Anticoagulation carries a tremendous therapeutic advantage in reducing morbidity and mortality with venous thromboembolism and atrial fibrillation. For over six decades, traditional anticoagulants like low molecular weight heparin and vitamin K antagonists like warfarin have been used to achieve therapeutic anticoagulation. In the past decade, multiple new direct oral anticoagulants have emerged and been approved for clinical use. Since their introduction, direct oral anticoagulants have changed the landscape of anticoagulants. With increasing indications and use in various patients, they have become the mainstay of treatment in venous thromboembolic diseases. The safety profile of direct oral anticoagulants is better or at least similar to warfarin, but several recent reports are focusing on spontaneous hemorrhages with direct oral anticoagulants. This narrative review aims to summarize the incidence of spontaneous hemorrhage in patients treated with direct oral anticoagulants and also offers practical management strategies for clinicians when patients receiving direct oral anticoagulants present with bleeding complications.

Warfarin has been utilized for decades as an effective anticoagulant in patients with a history of strong risk factors for venous thromboembolism (VTE). Established adverse effects include bleeding, skin necrosis, teratogenicity during pregnancy, cholesterol embolization, and nephropathy. One of the lesser-known long-term side effects of warfarin is an increase in systemic arterial calcification. This is significant due to the association between vascular calcification and cardiovascular morbidity and mortality. Direct oral anticoagulants (DOACs) have gained prominence in recent years, as they require less frequent monitoring and have a superior side effect profile to warfarin, specifically in relation to major bleeding. The cost and lack of data for DOACs in some disease processes have precluded universal use. Within the last four years, retrospective cohort studies, observational studies, and randomized trials have shown, through different imaging modalities, that multiple DOACs are associated with slower progression of vascular calcification than warfarin. This review highlights the pathophysiology and mechanisms behind vascular calcification due to warfarin and compares the effect of warfarin and DOACs on systemic vasculature.

(1) Background: Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. Diabetes mellitus (DM) has been shown to have adverse inflammatory effects on lung anatomy and physiology. We investigated the impact of DM on COPD patient outcomes during inpatient hospitalization. (2) Methods: We conducted a retrospective analysis using the Nationwide Inpatient Sample (NIS) over the years 2002–2014. Three groups, COPD without diabetes, COPD with diabetes but no complication, and COPD with DM and complication, were analyzed. (3) Results: A total of 7,498,577 were COPD hospitalization; of those, 1,799,637 had DM without complications, and 483,467 had DM with complications. After adjusting for clinical, demographic, and comorbidities, the odds of increased LOS in the COPD/DM with complication were 1.37 (confidence interval (CI): 1.326–1.368), and those of DM without complication were 1.061 (1.052–1.070) when compared with COPD alone. The odds of pneumonia, respiratory failure, stroke, and acute kidney injury were also higher in COPD hospitalizations with DM. Both DM with complication (odds ratio (OR): 0.751 (CI 0.727–0.777)) and DM without complication (OR: 0.635 (CI: 0.596–0.675)) have lesser odds of mortality during hospitalization than with COPD alone. (4) Conclusions: There is a considerable inpatient burden among COPD patients with DM in the United States.

Clinical trials have demonstrated the benefits of cardiac implantable electrical devices, which include pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT), with respect to key clinical outcomes and survival. Women more often require permanent pacing for sick sinus syndrome, whereas atrioventricular block is more common in men. Women appear to have a higher incidence of complications with pacemaker implantation, as well as with ICD and CRT implantation. The indications for ICDs and CRT do not have any distinctions based on sex, and outcomes are comparable in men and women. In fact, women often seem to have better outcomes with CRT compared with men. Despite the demonstrated benefits of these devices, ICDs and CRT are underutilized in women. In this review, we explore sex differences in utilization, outcomes, and complications with pacemakers, ICDs, and CRT.

DesCripTionA 69-year-old woman on apixaban for 4 years due to her atrial fibrillation presented with severe left lower abdominal pain. She was discharged from the hospital 4 days prior after treatment for influenza and had finished a course of oseltamivir. She did not receive any heparin products and was continued on apixaban during that admission. A few hours before presentation, she reported coughing severely with sudden onset of excruciating abdominal pain. She denied trauma or injury to the abdomen. On exam, she was alert, normotensive and tachycardic, with significant left lower quadrant tenderness in the abdomen. Laboratory results were significant for decreased haemoglobin from 15.2 to 12.9 g/ dL. CT of the abdomen showed acute left inferior rectus abdominis muscle haematoma (7.5 cm), along with stable and unchanged left adnexal cystic lesion (figure 1). Apixaban was discontinued, and the patient was closely monitored in the hospital with supportive care. Her haemoglobin remained stable and her pain improved. Repeat CT showed stable rectus sheath haematoma. She was asked to withhold apixaban for 1 week and was discharged to follow-up with her primary care physician to restart it.About one in six emergency department visits for adverse drug events is due to bleeding in patients taking anticoagulant medications, and direct oral anticoagulants (DOAC) account for 10% of these events.1 Only four cases of DOAC-associated rectus sheath haematoma have been reported, two associated with apixaban and two with rivaroxaban.2 Rectus sheath haematoma is a rare but serious complication associated with significant morbidity and occasional mortality. It is the result of bleeding into the rectus sheath from damage to the superior or inferior epigastric arteries. Common risk factors and causes of rectus sheath haematoma include anticoagulation, blunt or penetrating trauma, pregnancy, female gender, older age, hypertension, medical conditions such as collagen vascular disorders, and increased abdominal pressure from straining or severe coughing.2 Ultrasound is the initial test of choice, but CT of the abdomen will help to identify the origin, location and extent of bleeding. Management of rectus sheath haematoma depends on several factors such as the severity and size of the haematoma, the haemodynamic status of the patient and the extent of anticoagulation. Treatment includes usual supportive measures, including interventional source control when indicated.2 No guidelines exist to direct the timing of anticoagulation resumption in patients with spontaneous rectus sheath haematomas. The requirement for anticoagulation should be weighed against the risk of rebleeding once the haematoma is stable. For severe DOAC-related bleeding, prothrombin complex concentrate and recombinant activated factor VII have been recommended.1 Current research focuses on antidotes to neutralise the anticoagulant activity of DOACs, including both direct thrombin inhibitors and direct factor Xa (FXa) inhibitors. Idarucizumab is licensed for the rapid...