Therapeutic plasma exchange-free treatment for first-episode TTP: A systematic review
Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis. 2023;:103661
OBJECTIVE Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA), and therapeutic plasma exchange (TPE) is currently the standard treatment. However, TPE sometimes cannot be implemented. The aim of this study was to systematically review patients with a first TTP episode who were treated without TPE. METHOD The PubMed, Embase, Web of Science and Cochrane Library databases were searched by two investigators independently to collect case reports and clinical studies on TTP patients treated without TPE. After removing duplicate records and records that did not meet the inclusion criteria, the patients' data of eligible studies, including the basic characteristics, treatment regimens, and outcomes were extracted for further analysis. RESULTS A total of 5338 potentially relevant original studies were identified, from which 21 studies, including 14 cases, 3 case series and 4 retrospective studies, met eligibility requirements and were included. Treatment regimens in the absence of TPE were found to vary based on individual information. Most patients recovered, with normal platelet counts and ADAMT13 activity at discharge. In the meta-analysis of retrospective studies, the TPE-free group had no higher mortality than the TPE-treated group. CONCLUSION Our study shows that TPE-free treatment may not increase the mortality of TTP patients, which provides a new treatment concept for patients with first episodes of TTP. However, the current evidence is not high due to the lack of randomized controlled trials, so more well-designed prospective clinical trials are warranted to investigate the safety and efficacy of TPE-free treatment regimens in TTP patients.
Immunoadsorption for the Treatment of Acquired Hemophilia: New Observational Data, Systematic Review, and Meta-Analysis
Transfusion medicine reviews. 2021
The treatment of patients with acquired hemophilia is challenging due to life-threatening hemorrhages, delayed response, and adverse effects to immunosuppressive agents. Even though immunoadsorption (IA) rapidly removes autoantibodies against factor VIII, this intervention's effectiveness is still a matter of debate. We aimed to study important outcomes of IA as adjunctive treatment in patients with acquired hemophilia. We performed comprehensive literature searches in MEDLINE and EMBASE databases. Clinical and laboratory data of all patients treated in our institution were additionally included. Literature searching yielded 498 records, of which 10 studies describing 106 patients were finally included. The number of patients varied from 1 to 65, and patients' ages ranged between 14 and 89. Treatment criteria in most patients were (1) failed response to immunosuppressive treatment alone, and/or (2) uncontrollable bleeding episodes, and/or (3) high inhibitor titer. Methodological quality was moderate. The number of IA sessions varied from 1 to 24. Within our institution, 12 patients have been treated since 2002; median age was 76 years (range 34-86); median titer of factor VIII inhibitor was 20 Bethesda units (range 3-214). Pooled estimates, modeling a random-effect binominal distribution incorporating the Freeman-Tukey double arcsine transformation, were 86% in case of factor VIII recovery (95% confidence interval 76%-94%), 95% for reduction of factor VIII inhibitor (83%, 100%), and 7% in case of death (0%, 18%). Our data suggest that IA might be a beneficial adjunctive treatment in patients with high-risk acquired hemophilia, but future studies shall confirm this observation.
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.
Sjögren's Syndrome Associated With Thrombotic Thrombocytopenic Purpura: A Case-Based Review
Rheumatology and therapy. 2020
OBJECTIVE To review all published cases of the rare association between thrombotic thrombocytopenic purpura (TTP) and Sjögren's syndrome (SS). The authors report an additional case of this unique association. METHODS Systematic review of the literature and a case report. The database were articles published in PubMed/MEDLINE, Web of Science, LILACS, and SciELO, registered from 1966 to August 2020. The DESH terms were "Sjögren's syndrome" and "thrombotic thrombocytopenic purpura," without language limitation. RESULTS Most patients were female (88%), and the age varied from 30 to 75 years old. Concerning the sequence of disease appearance, SS followed by TTP was seen in seven articles, TTP and SS in three, and simultaneous appearance of both diseases in three studies. Primary SS was observed in 16 patients, and secondary SS was detected in two cases: dermatomyositis and rheumatoid arthritis. Anemia was the most common TTP manifestation, followed by thrombocytopenia, fever, consciousness alteration, renal impairment, and schistocytes' appearance on a blood smear. Treatment involved plasmapheresis, plasma exchange, rituximab, glucocorticoid, and cyclophosphamide. A good outcome was noted in most studies; few patients died. CONCLUSIONS TTP is a rare manifestation associated with SS. After the TTP diagnosis, plasmapheresis and/or plasma exchange should be immediately implemented.
Long-term outcomes of thrombotic microangiopathy treated with plasma exchange: a systematic review
American Journal of Hematology. 2016;91((6):):623-30
BACKGROUND With the adoption of plasma exchange as standard treatment for thrombotic microangiopathy (TMA), more patients are surviving and longer-term outcomes have greater relevance. OBJECTIVES We conducted a systematic review to synthesize and evaluate the quality of evidence on long-term outcomes of TMA among adults treated with plasma exchange and to identify factors that may be associated with a worse long-term prognosis. METHODS We searched databases from 1980 to 2013 for eligible articles published in any language. We included studies that reported outcomes in at least ten adults with a history of TMA treated with plasma exchange and followed for at least six months. We abstracted data in duplicate and assessed the methodological quality of each study using an assessment tool developed based on recommended validity criteria. RESULTS We screened 6672 articles, reviewed 213, and included 34 studies totaling 1182 patients (study median [range], 24 [10-118]). The mean (or median) follow-up ranged from 6 months to 13 years. The cumulative incidence of relapse and mortality was highly variable and ranged from 3 to 84% and 0 to 61%, respectively. The incidence of other outcomes across 10 studies also varied (outcomes included hypertension, kidney disease, preeclampsia, stroke, seizure, severe cognitive impairment, and depression); in 3 other studies long-term neurocognitive function and health-related quality of life were significantly lower than the general population. CONCLUSIONS Patients who survive an episode of TMA may be susceptible to long-term vascular complications, but the magnitude of this risk and how to mitigate it remains unclear. This article is protected by copyright. All rights reserved.
Chemotherapy with or without plasmapheresis in acute renal failure due to multiple myeloma: a meta-analysis
International Journal of Clinical Pharmacology & Therapeutics. 2015;53((5):):391-7.
BACKGROUND/AIM: The clinical benefits of plasmapheresis in the management of multiple myeloma-induced acute renal failure remain controversial. In this study, we conducted a meta-analysis to quantitatively evaluate the clinical efficacy of chemotherapy with or without plasmapheresis in the treatment of multiple myeloma patients with renal failure. METHODS Randomized controlled trials evaluating clinical efficacy of plasmapheresis were identified by searching PubMed (from 1980 to November 2013) and EMBASE (from 1980 to November 2013). Outcomes subjected to meta-analysis were 6-month survival and dialysis-dependent rate. RESULTS Three randomized controlled studies were selected for meta-analysis. A total of 63 patients received chemotherapy only and 84 patients were given both chemotherapy and plasmapheresis. No difference was observed in 6-month survival rate between plasmapheresis and control group (75% vs. 66.7%; risk ratio, 0.92; 95% CI, 0.76 - 1.11; p = 0.39). 6-month dialysis-dependent ratio was significantly lower in patients treated with both chemotherapy and plasmapheresis than chemotherapy only (15.6% vs. 37.2%; risk ratio, 2.02; 95% CI, 1.03 - 3.96; p = 0.04). CONCLUSION Our meta-analysis results showed that plasmapheresis used as an adjunct to chemotherapy had a benefit in the management of dialysisdependent multiple myeloma patients with renal failure.
Role of plasmapheresis in the management of myeloma kidney: A systematic review
Hemodialysis International. 2010;14((4):):355-63.
Multiple myeloma complicated by acute renal failure is a diagnosis often encountered by the practicing nephrologist. The role of plasmapheresis in such patients has been of interest for decades. Three randomized controlled trials (RCTs) and multiple observational trials have evaluated the potential role of plasmapheresis in the management of this condition. This systematic review presents the results of these trials regarding survival benefits, recovery from dialysis, and improvement in renal function. A comprehensive search revealed 56 articles. Of these, only 8 articles met our inclusion criteria (3 RCTs, 1 correction of results, and 4 observational trials). Two of the 3 RCTs showed no difference in survival benefit. Two of the 3 RCTs showed a greater percentage of patients stopping dialysis in the intervention group; however, these results were not reproduced in the largest trial. All the studies showed an improvement in renal function for patients receiving plasmapheresis; however, only 2 RCTs and 1 retrospective study showed a statistically significant improvement in renal function among patients who received plasmapheresis in comparison with a control group. Our systematic review does not suggest a benefit of plasmapheresis independent of chemotherapy for multiple myeloma patients with acute renal failure in terms of overall survival, recovery from dialysis, or improvement in renal function.
Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials
American Journal of Kidney Diseases. 2009;53((2):):259-72.
BACKGROUND Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are related conditions with similar clinical features of variable severity. The objective of this systematic review is to evaluate the benefits and harms of available interventions for HUS and TTP. SELECTION CRITERIA FOR STUDIES MEDLINE (1966 to June 2006), EMBASE (1980 to June 2006), the Cochrane Central Register, conference proceedings, and reference lists were searched to find randomized controlled trials (RCTs) of any intervention for HUS or TTP in patients of all ages selected for inclusion for this systematic review. INTERVENTIONS Trials that compared an intervention with placebo, an intervention with supportive therapy, or one or more different interventions for HUS or TTP. OUTCOMES For TTP trials, failure of remission at 2 weeks or less and at 1 month or longer, all-cause mortality rate, and relapse rate. For HUS trials, all-cause mortality, chronic reduced kidney function, and persistent proteinuria or hypertension at last follow-up. RESULTS For TTP in adults, we found 6 RCTs of 331 patients. Two trials compared plasma infusion with plasma exchange using fresh frozen plasma and showed failure of remission at 2 weeks (2 trials, 140 patients; relative risk, 2.87; 95% confidence interval, 1.41 to 5.84), and all-cause mortality (relative risk, 1.91; 95% confidence interval, 1.09 to 3.33) occurred more frequently in the plasma infusion group. Three trials compared plasma exchange using cryosupernatant plasma with plasma exchange using fresh frozen plasma, and a meta-analysis of these trials showed no difference. Seven RCTs in 476 young children with postdiarrheal HUS have been conducted. None of the evaluated interventions (fresh frozen plasma transfusion, heparin with or without urokinase or dipyridamole, Shiga toxin-binding protein, and steroid) were superior to supportive therapy alone for any outcomes. LIMITATIONS Limitations of this review include the small number and suboptimal quality of reporting of included trials, possibility of publication bias, small number of participants with atypical HUS, and failure to report results for patients with atypical and typical HUS separately. CONCLUSIONS No additional therapy has been shown to increase efficacy over plasma exchange for TTP. No intervention has been shown to be superior to supportive therapy in patients with postdiarrheal HUS.
Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura
Cochrane Database of Systematic Reviews. 2009;((1):):CD003595.
A systematic review of randomized controlled trials for plasma exchange in the treatment of thrombotic thrombocytopenic purpura
Transfusion Medicine. 2007;17((1):):17-35.
The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE). A systematic review was undertaken to summarize the randomized controlled trial (RCT) evidence, to date, on PE as treatment for TTP. Seven randomized RCTs were identified till May 2005. A statistical reduction in mortality was found in patients receiving PE compared with patients receiving plasma infusion (relative risk 0.31, 95% confidence interval 0.12-0.79). No statistical difference in mortality was found in trials comparing different replacement fluids for PE. There were few differences in the response to treatment and the resolution of the presenting signs of TTP in any trial. Lack of data prevented a full assessment of the incidence of adverse events. None of the studies included measured patients' quality of life. Further research is required to determine the benefits and side effects associated with different replacement fluids for PE. It is recommended that there should be consistency in the diagnostic criteria, measurement of clinical outcomes and length of follow up. Continued support of existing TTP patient registries and establishment of new registries would facilitate this.