Role Of Therapeutic Plasma Exchange Research Articles

Outcomes in necrotizing soft tissue infections treated with therapeutic plasma exchange.

Treatment of necrotizing soft tissue infections (NSTIs) includes prompt surgical debridement and antibiotics, but despite standard care, the morbidity and mortality remain high. Since therapeutic plasma exchange (TPE) has been considered for treatment of severe sepsis, this study evaluates the efficacy of TPE for patients with NSTI. This is a retrospective study of patients with diagnosis of NSTI who received treatment with and without TPE over an 11-year period. The primary outcome was in-hospital mortality. Fifty-two patients with NSTI treated with TPE (TPE group) and 125 patients with NSTI not treated with TPE (non-TPE group) were assessed. Nineteen (36.5%) patients died in the TPE group, and 35 (28%) patients died in the non-TPE group. Within the TPE group, there was significant improvement in white blood cell (WBC) count and sodium levels 7 days after TPE treatment, but no improvement in creatinine. Inverse probability weighting based on propensity scores was used to compare survival in the TPE and non-TPE groups and demonstrated that TPE was associated with an increased odds of death (odds ratio,2.8). A second analysis matched for six variables yielded 31 pairs and demonstrated no significant difference in mortality or length of stay. This study describes the largest series of patients with NSTIs treated with TPE and showed no evidence of clinical benefit. Further carefully designed studies with meaningful clinical endpoints would prove useful in assessing reproducibility and determining if there is a role for TPE in other forms of severe sepsis.

Role of Therapeutic Plasma Exchange in Reducing ABO Titers in Patients Undergoing ABO-Incompatible Renal Transplant

Abstract Background/aims Our study presents an analysis of the trends of ABO antibody titers and the TPE (therapeutic plasma exchange) procedures required pre- and post-ABO-incompatible renal transplant. Methods Twenty-nine patients underwent ABO-incompatible renal transplant during the study period. The ABO antibody titers were done using the tube technique and titer reported was the dilution at which 1+ reaction was observed. The baseline titers of anti-A and anti-B antibodies were determined. The titer targeted was ≤8. Patients were subjected to 1 plasma volume exchange with 5% albumin and 2 units of AB group FFP (fresh frozen plasma) in each sitting. TPE procedures posttransplant were decided on the basis of rising antibody titer with/without graft dysfunction. Results The average number of TPE procedures required were 4–5procedures/patient in the pretransplant and 2–3procedures/patient in the posttransplant period. An average titer reduction of 1serial dilution/procedure was noted for anti-A and 1.1serial dilution/procedure for anti-B. Number of procedures required to reach the target titer was not significantly different for anti-A and anti-B ( p =0.9). The number of TPE procedures required pretransplant does not differ significantly with the baseline titers ( p =0.062). Outcome of the transplant did not differ significantly by reducing titers to p =0.326). The difference in the anti-A and anti-B titers at 14th day posttransplant was not found to be clinically significant ( p =0.19). Conclusion With an average of 4–5 TPE procedures pretransplant and 2–3 TPE procedures posttransplants, ABO-incompatible renal transplantations can be successfully accomplished.

Moderate Deficiency of ADAMTS13 in Thrombotic Microangiopathy Is Associated with Poor Survival Regardless of Plasma Exchange

Introduction: The ADAMTS13 assay is routinely ordered as part of the work-up for thrombotic microangiopathies (TMAs). While severe deficiency of ADAMTS13 activity (≤10%) is specific for the diagnosis of idiopathic TTP and identifies a group of patients who respond well to treatment with therapeutic plasma exchange (TPE), the implications of mild-to-moderate deficiency (11-66%) remain unclear. This study aims to elucidate the presenting characteristics, clinical outcomes and diagnoses, and responses to TPE in TMA patients with non-critically low ADAMTS13 activity.Methods: Two hundred-fifty two adult TMA patients from 3 large academic medical centers over a 10-year period were identified based on the presence of microangiopathic hemolytic anemia (schistocytes on smear, platelets <150,000/μL) and available ADAMTS13 results. Sixty-eight patients with ADAMTS13 ≤10% were excluded from the current analysis. Three cohorts were identified from the remaining 184 patients based on their ADAMTS13 activity level: 45 moderately deficient (11-40%), 84 mildly deficient (41-66%), and 55 non-deficient (≥67%). The ANOVA and chi-square tests were used for intergroup comparisons. Kaplan-Meier curves with log-rank analysis were used to assess survival differences where day 0 was defined as the day ADAMTS13 assay was sent.Results: With the exception of younger age in the non-deficient group, the 3 cohorts were similar with respect to gender and ethnicity, presenting signs and symptoms, clinical history and laboratory values (Table 1). Whereas the frequency of secondary TMA attributable to drugs, malignancy, hypertension, hemolytic-uremic syndrome (HUS), and autoimmune disease was not different across these three cohorts, patients with moderate reduction in ADAMTS13 activity were more likely to have disseminated intravascular coagulation (DIC) and sepsis compared to the mildly- and non-deficient cohorts (p=0.001). Additionally, the moderately deficient cohort had slower recovery of platelet count by day 4 (p=0.043) and significantly lower 90-day survival (Figure 1, p=0.01 by log-rank). The role of TPE in patients with moderate ADAMTS13 deficiency was evaluated. TPE was performed in 10 of 45 patients (22%). Presenting features among these 10 patients were not significantly different from the 33 patients (73%) who did not receive TPE (2 patients receiving <3 treatments were excluded). The 90-day survival between these two subgroups was not significantly different (Figure 2, p=0.48 by log-rank).Conclusions: Moderate ADAMTS13 deficiency (11-40%) in patients with TMA is more frequently associated with an underlying diagnosis of DIC and sepsis and portends slower recovery as well as worse survival. A modest reduction of ADAMTS13 activity may be a result of disease manifestation rather than the cause. Therefore, therapy directed at the underlying disease processes may lead to better outcomes than routine plasma exchange for these patients. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Neurologic indications for therapeutic plasma exchange: 2013 update.

Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of conditions. This concise review considers the most common neurologic indications for TPE. It focuses on Guillain-Barré syndrome and myasthenia gravis and also the role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive multifocal leukoencephalopathy. As with any treatment, the proven efficacy, cost, side effects, and availability must be considered before initiation of therapy.

Acute liver failure caused by herpes simplex virus in a pregnant patient: Is there a potential role for therapeutic plasma exchange?

A young woman presented with a febrile illness in the third trimester of pregnancy. Laboratory investigation revealed severe acute hepatitis with thrombocytopenia and coagulopathy. Liver injury progressed despite emergent caesarian section and delivery of a healthy infant. Therefore, therapeutic plasma exchange (TPE) was performed on three consecutive days post-partum for a presumed diagnosis of acute liver failure (ALF) associated with pregnancy due to hemolysis, elevated liver enzymes, and low platelets (HELLP) or acute fatty liver of pregnancy (AFLP). Treatment with TPE was followed by biochemical and clinical improvement but during her recovery herpes simplex virus type 2 (HSV-2) infection was diagnosed serologically and confirmed histologically. Changes in the immune system during pregnancy make pregnant patients more susceptible to acute HSV hepatitis, HSV-related ALF, and death. The disease is characterized by massive hepatic inflammation with hepatocyte necrosis, mediated by both direct viral cytotoxicity and the innate humoral immune response. TPE may have a therapeutic role in acute inflammatory disorders such as HSV hepatitis by reducing viral load and attenuating systemic inflammation and liver cell injury. Further investigation is needed to clarify this potential effect. The roles of vigilance, clinical suspicion, and currently accepted therapies are emphasized.

Role of therapeutic plasma exchange in the complex treatment of severe kidney diseases

PURPOSE: The strongest effect of therapeutic plasma exchange (TPE) is achieved in diseases with immune and autoimmune genesis, hyperviscous conditions and intoxications of various origins. The aims of the study were to assess the long-term effect of TPE in the complex therapy of severe renal diseases and to highlight therapeutic strategies necessary to achieve good clinical results. MATERIAL AND METHODS: During the period 1980-2010, TPE was carried out in the form of a complex treatment of 87 patients with immune nephropathies and 44 patients with malignant myeloma. The primary diseases were the following: chronic glomerulonephritis - 42, lupus nephropathy - 31, Henoch-Schonlein nephritis - 8, Wegener granulomatosis ± four and Goodpasture syndrome - two patients. The diagnosis was confirmed after a puncture kidney biopsy in 72 (82.8%) patients with immune nephropathies. TPE was performed using centrifugal or filtration methods. RESULTS: The patients with immune nephropathies underwent between 5 and 7 consecutive plasma exchanges daily or every two days. A three consecutive days of corticosteroid pulse therapy was initiated after last procedure followed by conventional immunosuppressive therapy. After serial TPE a significant decrease in anti-GMB antibodies and circulating immune complexes was detected. Continuous clinical and paraclinical remission was achieved in 62.7% of the patients who received the combined treatment. CONCLUSION: TPE has a beneficial effect after being included in the complex treatment of patients with severe immune nephropathies. The immunomodulation contributes to the successful management of severe ongoing autoimmune processes. In patients with hyperviscosity, “supporting” TPE every 2 or 3 months is required to lower the increased viscosity, to prevent thromboembolic complications, and to slow-down nephropathy progression. Scripta Scientifica Medica 2013; 45(1): 66-70.

The Role of Therapeutic Plasma Exchange in Poisonings and Intoxications

Poisonings, intoxications, and drug overdoses are common occurrences and rapid lowering of the toxin level is a cornerstone of all effective therapies. Therapeutic plasma exchange (TPE) has several unique characteristics that allow it to be a potentially effective therapy in rapidly achieving this goal. Specifically, TPE allows for the removal of large molecular weight, protein-bound molecules that have a small volume of distribution. Due to the nature of poisonings, intoxications, and drug overdoses, no randomized controlled trials studying the efficacy of TPE in these situations exist. Thus, careful interpretation and analysis of case reports and series are required to assess the potential efficacy of this therapy. Recent data suggest that TPE may also be effective in the therapy of patients receiving biologic treatments who develop life-threatening complications due to therapy.

Neurologic indications for therapeutic plasma exchange: 2011 update

Neurologists commonly use therapeutic plasma exchange (TPE) to treat a number of conditions. This concise review examines the most common neurologic indications for TPE. It focuses on Guillain-Barre' syndrome and myasthenia gravis and also the role of TPE in chronic inflammatory demyelinating polyneuropathy, Lambert-Eaton syndrome, multiple sclerosis, neuromyelitis optica, paraproteinemic polyneuropathy, Sydenham's chorea, and natalizumab-associated progressive multifocal leukoencephalopathy (PML). As with any treatment, the proven efficacy, cost, side effects, and availability must be considered before initiation of therapy.

Emergency ABO‐incompatible liver transplant secondary to fulminant hepatic failure: Outcome, role of TPE and review of the literature

The increasing demand for solid organ transplants has brought to light the need to utilize organs in critical situations despite ABO-incompatibility. However, these transplantations are complicated by pre-existing ABO antibodies which may be potentially dangerous and makes the transplantation prone to failure due to rejection with resulting necrosis or intrahepatic biliary complications. We report the clinical outcome of an emergency ABO-incompatible liver transplant (due to fulminant hepatic failure with sudden and rapidly deteriorating mental status) using a modified therapeutic plasma exchange (TPE) protocol. The recipient was O-positive with an initial anti-B titer of 64 and the cadaveric organ was from a B-positive donor. The patient underwent initial TPE during the peri-operative period, followed by a series of postoperative daily TPE, and later a third series of TPE for presumptive antibody-mediated rejection. The latter two were performed in conjunction with the use of IVIg and rituximab. The recipient's anti-B titer was reduced and maintained at 8 or less 8 months post-op. However, an elevation of transaminases 3 months post-transplant triggered a biopsy which was consistent with cellular rejection and with weak C4d positive staining suggestive of antibody mediated rejection. Additional plasma exchange procedures were performed. The patient improved rapidly after modification of her immunosuppression regimen and treatment with plasma exchange. This case illustrates that prompt and aggressive plasma exchange, in conjunction with immunosuppression, is a viable approach to prevent and treat antibody mediated transplant rejection in emergency ABO-incompatible liver transplant.

The role of therapeutic plasma exchange in pemphigus vulgaris

The role of therapeutic plasma exchange in pemphigus vulgaris

Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A—An associated respiratory failure and hemodynamic shock

Acute pneumonitis with acute lung injury is a cause of significant mortality related to the 2009 pH1N1 influenza A virus. Widespread lung inflammation and increased pulmonary vascular permeability has been noted on autopsy. Also, many of these patients present with significant hemodynamic compromise suggesting systemic cytokine release. Therefore, attenuating circulating cytokines, and other mediators, by blood purification techniques is a theoretically attractive strategy. We report the use therapeutic plasma exchange in three children with 2009 H1N1 related acute lung injury with severe hemodynamic compromise that had failed conventional therapeutic interventions. Case series. Pediatric intensive care unit in a university children's hospital. Three children, aged 8, 11, and 17 yrs, with acute respiratory distress syndrome and hemodynamic compromise related to the 2009 pH1N1 influenza A virus documented by polymerase chair reaction. All patients were on mechanical ventilation and inhaled nitric oxide, and one patient was on extracorporeal membrane oxygenation. Therapeutic plasma exchange was used as a rescue strategy. Each patient received three exchanges of 35-40 mL/kg on consecutive days. All three patients had dramatic reduction in pediatric logistic organ dysfunction scores, oxygen requirements, and vasopressor requirements after two exchanges. All survived with good functional recovery. In this small series of patients with H1N1/acute respiratory distress syndrome and hemodynamic compromise, therapeutic plasma exchange appeared to benefit as a method of mitigating the associated cytokine storm. The procedure was well tolerated with no reported side effects. All three patients survived, defying the predicted mortality. Because these procedures used the filtration exchange method, it was performed in a timely fashion by intensive care unit personnel and on equipment already available in the intensive care unit for renal support. This very limited case series suggest there may be a role for therapeutic plasma exchange as a rescue therapy in severe shock and acute lung injury related to pH1N1 that has not responded to traditional therapy.

Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura - Therapeutic plasma exchange is the answer

The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia–eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management.

Therapeutic apheresis before and after kidney transplantation

Kidney transplantation is considered the treatment of choice for most individuals with end-stage kidney disease, as well as the most cost-effective renal replacement therapy for the health care system that serves them. Immunologic sensitization, defined by the presence of antibodies directed against foreign HLA (or so called, donor specific antibodies, or DSA), is a significant barrier to kidney transplantation. Further, the presence of DSA is associated with an increase in the incidence of antibody-mediated rejection and decreased graft survival following transplantation. Therapeutic plasma exchange, an extracorporeal therapy directed at removing plasma proteins, including DSA, has proven to be an important part of a comprehensive strategy to minimize the effect of sensitization before, and following kidney transplantation. As such, it offers the promise of increasing access to transplantation, as well as improving outcomes following transplantation. In this concise narrative review, we describe more specifically the benefits of kidney transplantation, the epidemiology of kidney transplantation in the United States, the clinical significance of anti-HLA antibodies, and the evidence supporting a role for therapeutic plasma exchange before and after kidney transplantation.

The role of therapeutic plasma exchange in pemphigus vulgaris

The treatment of pemphigus, an autoimmune bullous disease, is based on the combination of corticosteroids and adjuvant therapies, such as immunosuppressive drugs, anti-inflammatory drugs and immunomodulatory procedures, such as intravenous immunoglobulin and therapeutic plasma exchange (TPE). This study aims to assess our experience with TPE as a steroid-sparing modality in moderate and severe intractable pemphigus patients. A retrospective evaluation for all intractable pemphigus patients treated by TPE in a university-affiliated tertiary referral medical centre between the years 1998 and 2008. Treatment protocol included three TPE treatments weekly for 1-3 months, combined with monthly pulse therapy of dexamethasone and/or cyclophosphamide. Maintenance therapy was based on once/bi weekly TPE treatments or monthly intravenous immunoglobulin. Seven patients were included in the study, four with severe pemphigus vulgaris and three with moderate disease. Six of the seven patients responded to TPE: Four patients (57%) achieved complete remission and two patients (28%) achieved partial remission on minimal therapy. Mild adverse effects related to TPE were observed in two patients and included dizziness and mild headache. TPE is a well-tolerated effective steroid-sparing agent in recalcitrant pemphigus patients.

Plasma exchange for anti GAD associated non paraneoplastic limbic encephalitis

Limbic encephalitis (LE) is a neurological syndrome usually presenting in a paraneoplastic form. Recently many cases were reported with no concurring neoplasia, presenting with specific antibodies for voltage-gated potassium channel or for neuronal membrane antigens. Anti-glutamic acid decarboxylase (GAD) antibodies act against GABAergic receptors of the central nervous system. These antibodies were found in coeliac disease serum and in neurologic patients. We are reporting a case of a 21-year-old coeliac woman manifesting complex multiple-daily partial drug-resistant seizures for 7 years. The diagnosis was of a non paraneoplastic limbic encephalitis, unresponsive to high dose cortisone and IGIV infusion. The use of therapeutic plasma exchange (TPE) has resulted in an improvement in symptoms with quite a long disease-free period of time. When the frequency of the procedures was decreased, seizures appeared again and, after suspension of TPE, the clinical status worsened. The role of TPE in the treatment of LE still has to be defined.

Evidence based therapeutic apheresis in autoimmune and other hemolytic anemias

This article reviews recent publications that bear on the evidential basis for therapeutic apheresis in diseases in which hemolytic anemia is a prominent feature. Therapeutic plasma exchange continues to be reported sporadically in severe autoimmune hemolytic anemia, with inconsistent results. Autoimmune deficiency of ADAMTS13 has provided a compelling rationale for therapeutic plasma exchange in some patients with thrombotic thrombocytopenic purpura; conversely such deficiency is consistently absent in certain clinically similar syndromes for which therapeutic plasma exchange is not or may not be beneficial. Refinements in assays for ADAMTS13 should further clarify its role in idiopathic thrombotic thrombocytopenic purpura. Oral iron chelators have shown promise in recent trials in chronically transfused patients with sickle cell disease and may provide an alternative to red cell exchange to prevent iron overload. The proper role of therapeutic plasma exchange in the treatment of autoimmune hemolytic anemia remains uncertain. Therapeutic plasma exchange continues to be indicated for idiopathic thrombotic thrombocytopenic purpura regardless of ADAMTS13 levels, but more accessible and physiological ADAMTS13 assays may raise questions about the rationale for and value of plasma exchange in ADAMTS13 nondeficient patients. Oral iron chelation may obviate the need for red cell exchange as a means to prevent iron overload in chronically transfused patients with sickle cell disease.

The role of therapeutic plasma exchange in the catastrophic antiphospholipid syndrome

The catastrophic antiphospholipid syndrome (CAPS) is a life-threatening sub-entity of the antiphospholipid syndrome (APS) resulting in multiorgan failure and a mortality rate that may reach 50%. The optimal treatment regimen for CAPS is unknown. To evaluate the benefit of therapeutic plasma exchange (TPE) therapy in CAPS, we undertook a computer-assisted (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature to locate all cases of CAPS (case reports and reviews) treated with TPE. In view of the published literature so far, TPE has shown reasonable therapeutic benefits and improved survival for patients with CAPS. The use of this technique, along with anticoagulation and if needed pharmacological immunosuppression, should be considered for the acute management of patients who present with this life-threatening condition.