of rivaroxaban and warfarin on the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation: Systematic review and meta‐analysis

To assess the risk of gastrointestinal bleeding and intracranial hemorrhage in patients with atrial fibrillation (AF) after the use of rivaroxaban or warfarin. To investigate the effects of rivaroxaban and warfarin on gastrointestinal and intracranial hemorrhage in patients with AF, we searched PubMed, Embase, and Medline from the establishment of databases up to 2020. We finally included 38 observational studies involving 1 312 609 patients for the assessment of intracranial hemorrhage, and 33 observational studies involving 1 332 956 patients for the assessment of gastrointestinal bleeding. The rates of intracranial hemorrhage were 0.55% in the rivaroxaban group versus 0.91% in the warfarin group (OR 0.59; 95% CI 0.53–0.66; p < .00001, I2 = 78%). The rates of gastrointestinal bleeding were 2.63% in patients with rivaroxaban versus 2.48% in those with warfarin (OR 1.06; 95% CI 0.96–1.17; p < .00001, I2 = 94%). Rivaroxaban could significantly reduce the risk of intracranial hemorrhage in patients with AF than warfarin, but the risk of gastrointestinal bleeding remained controversy due to no statistical significant difference. Notably, a subgroup analysis demonstrated that patients in rivaroxaban group with severe chronic renal diseases or undergoing hemodialysis exposed to less gastrointestinal hemorrhage risk than the group from warfarin.     

Prevalence of mid-gastrointestinal bleeding in patients with acute overt gastrointestinal bleeding: multi-center experience with 1,044 consecutive patients

Background  Video capsule endoscopy (VCE) and double-balloon enteroscopy (DBE) enable the detection of small intestinal lesions. Aim  To examine causes of acute overt gastrointestinal (GI) bleeding and the prevalence of mid-GI bleeding, defined as small intestinal bleeding from the ampulla of Vater to the terminal ileum, in a multi-center experience in Japan in the VCE/DBE era. Methods  Data were collected retrospectively from consecutive patients with acute overt GI bleeding in ten participating hospitals. All patients were examined by esophagogastroduodenoscopy and/or colonoscopy. When the source of bleeding was not identified after these procedures, patients suspected to have mid-GI bleeding were referred to our hospital and VCE/DBE was performed to determine the source of bleeding. Results  Of the 1044 patients with acute overt GI bleeding, 524 (50.2%) patients were diagnosed with upper GI bleeding, 442 (42.3%) with lower GI bleeding, and 13 (1.2%) with mid-GI bleeding. Gastric ulcer was the most common cause of bleeding (20.4%). Among cases of mid-GI bleeding, ulcers were found in 4 (30.8%) patients, erosions in 3 (23.1%), angiodysplasia in 3 (23.1%), submucosal tumor in 2 (15.4%), and hemangioma in one (7.7%). Seven lesions were located in the jejunum, 5 in the ileum, and one in both the jejunum and ileum. Analysis of age-related cause showed that the prevalence of mid-GI bleeding among younger patients under 40 years of age was higher (5%) than in other age groups (1–2%). Conclusion  mid-GI bleeding is rare among Japanese patients with acute overt GI bleeding.     

Single-center experience of 309 consecutive patients with obscure gastrointestinal bleeding

AIM: To investigate the diagnostic yield of capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB), and to determine whether the yield was affected by different bleeding status.METHODS: Three hundred and nine consecutive patients (all with recent negative gastric and colonic endoscopy results) were investigated with CE; 49 cases with massive bleeding and 260 cases with chronic recurrent overt bleeding. Data regarding OGIB were obtained by retrospective chart review and review of an internal database of CE findings.RESULTS: Visualization of the entire small intestine was achieved in 81.88% (253/309) of cases. Clinically positive findings occurred in 53.72% (166/309) of cases. The positivity of the massive bleeding group was slightly higher than that of the chronic recurrent overt bleeding group but there was no significant difference (59.18% vs 52.69%, P > 0.05) between the two groups. Small intestinal tumors were the most common finding in the entire cohort, these accounted for 30% of clinically significant lesions. In the chronic recurrent overt bleeding group angioectasia incidence reached more than 29%, while in the massive bleeding group, small intestinal tumors were the most common finding at an incidence of over 51%. Increasing patient age was associated with positive diagnostic yield of CE and the findings of OGIB were different according to age range. Four cases were compromised due to the capsule remaining in the stomach during the entire test, and another patient underwent emergency surgery for massive bleeding. Therefore, the complication rate was 1.3%. CONCLUSION: In this study CE was proven to be a safe, comfortable, and effective procedure, with a high rate of accuracy for diagnosing OGIB.     

Use of rivaroxaban in sickle cell disease and venous thromboembolism: A case report

Introduction:Sickle cell disease (SCD) is a hematological disorder characterized by sickling of red blood cells. Patients are at increased risk of venous thromboembolism. There are no guidelines for the management of venous thromboembolism in sickle cell disease specifically in terms of the anticoagulant of choice.Patient concerns:Here, we report a case of a 30-year-old lady with past medical history of sickle cell disease who came with chest pain and shortness of breath.Diagnosis:We found that she has bilateral pulmonary embolism (PE).Intervention:She was started on rivaroxaban.Outcome:The patient was followed for 18 months, she did not suffer from recurrence of PE, and she did not develop any complications related to rivaroxaban.Conclusion:We concluded that rivaroxaban is effective in treating PE in sicklers and also it is safe.     

In vivo reversal of the anticoagulant effect of rivaroxaban with four‐factor prothrombin complex concentrate

Four‐factor prothrombin complex concentrate (PCC) 50 iu/kg is able to swiftly restore haemostatic parameters in healthy subjects on rivaroxaban. We hypothesized that lower dosages of PCC may be sufficient to restore normal haemostasis. In this double‐blind, crossover, placebo‐controlled study, we compared the effects of PCC 37·5 iu/kg, PCC 25 iu/kg, and placebo on thrombin generation (endogenous thrombin potential, ETP) and prothrombin time in six healthy subjects receiving twice‐daily rivaroxaban 15 mg for 2·5 days. Fifteen min after infusion of PCC 37·5 iu/kg, ETP increased from 47 ± 16% to 64 ± 22% (P = 0·03; pre‐rivaroxaban ETP: 92 ± 14%) and remained higher than after placebo over 24 h (P = 0·001). PCC 25 iu/kg did not modify ETP within 15 min (53 ± 11% to 59 ± 12%; P = 0·14) and was not different from placebo over 24 h (P = 0·31). ETP reached pre‐rivaroxaban levels within 6 h after PCC 37·5 iu/kg infusion and within 12–24 h after PCC 25 iu/kg infusion. Both dosages restored rivaroxaban‐induced prothrombin time prolongation after 15 min (P < 0·001). Placebo did not have an effect on coagulation parameters. 37·5 iu/kg of PCC leads to partial restoration of thrombin generation, whereas 25 iu/kg does not. PCC 37·5 iu/kg may be insufficient for immediate full reversal of peak therapeutic rivaroxaban levels.     

Efficacy of rivaroxaban for the treatment of Chinese patients with acute pulmonary embolism: A retrospective study

Pulmonary embolism (PE) is a life-threatening disease, which accounts for the major type of venous thromboembolism. Currently, there is limited understanding and management for PE. Rivaroxaban is reported to treat patients with PE. However, there is still insufficient evidence on rivaroxaban for the treatment of Chinese patients with acute PE. Thus, this retrospective study investigated the benefits and safety of rivaroxaban for Chinese patients with acute PE.A total of 72 Chinese patient cases with acute PE were analyzed in this study. Of these, 36 cases who received rivaroxaban mono-therapy were assigned to the treatment group, while the remaining 36 cases who received standard therapy were assigned to the control group. The benefits were assessed by the duration of hospital stay, treatment satisfaction, and safety.After treatment, rivaroxaban mono-therapy showed better benefits in decreasing the duration of hospital stay (P < .01), increasing treatment satisfaction (P < .01), and reducing mild bleeding (P = .02) in Chinese patients with acute PE, than standard therapy.The results of this study indicated that rivaroxaban may provide more benefits than the standard therapy for Chinese patients with acute PE. Future studies are still needed to warrant the current results.     

利伐沙班在高龄非瓣膜性心房颤动患者中的安全性评价

目的 探讨高龄非瓣膜性心房颤动(房颤)患者口服利伐沙班的安全性.方法 回顾性分析2018年1月-2019年3月,复旦大学附属静安区中心医院心内科门诊或病房≥60岁口服利伐沙班的非瓣膜性房颤患者相关资料,根据患者的年龄分为≥80岁高龄组(n=104)和＜80岁低龄组(n=56).随访患者出血等并发症临床情况.结果 160...     

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE‐LY trial

Background

Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives

To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE‐LY trial.

Methods

HAS‐BLED, ORBIT, ATRIA and HEMORR₂HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results

There were 1182 (6.5%) major bleeding events during a median follow‐up of 2.0 years. For all the four schemes, high‐risk subgroups had higher risk of major bleeding (all P  < 0.001). The ORBIT score showed the best discrimination with c‐indices of 0.66, 0.66 and 0.62, respectively, for major, life‐threatening and intracranial bleeding, which were significantly better than for the HAS‐BLED score (difference in c‐indices: 0.050, 0.053 and 0.048, respectively, all P  < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P  = 0.0019), ATRIA (P  < 0.001) and HEMORR₂HAGES (P  < 0.001) scores. HAS‐BLED score showed a nonsignificant trend for interaction (P  = 0.0607).

Conclusions

Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

     

Unrecognized major bleeding following thrombolysis for acute myocardial infarction presenting with syncope

Complete atrioventricular block and syncope sometimes are the presenting signs of acute myocardial infarction. In a presyncopal attempt to assume sitting position, the patient may fall and suffer consequent trauma. Once in hospital, this sequence of events may be overlooked by both the patient and admitting physicians. Moreover, physical examination initially may not be revealing. We report on two such patients who developed massive subcutaneous bleeding following thrombolytic and heparin treatment. We conclude that these patients constitute a specific group with a relatively high risk of trauma and bleeding at the gluteal region following thrombolytic therapy. Special attention must be given to these patients.     

High intensity of oral anticoagulant therapy in patients with cerebral haemorrhage: cause or consequence of the bleeding?

In assessing the optimal intensity of anticoagulant therapy, the International Normalized Ratio (INR) at admission is used as a basis for INR-specific incidence rates. In 47 patients suffering a haemorrhagic stroke we tested the assumption that the INR at admission is an acceptable measure for the INR that preceded the haemorrhage. We found high D-dimer levels in 70% of the patients, which indicated activated coagulation and fibrinolysis. This was not of such an extent that it could also be measured with other routine coagulation tests, with the possible exception of two patients. We found normal INRs in 33 non-anticoagulated patients, and only a mildly prolonged INR of 1.9 in one patient, which was most probably caused by a vitamin K deficiency. We concluded that the INR at admission can be used in studies to assess the optimal level of anticoagulation.