Hypocalcemic toxicity and atypical reactions in therapeutic plasma exchange

Hypocalcemic toxicity accounts for the most common adverse effects of therapeutic plasma exchange. The symptoms can be related to a fall in plasma ionized calcium. Citrate-based anticoagulants, notably sodium citrate and ACD formula A, have been indicated as the major cause of hypocalcemic toxicity, but colloid replacement fluids containing human serum albumin are also at fault. Recognition of the signs and symptoms of hypocalcemic toxicity is important because several clinical measures are available to deal with them and to ensure patient comfort. A typical reactions, characterized by flushing and hypotension during plasma exchange, have been attributed to the effects of angiotensin converting enzyme inhibitors. Both exchange and adsorption apheresis procedures can result in atypical reactions in patients who have been taking this class of drugs within 48 to 72 hours of an apheresis procedure. These reactions are less common than hypocalcemic toxicity, but can be prevented by paying attention to detail.     

Partial plasma protein replacement in therapeutic plasma exchange

We wished to determine whether subtotal replacement of protein in plasma removed at plasma exchange would be adequate to prevent hypovolemia and hypoproteinemia. Seven well nourished outpatients with chronic progressive multiple sclerosis underwent 60 plasma exchanges in which two liters of plasma were replaced with 750 ml saline followed by 1250 ml of a 5% albumin solution (62.5% albumin replacement). Total serum protein, protein electrophoresis, and immunoglobulin levels were measured before and after each exchange. Clinically, the exchanges were well tolerated. Total serum protein dropped by a mean of only 18% during the study and mean preexchange serum albumin levels were unchanged, even though immunoglobulins decreased by 57–72%. We conclude that in well nourished patients, partial albumin replacement of this magnitude is an adequate substitute for plasma removed in a plasma exchange.     

Toronto General Hospital controlled trial data plasma exchange therapy in Guillain-Barré' syndrome

The mechanism by which plasma exchange (PE) may benefit patients with acute Guillain-Barre' syndrome (AGBS) is unclear. It is possible, therefore, that the response of patients with AGBS is influenced by the choice of replacement solution (whole plasma vs. albumin or similar protein-containing solution). This report compares the outcome in 57 patients with AGBS treated at the Toronto General Hospital (TGH) using conventional therapy (27), PE with plasma replacement (15) and PE with albumin replacement (15). Fifteen patients (5 treated conventionally, 8 by PE with plasma replacement, 2 by PE with albumin replacement) were treated before the Baltimore coordinated multicenter trial. Forty-two patients (22 treated conventionally, 7 by PE with plasma replacement and 13 by PE with albumin replacement) were then entered at the TGH into the multicenter trial. The best outcome was observed in those patients (9) in whom PE was started within 14 days of the first neuropathic symptoms and plasma was used as replacement. The mean improvements in clinical grade in this subgroup of patients of 1.11 at four weeks after starting treatment and 1.71 at six weeks were significantly better than the corresponding improvements in the conventionally treated group of 0.35 (p less than 0.01) and 0.94 (p less than 0.05). The response of patients (9) exchanged within 14 days of onset, but replaced with albumin (grade change of 0.67 at four weeks and 0.86 at six weeks), was not significantly different from that of the conventionally treated patients. These data support the need for a randomized trial to compare PE using plasma replacement and PE using albumin replacement in patients with AGBS.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of 50% albumin/plasma replacement fluid in therapeutic plasma exchange for thrombotic thrombocytopenic purpura

Background: Acquired thrombotic thrombocytopenic purpura (TTP) is caused by a deficiency of von Willebrand factor‐cleaving protease (ADAMTS13) and is often associated with the presence of an antibody inhibiting the activity of the protease. Typically, 1–1.5 plasma volume exchanges are performed daily until symptoms have resolved and the platelet count exceeds 150,000/µl. Plasma is the usual replacement fluid as it provides a source of functional ADAMTS13, thus exposing patients to large volumes of plasma. Historically, Puget Sound Blood Center (PSBC) has performed therapeutic plasma exchange (TPEs) for TTP using 5% albumin for the first half of the procedure followed by plasma for the remainder. We sought to assess the efficacy of this approach. Study Design and Methods: All TPEs performed for the diagnosis of TTP by the PSBC apheresis service from January 1, 2004 through December 31, 2011 were reviewed. Response time, remission rates, relapses, and adverse events were evaluated for those patients with documented ADAMTS13 levels ≤10%. Comparisons were made with published data on TTP patients treated using 100% plasma replacement. Results: Twenty‐one patients required a median of 11 TPEs. Median time to response was 14 days. Ninety percent of patients responded to TPE. Among patients achieving remission, 53% relapsed. Out of 283 total procedures, there were 74 procedures with a documented adverse event (26%), mostly mild allergic reactions. Conclusions: TPE with an albumin/plasma replacement is safe and well‐tolerated. Remission and relapse rates were comparable to those reported using 100% plasma replacement. J. Clin. Apheresis, 28:416–421, 2013. © 2013 Wiley Periodicals, Inc.     

Survival of a Jehovah's Witness with thrombotic thrombocytopenic purpura without using plasma: A case report and review of the literature

Acquired thrombotic thrombocytopenic purpura (aTTP) is a serious disorder with arteriolar and capillary thrombosis for which the treatment usually requires plasma exchange with plasma as the replacement fluid. Management of patients who do not accept blood products is a serious challenge. We present the case of a Jehovah's Witness patient who achieved clinical response after treatment with plasma exchange using human albumin solution as the replacing fluid, high dose corticosteroids, and rituximab. The patient also received ADAMTS13 containing plasma cryoprecipitate and von Willebrand factor VIII concentrates. She had an exacerbation of her TTP in less than 3 weeks. She was treated with further plasma exchange with human albumin solution as the replacement fluid, high dose steroids, and rituximab. Bortezomib and N-acetylcysteine were added. The patient eventually improved clinically and achieved remission that is ongoing for more than 7 months. A review of the literature shows that all five previously reported cases of aTTP in Jehovah's Witnesses survived although none received plasma. Two were not even treated with plasma exchange. The experience of this case and those in the literature demonstrates that remission of aTTP may be achieved without using plasma or plasma exchange.     

Plasma Exchange for Neuromyelitis Optica Spectrum Disorders in Chinese Patients and Factors Predictive of Short-term Outcome

Purpose

The purposes of this article were to evaluate the short-term outcome of plasma exchange (PLEX) for neuromyelitis optica spectrum disorders (NMOSDs) in Chinese patients and to identify the factors predictive of a favorable response to therapy.

免疫调节疗法治疗重症肌无力临床观察

目的观察应用静脉注射用免疫球蛋白（IVIg）或血浆置换治疗全身型重症肌无力（MG）的临床疗效和安全性。方法对56例病情恶化需IVIg或血浆置换治疗的全身型重症肌无力患者分两组，27例应用IVIg治疗，29例应用血浆置换治疗。在接受治疗后14天、1个月、3个月分别进行疗效评估。结果两组患者治疗前后评分差异均有统计学意义，并且都能很好地耐受，在治疗初期两种方案疗效相差不大，有效率分别为77．8％（21／27）、75．9％（22／29）。好转后都可维持较长时间，但IVIg维持时间稍长于血浆置换。结论重症肌无力患者中IVIg的治疗效果可与血浆置换匹敌。IVIg在3个月后的评估中疗效优于血浆置换。但在病情恶化初期，患者可根据所在医院的医疗条件选择任一种方案。     

Atypical reactions associated with use of angiotensin-converting enzyme inhibitors and apheresis

BACKGROUND: Anaphylactic or atypical reactions, characterized by flushing, hypotension, dyspnea, and bradycardia, have been reported in patients undergoing hemodialysis, low-density lipoprotein apheresis, IgG affinity column apheresis, therapeutic plasma exchange, and desensitization immunotherapy while receiving angiotensin-converting enzyme (ACE) inhibitor therapy. STUDY DESIGN AND METHODS: Records were reviewed of 299 consecutive patients undergoing therapeutic plasma exchange with colloid replacement at the University of North Carolina Hospitals from September 1981 through December 1993. Charts were selected for further analysis if atypical reactions (flushing or hypotension defined as a mean decrease in blood pressure of 20 torr or greater) occurred during apheresis or if there was concurrent administration of an ACE inhibitor. RESULTS: Fourteen (4.7%) of 299 patients were receiving ACE inhibitor therapy at the time of apheresis; all 14 experienced an atypical reaction. In contrast, 20 (7%) of 285 patients not receiving ACE inhibitors developed atypical reactions (p < 0.001). The 14 ACE inhibitor patients accounted for 41 percent (14/34) of all patients having atypical reactions during apheresis. CONCLUSION: Patients receiving ACE inhibitor therapy who are undergoing therapeutic plasma exchange with albumin replacement solutions are at high risk (100%) for atypical reactions. It is recommended that ACE inhibitors be withheld for at least 24 hours before that procedure.     

The management of anticoagulation in patients undergoing therapeutic plasma exchange: A concise review

We surveyed multiple apheresis centers represented by the authors for their clinical approach to the management of anticoagulation issues during therapeutic plasma exchange (TPE). We present the results of their practices and a review of the pertinent literature. As plasma is removed during TPE, replacement with all or partial non‐plasma‐containing fluids (eg, 5% albumin) may lead to significant changes in hemostasis. These changes are amplified in patients who are receiving anticoagulation. We discuss various anticoagulants as well as the monitoring and adjustment of anticoagulation before, during, and after TPE. No single guideline can be applied, but rather, patients must be monitored individually, taking into account their often complex clinical conditions and medication profiles.     

Emerging insights into the role of albumin with plasma exchange in Alzheimer’s disease management

Alzheimer’s disease (AD) is a neurodegenerative process that inexorably leads to progressive deterioration of cognition function and, ultimately, death. Central pathophysiologic features of AD include the accumulation of extracellular plaques comprised of amyloid-β peptide (Aβ) and the presence of intraneuronal neurofibrillary tangles. However, a large body of evidence suggests that oxidative stress and inflammation are major contributors to the pathogenesis and progression of AD. To date, available pharmacologic treatments are only symptomatic. Clinical trials focused on amyloid and non-amyloid-targeted treatments with small molecule pharmacotherapy and immunotherapies have accumulated a long list of failures. Considering that around 90 % of the circulating Aβ is bound to albumin, and that a dynamic equilibrium exists between peripheral and central Aβ, plasma exchange with albumin replacement has emerged as a new approach in a multitargeted AD therapeutic strategy (AMBAR Program). In plasma exchange, a patient’s plasma is removed by plasmapheresis to eliminate toxic endogenous substances, including Aβ and functionally impaired albumin. The fluid replacement used is therapeutic albumin, which acts not only as a plasma volume expander but also has numerous pleiotropic functions (e.g., circulating Aβ- binding capacity, transporter, detoxifier, antioxidant) that are clinically relevant for the treatment of AD. Positive results from the AMBAR Program (phase 1, 2, an 2b/3 trials), i.e., slower decline or stabilization of disease symptoms in the most relevant clinical efficacy and safety endpoints, offer a glimmer of hope to both AD patients and caregivers.     

Plasma adsorption in critical care.

Plasmapheresis therapies such as plasma exchange (PE), double filtration plasmapheresis (DFPP), or immunoadsorption plasmapheresis (IAPP) have become therapeutic tools in critical care. PE or DFPP are limited by their non- or semiselective removal of all plasma components. Replacement fluids such as fresh frozen plasma and albumin are necessary during PE or DFPP. There is the risk of infection and allergic reactions whenever such fluids are used. On the other hand, IAPP is superior to PE and DFPP because it does not require any replacement fluid. There has been development of many adsorbent columns used for removing specific pathogenic substances, and patients with various kinds of critical illness have been treated with IAPP. However, IAPP can be applied only for certain diseases because of the limitations of the commercially available columns. It is concluded that the development of new adsorption therapy may improve the high mortality and morbidity rate in critically ill patients.     

Therapeutic plasma exchange in a critically ill Covid‐19 patient

Here we describe the effect of therapeutic plasma exchange with 5% albumin as sole replacement solution for the management of Covid‐19. A 74‐year‐old man was admitted for severe Covid‐19 acute respiratory distress syndrome. Based on the growing body of evidence that cytokine release syndrome, and especially interleukin‐6, plays a key role in critically ill Covid‐19 patients, we decided to implement therapeutic plasma exchange as a rescue therapy. The patient's clinical status rapidly improved, and biological records showed convincing results of decrease in interleukin‐6 and inflammatory parameters under treatment. This case presents a proof‐of‐concept for the use of therapeutic plasma exchange with 5% albumin as sole replacement solution in a critically ill Covid‐19 patient with cytokine release syndrome. This could constitute a major benefit in terms of security compared to long‐lasting immunosuppressive monoclonal antibodies, or to therapeutic plasma exchange with plasma as replacement fluid. Hence, we think that a further evaluation of risk‐benefit balance of this therapy in severe cases of Covid‐19 should rapidly be undertaken.     

Protein and colloid osmotic pressure changes with albumin and/or saline replacement during plasma exchange

Colloid osmotic pressure (COP) has been used as a predictor of fluid egress from the vascular space and edema development in the lungs and elsewhere. We investigated the relative safety, as predicted by the COP, of 5 percent albumin plus saline and 5 percent albumin alone as replacement fluids during plasma exchange. Fifty-three one and one-half plasma volume exchanges were performed in 15 patients with a variety of diagnoses using intermittent flow cell separators. On specimens obtained, before, during, and after each plasma exchange, the COP was measured directly with a membrane oncometer, and total protein, albumin, and protein electrophoresis were determined using standard biochemical techniques. COP dropped significantly with one to one 5 percent albumin replacement but even more with one-half 5 percent albumin and one-half saline replacement during the exchange. COP did not fall below 12.5 torr at the end of the plasma exchange, even with one-half saline replacement, compared to the 10 to 12 torr level at which pulmonary edema might be expected. The fall in COP during exchange when saline was given first did approach this range but rapidly reversed itself with albumin administration. Clinically, no evidence of tissue or pulmonary edema was observed. Recovery in total protein and COP between plasma exchanges was significant.     

Clinical evaluation of a staphylococcal protein A immunoadsorption system in the treatment of myasthenia gravis patients

BACKGROUND: The role of plasma exchange is well established in the management of myasthenia gravis, an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor. Plasma antibody removal by conventional means, however, is nonselective and uses replacement fluids (chiefly, albumin solution) derived from human plasma. STUDY DESIGN AND METHODS: The Canadian Apheresis Group undertook a study at two Canadian apheresis centers to clinically evaluate a staphylococcal protein A immunoadsorption system (EXCORIM) in myasthenia gravis patients. RESULTS: The immunoadsorption system was safe and well tolerated. Ten of 12 patients had improvement in their neurologic status, as measured by a 20-point scoring system. The mean improvement in the weakness score was significant for the group (p = 0.0013). CONCLUSION: Patients with myasthenia gravis respond to treatment with plasma immunoadsorption. Further studies are required for a cost-benefit analysis.     

Patients’ quality of life after stopping plasma exchange: A pilot study

BackgroundPlasma exchange is being widely used to treat various serious medical conditions. There has been very little follow-up data to describe the quality of life (QOL) of plasma exchange-recipients after active plasma exchange has stopped.ObjectiveTo assess the QOL of plasma exchange recipients after stopping plasma exchange.MethodsA pilot study, based on responses to a postal questionnaire and clinical data obtained from the patients’ charts, was carried out. The scores were computed from questionnaire responses and analyzed.ResultsThe response rate was 59% with 58 patients completing a questionnaire three months after their final plasma exchange therapy. We identified significant heterogeneity in the quality of life of plasma exchange recipients after stopping plasma exchange therapy. This could be driven by different patient co-morbidities. We recommend that during follow up visits, a multi-disciplinary approach including consultation with a social worker might be considered for patients who may continue to have some limitations in their psychosocial activities post-discontinuation of plasma exchange. The high response rate to the questionnaire indicates that PLEX patients are interested in being involved in QOL studies, which suggests potential support for a prospective study of QOL with pre and post questionnaires and more detailed tracking of baseline co-morbidities.     

High doses of hydroxyethyl starch and human albumin have similar effects on monocyte function and oncotic pressure

The accumulation of hydroxyethyl starches (HES) in monocytes/macrophages has raised concern over their potential detrimental effects on host defences. We assessed prospectively the function of circulating monocytes isolated from patients treated with plasma exchange (PE) using HES. The study was carried out in the medical intensive care unit of a university hospital. Eight patients underwent PE for neurological disorders. Each patient underwent three PEs, 48 h apart. The total exchange volume was 4 L per PE. Only 4% human albumin was used for the first PE. In the second and third PEs, the plasma substitute was 2 L of HES (200 000/6%/0.62) and 2 L of albumin. Mononuclear cells were collected before and immediately after each PE and 48 h after the last PE. They were placed in suspension culture and incubated with lipopolysaccharide (LPS). Monocyte function was assessed in terms of procoagulant activity (PCA) and tumour necrosis factor alpha (TNF-α) production. LPS-stimulated PCA increased after the first PE ( P  < 0.05). Stimulated TNF-α production increased, but not significantly so. Similar effects were observed after the second and third PE ( P  < 0.05 for stimulated TNF-α). Values 48 h after the last PE were similar to those obtained before the second PE, suggesting that repeated infusions of HES had no detrimental effect on monocyte function. Furthermore, plasma oncotic pressure was preserved after PE with HES. These results support the partial replacement of costly human albumin with HES during repetitive PE, and suggest that HES might be a safe plasma expander in septic patients.     

Therapeutic plasma exchange in patients with neurological diseases: Multicenter retrospective analysis

Therapeutic plasma exchange (TPE), is a procedure, changing pathologic substances in the plasma of patients with replacement fluid. TPE has an increasing list of indications in recent years such as neurological, connective tissue, hematological, nephrological, endocrinological and metabolic disorders. We report our multicenter data about therapeutic plasma exchange in patients with neurological diseases. Six University Hospitals’ aphaeresis units medical records about neurologic diseases were reviewed retrospectively. Hundred and fifteen patients and 771 TPE sessions from six aphaeresis units’ were included to this study. Of the 115 patients, 53 (46%) were men and 62 (54%) were women. The median age was 50 (range: 5–85) years. Of these patients 58.3% were Guillain–Barre syndrome (GBS), 17.4% were acute disseminated encephalomyelitis (ADEM), 10.4% were chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 7% were multiple sclerosis, 6.1% were myasthenia gravis (MG) and 0.9% were Wilson disease (WD). The median number of TPE sessions per patient was 5 (range 1–72). Human albumin was used as a replacement fluid in 66% and fresh frozen plasma was used in 34% of cases. TPE was done through central venous catheters in 66%, and peripheral venous access in 34% of patients. Some complications were seen in patients (18.3%) during TPE sessions. These complications were, complications related to catheter placement procedure (8.7%), hypotension (3.5%), hypocalcaemia (3.5%) and allergic reactions (1.7%). The complication ratios were 2.7% in total 771 TPE procedures. TPE procedure was terminated in 6% of sessions depending on these complications. Overall responses to TPE were noted in 89.5% of patients.In conclusion; Therapeutic plasma exchange is an effective treatment option in several neurologic diseases.     

Plasma exchange using dextran 40-electrolyte solution as the sole replacement fluid in malignant paraproteinemia

The relative safety of 3 percent Dextran 40-electrolyte solution alone as replacement fluid during plasma exchange is described. Using an automated blood cell separator, the authors exchanged 3.21 of plasma 64 times in 11 patients with paraproteinemia secondary either to Waldenstrom's macroglobulinemia or multiple myeloma (malignant paraproteinemia). Then they replaced the plasma with an equal volume of 3 percent Dextran 40-electrolyte solution. They administered no protein- containing solutions during or after the plasma exchanges. Despite marked hypoalbuminemia immediately after plasma exchange, the plasma colloid osmotic pressure level fell only slightly because of the high concentration of plasma low-molecular dextran. The hemostatic abnormalities were similar to those seen in patients whose plasma was replaced with albumin solution. The exchanges were tolerated well clinically and no serious complications occurred during or after exchange. The authors believe that the 3 percent Dextran 40-electrolyte solution can be used safely as the sole replacement fluid in intensive plasma exchange programs for patients with malignant paraproteinemia.     

人工肝血浆置换术治疗肝衰竭的护理

目的探讨人工肝血浆置换术治疗肝衰竭的护理措施。方法对本科2008年1月~2009年11月收治的80例肝衰竭患者分成观察组和对照组,观察组40例在内科支持治疗的基础上行人工肝血浆置换术。对照组40例未行人工肝血浆置换术,观察两种治疗方法平均住院日、好转率。结果行人工肝血浆置换术治疗后临床症状及生化指标均有不同程度的改善,缩短了平均住院日,治愈好转率达到77.5%。结论血浆置换为主的人工肝支持系统是治疗肝衰竭的有效手段。患者的术前准备、术中监测、观察、处理和术后护理是保证治疗成功的重要基础。     

血浆置换在重症肌无力患者实施胸腺切除术前的应用与护理

目的探讨血浆置换在重症肌无力患者实施胸腺切除术中的应用。方法回顾性分析22例重症肌无力患者实施胸腺切除术前应用血浆置换的病例,总结护理要点。结果全部患者经血浆置换治疗后,肌无力症状明显好转,相关指标达到手术所需指征。结论重症肌无力患者实施胸腺切除术前应用血浆置换可及时改善患者的临床症状,使手术治疗更为安全有效,血浆置换过程中护理措施得当,可保证血浆置换治疗顺利进行。