Management of Older Adults with Sickle Cell Disease: Considerations for Current and Emerging Therapies.

People with sickle cell disease (SCD) are living longer than ever before, with the median survival increasing from age 14 years in 1973, beyond age 40 years in the 1990s, and as high as 61 years in recent cohorts from academic centers. Improvements in survival have been attributed to initiatives, such as newborn screening, penicillin prophylaxis, vaccination against encapsulated organisms, better detection and treatment of splenic sequestration, and improved transfusion support. There are an estimated 100,000 people living with SCD in the United States and millions of people with SCD globally. Given that the number of older adults with SCD will likely continue to increase as survival improves, better evidence on how to manage this population is needed. When managing older adults with SCD (defined herein as age ≥ 40 years), healthcare providers should consider the potential pitfalls of extrapolating evidence from existing studies on current and emerging therapies that have typically been conducted with participants at mean ages far below 40 years. Older adults with SCD have historically had little to no representation in clinical trials; therefore, more guidance is needed on how to use current and emerging therapies in this population. This article summarizes the available evidence for managing older adults with SCD and discusses potential challenges to using approved and emerging drugs in this population.

Initiation of Emicizumab Therapy in an Adult Patient With Hemophilia A With Inhibitors and Associated Drug Cost Savings.

Objective: To report the utilization of emicizumab in a patient with severe hemophilia A with inducible inhibitors and the reduction of drug costs related to decreased on-demand recombinant factor VIIa use. Case Summary: A 65-year-old African American man with established hemophilia A with an inducible factor VIII inhibitor presented with a bleeding hematoma from the right posterior thigh. The patient was historically managed on frequent administration of recombinant factor VIIa to achieve hemostasis and was started on every 2-hour dosing during this admission. Emicizumab, a new therapy for hemophilia A, became available during this admission, and the patient discontinued recombinant factor VIIa and transitioned to weekly emicizumab injections. The patient did not require any recombinant factor VIIa during the following 12 months resulting in substantial drug cost savings. Discussion: After initiation of emicizumab therapy, the patient no longer required on-demand treatment with recombinant factor VIIa for bleeds. Through this reduction in recombinant factor VIIa, there was a large decrease in inpatient drug costs and inpatient admissions for bleeding events. Conclusion: The potential reduction in drug costs and inpatient admissions should be considered when determining if emicizumab therapy is appropriate for hemophilia A patients with inhibitors. Further research is needed to confirm that continued long-term use of emicizumab remains associated with a reduction in on-demand treatment.

Effects of therapeutic plasma exchange on anticoagulants in patients receiving therapeutic anticoagulation: a systematic review.

Therapeutic plasma exchange (TPE) removes coagulation proteins, but its impact on therapeutic anticoagulation is unknown. We performed a systematic review of the literature to determine the coagulation effects of TPE in patients receiving systemic anticoagulation. We searched MEDLINE, CINAHL, EMBASE, and Web of Science until June 2018 for studies combining controlled vocabulary and keywords related to therapeutic plasma exchange, plasmapheresis, anticoagulants, and therapy. The primary outcome was the effect of TPE on anti-Xa activity, activated partial thromboplastin time (aPTT), or international normalized ratio (INR). The secondary outcome was reports of post-TPE bleeding or thrombosis. A total of 1830 references were screened and eight studies identified. Our selected studies (five case reports and three case series) involved 23 patients and evaluated the effects of seven anticoagulants. Six studies of unfractionated heparin, low-molecular-weight heparins, and direct oral anticoagulants demonstrated an anti-Xa level decline. Two studies of unfractionated heparin and low-molecular-weight heparins showed an aPTT increase. One study of warfarin showed a post-TPE INR increase. Reports of post-TPE bleeding occurred in two patients and thrombosis in one. In patients receiving therapeutic anticoagulation, TPE is associated with anti-Xa activity decline and aPTT and INR increase. These coagulation changes do not appear to significantly increase bleeding or thrombotic risk. Our data suggest the need for prospective studies to investigate the true clinical impact of TPE on therapeutic anticoagulation.

Role of platelet inhibition in microvascular surgery.

Thrombosis remains a significant complication of microvascular free tissue transfer. Recent discoveries in the field of vascular biology have led to a greater understanding of thrombogenesis and the pivotal role that platelets play in the formation of a clot. However, current antithrombotic strategies in the clinical practice of free tissue transfer have not typically focused on platelet inhibition. Decades of cardiovascular clinical trials have delineated the essential role of platelet inhibitor therapy in patients with acute coronary syndromes and those undergoing percutaneous coronary interventions. Understanding the current treatment guidelines for antiplatelet therapy across the spectrum of patients with coronary heart disease may provide insights into their use in the prevention and treatment of thrombosis in microvascular surgery. In this review, we examine the current antiplatelet agents in clinical use and discuss the potential role of platelet inhibition in free flap surgery, particularly in the setting of repeated microvascular thrombosis.

New classes of anticoagulation and antiplatelet agents: preprocedure management and safety guidelines for imaging-guided intervention.

OBJECTIVE: New medications are available for prophylaxis of deep venous thrombosis, the treatment of venous thromboembolism, and also to reduce the risk of acute coronary syndrome and stroke. The purpose of this review is to provide the radiologist a practical and succinct summary of the new anticoagulation and antiplatelet medications and how to manage these medications in patients who are in need of a radiology intervention. CONCLUSION: This article provides recommendations for preprocedure management of new anticoagulants and antiplatelet agents in patients undergoing radiology intervention.