Report of the ASFA apheresis registry on muscle specific kinase antibody positive myasthenia gravis

Background : Anti‐muscle specific kinase antibody positive (MuSK Ab) myasthenia gravis (MG) patients are known to have different clinical course compared to anti‐acetylcholine receptor Ab positive MG patients. Therapeutic plasma exchange (TPE) has been reported to be effective; however, little is known of the response and of TPE procedural information. An ASFA Apheresis Registry was developed to analyze those data. Methods : The study collected detailed de‐identified patient data, TPE procedures, and treatment outcome/complications. Collected data was described in aggregate. Results : A total of 15 MuSK Ab MG patients with exacerbation of MG symptoms, 13 females/2 males, median age 44, were investigated. Thirty TPE courses (median 5 procedures/course, total 145 procedures) were evaluated. All TPE procedures were performed with citrate anticoagulation, 1 − 1.25 plasma volume exchange in 100% fluid balance, and 90% of courses used only albumin as replacement. Calcium was added to albumin or given orally as needed. TPE was performed every other day in 55% of courses. Adverse events occurred in 3.4% of procedures. Ten patients (67%) experienced relapses within a median of 7 weeks. Objective symptoms were resolved in more than 75% of courses. Overall subjective improvement rates were 94.1%/93.3% after 3/4 TPE procedures, respectively. Thirty‐one percent of patients responded poorly with minimal recovery. Conclusion : Overall subjective improvement was seen up to 94% of patients after one course of TPE. Some patients were poor‐responders. Five TPE may be adequate for initial course with additional TPE as needed. Based upon this preliminary data, we will modify our future data collection. J. Clin. Apheresis 32:5–11, 2017. © 2016 Wiley Periodicals, Inc.     

Starch and albumin mixture as replacement fluid in therapeutic plasma exchange is safe and effective

Therapeutic plasma exchange (TPE) is an effective treatment in Myasthenia gravis (MG) and Guillain‐Barré syndrome (GBS) and 5% human albumin is the replacement fluid of choice; however, it is expensive. More recently, it has been suggested that starch is a safe and cheaper choice to human albumin. Objective: To evaluate our 5‐year experience using 3% hydroxyethyl starch (HES) and 5% human albumin mixture, as replacement fluid in TPE for these diseases. Materials and methods: Retrospective study carried out from January 2001 through September 2006. We included those patients with MG and GBS undergoing TPE. We analyzed clinical outcome (CO) and adverse events (AE) and our results were compared with a previous study which included similar patients undergoing TPE using just 5% human albumin. Results: Thirty‐one procedures were carried out in 26 patients, a total of 147 TPE sessions. In the group of MG we had 57% complete responses (CR) and 86% overall response (OR) while in the group of GBS we had 40% CR and 60% OR. When we analyzed our CO with the previous study no statistical differences were found. Mean processed plasma volume (PPV) was 4.2 in MG and 5.5 in GBS. Twenty patients had AE, being hypotension and catheter dysfunction the most frequent ones, while tachycardia, hypertension and paresthesias were statistically more frequent in the HES/albumin group. Conclusions: TPE with a mixture of 3% HES and 5% human albumin is as effective and safe as 5% human albumin alone for patients with these diseases. J. Clin. Apheresis, 2008. © 2008 Wiley‐Liss, Inc.     

Induction of myasthenia by immunization against muscle-specific kinase

Muscle-specific kinase (MuSK) is critical for the synaptic clustering of nicotinic acetylcholine receptors (AChRs) and plays multiple roles in the organization and maintenance of neuromuscular junctions (NMJs). MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering at the postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK have been found in a proportion of patients with generalized myasthenia gravis (MG), it is unclear whether MuSK autoantibodies are the causative agent of generalized MG. In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJs. The autoantibodies activated MuSK and blocked AChR clustering induced by agrin or by mediators that do not activate MuSK. Thus MuSK autoantibodies rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that broadens our general comprehension of the pathogenesis of MG.     

Patients with thrombotic thrombocytopenic purpura commonly develop metabolic alkalosis during therapeutic plasma exchange

Thrombotic thrombocytopenic purpura (TTP) and myasthenia gravis (MG) are category I indications for therapeutic plasma exchange (TPE). This study was based on the hypothesis that the development of metabolic alkalosis during TPE is more common in TTP than in MG, based on our previous observations. In order to test it, we compared the levels of bicarbonate and potassium in both groups of patients undergoing plasmapheresis. Fifteen patients with TTP (190 procedures) and ten MG patients seen concurrently were studied. While baseline bicarbonate levels were similar among all patients, the post‐procedure bicarbonate levels in TTP patients were mostly elevated with a mean ± SD of 29.4 ± 3.5 mEq/L, as opposed to decreased or unchanged in MG patients 26.3 ± 3.1 mEq/L (mean ± SD) (P = 1.4 × 10^?8). Furthermore, alkalosis in the TTP group persisted throughout subsequent daily treatments. There was also a significant decrease between pre‐ and post‐TPE potassium levels in TTP patients (P = 3 × 10^?21) by paired Student's t test. Additionally, samples with levels <3.3 mEq/L were alkalotic 75% of the time. In the MG group, however, potassium was normal in 85% and 83% of the pre‐ and post‐TPE samples, respectively. Consequently, the hypokalemia was significantly more marked in the TTP group (P = 0.0008). These data confirm that plasmapheresis commonly induces metabolic alkalosis in TTP patients, probably due to high citrate in fresh frozen plasma, the frequency of treatments, and perhaps decreased renal clearance due to disease involvement of the kidneys. J. Clin. Apheresis. 16:120–124, 2001. © 2001 Wiley‐Liss, Inc.     

重症肌无力合并胸腺病变患者血清乙酰胆碱受体抗体、肌联蛋白抗体和肌肉特异性酪氨酸激酶抗体的检测意义

目的探究对重症肌无力合并胸腺病变的患者血清中乙酰胆碱受体（acetylcholine receptors, AchR）抗体、肌联蛋白（Titin）抗体和肌肉特异性酪氨酸激酶（muscle specific tyrosine kinase, MuSK）抗体的检测意义。方法选取我院收治的80例重症肌无力患者,根据是否存在胸腺病变分为胸腺病变组48例和非胸腺病变组32例,另取80例健康个体作为对照组,通过免疫酶联吸附试验对3组成员血清中AchR抗体、Titin抗体和MuSK抗体进行检测并比较。结果重症肌无力患者血清AchR抗体和Titin抗体阳性率（76.3%,52.5%）均明显高于对照组（11.3%,5.0%）（P<0.05）;重症肌无力组及对照组患者血清MuSK抗体阳性率均为0,但前者血清中MuSK抗体水平明显高于后者（P<0.05）;AchR,Titin两种抗体联合检测可明显提高检测重症肌无力的灵敏度;AchR和Titin抗体在胸腺病变组中的阳性率明显高于非胸腺病变组（P<0.05）;全身型重症肌无力患者的血清AchR抗体和Titin抗体阳性率明显高于眼肌型（P<0.05）。结论AchR抗体和Titin抗体的阳性率与重症肌无力患者的病情相关,病情严重或合并胸腺病变可明显提高两者的阳性率,此外两者联合检测可提高诊断的灵敏度。而MuSK抗体在我国重症肌无力患者中的阳性率较低。     

Overview: MuSK/Dok-7

MuSK/Dok-7 mediate the clustering of acetylcholine receptor (AChR) during synapse formation and are expressed at the mature neuromuscular junction. These proteins are deeply associated with myasthenia gravis (MG) and congenital myasthenic syndrome (CMS). Compared with MG patients with AChR antibodies, those with muscle-specific tyrosine kinase (MuSK) antibodies are more likely to present oculobulbar than limb weakness, myasthenic crisis and muscle wasting. None have thymoma, so the indication for thymectomy should be investigated. MuSK antibodies do not appear to cause complement-mediated morphological motor endplate damage, but how they cause myasthenic symptoms is unclear. As the results, the three types of MG presently characterized by known antibody targets are classified into 1) AChR antibody-positive, 2) MuSK antibody -positive, and 3) double seronegative type which the above-mentioned antibodies are negative. In 2006, MuSK-interacting cytoplasmic protein termed Dok-7 has been found. Subsequently, mutations in Dok-7 as a cause of CMS were identified, providing evidence for a crucial role of Dok-7 in maintaining synaptic structure. Their effect on MuSK/Dok -7 function needs to be explored.     

Myasthenia gravis during pregnancy

Question One of my patients who has been diagnosed with myasthenia gravis (MG) is planning pregnancy. Her MG is controlled with medications. Can her condition or her medications adversely affect her pregnancy?Answer The course of MG during pregnancy is unpredictable, but there is no evidence that MG can adversely affect pregnancy outcomes. Examination of most of the medications used for symptom control has so far shown reassuring results. Prepregnancy thymectomy might decrease the need for medications during pregnancy. The newborn should be carefully monitored for signs of transitory MG.     

A comparison of long-term post-thymectomy outcome of anti-AChR-positive,anti-AChR-negative and anti-MuSK-positive patients with non-thymomatous myasthenia gravis

Objective: A single-centre, non-randomized, non-controlled study was designed to compare the long-term post-thymectomy clinical outcome in anti-AChR-positive, anti-AChR-negative and anti-MuSK-positive patients with non-thymomatous myasthenia gravis (MG). Methods: A total of 331 consecutive patients with seropositive MG, 55 with seronegative MG and 10 with anti-MuSK-positive MG underwent extended transsternal thymectomy (T-3b according to Myasthenia Gravis Foundation of America). The primary endpoint was to assess differences in the rate of complete stable remission (CSR) in patients with and without anti-AChR and anti-MuSK antibodies. Results: The mean follow-up was 218.3 (SD 128.1) months in the seropositive MG group, 149.8 (SD 131.1) in the seronegative group and 169.9 (SD 116) in the anti-MuSK-positive group. In the seropositive MG group, the probability of obtaining CSR at 5 years post-thymectomy was 51.1% for the seropositive group compared with 40 for the seronegative group (p = 0.05) and 20 for the anti-MuSK-positive group (p = 0.03). Differences between the seronegative and anti-MuSK-positive groups were not observed. The estimated median follow-up to obtain a CSR was 17.8 months (95% confidence interval [CI] 15.7 – 19.8 months) in seropositive MG patients, 22.1 (95% CI 16.7 – 27.4 months) in seronegative MG patients and 20.6 (95% CI 13.3 – 27.9 months) in anti-MuSK-positive MG patients (long-rank test, p = 0.07). Conclusions: Long-term post- thymectomy clinical outcome was better in patients with conventional anti-AChR antibodies than in those with seronegative disease. In seronegative anti-MuSK-positive MG, thymectomy seems to be less effective than in anti-MuSK-negative MG but this study cannot answer the question of whether thymectomy should be undertaken in anti-MuSK-positive patients.     

Haemolysis after treatment with intravenous immunoglobulin due to anti-A

Background: Intravenous immunoglobulin (IVIG) is used to treat an increasing number of conditions. IVIG contains immunoglobulin G (IgG) directed against many targets, including red blood cell (RBC) antigens. Methods/materials: We report on three patients identified within a 7‐month period in a single institution who developed haemolysis because of passively transferred anti‐A. Results: The patients were a 34‐year‐old A (non‐A₁) D‐positive male with aplastic anaemia, a 61‐year‐old A₁ D‐negative female with myasthenia gravis and a 57‐year‐old AB D‐positive female lung transplant recipient. The haemoglobin decreased from 11·1 to 5·3 g dL^?1 over 2 days, 12·8 to 7·8 g dL^?1 over 6 days and 7·8 to 6·0 g dL^?1 over several hours, respectively. All three patients had a negative antibody screen, positive direct antiglobulin test for IgG only and an elution containing anti‐A₁ reactivity. The patients were transfused with O RBC with an appropriate rise in haemoglobin. Conclusion: These cases illustrate the potential severity of haemolysis after IVIG because of passively transferred antibodies to blood group antigens. Lack of recognition of IVIG as a cause for haemolysis by clinicians may be further confounded if routine testing fails to detect the passively transferred ABO blood group antibodies.     

Myasthenia gravis induced by autoantibodies against MuSK

Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies. That is, the binding of autoantibodies to postsynaptic membranes in neuromuscular junctions (NMJ) results in weakening of the ocular, bulbar and limb muscles and produces the characteristic syndrome of MG. About 80 to 85% of patients witth MG have autoantibodies against acetylcholine receptors (AChR). Antibodies against muscle-specific kinase (MuSK) have been found in 30% of MG patients without AChR antibodies. Here we describe recent progress toward understanding the pathogenic role of MuSK antibodies in the decline of muscle strength that typifies MG.     

Antibodies against low-density lipoprotein receptor–related protein 4 induce myasthenia gravis

Myasthenia gravis (MG) is the most common disorder affecting the neuromuscular junction (NMJ). MG is frequently caused by autoantibodies against acetylcholine receptor (AChR) and a kinase critical for NMJ formation, MuSK; however, a proportion of MG patients are double-negative for anti-AChR and anti-MuSK antibodies. Recent studies in these subjects have identified autoantibodies against low-density lipoprotein receptor–related protein 4 (LRP4), an agrin receptor also critical for NMJ formation. LRP4 autoantibodies have not previously been implicated in MG pathogenesis. Here we demonstrate that mice immunized with the extracellular domain of LRP4 generated anti-LRP4 antibodies and exhibited MG-associated symptoms, including muscle weakness, reduced compound muscle action potentials (CMAPs), and compromised neuromuscular transmission. Additionally, fragmented and distorted NMJs were evident at both the light microscopic and electron microscopic levels. We found that anti-LRP4 sera decreased cell surface LRP4 levels, inhibited agrin-induced MuSK activation and AChR clustering, and activated complements, revealing potential pathophysiological mechanisms. To further confirm the pathogenicity of LRP4 antibodies, we transferred IgGs purified from LRP4-immunized rabbits into naive mice and found that they exhibited MG-like symptoms, including reduced CMAP and impaired neuromuscular transmission. Together, these data demonstrate that LRP4 autoantibodies induce MG and that LRP4 contributes to NMJ maintenance in adulthood.     

快速检测重症肌无力患者的抗乙酰胆碱受体抗体的研究

目的：建立一种简便，快速的方法以及检测血清中的抗乙酰胆碱受体抗体（AchR-Ab）。方法：分别用本法和常规ELISA对90份临床确诊标本进行检测，并对两种检测结果进行比较分析。结果：60例重症肌无力患者经本法和常规ELISA检测后，AchR-Ab阳性率分别为88．3％和86．7％。本检测法的敏感性达88．3％，特异性为93．3％，重复性较好（CV＜7．94％）。结论：与常规ELISA相比，本检测法具有方便，快速，敏感的特点，在重症肌无力患者的AchR-Ab检测中有较好的应用价值。     

胸腺瘤切除术后重症肌无力危象的临床分析

目的:探讨胸腺瘤切除术后发生重症肌无力危象的原因及治疗方法。方法:回顾性分析1998～2005年诊治的14例胸腺瘤切除术后发生重症肌无力危象的患者的病例资料。结果:14例患者中1例死亡,其余治愈出院。重症肌无力危象主要发生于术后早期,Osserman临床分型属于Ⅲ型、Masqoka分期属于Ⅱ期、术前准备不充分,服用抗胆碱酯酶药物剂量较大、术前曾发生危象和肺部感染、中度或重度通气功能障碍等是术后发生危象的最常见诱因。结论:重症肌无力危象患者及时气管插管或气管切开,应用呼吸机,预防感染,肾上腺皮质激素冲击治疗,静脉注射大剂量免疫球蛋白等综合抢救措施,可明显缩短病程,显著降低死亡率。     

The top clinical trial opportunities in therapeutic apheresis and neurology

Objective: The National Heart, Lung, and Blood Institute, of The National Institutes of Health, convened the 2012 State‐of‐the‐Science Symposium in therapeutic apheresis (TA) with the goals of identifying and prioritizing future research concept proposals to optimize the use of TA over the next decade. Methods: Six subcommittees, including neurology, were formed based on organ system, pathophysiology, and technology/special considerations. The subcommittees consisted of physicians, clinical subject matter experts, and basic scientists. Each subcommittee developed concept proposals that were presented, evaluated, and prioritized based on scientific importance, clinical significance, and feasibility. Results: The neurology subcommittee developed eight concept proposals. The proposals include therapeutic plasma exchange (TPE) in neuromyelitis optica; TPE versus intravenous immunoglobulin (IVIG) in anti‐muscle specific kinase associated myasthenia gravis, severe acute disseminated encephalomyelitis, and anti‐NMDA encephalitis; extracorporeal photopheresis in relapsing remitting multiple sclerosis and polymyositis; fibrinogen/low‐density lipoprotein apheresis in idiopathic sudden sensorineural hearing loss; and creation of a rare neurologic disease registry and biorepository. Conclusions: Key clinical research priorities to evaluate and optimize the use of TA on selected neurologic disorders exist. The research opportunities if addressed would provide evidence‐based data to inform the care of patients with these selected neurologic diseases. J. Clin. Apheresis 29:331–335 2014. © 2014 Wiley Periodicals, Inc.     

The critical role of plasmapheresis in ABO-incompatible renal transplantation

BACKGROUND: Thousands of patients with chronic renal failure die yearly and are unable to have a kidney transplant due to the severe shortage of donors. Therapeutic plasma exchange (TPE) is performed to remove ABO antibodies and permit ABO‐incompatible (ABO‐I) kidney transplants, but there is only limited research within this area and a lack of standardized protocols for TPE. This article reviews the literature to provide a historical perspective of TPE for ABO‐I kidney transplantation and also provides the Johns Hopkins Hospital protocol with a focus on both titers and TPE. STUDY DESIGN AND METHODS: The TPE treatment plan is based on ABO titers with the goal of a titer of 16 or less at the anti‐human globulin (AHG) phase before surgery. Pretransplant therapy consists of every‐other‐day TPE followed immediately by cytomegalovirus hyperimmune globulin. ABO antibody titers are closely monitored before and after transplantation. After transplantation, TPE therapy is performed for all patients to prevent rebound of anti‐A and anti‐B titers until tolerance or accommodation occurs. TPE is discontinued and reinstituted based on the clinical criteria of creatinine levels, biopsy results, and ABO titer. RESULTS: Fifty‐three ABO‐I kidney transplants have been completed with no episodes of hyperacute antibody‐mediated rejection (AMR) and only three episodes of AMR. One‐year death‐censored graft survival is 100 percent and patient survival is 97.6 percent. CONCLUSIONS: While randomized clinical trials are needed to evaluate the optimal method and protocol to remove ABO antibodies, the current literature and our results indicate a critical role for TPE in ABO‐I renal transplantation.     

Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study

Summary. Objective: To evaluate the role of anti‐prothrombin (anti‐PT) antibodies in predicting thrombosis in patients with systemic lupus erythematosus (SLE). Methods: An inception cohort of 101 SLE patients (12 males, 89 females; mean age 30 ± 8 years), was considered. Clinical and laboratory evaluations were regularly performed during a 15‐year follow‐up (median 108 months) with a special focus on thromboembolic events. Serum samples were collected at time of diagnosis and at least once a year thereafter. IgG and IgM anti‐PT, anti‐cardiolipin (aCL) and anti‐β₂glycoprotein I (β₂GPI) antibodies were measured by enzyme‐linked immunosorbent assay (ELISA); lupus anticoagulant (LAC) was assayed by the dilute Russell’s viper venom time and activated partial thromboplastin time tests. The analytical specificity of anti‐PT ELISA was investigated. The timing of thrombosis occurrence was calculated using the Kaplan–Meier method. Results: In the 15‐year follow‐up, thrombosis occurred in 14 out of the 101 patients: venous thrombosis in nine cases and arterial thrombosis in five. IgG and/or IgM anti‐PT, anti‐β₂GPI and aCL antibodies, and LAC activity were detected in ten, nine, seven, and nine cases, with sensitivity for thrombosis of 71.4%, 64.3%, 50% and 64.3%, respectively. Thrombosis‐free survival was 90% at 5 years and 85.8% at 10 and 15 years, respectively. Thrombosis was predicted by anti‐PT (P = 0.001), anti‐β₂GPI antibodies (P = 0.002) and LAC activity (P = 0.001). Moreover, the risk of thrombosis progressively increased with the number of positive antiphospholipid antibody tests. The presence of four positive antibody tests was associated with a risk of thrombosis thirtyfold higher than in their absence. Conclusions: This longitudinal study shows that IgG anti‐PT antibodies are predictors of thrombosis in SLE patients.     

Anti‐C1q antibodies: association with nephritis and disease activity in systemic lupus erythematosus

Background: Anti‐C1q antibodies have been described in systemic lupus erythematosus (SLE) as well as in other connective tissue diseases. They have been considered as a marker for disease activity and presence of nephritis. Objective: The aim of this study was to determine the prevalence of anti‐C1q antibodies in Brazilian lupus patients as well as analyze their association with different clinical and serologic parameters. Methods: Sera from 81 SLE patients, based on the American College of Rheumatology (ACR) criteria, were collected from a lupus referral outpatient clinic in Salvador, Brazil. Antibodies to C1q were detected by an enzyme‐linked immunoassay (ELISA) kit and antibodies to other cellular antigens identified by indirect immunofluorescence on HEp‐2 cell substrate (ANA), or Crithidia luciliae (dsDNA), and to nucleosome by ELISA. A cutoff of 20 U wasestablished for anti‐C1q and antinucleosome assays. Results: Anti‐C1q antibodies were detected in 39.5% (32/81) of SLE sera. The presence of anti‐C1q antibodies was associated with proteinuria (P=0.028) but not with other laboratory or clinical features, such as antinucleosome or anti‐dsDNA antibodies, hematuria, urinary casts or renal failure, leukopenia, pericarditis, pleuritis, malar rash, seizures, and psychosis. There was a positive correlation between the titers of anti‐C1q antibodies and the systemic lupuis erythematosus disease activity index (SLEDAI) score (r=0.370; P=0.001). Conclusion: This study in Brazilian SLE patients confirms previous findings of the association of anti‐C1q antibodies with nephritis and disease activity. J. Clin. Lab. Anal. 23:19–23, 2009. © 2009 Wiley‐Liss, Inc.     

Therapeutic plasma exchange in patients with neurologic diseases: retrospective multicenter study.

Therapeutic plasma exchange (TPE) is commonly used in many neurological disorders where an immune etiology was known or suspected. We report our experience with TPE performed for neuroimmunologic disorders at four university hospitals. The study was a retrospective review of the medical records of neurological patients (n=57) consecutively treated with TPE between April 2006 and May 2007. TPE indications in neurological diseases included Guillain-Barrè Syndrome (GBS) (n=41), myasthenia gravis (MG) (n=11), acute disseminated encephalomyelitis (ADEM) (n=3), chronic inflammatory demyelinating polyneuropathy (CIDP) (n=1) and multiple sclerosis (MS) (n=1). Patient median age was 49; there was a predominance of males. Twenty-two patients had a history of other therapy including intravenous immunoglobulin (IVIG), steroid, azothioprin, and pridostigmine prior to TPE. Another 35 patients had not received any treatment prior to TPE. All patients were classified according to the Hughes functional grading scores pre- and first day post-TPE for early clinical evaluation of patients. The TPE was carried out 1-1.5 times at the predicted plasma volume every other day. Two hundred and ninety-four procedures were performed on 57 patients. The median number of TPE sessions per patient was five, and the median processed plasma volume was 3075mL for each cycle. Although the pre-TPE median Hughes score of all patients was 4, it had decreased to grade 1 after TPE. While the pre-TPE median Hughes score for GBS and MG patients was 4, post-TPE scores were decreased to grade 1. Additionally, there was a statistically significant difference between post-TPE Hughes score for GBS patients with TPE as front line therapy and patients receiving IVIG as front line therapy (1 vs. 3.5; p=0.034). Although there was no post-TPE improvement in Hughes scores in patients with ADEM and CIDP, patients with MS had an improved Hughes score from 4 to 1. Mild and manageable complications such as hypotension and hypocalcemia were also observed. TPE may be preferable for controlling symptoms of neuroimmunological disorders in early stage of the disease, especially with GBS.     

Therapeutic plasma exchange as a therapeutic modality for the treatment of IVIG complications

Intravenous immunoglobulin (IVIG) is used for the treatment of a number of inflammatory conditions. Hemolysis due to passive transfer of blood group antibodies is a well recognized complication of IVIG therapy. Therapy is largely supportive and consists of blood product support and hemodialysis. We report the use of therapeutic plasma exchange (TPE) as adjunct therapy for three patients with complications attributed to IVIG. Two patients had hemolysis attributed to IVIG; one patient was blood group A and the other blood group O. The third patient was an orthotopic heart transplant recipient with a type A donor heart, and anti‐A antibodies detected after infusion of IVIG for suspected antibody mediated rejection. Two patients had anti‐A titers available that decreased after initiation of plasma exchange. The blood group O patient with hemolysis had a gradual stabilization of hemoglobin and resolution of the positive DAT. TPE may be useful therapy for patients with severe hemolysis caused by IVIG or at risk for tissue damage by blood group antibodies. J. Clin. Apheresis 30:371–374, 2015. © 2015 Wiley Periodicals, Inc.     

Therapeutic plasma exchange rapidly improves cardiac allograft function in patients with presumed antibody‐mediated rejection

Background: Allograft dysfunction due to presumed antibody‐mediated rejection (pAMR) is one of the most serious complications of heart transplantation. Combination therapies of high‐dose steroids, intravenous immune globulin, and/or therapeutic plasma exchange (TPE) are often used in this setting. Methods: We performed a 9‐year retrospective review of all episodes of pAMR treated with TPE at our institution. pAMR diagnosis was based on clinical and pathologic findings. Left ventricular ejection fraction (LVEF) was measured at baseline, prior to initiation of TPE, and during the course of treatment. Results: There were 42 patients with 47 episodes of pAMR treated with TPE. The majority of episodes were treated with three TPE; however, eight required only two TPE and five episodes required >3 TPE. All episodes of pAMR had LVEF measured before and after the series of TPEs. The mean pre‐TPE LVEF was 38% compared with a post‐therapy mean LVEF of 50% (P < 0.0001). In 16 episodes of pAMR, for which LVEF was measured following each apheresis, there was significant improvement of allograft function after the first TPE (pre‐TPE mean LVEF of 31% and post‐first TPE mean LVEF of 37%; P = 0.02). Incremental and significant improvement in allograft function continued following each TPE. Changes in human leukocyte antigen‐donor specific antibodies and fibrinogen did not correlate with ejection fraction response. Conclusions: The rapid improvement in allograft function in our patients is most likely due to TPE as other pharmacologic interventions have longer onset. TPE should be considered a first‐line intervention in the setting of pAMR. J. Clin. Apheresis 29:316–321 2014. © 2014 Wiley Periodicals, Inc.