In hospitalized patients undergoing therapeutic plasma exchange, major bleeding prevalence depends on the bleeding definition: An analysis of The Recipient Epidemiology and Donor Evaluation Study-III.

BACKGROUND: Major bleeding in patients undergoing therapeutic plasma exchange (TPE) has been studied in large databases; but without standardizing bleeding definitions. Therefore, we used standardized definitions to evaluate major bleeding in hospitalized patients undergoing TPE using public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). STUDY DESIGN AND METHODS: In a retrospective cross-sectional analysis, we identified TPE-treated adults in a first inpatient encounter. We evaluated major bleeding prevalence using (1) International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) codes, (2) packed red blood cell (PRBC) transfusion, or (3) hemoglobin (Hgb) decline. Patients with major bleeding prior to their first TPE were excluded from the analysis. RESULTS: Among 779 patients undergoing TPE, major bleeding by at least one of the three bleeding definitions occurred in 135 patients (17.3%). For each of the ICD/CPT, PRBC, and Hgb definitions, the prevalence of major bleeding was 2.8% (n = 31), 7.4% (n = 81), and 5.4% (n = 59), respectively. Only 3.7% of bleeds (5/135) were captured by all three definitions and 19.3% (26/135) exclusively by any two pairwise definitions. The addition of PRBC transfusion and Hgb decline to ICD/CPT code definitions increased bleeding prevalence threefold. CONCLUSION: Among hospitalized adults undergoing TPE in the REDS-III study, the prevalence of major bleeding was 17.3%. The addition of PRBC and Hgb decline to ICD codes increased bleeding prevalence threefold. Future studies are needed to develop validated models that identify patients at risk for major bleeding during TPE.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Ninth Special Issue.

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 166 graded and categorized indications. This includes seven new fact sheets, nine new indications on existing fact sheets, and eight changes in the category for existing indications. The Ninth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.

Bleeding outcomes of inpatients receiving therapeutic plasma exchange: A propensity-matched analysis of the National Inpatient Sample.

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.

Hemostatic effects of therapeutic plasma exchange: A concise review.

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.

Central venous catheters are associated with thrombosis among adult inpatients undergoing therapeutic plasma exchange.

BACKGROUND: For inpatients undergoing therapeutic plasma exchange (TPE) in the United States, the primary mode of venous access is the central venous catheter (CVC). To evaluate the impact of CVC on thrombosis outcomes of patients undergoing TPE, we analyzed the National Inpatient Sample (NIS) database. STUDY DESIGN AND METHODS: In a cross-sectional analysis of the NIS, we identified hospital discharges of adult patients treated with TPE. Cases were classified into two groups based on CVC status. The primary outcome was thrombosis. Secondary outcomes were major bleeding, packed red blood cell (PRBC) transfusion, in-hospital mortality, hospital length of stay (LOS), and charges. RESULTS: Among 9863 TPE-treated discharges, CVC was used in 5988 (60%). These numbers correspond to weighted national estimates of 49 315 and 29 940, respectively. There was a positive and significant association between CVC and thrombosis (OR = 1.23, 95% 1.04-1.46, P = 0.0174), PRBC transfusion (OR = 1.15, 95% 1.03-1.29, P = 0.0121), in-hospital mortality (OR = 1.36, 95% 1.10-1.68, P = 0.0043), hospital LOS (15.63 vs 12.45 days, P < 0.0001) and hospital charges ($166 387 vs. $132 655, P < 0.0001). CONCLUSION: In hospitalized patients undergoing TPE, CVC use is associated with increased rates of thrombosis. Future studies are needed to investigate strategies to decrease CVC use and/or prevent CVC-associated complications in TPE-treated inpatients.

Clinical outcomes of cardiac surgery patients undergoing therapeutic plasma exchange for heparin-induced thrombocytopenia.

BACKGROUND AND OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated condition that leads to thrombocytopenia and possible thrombosis. Patients with HIT who require cardiac surgery pose a challenge as high doses of heparin or heparin alternatives are required to permit cardiopulmonary bypass (CPB). Intraoperative therapeutic plasma exchange (TPE) is a valuable adjunct in the management of antibody-mediated syndromes including HIT. The clinical impact of TPE on thromboembolic events, bleeding and mortality after heparin re-exposure is not well established. We hypothesized that TPE with heparin re-exposure will not lead to HIT-related thromboembolic events, bleeding or increased mortality after cardiac surgery with CPB. MATERIALS AND METHODS: We reviewed 330 patients who received perioperative TPE between September 2012 and September 2017. RESULTS: Twenty four patients received TPE for HIT before anticipated heparin use for CPB. Most patients were males (79%) scheduled for advanced heart failure therapies. Three patients (12·5%) died within 30 days after surgery but none of the deaths were considered HIT-related. Thromboembolic events (TE) occurred in 3 patients within 7 days of surgery; of those, two were possibly HIT-related. CONCLUSION: Therapeutic plasma exchange with heparin re-exposure was not strongly associated with HIT-related thrombosis/death after cardiac surgery with CPB.

Use of therapeutic plasma exchange in heparin-induced thrombocytopenia: A population-based study.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is characterized by anti-heparin/platelet factor 4 immune complexes, which are removed by therapeutic plasma exchange (TPE). Our main objective was to study TPE outcomes in HIT using a large administrative claims database. STUDY DESIGN AND METHODS: We used the National Inpatient Sample (NIS) to identify hospital discharges of adult patients (≥18) with a primary or secondary diagnosis of HIT. Cases were classified into two groups based on TPE use. The primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, hospital length of stay (LOS), and charges. Multivariable regression analysis, controlling for age and medical comorbidities, was used to examine the association of TPE with study outcomes. RESULTS: A HIT diagnosis was made in 22 165 discharges, of which 90 (0.4%) received TPE. Corresponding national estimates are 106 435 and 439, respectively. TPE was not associated with decreased in-hospital mortality (OR = 1.72; 95%CI: 0.93-3.17, P = .085). However, TPE was associated with a higher likelihood of major bleeding (OR = 2.35; 95%CI: 1.40-3.68, P = .0009), primarily driven by gastrointestinal bleeding (OR = 2.21; 95%CI: 1.17-4.17, P = .015). TPE was also associated with higher hospital LOS (20.5 vs 10 day, P < .0001) and charges (USD 211181 vs USD 81654, P < .0001). CONCLUSION: TPE's association with increased bleeding and a prolonged hospital course indicates that it is being used in HIT cases with a severe clinical phenotype. Future studies are needed to better characterize the HIT phenotype that will most benefit from TPE.

Activated Coagulation Time and Hepcon Protamine Titration Device to Manage Unfractionated Heparin During Cardiopulmonary Bypass in a Hemophilia A Patient on Emicizumab.

In the perioperative management of patients with hemophilia A, emicizumab prevents the accurate measurement of common clotting assays, including the activated clotting time (ACT), which is essential for high-dose heparin monitoring during cardiopulmonary bypass surgery. The authors describe the successful perioperative management of a hemophilia A patient on maintenance emicizumab who, following a non-ST myocardial infarction, underwent cardiopulmonary bypass grafting surgery with heparin monitoring using both the ACT and heparin levels from the Hepcon protamine titration device. Postoperatively, the patient was transitioned to recombinant factor VIII replacement therapy. In hemophilia A patients on emicizumab who require heparin titration on cardiopulmonary bypass surgery, the ACT, combined with Hepcon heparin levels, may be used to complete the surgery successfully without excessive bleeding or morbidity.

Strategies to Aid Identification of Apheresis PowerFlow Ports: A Case Report.

INTRODUCTION: The PowerFlow implantable apheresis intravenous port is a venous access device for therapeutic apheresis procedures. In this case review article, we identify key similarities and differences between apheresis PowerFlow ports and traditional ports. We also list strategies that emergency departments can implement to aid in correct port identification. METHODS: Using a case review format, we describe the clinical presentation of a 33-year-old female with neuromyelitis optica who was evaluated in the emergency department for an acute exacerbation. She had a history of outpatient apheresis procedures that made use of bilateral PowerFlow ports. Mistaken for a conventional port, the right PowerFlow port was accessed with a Huber needle rather than the appropriate catheter-over-needle device. On infusion of intravenous fluids, the patient experienced pain and swelling. Ultimately, the port malfunctioned and was eventually replaced. RESULTS: A subsequent root cause analysis identified opportunities for education and aids to improve port identification. To this end, strategies were implemented to appropriately identify the PowerFlow port using at least 2 of the following methods: (1) look in the patient's chart for record of an implantable apheresis intravenous port; (2) check the port identification card, bracelet, or keychain issued at insertion; (3) palpate the port to look for the rounded top and hollow concave entry point; and (4) use x-ray or fluoroscopy to identify radiopaque port markers. CONCLUSION: When a patient with a history of apheresis procedures presents with an implanted port, steps should be taken to ensure correct identification and access.

Therapeutic plasma exchange and intravenous immune globulin in the treatment of heparin-induced thrombocytopenia: A systematic review.

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 equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. CONCLUSION: In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.

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.

Therapeutic plasma exchange for management of heparin-induced thrombocytopenia: Results of an international practice survey.

INTRODUCTION: Anti-heparin/platelet factor 4 antibody immune complexes resulting from heparin-induced thrombocytopenia (HIT) are removed by therapeutic plasma exchange (TPE). We sought to define TPE in HIT practice patterns using an international survey. METHODS: A 31-item online survey was disseminated through the American Society for Apheresis. After institutional duplicate responses were eliminated, a descriptive analysis was performed. RESULTS: The survey was completed by 94 respondents from 78 institutions in 18 countries. Twenty-nine institutions (37%) used TPE for HIT (YES cohort) and 49 (63%) did not (NO cohort). Most NO respondents (65%) cited "no requests received" as the most common reason for not using TPE. Of the 29 YES respondents, 10 (34%) gave incomplete information and were excluded from the final analysis, leaving 19 responses. Of these, 18 (95%) treated ≤10 HIT patients over a 2-year period. The most common indications were cardiovascular surgery (CS; 63%) and HIT-associated thrombosis (HT; 26%). The typical plasma volume processed was 1.0 (63% CS and 58% HT). For CS, the typical replacement fluid was plasma (42%) and for HT, it was determined on an individual basis (32%). For CS, patients were treated with a set number of TPE procedures (37%) or laboratory/clinical response (37%). For HT, the number of TPE procedures typically depended on laboratory/clinical response (42%). CONCLUSION: In a minority of responding institutions, TPE is most commonly used in HIT to prophylactically treat patients who will undergo heparin re-exposure during CS. Prospective studies are needed to more clearly define the role of TPE in HIT.

ASFA Category IV becomes Category I: Idiopathic thrombotic thrombocytopenic purpura in a patient with presumed gemcitabine-induced thrombotic microangiopathy.

In the implementation of American Society for Apheresis national guidelines, the decision for therapeutic plasma exchange may be confounded by a clinical presentation that fits both a Category I and IV designation. We report the case of a 45-year-old female who presented with concern for a Category IV disorder, gemcitabine-induced thrombotic microangiopathy, and was ultimately diagnosed with a Category I disorder, idiopathic thrombotic thrombocytopenic purpura. This case highlights the importance of ruling out idiopathic TTP by a thorough evaluation for ADAMTS13 activity and inhibitor, even when an alternate thrombotic microangiopathy diagnosis may be likely.

Therapeutic white blood cell and platelet depletions using the spectra OPTIA system continuous mononuclear cell protocol.

The Spectra Optia apheresis system has only recently been approved by the Food and Drug Administration (FDA) for therapeutic white blood cell (WBC) depletions and is not yet approved for platelet depletions. Prior to FDA-approval of the WBC depletion protocol, when our available COBE Spectra apheresis systems were out of service, we successfully performed WBC depletion using a modified Spectra Optia apheresis system Continuous Mononuclear Cell (CMNC) protocol. Using this modified Spectra Optia CMNC protocol, we created institutional protocols for WBC and platelet depletions. We performed 10 WBC depletions in 9 patients and 2 platelet depletions in 2 patients. We compared pre- and post-procedure WBC, platelet count, and hemoglobin to the same data from patients previously treated on the COBE Spectra and found no difference in % WBC and platelet reduction. We also found no significant difference in post-procedural hematocrit decline. Additionally, adverse reactions were not increased. Therefore, we conclude that the Spectra Optia CMNC protocol can be successfully modified for effective WBC and platelet depletions without increase in adverse reactions.

Indications for and outcomes of therapeutic plasma exchange after cardiac transplantation: A single center retrospective study.

INTRODUCTION: Limited data are available describing indications for and outcomes of therapeutic plasma exchange (TPE) in cardiac transplantation. METHODS: In a retrospective study of patients who underwent cardiac transplantation at Duke University Medical Center from 2010 to 2014, we reviewed 3 TPE treatment patterns: a Single TPE procedure within 24 h of transplant; Multiple TPE procedures initiated within 24 h of transplant; and 1 or more TPE procedures beginning >24 h post-transplant. Primary and secondary outcomes were overall survival (OS) and TPE survival (TS), respectively. RESULTS: Of 313 patients meeting study criteria, 109 (35%) underwent TPE. TPE was initiated in 82 patients within 24 h, 40 (37%) receiving a single procedure (Single TPE), and 42 (38%) multiple procedures (Multiple TPE). Twenty-seven (25%) began TPE >24 h after transplant (Delayed TPE). The most common TPE indication was elevated/positive panel reactive or human leukocyte antigen antibodies (32%). With a median follow-up of 49 months, the non-TPE treated and Single TPE cohorts had similar OS (HR 1.08 [CI, 0.54, 2.14], P = .84), while the Multiple and Delayed TPE cohorts had worse OS (HR 2.62 [CI, 1.53, 4.49] and HR 1.98 [CI, 1.02, 3.83], respectively). The Multiple and Delayed TPE cohorts also had worse TS (HR 2.59 [CI, 1.31, 5.14] and HR 3.18 [CI, 1.56, 6.50], respectively). Infection rates did not differ between groups but was independently associated with OS (HR 2.31 [CI, 1.50, 3.54]). CONCLUSIONS: TPE is an important therapeutic modality in cardiac transplant patients. Prospective studies are needed to better define TPE's different roles in this patient population.

Role of C1q complement fixing antibody assay in therapeutic plasma exchange management of pediatric cardiac antibody mediated rejection.

Pediatric cardiac transplant patients with antibody-mediated rejection (AMR) often undergo therapeutic plasma exchange (TPE) to remove pathologic donor specific antibodies (DSA). In cases where DSA persist, it is unclear how long TPE should be continued. We report a case of a 17-year-old cardiac transplant patient with AMR where use of a C1q complement fixing antibody assay helped guide TPE cessation. This report adds to the existing literature that highlights the potential clinical significance of C1q antibodies in AMR management.