Refractory idiopathic thrombocytopenic purpura treated with immunoadsorption using tryptophan column

The treatment of refractory idiopathic thrombocytopenia in adult is a challenge. Here we report successful treatment of an adult ITP patient with immunoadsorption using tryptophan column who were refractory to steroids, splenectomy, eltrombopag and various immunosuppressive medications.     

Two cases of refractory endocrine ophthalmopathy successfully treated with extracorporeal immunoadsorption.

Endocrine ophthalmopathy (EO) is a severe disease entity that is characterized by retrobulbar swelling due to accumulation of glycosaminoglycans on an autoimmune basis. This disorder can lead to the loss of vision and often is resistant to conventional therapy. There is a relation to Graves' hyperthyroidism, but probably no close association. Two patients with severe EO that was resistant to usual therapeutic approaches including steroids and radiological and surgical measures underwent a 20 session course of intensive immunoadsorption therapy (Plasmaselect/Therasorb Anti-IgG) with a mean 2- to 3-fold plasma volume treated. After the first sessions, both patients voiced an impressive relief of their major symptoms, which was confirmed by ophthalmological investigation. Throughout the time of therapy until present, these patients have remained at their respective levels of improvement. We consider immunoadsorption an effective therapeutic opportunity in severe EO resistant to conventional treatment.     

Low density lipoprotein apheresis in treatment of hyperlipidemia: experience with four different technologies.

The prognosis of patients suffering from severe hyperlipidaemia (HLP), sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease (CHD) refractory to diet and lipid lowering drugs is poor. A new therapeutic option for such patients is regular treatment with low density lipoprotein (LDL) apheresis. In total 33 patients (16 males, 17 female, aged 43.8+/-14.3 years), suffering from severe HLP resistant to diet and lipid lowering drugs, were treated for 62.3+/-21.3 (range, 1-113) months with LDL-apheresis. Four different LDL-apheresis systems were used: the dextran sulfate adsorption for 28 of 33 (Liposorber, Kaneka, Japan), immunoadsorption for 2 of 33 (Therasorb, Baxter, Germany), LDL-hemoperfusion for 2 of 33 (Dali, Fresenius, Germany), and the immunoadsorption system with special antilipoprotein (a) columns for 1 of 33 patients (Lipopak, Pocard, Russia). Before applying LDL-apheresis, 27 of 33 patients suffered from CHD with severe angina pectoris symptoms, a history of myocardial infarction or coronary artery venous bypass (CAVB). With LDL-apheresis, reductions (p < 0.05) of 46% for total cholesterol, 49% for LDL, 28% for Lp(a), and 38% for triglycerides were reached. Severe side-effects, such as shock or allergic reactions, were very rare (0.5%). In the course of treatment an improvement in general well-being and increased performance were experienced in 29 of 33 patients. In 23 of 27 patients suffering from CHD, a reduction of 60 to 100% of nitrate medication was observed. Regarding the different apheresis systems used, there were no significant differences with respect to the clinical outcome and concerning total cholesterol, LDL, HDL, and triglyceride concentrations. But, in respect to elevated lipoprotein (a) levels, the immunoadsorption method using special anti-lipoprotein (a) columns seems to be the most effective (-57% versus -25% [Kaneka, p < 0.05] or -23% [Baxter, p < 0.05]). The present data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe HLP, refractory to maximum conservative therapy, is effective and safe in long-term application.     

Immunoadsorption in neurological disorders

In recent years, immunoadsorption has been increasingly recognized as an alternative to therapeutic plasma exchange and used for the treatment of neurological disorders such as Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, neuromyelitis optica spectrum disorders, and multiple sclerosis, as well as autoimmune encephalitis. Unlike therapeutic plasma exchange, which requires fluid replacement with a blood solution such as fresh frozen plasma or albumin, immunoadsorption is a blood purification technique that enables the selective removal of humoral factors from separated plasma through a high-affinity adsorbent with tryptophan or phenylalanine. Although the mechanisms underlying the therapeutic effects of immunoadsorption treatment remain to be fully elucidated, they are based on the removal of pathogenic humoral factors from circulating blood, such as disease-specific autoantibodies, complement, and inflammatory cytokines. The American Society for Apheresis has published evidence-based guidelines on the use of therapeutic apheresis in clinical practice, with specific instructions on 16 neurological disorders. However, the modality recommended in the guidelines for most of these disorders is therapeutic plasma exchange. This part of our review focuses on the clinical aspects of immunoadsorption. We also describe the efficacy of immunoadsorption and the evidence obtained by previous studies of the treatment of neurological disorders. Immunoadsorption could greatly improve the treatment of patients with autoimmune neurological disorders but further evidence is needed to confirm the efficacy of immunoadsorption in clinical practice.     

Dramatic fate of a young coronary heart disease patient rescued with specific lipoprotein(a) apheresis

Lipoprotein(a) [Lp(a)] is acknowledged to be an independent atherothrombotic risk factor. Although genetic studies have highlighted the causal relationship between coronary disease and Lp(a), it is uncertain which strategies maximize the therapeutic benefit of patients with high Lp(a) levels. We report the challenging case of a young coronary heart disease (CHD) patient who underwent 10 percutaneous coronary interventions due to repeated acute coronary syndromes (2006–2009) despite an optimally controlled, traditional risk‐factor profile. For the first time, we performed specific Lp(a) immunoadsorption in the presence of very low levels of low‐density lipoprotein cholesterol (LDL‐C) while the patient was on a high‐dose statin regimen. There have been no previous reports of patients with high Lp(a) levels who achieved LDL‐C goals when treated with an isolated Lp(a)‐lowering method. Despite the very high risk of cardiovascular death, targeting Lp(a) resulted in dramatic improvement of the patient's clinical condition. Thus, we suggest that specific Lp(a) apheresis should be considered an effective new treatment strategy for patients with progressive CHD who have reached LDL‐C goals but harbor elevated Lp(a) levels. J. Clin. Apheresis 30:193–195, 2015. © 2014 Wiley Periodicals, Inc.     

重型颅脑损伤合并多发伤216例救治体会

目的探讨重型颅脑损伤合并多发伤的救治方法。方法回顾性分析收治重型颅脑损伤合并多发伤216例的临床资料。结果预后按格拉斯哥昏迷评分法(GOS评分),恢复良好78例(36.1%),轻残43例(19.9%),重残26例(12.0%),植物生存12例(5.6%),死亡57例(26.4%)。结论重型颅脑损伤合并多发伤应早期诊断及早期判断伤情,首先处理危及生命的损伤是抢救成功的关键,动态观察反复评估病情是避免漏诊和误诊重要手段,系统的重症监护及术后综合治疗可提高抢救成功率,降低伤残率及病死率。     

Immunoadsorption may provide a cost-effective approach to management of patients with inhibitors to FVIII

BACKGROUND: Immunoadsorption of plasma with Staphylococcal protein A removes immunoglobulins and immune complexes; hence, it should effectively remove inhibitors to FVIII in acquired or congenital hemophilia. The procedure may be cost effective, given the expense of therapies used to treat patients with inhibitors, particularly in an acute setting. STUDY DESIGN AND METHODS: Three patients with inhibitors to FVIII were treated with the Excorim Immunosorba system (two columns used in tandem). Costs for immunoadsorption and for other therapeutic products administered to the patients were calculated. RESULTS: Two patients had acquired hemophilia and severe bleeding associated with low levels of circulating FVIII and high levels of inhibitors to FVIII. They failed to achieve a satisfactory response to management with immunosuppression, pFVIII, recombinant FVIIa or IVIG but responded rapidly, with long-term benefit, to immunoadsorption therapy. The third patient had congenital hemophilia and immunoadsorption was effective in reducing his inhibitor level, allowing him to undergo immune tolerance therapy. Costs of treatment before immunoadsorption were markedly higher than those associated with the immunoadsorption procedures (i.e., >Can 350,000 dollars and >Can 1,000,000 dollars vs. < 20,000 dollars). CONCLUSION: Immunoadsorption appears to be an effective and cost-effective alternative in the management of patients with inhibitors to FVIII.     

免疫吸附治疗重度活动性系统性红斑狼疮的疗效观察

目的探讨应用DNA-280免疫吸附治疗重度活动性系统性红斑狼疮患者的临床疗效及安全性。方法应用DNA-280免疫吸附柱对10例重度活动性系统性红斑狼疮患者进行免疫吸附治疗,观察吸附治疗前后患者症状、抗核抗体（ANA）、抗dsDNA抗体、IgG、补体C3、C4水平、血常规、肝功能、肾功能、电解质、系统性红斑狼疮疾病活动指数（SLEDAI评分）,并随访观察。结果经免疫吸附治疗后,患者SLEDAI评分下降,ANA、抗dsDNA抗体滴度、免疫球蛋白IgG水平下降,补体C3、C4水平升高（P〈0．05）,治疗前后血常规、肝功能、肾功能、电解质无明显变化（P〉0．05）,整个吸附过程患者均能较好地耐受。所有患者随访观察2年,患者病情稳定（SLEDAI≤4分）。结论免疫吸附能迅速消除系统性红斑狼疮患者体内的自身抗体,控制狼疮活动;采用DNA-280免疫吸附治疗重度活动性系统性红斑狼疮安全有效。     

Utilization of nanoparticle technology in rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is one of the common and severe autoimmune diseases related to joints. This chronic autoimmune inflammatory disease, leads to functional limitation and reduced quality of life, since as there is bone and cartilage destruction, joint swelling and pain. Current advances and new treatment approaches have considerably postponed disease progression and improved the quality of life for many patients. In spite of major advances in therapeutic options, restrictions on the routes of administration and the necessity for frequent and long-term dosing often result in systemic adverse effects and patient non-compliance. Unlike usual drugs, nanoparticle systems are planned to deliver therapeutic agents especially to inflamed synovium, so avoiding systemic and unpleasant effects.The present review discusses about some of the most successful drugs in RA therapy and their side effects and also focuses on key design parameters of RA-targeted nanotechnology-based strategies for improving RA therapies.     

Treating rheumatoid arthritis to target: physician and patient adherence issues in contemporary rheumatoid arthritis therapy

Development of the treat‐to‐target (T2T) strategy, the process whereby drug therapy is adjusted until the therapeutic goal is achieved, has revolutionized how rheumatoid arthritis (RA) patients are treated. With the advent of T2T, the management of RA is more effective than ever, with the possibility of remission and other favorable clinical and patient‐reported outcomes. Effective implementation of a T2T strategy in routine clinical practice mainly depends on the long‐term commitment of physician and patient to T2T treatment recommendations. However, as T2T is a complex process involving aggressive early management with several steps of therapy modifications requiring frequent close monitoring of disease activity and drug toxicities, it may be more liable to suboptimal adherence in real‐life clinical practice. The aim of the review is to present key issues related to patient medication adherence and physician adherence to the current RA treatment recommendations and their importance in optimizing the outcome of treatment in RA treated according to T2T strategy.     

Challenging rescue of a 4 years old boy with H1N1 infection by extracorporeal membrane oxygenator: A case report

Introduction: World Health Organization announced on April 2009 a public health emergency of international concern caused by swine-origin influenza A (H1N1) virus. Acute respiratory distress syndrome (ARDS) has been reported to be the most devastating complications of this pathogen. Extracorporeal membrane oxygenator (ECMO) therapy for patients with H1N1 related ARDS has been described once all other therapeutic options have been exhausted. Here, we report the case of a child (German, male) with H1N1-associated fulminate respiratory and secondary hemodynamic deterioration who was rescued by initial emergent ECMO established through a dialysis catheter and subsequent switch to central cannulation following median sternotomy. This report highlights several important issues. First, it describes a successful use of a dialysis catheter for the establishment of a veno-venous ECMO in an emergency case by child. Second, it highlights the importance of a closely monitoring of clotting parameters during ECMO therapy and third, if severe respiratory failure is complicated by cardiogenic shock, veno-atrial ECMO support via median sternotomy should be considered as a viable treatment option without further delay.     

Management of familial hypertriglyceridemia during pregnancy with plasma exchange

Hypertriglyceridemia‐induced pancreatitis is a serious complication of familial dyslipidemias. Hormonal influences during pregnancy can compromise otherwise controlled lipid levels in women with familial hypertriglyceridemia and predispose to pancreatitis leading to increased morbidity in both mother and fetus. We report the successful use of therapeutic plasma exchange (TPE) in the management of hypertriglyceridemia during pregnancy resulting in avoidance of pancreatitis and delivery of a healthy term infant. Thirteen TPEs were performed from 19 to 36 weeks gestation to maintain tight control of triglyceride levels. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Possible association of severe major depression with acute cessation of long‐term excessive triptan use

What is known and Objective: Triptans are approved medications introduced for the acute treatment of migraine, classified as high‐affinity serotonin 5‐HT_1B/D receptor agonists with lower affinity for 5‐HT_1A receptors. Both migraine and treatment of migraine with triptans have been associated with the development of major depression. However, little is known about the adverse effects of acute cessation of long‐term overdose triptan use. Case summary: We report a case of a 49‐year‐old male patient with first onset of severe major depression following cessation of daily excessive triptan use for 8 years. The depressive disorder was resistant to prior serotonergic antidepressant therapy. Antidepressant treatment with a non‐serotonergic agent was successful in resolving depressive symptoms. What is new and Conclusion: The present case report demonstrates for the first time that acute cessation of long‐term excessive triptan use has the potential to induce severe major depression, presumably due to persistent alterations in the serotonergic system including downregulation and desensitization of 5‐HT₁ receptors. In this case, treatment with a non‐serotonergic agent could be a promising therapeutic strategy.     

Immunoadsorption of human plasma with protein A-sepharose columns

Four patients with refractory acute leukemia were treated a total of 31 times with an immunoadsorption system consisting of protein A-sepharose columns, a cell separator, and an elution monitor to test its safety and capacity to remove immunoglobulins. The procedure was tolerated well, and acutely reduced plasma IgG levels by approximately 18 percent. When the procedure was repeated two to three times per week for 3 weeks, IgG levels dropped by 30 to 40 percent, but they gradually returned to pretreatment levels after completion of the course of treatment. Single columns became saturated with IgG after approximately 1500 ml of plasma had passed through the columns. The use of multiple columns sequentially provided continuous extraction of immunoglobulin. One patient regained responsiveness to platelet transfusions after removal of platelet antibodies. These preliminary studies suggest that this immunoadsorption system is effective for specifically removing IgG and that it merits further clinical testing.     

Plasma exchange for rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common inflammatory joint disease. Even though, physiopathology of rheumatoid arthritis remains unclear, the presence of circulating immune complexes and rheumatoid factors had led to the use of plasma exchange (PE). Even though PE procedures have evolved over the last decades, their indications and use in RA must be replaced in the context of the evolution of disease-modifying anti-rheumatic drugs. Results of PE and leukapheresis were disappointing in patients with severe and resistant RA. Conversely, immunoadsorption, and particularly over a Staphylococcus aureus protein A column, has resulted in some good responses in refractory RA patients. But, the emergence of effective biologics has clearly restrained their use and limited their indications to some rare patients with refractory and severe RA.     

New trends in specific immunoadsorption

Plasma exchange is widely accepted to remove pathogenic substances from patients' blood that cannot be eliminated otherwise like cholesterol in severe forms of familial hypercholesterolaemia or immunoglobulins and circulating immune complexes (CIC) in many autoimmune disorders. But dilution of other plasma proteins, as well as side effects and costs of substitution fluids, limit its efficiency. In immunoadsorption, the pathogen is bound specifically, generally no substitution fluids are needed and plasma can be conducted over the immunoadsorption columns as often as needed to achieve any reduction that one aims at, in some instances below the detection limit (e.g. HLA-antibodies in transplantations). The frequency of aphaereses is determined by the speed of the patients' improvement and the rebound of the eliminated substance, which can in some disorders be slowed down or stopped by concomitant immunosuppression. Generally, immunoadsorption is used in patients, where less expensive and demanding treatment options have failed, like severe hypercholesterolaemia, autoimmune disorders or hyperviscosity syndromes.     

Immunoadsorption for the treatment of rheumatoid arthritis: final results of a randomized trial. Prosorba Trial Investigators.

A double-blind, randomized, placebo controlled study was conducted to determine the efficacy of a promising immunoadsorption treatment device containing staphylococcal protein A (Prosorba Immunoadsorption Column, Cypress Bioscience, Inc., San Diego, CA, U.S.A.) in patients with refractory rheumatoid arthritis (RA). Eligibility criteria required adult RA patients who had failed either methotrexate or 2 other disease modifying antirheumatic drugs (DMARD) and who had predefined active disease. All disease-modifying agents were discontinued at least 30 days prior to entry. Patients received 12 weekly procedures after being randomized to the active treatment arm or to the sham treatment arm (apheresis only). Evaluations were double-blinded and occurred at baseline and periodically for 24 weeks thereafter. Primary efficacy was assessed at 7 and 8 weeks after the completion of 12 treatments (at trial Weeks 19 and 20) using the American College of Rheumatology (ACR) definition of improvement (1,2), and results from the assessments at Weeks 19 and 20 were averaged. Ninety-nine randomized patients had a mean disease duration of 15.4 years and received an average of greater than 5 DMARD regimens prior to entry. Analysis of patients who completed all treatments and follow-up indicated that 15 of 36 (41.7%) column-treated patients responded compared to 5 of 32 (15.6%) sham-treated patients (p < or = 0.003). Intent to treat analysis of all patients who were randomized in the study indicated 15 of 52 (28.9%) column-treated patients responded compared to only 5 of 47 (10.6%) patients who received sham treatments (p = .005). Common adverse events (AEs) included joint pain, fatigue, joint swelling, and hypotension. Central line usage was clearly associated with significant AEs during this trial and is not recommended. Hemoglobin, hematocrit, and mean corpuscular volume values decreased similarly in both treatment arms, attributed to phlebotomy for laboratory and scientific studies and to small, repetitive (normal) apheresis losses. Other AEs such as nausea, rash, pruritis, flushing, and fever occurred in 1 to 6% of treatments in each arm (NS). There was no significant increase in AEs in column-treated patients compared to sham-treated patients. Protein A immunoadsorption was proven to be a new therapeutic alternative in patients with severe, refractory disease.     

Resolution of refractory, classic thrombotic thrombocytopenic purpura after staphylococcal protein A immunoadsorption

BACKGROUND: Multiple therapeutic interventions are available for treatment of thrombotic thrombocytopenic purpura. Resolution of thrombotic thrombocytopenic purpura may require use of several of these interventions. CASE REPORT: A patient presenting with classic (non- cancer chemotherapy-associated) thrombotic thrombocytopenic purpura had an initial response to intensive, daily plasma exchange with fresh- frozen plasma and cryosupernatant. Multiple attempts over a period of 2 months to decrease the frequency of plasma exchange resulted in exacerbations of disease activity, indicated by increased schistocytosis, decreased hematocrit, increased serum lactate dehydrogenase, and decreased platelet counts. After a total of 39 plasma exchanges, the patient was begun on immunoadsorption therapy utilizing a staphylococcal protein A immunoadsorption treatment column. After six 2000-mL protein A immunoadsorption treatments, the patient's platelet count, lactate dehydrogenase, and peripheral smear normalized, and they have remained normal over nearly 4 months of follow-up. CONCLUSION: Treatment by protein A immunoadsorption may be of benefit in patients with classic thrombotic thrombocytopenic purpura who are not achieving a sustained remission with conventional plasma exchange therapy.     

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.     

Treating to target in rheumatoid arthritis: biologic therapies

Treating to target is an established concept in the management of a number of long-term conditions to improve outcomes and prevent disease progression. Treatment targets in rheumatoid arthritis (RA) are to control the signs and symptoms of significant inflammatory disease activity, with the ultimate goal of remission from disease. The previous article in this series (Firth, 2011) outlined treating RA to target with conventional disease modifying drugs (DMARDs), including the role of the nurse in assessing disease activity, promoting shared clinical-decision making and monitoring treatment. In recent years, biologic agents have increased the treatment options for RA, but their use is reserved for patients with severe disease activity who fail to respond to treatment with two or more DMARDs. This article outlines the role of biologic therapies in treating RA to target, including eligibility criteria and the role of the nurse in optimizing outcomes.