De-novo immune-mediated thrombotic thrombocytopenic purpura following surgical and non-surgical procedures: A systematic review.

When de-novo immune-mediated thrombotic thrombocytopenic purpura (TTP) is diagnosed following an invasive procedure, clinical presentation patterns and outcomes are poorly defined. Therefore, in a systematic literature review of patients diagnosed with TTP following an invasive surgical or non-surgical procedure, we identified 19 studies reporting data on 25 patients. These data suggest that 1) TTP pathogenesis likely begins prior to the invasive procedure, 2) patients experience significant diagnostic delays, and 3) there is a high incidence of renal replacement therapy. Although invasive procedures may trigger TTP, further studies are needed to clarify the mechanisms underlying this association.

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.

Patient-Reported Outcome Measures in Patients with Thrombotic Thrombocytopenic Purpura: A Systematic Review of the Literature.

Health-related quality of life (HRQoL) impacts of thrombotic thrombocytopenic purpura (TTP) have been captured in clinical studies using patient-reported outcome (PRO) measures (PROMs) that are validated for other diseases. However, the validity evidence to support the use of existing PROMs in patients with TTP is unknown. In a systematic review of the literature, including studies of adults and children with TTP, we assessed the validity evidence for use of PROMs in clinical research and clinical practice, characterized HRQoL, described the integration of PROMs in clinical practice and evaluated PRO scores for patients with TTP compared with reference populations. From an initial 4518 studies, we identified 14 studies using 16 PROMs to assess general HRQoL domains in patients in remission. No identified studies assessed the validity of PROMs for the context of use of TTP and no studies described PROM integration into TTP clinical practice or evaluated PROMs that were specific for patients with TTP. Moreover, PRO scores were worse in patients with TTP compared with reference populations and other chronic conditions. We conclude that, in patients with TTP, PROMs pick up on important patient experiences not captured by clinical outcomes at present. There is, therefore, a need for studies that assess the validity of existing PROMs in patients with TTP to determine if TTP-specific PROMs specific to patients with TTP should be developed.

In patients with suspected immune TTP, admission source impacts hospital length of stay and time to therapeutic plasma exchange impacts clinical outcomes.

INTRODUCTION: When immune thrombotic thrombocytopenic purpura (TTP) is suspected, outcomes are impacted by time to therapeutic plasma exchange (TPE). We evaluated the impact of time to TPE on outcomes in suspected TTP cases admitted through the Emergency Department (ED) vs. transferred from another facility (Transfer). MATERIALS AND METHODS: In a retrospective analysis of the National Inpatient Sample, we examined the association between TTP outcomes and admission source (ED vs. Transfer) for the primary outcome of time to TPE. A second stratified analyses within each analytic group examined the association of time to TPE (<1 day, 1 day, 2 days, and >2 days) and outcomes for the composite outcome of mortality, major bleeding and thrombosis. RESULTS: Of 1195 cases, 793 (66 %) were admitted through the ED and 402 (34 %) were transferred. Compared to ED cases, Transfers had a longer hospital length of stay (14.69 vs. 16.65 days, p = 0.0060). For ED cases, TPE after >2 days was associated with higher odds of the composite outcome (OR = 1.68 95 % CI: 1.11-2.54; p = 0.0150) and mortality (OR = 3.01 95 % CI: 1.38-6.57; p = 0.0056). For Transfers, TPE on day 2 was associated with higher odds of the composite outcome (OR = 3.00 95 % CI: 1.31-6.89; p = 0.0096) and mortality (OR = 4.95 95 % CI: 1.12-21.88; p = 0.0350). CONCLUSIONS: In suspected TTP admitted through the ED or transferred, there was no significant difference in time to TPE. A longer time to TPE was associated with worse outcomes. Future studies should evaluate strategies to decrease initial time to TPE.

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.

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.

A population-based analysis on the use of therapeutic plasma exchange and intravenous immunoglobulin in heparin-induced thrombocytopenia.

INTRODUCTION: In heparin-induced thrombocytopenia (HIT), selected patients are treated with therapies directed at the immune response, intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE). To determine IVIG and TPE characteristics and outcomes in HIT, we analyzed the National Inpatient Sample (NIS) database. METHODS: In a population-based analysis of the NIS, we identified hospital discharges of adult patients with a HIT diagnosis. A two-level statistical analysis was performed comparing cases as follows 1) IVIG or TPE vs. none; and 2) IVIG vs. TPE. For each analysis, the primary outcome was in-hospital mortality. Secondary outcomes were thrombotic events, major bleeding, infections, hospital length of stay, and total charges. RESULTS: Among 22,152 discharges with a HIT diagnosis, 77 (0.34%) and 52 (0.23%) received TPE and IVIG, respectively. In the first level analysis of TPE or IVIG vs. no treatment, TPE or IVIG treatment was associated with a higher likelihood of in-hospital mortality (OR = 1.85; 95%CI: 1.13-3.03, p = 0.0104), major bleeding (OR = 1.91; 95%CI: 1.25-2.93, p = 0.0030), gastrointestinal bleeding (OR = 1.89; 95%CI: 1.08-3.30, p = 0.0259), and infection (OR = 1.65; 95% CI:1.13-2.41, p = 0.0095). In the second-level analysis comparing IVIG vs. TPE, there were no significant differences in patient characteristics or outcomes in both unadjusted and adjusted analyses. CONCLUSIONS: In this population-based analysis of HIT, we found similar outcomes of IVIG and TPE-treated cases. Given the small sample size, future studies are needed to confirm this observation.

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.

Bleeding is associated with intravenous immunoglobulin and therapeutic plasma exchange use in heparin-induced thrombocytopenia: A propensity matched analysis.

Intravenous immunoglobulin (IVIG) and therapeutic plasma exchange (TPE) are used in select cases with heparin-induced thrombocytopenia (HIT). In a cross-sectional analysis, a propensity matched sample was generated by IVIG or TPE treatment status to assess the primary outcome of mortality. In 500 HIT cases, IVIG or TPE was not associated with increased mortality (OR = 1.46; 95% CI: 0.81-2.63, p = 0.2052) but was associated with a higher likelihood of major bleeding (OR = 1.75; 95% CI: 1.03-2.96, p = 0.0376). The use of IVIG or TPE in HIT cases with bleeding contraindications to standard therapies should be further investigated.