Background: In the PAUSE (Perioperative Anticoagulant Use for Surgery Evaluation) Study, a simple, standardized, perioperative interruption strategy was provided for patients with nonvalvular atrial fibrillation taking direct oral anticoagulants (DOACs). Our objective was to define the factors associated with perioperative bleeding. Methods and Results: We analyzed bleeding as the composite of major and clinically relevant nonmajor bleeding. Putative predictors of bleeding, and preoperative DOAC level were prospectively collected during recruitment. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. There were 3007 patients requiring perioperative DOAC interruption. More than one third of the included patients underwent a high bleeding risk procedure. The 30‐day rates of major and clinically relevant nonmajor bleeding were 3.02% in apixaban (n=1257), 2.84% in dabigatran (n=668), and 4.16% for rivaroxaban (n=1082). Multivariate analysis stratified by region found more bleeding for hypertension (odds ratio [OR], 1.79; 95% CI 1.07‐2.99; P =0.027), and prior bleeding (OR, 1.71; 95% CI, 1.08‐2.71; P =0.021). Surgical bleed risk classification (high‐ versus low‐risk) as a predictor of bleeding was only significant in the univariate analysis. The prediction model for major and clinically relevant nonmajor bleeding had an area under the curve of 0.71, and the preoperative DOAC level did not improve the area under the curve of the model. Conclusions: In patients treated with DOACs who required an elective surgery/procedure and were managed with standardized DOAC interruption and resumption, there we did not find reversible risk factors for bleeding, suggesting that adjustment of the PAUSE management protocol to mitigate against bleeding is not needed.

Extended thromboprophylaxis given to medically ill patients for up to 45 days following an acute hospitalization remains an emerging topic among many hospital-based health care providers. Recent advancements in the field of extended thromboprophylaxis using risk stratification and careful patient selection criteria have led to an improved safety profile of direct oral anticoagulants (DOACs) and established net clinical benefit when given to key patient subgroups at high risk of venous thromboembolism (VTE) and low risk of bleeding. The Food and Drug Administration (FDA) has now approved the DOACs betrixaban and rivaroxaban for both in-hospital and extended thromboprophylaxis in medically ill patients in these key subgroups, which represents more than one-quarter of hospitalized medically ill patients. This has potential to significantly reduce VTE-related morbidity and mortality for these patients. Emerging data also supports reductions in the risk of arterial thromboembolism in medically ill patients with extended thromboprophylaxis post-hospital discharge using DOACs. This article aims to review the most recent concepts of predicting and preventing VTE and to discuss emerging paradigms of extended thromboprophylaxis in hospitalized medically ill patients utilizing an individualized, risk-adapted approach.

Intensive care physicians may assume the primary care of patients with transplant-associated thrombotic microangiopathy (TA-TMA), an uncommon but potentially critical complication of hematopoietic stem cell transplants (HSCTs) and solid organ transplants. TA-TMA can have a dramatic presentation with multiple organ dysfunction syndrome (MODS) associated with high morbidity and mortality. The typical presenting clinical features are hemolytic anemia, thrombocytopenia, refractory hypertension, proteinuria and worsening renal failure. Intestinal involvement, with abdominal pain, nausea and vomiting, gastrointestinal bleeding, and ascites are also common. Cardiopulmonary involvement may develop from various causes including pulmonary arteriolar hypertension, pleural and pericardial effusions, and diffuse alveolar hemorrhage. Due to other often concurrent complications after HSCT, early diagnosis and effective management of TA-TMA may be challenging. Close collaboration between ICU and transplant physicians, along with other relevant specialists, is needed to best manage these patients. There are currently no approved therapies for the treatment of TA-TMA. Plasma exchange and rituximab are not recommended unless circulating factor H (CFH) antibodies or thrombotic thrombocytopenic purpura (TTP; ADAMTS activity < 10%) are diagnosed or highly suspected. The role of the complement pathway activation in the pathophysiology of TA-TMA has led to the successful use of targeted complement inhibitors, such as eculizumab. However, the relatively larger studies using eculizumab have been mostly conducted in the pediatric population with limited data on the adult population. This review is focused on the role of intensive care physicians to emphasize the clinical approach to patients with suspected TA-TMA and to discuss diagnosis and treatment strategies.

Vancomycin-induced immune thrombocytopenia (ITP) is a rare, potentially life-threatening complication from an antibiotic frequently used in medical practice. We report a case of an 81-year-old male with recent removal of an infected right knee prosthesis and insertion of an articulating antibiotic spacer, presenting from rehabilitation for severe thrombocytopenia (1 X 10³/µL). The patient’s thrombocytopenia was initially falsely attributed to rifampin-induced ITP, a much more common cause of drug-induced thrombocytopenia. Only later, after a second precipitous drop in platelet count, vancomycin was correctly identified as the culprit. The patient’s serum was tested for drug-dependent platelet antibodies with and without vancomycin. A positive reaction for IgG was detected by flow cytometry in the absence of vancomycin, which was potentiated in the presence of vancomycin. The result indicated the presence of vancomycin-dependent and nondrug-dependent platelet reactive antibodies and confirmed the diagnosis of vancomycin-induced ITP. In this case, the correct diagnosis was masked by the simultaneous administration of two drugs that cause drug-induced ITP and highlights the importance of early recognition of rare, vancomycin-induced ITP.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a translocation of chromosomes 15 and 17, creating an alternation in the retinoic acid receptor-alpha (RAR-alpha) gene. This leads to excessive medullary production of promyelocytic blasts, which are frequently associated with the hemorrhagic complications seen in APL. In contrast, APL-associated thrombosis occurs much less frequently and is an underappreciated life-threatening manifestation of the disease. Most thrombotic events occur during induction chemotherapy with all-transretinoic acid and are rarely seen as the initial presentation on APL. Here we report an exceedingly rare case of a patient with recurrent venous and arterial thrombotic events, including deep vein thrombosis, bilateral segmental pulmonary embolism, an ischemic stroke, splenic infarcts, and renal infarcts, later found to have APL. We aim to discuss the most recent understanding of the pathogenesis of APL-associated thrombosis and to summarize the literature of this rare presentation of APL.