Background: Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. Study Design and Methods: We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. Results: After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were

Transfusion therapy in postpartum hemorrhage (PPH) traditionally has been modeled after precedents set in the Vietnam and Korean wars. However, data from recent military combat casualties suggest a different transfusion strategy. Transfusion of packed red blood cells, fresh frozen plasma, and platelets in a ratio of 1:1:1 improves dilutional coagulopathy and survival. Women who present with low fibrinogen at the time of diagnosis of PPH have poorer outcomes and might benefit from early fibrinogen replacement. The antifibrinolytic agent, tranexamic acid, decreases bleeding and progression to severe PPH, but its role in PPH management is evolving. Observational data suggest that the use of recombinant factor VIIa should be limited to bleeding that has not responded to an optimal transfusion strategy. Point-of-care testing using thromboelastography is helpful in guiding the selection of blood products to be transfused. Additionally, massive transfusion protocols can decrease the overall number of products transfused and improve outcomes.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. In the Ninth Edition, the JCA Special Issue Writing Committee has incorporated systematic review and evidence-based approaches in the grading of evidence and categorization of apheresis indications to make recommendations on the use of apheresis in a wide variety of diseases and conditions. This edition has largely maintained the general layout and concept of a fact sheet introduced in the Fourth Edition (2007). Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease or medical condition. The Ninth Edition of the JCA Special Issue comprises 91 fact sheets and

The thrombotic microangiopathies (TMAs) are rare, life-threatening thrombotic disorders of diverse etiologies. Systematic studies of TMA have been difficult to perform due to their rare occurrence, disease heterogeneity and, lack of an organized research network in the United States. Whereas a multi-institutional approach has been used in Europe and Canada, TMA research in the US has been largely single-center based. To overcome the limitations of single institutional registries and to expand the number of TMA patients available for study, four academic centers convened during the 2013 ASFA annual meeting to establish the TMA Registry of North America (TRNA) with the following goals: (1) design and develop a registry to define "best practices" for the diagnosis, treatment, and management of TMA; (2) develop a platform for conducting observational and interventional clinical trials; (3) and, establish a national bio-repository of samples from patients with TMA to facilitate future studies. This abstract reports the first multi-institutional network in the United States designed to study TMA. Members met through bimonthly tele-conferences to develop a clinical registry using REDCap (Research Electronic Data Capture), a HIPAA-compliant, internet-based software program for data entry. To facilitate a cohesive and streamlined review of IRB applications, the TRNA utilized IRBshare, a portal for rapid approval of multi-site investigations. IRB consent included participation in a bio-repository arm for collecting blood and apheresate. Following approval through the Duke IRB in June 2014, study documents were uploaded to the IRBshare website. Since August 2015, 16 study participants with TMA have been consented, 13 of which have had their clinical information entered into the database. Preliminary data shows our population is 73% African-American and female. Average laboratory values at presentation included hemoglobin of 9.7 g/dL, platelets 53 x10^9/L, and LDH 1,150 u/L. ADAMTS13 testing was performed in 77% (10/13), of which 60% (6/10) measured at <10%. Current efforts include expansion of network sites to expand the registry and to develop clinical protocols for future studies. With its clinical and IRB infrastructure in place, the TRNA, which is the first U.S. research network designed to study TMA, is poised to perform cooperative observational and interventional trials in the near future. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Heparin-induced thrombocytopenia (HIT) remains an important diagnosis to consider in hospitalized patients developing thrombocytopenia. HIT is an immune-mediated prothrombotic disorder caused by antibodies to platelet factor 4 (PF4) and heparin. Recent basic scientific studies have advanced our understanding of disease pathogenesis through studies of the PF4/heparin structure, immune mechanisms, and cellular basis of thrombosis. Clinical advances have also occurred in areas of HIT prevention, description of disease variants, and diagnostic strategies. Emerging anticoagulants with the potential to change HIT treatment are evolving, although with limited data. This review will provide a current perspective on HIT pathogenesis, disease features, diagnostic strategies, and role of emerging therapies for the management of HIT.

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.

Therapeutic plasma exchange (TPE) alters the hemostatic balance. Contributing to TPE's hemostatic effects is the mechanical processing of blood in the extracorporeal circuit, circuit anticoagulant, type of replacement fluid, TPE schedule and number of procedures, TPE timing relative to invasive procedures, and removal of nontargeted components such as platelets, coagulation proteins, and cytokines. Although TPE's hemostatic effects are well established, how it impacts the bleeding risk is not clearly understood. In this concise review, we describe the effects of the above TPE‐related factors on hemostatic balance, present data on the effects of TPE on blood hemostasis, including its effects on platelet counts and clotting assays, and review the literature on the impact of TPE‐induced hemostatic changes on TPE‐associated bleeding events. Finally, we discuss risk factors associated with bleeding during TPE and review the literature on TPE‐associated hemostatic effects in the pediatric population.

Background Although therapeutic plasma exchange (TPE) is associated with hemostatic abnormalities, its impact on bleeding outcomes is unknown. Therefore, the main study objective was to determine bleeding outcomes of inpatients treated with TPE. Study Design and Methods In a cross‐sectional analysis of the National Inpatient Sample (NIS), discharges were identified with 10 common TPE‐treated conditions. A 1:3 propensity‐matched analysis of TPE‐ to non‐TPE‐treated discharges was performed. The primary outcome was major bleeding and secondary outcomes were packed red blood cell (PRBC) transfusion, mortality, disposition, hospital length of stay (LOS), and charges. Multivariable regression analyses were used to examine the association between TPE and study outcomes. Results The study population was 15,964 discharges, of which 3991 were TPE‐ treated. The prevalence of major bleeding was low (5.4%). When compared to non‐TPE discharges, TPE had a significant and positive association with major bleeding (OR = 1.37, 95% CI: 1.16–1.63, p = .0003). TPE was also associated with PRBC transfusion (OR = 1.66, 95% CI: 1.42–1.94, p < .0001), in‐hospital mortality (OR = 1.45, 95% CI: 1.10–1.90, p = .0008), hospital length of stay (12.45 [95% CI: 11.95–12.97] vs. 7.38 [95% CI: 7.12–7.65] days, p < .0001) and total charges, ($125,123 [95% CI: $119,220–$131,317] vs. $61,953 [95% CI: $59,391–$64,625], p < .0001), and disposition to non‐self‐care (OR = 1.29, 95% CI: 1.19–1.39, p < .0001). Discussion The use of TPE in the inpatient setting is positively associated with bleeding; however, with low prevalence. Future studies should address risk factors that predispose patients to TPE‐associated bleeding.