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.
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