Ibrutinib is an irreversible inhibitor of Bruton’s tyrosine kinase (Btk) that has proven to be an effective therapeutic agent for multiple B-cell mediated lymphoproliferative disorders. Ibrutinib, however, carries an increased bleeding risk compared to standard chemotherapy. Bleeding events range from minor mucocutaneous bleeding to life-threatening hemorrhage, due in large part to the effects of ibrutinib on several distinct platelet signaling pathways. There is currently minimal data to guide clinicians regarding the use of ibrutinib in patients at high risk for bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk for vascular disease is unknown. Patients should be cautioned against using nonsteroidal anti-inflammatory drugs, fish oils, vitamin E, and aspirin-containing products, and consider replacing ibrutinib with a different agent if dual antiplatelet therapy is indicated. Patients should not take vitamin K antagonists concurrently with ibrutinib; direct oral anticoagulant should be used if extended anticoagulation is strongly indicated. In this review, we describe the pathophysiology of ibrutinib-mediated bleeding and suggest risk reduction strategies for common clinical scenarios associated with ibrutinib.

Direct oral anticoagulant use in patients with cirrhosis may be as safe as traditional anticoagulants. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or thrombosis.

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation a Authors share co-first authorship. b Authors share co-senior authorship.

Clinically significant bleeding can occur as a consequence of surgery, trauma, obstetric complications, anticoagulation, and a wide variety of disorders of hemostasis. As the causes of bleeding are diverse and not always immediately apparent, the availability of a safe, effective, and non-specific hemostatic agent is vital in a wide range of clinical settings, with antifibrinolytic agents often utilized for this purpose. Tranexamic acid (TXA) is one of the most commonly used and widely researched antifibrinolytic agents; its role in postpartum hemorrhage, menorrhagia, trauma-associated hemorrhage, and surgical bleeding has been well defined. However, the utility of TXA goes beyond these common indications, with accumulating data suggesting its ability to reduce bleeding and improve clinical outcomes in the face of many different hemostatic challenges, without a clear increase in thrombotic risk. Herein, we review the literature and provide practical suggestions for clinical use of TXA across a broad spectrum of bleeding disorders.

Extracorporeal membrane oxygenation (ECMO) causes both thrombosis and bleeding. Major society guidelines recommend continuous, systemic anticoagulation to prevent thrombosis of the ECMO circuit, though this may be undesirable in those with active, or high risk of, bleeding. We aimed to systematically review thrombosis and bleeding outcomes in published cases of adults treated with ECMO without continuous systemic anticoagulation. Ovid MEDLINE, Cochrane CENTRAL and CDSR, and hand search via SCOPUS were queried. Eligible studies were independently reviewed by two blinded authors if they reported adults (≥18 years) treated with either VV- or VA-ECMO without continuous systemic anticoagulation for ≥24 hours. Patient demographics, clinical data, and specifics of ECMO technology and treatment parameters were collected. Primary outcomes of interest included incidence of bleeding, thrombosis of the ECMO circuit requiring equipment exchange, patient venous or arterial thrombosis, ability to wean off of ECMO, and mortality. Of the 443 total publications identified, 34 describing 201 patients met our inclusion criteria. Most patients were treated for either acute respiratory distress syndrome or cardiogenic shock. The median duration of anticoagulant-free ECMO was 4.75 days. ECMO circuity thrombosis and patient thrombosis occurred in 27 (13.4%) and 19 (9.5%) patients, respectively. Any bleeding and major or “severe” bleeding was reported in 66 (32.8%) and 56 (27.9%) patients, respectively. Forty patients (19%) died. While limited by primarily retrospective data and inconsistent reporting of outcomes, our systematic review of anticoagulant-free ECMO reveals an incidence of circuity and patient thrombosis comparable to patients receiving continuous systemic anticoagulation while on ECMO.

Objective— Factor XI (FXI) contributes to thrombotic disease while playing a limited role in normal hemostasis. We generated a unique, humanized anti-FXI antibody, AB023, which blocks factor XIIa-mediated FXI activation without inhibiting FXI activation by thrombin or the procoagulant function of FXIa. We sought to confirm the antithrombotic activity of AB023 in a baboon thrombosis model and to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adult subjects. Approach and Results— In a primate model of acute vascular graft thrombosis, AB023 reduced platelet and fibrin accumulation within the grafts by >75%. To evaluate the safety of AB023, we performed a first-in-human study in healthy adult volunteers without any serious adverse events. Overall, 10 of 21 (48%) subjects experienced 20 treatment-emergent adverse events, with 7 of 16 (44%) subjects following active treatment and 3 of 5 (60%) subjects following placebo. AB023 did not increase bleeding or prothrombin times. Anticoagulation was verified by a saturable ≈2-fold prolongation of the partial thromboplastin time for over 1 month after the highest dose. Conclusions— AB023, which inhibits contact activation-initiated blood coagulation in vitro and experimental thrombus formation in primates, produced a dose-dependent duration of limited anticoagulation without drug-related adverse effects in a phase 1 trial. When put in context with earlier observations suggesting that FXI contributes to venous thromboembolism and cardiovascular disease, although contributing minimally to hemostasis, our data further justify clinical evaluation of AB023 in conditions where contact-initiated FXI activation is suspected to have a pathogenic role. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT03097341.

Clinicians, including hematologists, are more frequently encountering transgender individuals in practice; however, most lack training on the management and complications of transgender medicine. Hormonal therapy forms the backbone of medical interventions for patients undergoing gender transition. While supplementing an individual's intrinsic sex hormone is associated with a variety of hematologic complications including increased rates of venous thrombosis, cardiovascular events, erthyrocytosis, and malignancy, the risks of supplementing with opposing sex hormones are not well understood. Data on the hematologic complications of these therapies are accumulating but remain limited, and clinicians have little experience with their management. This review highlights the current interventions available in transgender medicine and related potential hematologic complications, and it suggests simple, evidence-based management going forward.

Safety and efficacy of pharmacological thromboprophylaxis for hospitalized patients with cirrhosis: a single-center retrospective cohort study. J Thromb Haemost 2015; 13: 1245-53. Summary. Background: Hospitalized patients with cirrhosis are at increased risk for venous thromboembolism (VTE). The benefits and risks of pharmacological thromboprohylaxis in these patients have not been well studied. Objectives: To examine the safety and efficacy of pharmacological VTE prophylaxis in hospitalized cirrhotic patients. Patients/Methods: Retrospective cohort study of patients with cirrhosis hospitalized at an academic tertiary care referral center over a 5-year period. Results: Six hundred hospital admissions accounting for 402 patients were included. VTE prophylaxis was administered during 296 (49%) admissions. Patients receiving VTE prophylaxis were older (59 years vs. 55 years, P < 0.001), had longer lengths of stay (9.6 days vs. 6.8 days, P = 0.002), and lower Model for End-Stage Liver Disease scores (13.2 vs. 16.1, P < 0.001). In-hospital bleeding events (8.1% vs. 5.5%, P = 0.258), gastrointestinal bleeding events (3.0% vs. 3.2% P = 0.52), new VTE events (2.37% vs. 1.65%, P = 0.537), and mortality (8.4% vs. 7.3%, P = 0.599) were similar in the two groups. VTE prophylaxis did not reduce the risk of VTE (odds ratio 0.94, 95% confidence interval 0.23-3.71), and patients receiving unfractionated heparin, but not low molecular weight heparin, were at increased risk for in-hospital bleeding events (odds ratio 2.38, 95% confidence interval 1. 15-4.94 vs. 0.87, 0.37-2.05, respectively). Conclusion: The rate of VTE in this cohort of hospitalized cirrhotic patients was low and was unaffected by pharmacological thromboprophylaxis. Unfractionated heparin was associated with an increased risk for in-hospital bleeding, suggesting that if thromboprophylaxis is indicated, low molecular weight heparin may be favored.