Joseph J. Shatzel

Ibrutinib‐associated bleeding: pathogenesis, management and risk reduction strategies

Ibrutinib is an irreversible inhibitor of Brutons 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 with 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 a minimal amount of data to guide clinicians regarding the use of ibrutinib in patients at high risk of bleeding or on anticoagulant or antiplatelet therapy. In addition, the potential cardiovascular protective effects of ibrutinib monotherapy in patients at risk of vascular disease are unknown. Patients should be cautioned against using non‐steroidal 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 anticoagulants 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.

The efficacy and safety of direct oral anticoagulants vs traditional anticoagulants in cirrhosis

The coagulopathy of cirrhosis is complex, placing patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have equivalent or superior efficacy and safety as compared to vitamin K antagonists (VKAs); however, their efficacy and safety in liver cirrhosis has not been studied. To better define this, we evaluated outcomes of patients with cirrhosis prescribed DOACs compared to other anticoagulants at our center.

Syndromes of Thrombotic Microangiopathy

Thrombotic thrombocytopenia purpura (TTP) and the hemolytic uremic syndrome (HUS) are rare thrombotic microangiopathies that can be rapidly fatal. Although the acquired versions of TTP and HUS are generally highest on this broad differential, multiple rarer entities can produce a clinical picture similar to TTP/HUS, including microangiopathic hemolysis, renal failure, and neurologic compromise. More recent analysis has discovered a host of genetic factors that can produce microangiopathic hemolytic syndromes. This article discusses the current understanding of thrombotic microangiopathy and outlines the pathophysiology and causative agents associated with each distinct syndrome as well as the most accepted treatments.

Thrombotic issues in transgender medicine: A review

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 individuals 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. Am. J. Hematol. 92:204–208, 2017.

Andexanet Alfa for Factor Xa Inhibitor Reversal.

1. Murphy MF, Dumont LJ, Greinacher A. Interference of new drugs with compatibility testing for blood transfusion. N Engl J Med 2016; 375: 295-6. 2. Summary of product characteristics: DARZALEX 20 mg/mL concentrate for solution for infusion. London: European Medicines Agency, 2016 (http://www .ema .europa .eu/ docs/ en_GB/ document_library/ EPAR_-_Product_Information/ human/ 004077/ WC500207296 .pdf). 3. Regan DM, Markowitz MA. Mitigating the anti-CD38 interference with serologic testing. AABB bulletin #16-02. Bethesda, MD: American Association of Blood Banks, 2016. 4. Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375: 754-66.

Rapid and durable response to intravenous immunoglobulin in delayed heparin-induced thrombocytopenia: a case report

Heparin‐induced thrombocytopenia (HIT) results in platelet consumption and a virulent thrombotic state, which generally responds to cessation of heparin and initiation of anticoagulation. Rarely, delayed HIT can occur and/or persist after heparin is discontinued.

Non-vitamin K antagonist oral anticoagulants for heparin-induced thrombocytopenia. A systematic review of 54 reported cases.

Non-vitamin K antagonist oral anticoagulants for heparin-induced thrombocytopenia. A systematic review of 54 reported cases -

Treatment of individuals who cannot receive blood products for religious or other reasons

By virtue of their religious principles, Jehovahs Witnesses (JWs) generally object to receiving blood products, raising numerous ethical, legal, and medical challenges for providers who care for these patients, especially in the emergent setting. In this review, we discuss several areas relevant to the care of JWs, including the current literature on “bloodless” medical care in the setting of perioperative and intraoperative management, acute blood loss, trauma, pregnancy, and malignancy. We have found that medical and administrative efforts in the form of bloodless medicine and surgery programs can be instrumental in helping to reduce risks of morbidity and mortality in these patients. Planning prior to an anticipated event associated with blood loss or anemia (such as elective surgery, pregnancy, and chemotherapy) is critical. Specifically, bloodless medicine programs should prioritize vigilant early screening and management of anemias, early establishment of patient wishes regarding transfusion, and the incorporation of those wishes into multidisciplinary medical and surgical care. Although there are now a variety of human‐based and nonhuman‐based products available as transfusion alternatives, the degree and quality of evidence to support their use varies significantly between products and is also largely dependent on the clinical setting.

Drug eluting biliary stents to decrease stent failure rates: A review of the literature.

Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.

Management of Anticoagulation in Patients With Prostate Cancer Receiving Enzalutamide

Enzalutamide, a novel, oral androgen receptor antagonist used for the treatment of metastatic, castration-resistant prostate cancer, has been shown to improve overall and progression-free survival, prolong time to initiation of chemotherapy, reduce skeletal-related events, and carry a favorable adverse effect profile. Metastatic prostate cancer is a disease of older men, a population with an increased incidence of medical comorbidities warranting anticoagulation. Prostate cancer itself, along with some of its therapies, is also prothrombotic. Enzalutamide interacts with several anticoagulants through various mechanisms, making their concurrent use clinically challenging. As such, complex decisions about anticoagulation in these patients are frequently encountered by treating physicians. In this review, we describe the potential interactions between enzalutamide and various anticoagulants, and suggest management paradigms based on the current body of knowledge for patients with atrial fibrillation, venous thromboembolism, and mechanical heart valves.