Intensive Plasmapheresis Research Articles

Review and assessment of the donor safety among plasma donors.

Review and assessment of the donor safety among plasma donors.

Can Kunxian Capsule, a Novel Tripterygium Preparation be Used as an Adjuvant Treatment of Early Recurrent Focal Segmental Glomerular Sclerosis After Renal Transplantation? A Case Report

Focal segmental glomerular sclerosis (FSGS) tends to recur after kidney transplantation, particularly when genetic testing is negative. Once the recurrence happens, the renal graft function can rapidly become impaired, following a massive urine protein loss. Despite intensive plasmapheresis and high-dose rituximab treatment, the complete remission rate remains below 50%. The Kunxian capsule, representing a new generation of tripterygium preparation, has shown promising results in controlling proteinuria in patients with IgA nephropathy. It is unclear whether Kunxian capsule treatment would also produce a favorable response in cases of FSGS recurrence. Here we report favorable results with this approach in a patient with early recurrent FSGS after kidney transplantation; we treated this patient successfully with a Kunxian capsule, a low dose of rituximab (200 mg), and reduced sessions of plasmapheresis. Complete remission, with a 90% reduction in total urine protein (0.81 g/24 h vs 8.3 g/24 h), was achieved within 2 weeks post-treatment. Of interest, the complete remission state in this patient has been maintained over 20 months with continuous administration of Kunxian capsules after the cessation of plasmapheresis. The potential mechanisms involved here include direct podocyte protection and the anti-inflammatory and immunosuppressive properties of triptolide in the Kunxian capsule. Our case may offer a new reference option for treating recurrent FSGS in the future.

Successful treatment with intense immunosuppressive therapy in an initially 100% crescentic lesion of anti-GBM nephritis

Anti-glomerular basement membrane (anti-GBM) nephritis is uncommon glomerular disease caused by autoantibodies targeting the capillary beds of the kidney. The clinical presentation of the disease is a variable nephritic syndrome, rapidly progressing to glomerulonephritis. Treatment outcomes are dependent on predictors at first diagnosis. We presented a case of 58-year-old man who did not have underlying disease presented with marked abdominal distension and acute kidney injury. He had no evidence of chronic renal disease before admission however, laboratory test showed microscopic haematuria (RBC 30-50 per high-powered field), proteinuria (2.9 g/d), and renal failure (serum creatinine 610 µmol/L) compatible with rapidly progressive glomerulonephritis; hence, a renal biopsy was conducted. The pathology showed 100% crescentic glomerulonephritis with IgG deposits in a linear pattern at the GBM. The initial serum anti-GBM titre was 105.59 RU/mL. This patient had poor renal prognosis factors for treatment response. After a discussion regarding treatment option with the patient, we decided to give intensive immunosuppressive therapy and plasmapheresis due to his good baseline functional status. The patient achieved partial remission and is not dialysis dependent. In conclusion, despite a poor renal prognosis with 100% crescents and serum creatinine ≥ 600 µmol/L, the treated patient had a good survival status and did not become dialysis-dependent. However, immunosuppressive treatment should be performed along with careful monitoring for infection to avoid infection-related morbidity and mortality.

Plasmapheresis, Photopheresis, and Endovenous Immunoglobulin in Acute Antibody-mediated Rejection in Kidney Transplantation

IntroductionAcute antibody-mediated rejection (AAMR) is the subject of much research. It is diagnosed by C4d staining at biopsy and circulating donor-specific antibodies (DSA). The combination of intensive plasmapheresis and intravenous immunoglobulin (IVIG) has been recognized as an effective treatment for AAMR. We report our single-center experience on AAMR treatment. Materials and MethodsWe treated 23 transplanted patients (group A) with protein-A immunoadsorption (IA) and 7 patients (group B) with double-filtration plasmapheresis. All patients were treated with IVIG (400 mg/kg/d). Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). A subgroup of 3 patients (3/7; group B1) was treated with photopheresis. ResultsIn both groups, the mean number of extracorporeal procedures was 7.3 ± 4.5 and 5.5, respectively; the mean duration of treatment was 12.3 ± 10.2 and 14.5 days, respectively. In group A, we observed negative cross-matching in 96% after mean of 18 days; 1 patient died from sepsis, and 6 lost their grafts. In group B, negative circulating DSA were observed in all patients after a mean of 25 days, and 1 patient lost their allograft. ConclusionsIn our observation, the 2 extracorporeal procedures had similar effects in terms of graft survival, DSA removal, and cross-match negativity (group A 74% vs 86%; 95.6% vs 100%). IA was faster for DSA removal. In our opinion, the higher costs of IA suggests its use just in high-risk cases, such as in hyperimmune or sensitized patients. Further studies are necessary to improve our knowledge.

Renal Outcomes After Treatment With Intensive Plasmapheresis and Intravenous Immunoglobulin in Renal Allograft Patients With Antibody-Mediated Rejection: A Single-Center Experience.

Renal Outcomes After Treatment With Intensive Plasmapheresis and Intravenous Immunoglobulin in Renal Allograft Patients With Antibody-Mediated Rejection: A Single-Center Experience.

Long-term Plasmapheresis in Conjunction With Thalidomide and Dexamethasone for the Treatment of Cutaneous Ulcers and Neovascular Glaucoma in Recalcitrant Type I Cryoglobulinemia

Cryoglobulins are cold-precipitating immunoglobulins that occur secondary to lymphoproliferative disorders, chronic viral infections, and autoimmune disorders. The treatment of cryoglobulinemia should target the underlying disorder; however, such an approach may be difficult, and therapeutic options remain limited for type I cryoglobulinemia. We report a case of recalcitrant type I cryoglobulinemia treated successfully with long-term plasmapheresis in conjunction with thalidomide and dexamethasone. A woman in her 50s with cryoglobulinemia and bilateral lower extremity ulcers of 1 year's duration developed acute angle-closure glaucoma following the appearance of new macules on her upper extremities. An initial short course of 5 plasmapheresis treatments improved the patient's cutaneous lesions as well as the glaucoma. Three weekly doses of rituximab were not associated with any evidence of clinical improvement, so thalidomide and dexamethasone were administered as replacement therapy. Because of the increasing pain and persistence of the woman's ulcers, intensive plasmapheresis was resumed and continued 3 to 4 times per week for approximately 4 months, after which a slow tapering regimen was initiated. This therapy was associated with progressive, rapid healing of the ulcers, stabilization of the skin lesions, and control of the patient's intraocular pressure. The long-term use of plasmapheresis may be a well-tolerated treatment option for therapeutically challenging cases of cryoglobulinemia.

La myasthénie du côté de l’interniste

Myasthenia gravis is an autoimmune disease due to specific antibodies inducing a neuromuscular transmission defect causing muscle fatigability. If onset of the disease may be at any age, myasthenia gravis concerns mostly young adults, in majority females. The disease characteristic features are the following: ocular symptoms (ptosis or diplopia) as main initial manifestation, extension to other muscles in 80 % of the cases, variability of the deficit, effort induced worsening, successive periods of exacerbation during the disease course, severity depending on respiratory and swallowing impairment (if rapid worsening, a myasthenic crisis is to be suspected), association with thymoma in 20 % of patients and with other various autoimmune diseases, most commonly hyperthyroidism and Hashimoto's disease. Diagnosis relies on the clinical features, improvement with cholinesterase inhibitors, detection of specific autoantibodies (anti-AChR or anti-MuSK), and significant decrement evidenced by electrophysiological tests. The points concerning specifically the internist have been highlighted in this article: diagnostic traps, associated autoimmune diseases, including inflammatory myopathies that may mimic myasthenia gravis, adverse effects of medications commonly used in internal medicine, some of them inducing myasthenic syndromes. The treatment is well codified: the treatment is well codified: (1) respect of adverse drugs contra-indications, systematically use of cholinesterase inhibitors, (2) thymectomy if thymoma completed with radiotherapy if malignant, (3) corticosteroids or immunosuppressive agent in severe or disabling form, (4) intensive care unit monitoring, plasmapheresis or intravenous immunoglobulins for patients with myasthenic crisis.

Antibody-mediated kidney allograft rejection: therapeutic options and their experimental rationale

With the advent of novel therapies to directly intervene with B cell immunity and complement activation, antibody-mediated kidney allograft rejection (AMR) has come into the focus of transplant immunologists. Intravenous immunoglobulin, rituximab, bortezomib, and eculizumab have been used to treat patients with acute AMR, apart from the standard treatment of antibody removal with plasma exchange or immunoadsorption and steroid pulses. This article describes the experimental rationale and summarizes the still limited clinical experience with these novel therapies in the transplant setting. Results with the standard treatment for acute AMR, including intense plasmapheresis, intravenous immunoglobulins, and steroids are good with a graft survival of 80% at 18 months. In contrast, patients suffering from chronic AMR have significant irreversible damage in their grafts with substantially impaired graft survival. Thus, the authors propose a step-wise escalation of therapy in refractory cases of acute AMR and advocate an urgent need for controlled therapeutic trials for acute and chronic AMR not to inflict unnecessary harm on our patients by uncontrolled polypragmasy.

Successful Living Donor Liver Transplantation for Fulminant Hepatic Failure That Manifested Immediately After Cesarean Delivery

A 31-year-old pregnant woman was diagnosed as having acute hepatitis of unknown etiology and conservatively treated. An emergency cesarean delivery was performed 5 days later at 33 weeks and 3 days of gestation because of a gradual deterioration in liver function. Two days after the cesarean delivery, she lost consciousness in the evening (Glasgow coma scale [GCS] = 9) because of hepatic encephalopathy and was diagnosed as having fulminant hepatic failure (FHF). Five days after the cesarean delivery, the patient (blood type B) underwent a successful left lobe with caudate lobe (S1+2+3+4) liver transplantation from her father (blood type AB), an ABO-incompatible donor. At 1 year follow-up, she and her baby are in good medical condition. The drastic deterioration in hepatic function, despite intensive plasmapheresis and continuous hemodiafiltration, during the early postpartum period suggested a possible causative association between the termination of pregnancy and progression of FHF from acute hepatitis of unknown etiology.

AA-amyloidosis in a kidney biopsy on top of pauci-immune crescentic glomerulonephritis.

In March 2011, a 56-year-old woman presented with fever of unknown origin accompanied with symmetric arthralgias and sinusitis. Her medical history was notable for diabetes mellitus Type 2, hypertension, smoking and multiple episodes of sinusitis. Admission blood chemistry tests revealed a leucocyte count of 14.3 × 109/L, a C-reactive protein (CRP) level of 4.4 mg/dL (<0.5 mg/dL), a creatinine level of 266.6 μmol/L and a blood urea nitrogen (BUN) level of 47 mg/dL. Urinalysis demonstrated gross proteinuria with a total protein/creatinine ratio of 6.4 g/g and nephritic sediment. Anti-nuclear, anti-GBM and MPO-ANCA antibodies were negative, Complement factor 3 and 4 in the normal range but PR3-ANCA antibodies were clearly detectable. Of note, computed tomography of her head and thorax displayed signs of pansinusitis but no pulmonary changes. A kidney biopsy was performed which revealed pauci-immune crescentic glomerulonephritis with crescent formation in 9 of 14 glomeruli. Most interestingly, glomeruli demonstrated Periodic Acid Schiff (PAS)-negative mesangial and perihilar deposits (Figure 1), which were positive for congo red (Figure 2, upper left insert). Immunohistochemistry revealed positivity for amyloid-P and amyloid-A (Figure 2, lower right insert). Electron microscopy confirmed fibrillary deposits consistent with amyloid (Figure 2). Amyloid was also present in arteriolar walls in the kidney. Since all other causes of AA-amyloidosis were excluded, the most probable underlying cause for AA-amyloidosis in our patient is long lasting granulomatosis with polyangiitis (Wegener’s). Since our patient suffered from multiple episodes of sinusitis in her medical history, it might be speculated that granulomatosis with polyangiitis (Wegener’s) was long-lasting, allowing the development of AA-amyloidosis. Fig. 1. A cellular crescent and PAS-negative perihilar and mesangial amyloid deposits (arrows) are present within one and the same glomerulum (PAS stain). Fig. 2. Typical fibrillary structure of amyloid deposits on transmission electron microscopy (uranyl acetate and lead citrate). Upper left inset: positive congo red staining of amyloid deposits. Lower right inset: positive immunohistochemistry for Amyloid A. Treatment of the patient was started with corticosteroids and intravenous cyclophosphamide. Because of a further decrease of kidney function requiring haemodialysis treatment, plasmapheresis was performed. After daily intensive plasmapheresis treatment for >2 weeks PR3-ANCAs became negative and fever as well as arthralgias resolved, but the patient’s kidney function has not recovered as yet.

Case Report: Successful Treatment of Recurrent Focal Segmental Glomerulosclerosis with a Novel Rituximab Regimen

Focal segmental glomerulosclerosis (FSGS) is the cause of renal failure in more than 10% of pediatric patients undergoing renal transplantation. Recurrent FSGS is a major cause of pediatric allograft failure, with the risk increasing for patients undergoing retransplantation. Standard therapy for recurrent posttransplantation FSGS includes the use of intensive plasmapheresis (PP) in conjunction with cyclophosphamide or high-dose cyclosporine. However, many patients exhibit refractory disease, with rapid progression to allograft loss despite these interventions. Prior studies have reported conflicting data on the efficacy of adding rituximab therapy to the standard treatment regimen for recurrent posttransplantation FSGS. Here we present a successful therapeutic protocol with rapid elimination of PP after initiation of rituximab therapy for an adolescent patient with recurrent FSGS in the immediate postoperative period. The patient has maintained excellent allograft function through 12 months posttransplantation.

Intensive plasmapheresis donations contain less immunoglobulin and albumin: consequences for donor health

Intensive plasmapheresis donations contain less immunoglobulin and albumin: consequences for donor health

Posttransplant Recurrence of Primary Glomerulonephritis

All forms of primary GN may recur after kidney transplantation and potentially jeopardize the survival of the graft. IgA nephritis (IgAN) may recur in approximately one third of patients, more frequently in younger patients and in those with a rapid progression of the original disease. However, with the exception of few patients with rapid progression, there is no evidence that recurrence of IgAN has a deleterious effect on graft survival at least up to 10 years. Recurrence of focal segmental glomerulosclerosis (FSGS) is often associated with nephrotic proteinuria and is more frequent in children, in patients with rapid progression of the original disease, and in those who lost a previous transplant from recurrence. The natural course of recurrent FSGS is usually unfavorable. Early and intensive plasmapheresis may obtain complete or partial response in several patients. Good results have also been reported with rituximab. Idiopathic membranous nephropathy (IMN) may recur in 30% to 40% of patients. The graft survival in patients with IMN is not different than that of patients with other renal diseases. Good results with rituximab have been reported. Membranoproliferative GN (MPGN) may recur in 27% to 65% of patients. The recurrence is more frequent and the prognosis is more severe in type II MPGN. Although recurrent GN is relatively frequent and may worsen the outcome of renal allografts in some patients, its effect is diluted by several other risk-factors that may have a greater effect than recurrent GN on the long-term graft survival.

A prospective multicentre study on the safety of long‐term intensive plasmapheresis in donors (SIPLA)

The safety of chronic intensive donor plasmapheresis has not been determined in large prospective studies examining dropout rates, dropout reasons and predictors of withdrawals. Twenty-one plasma centres recruited 3783 donors who were switched from a moderate to an intensive plasmapheresis programme and observed over a 3-year period. Individuals weighing < 70 kg and > or = 70 kg donated 750 ml and 850 ml of plasma per session, respectively. The maximum of annual donations was limited to 60. Total serum protein (TSP) and haemoglobin (Hb) or haematocrit (Hct) were determined at each donation, and immunoglobulin G (IgG) at every fifth donation. Dropout rates, dropout reasons and potential predictors of withdrawal were analysed. Dropouts were predominantly due to socioeconomic (49.2% of all donors) or medical reasons not related to plasma donations (10.4% of all donors). Sixteen per cent of donors dropped out when IgG, TSP or Hb levels fell below threshold values. Severe clinical adverse events related to plasmapheresis were observed in five subjects. The incidence in severe cardiovascular diseases was lower in donors than in the general population. The risk factors that led to dropping out as a result of low IgG, TSP or Hb levels included younger age, female gender, low initial IgG levels and a high donation frequency. Neither body weight nor the amounts of plasma donated per kilogram of body weight per session were associated with ceasing due to medical reasons, whether related or unrelated to plasma donations. Females and males within the respective lowest body weight category were not at higher risk of dropping out. Long-term intensive donor plasmapheresis under conditions investigated in this study is safe. All donors weighing > or = 70 kg are safely able to donate 850 ml of plasma in each session up to 60 times per year, provided that they are carefully monitored.

A prospective trial on the safety of long‐term intensive plasmapheresis in donors

There are still concerns about the safety of long-term intensive donor plasmapheresis, because the reasons that donors drop out of plasmapheresis programmes have not been determined in prospective studies. Seventy-two donors were switched from a moderate plasmapheresis programme to an intensive plasmapheresis programme and observed over a 3-year period. In addition to measuring total serum protein (TSP), albumin, immunoglobulin G (IgG) and haemoglobin (Hb) levels, parameters of iron metabolism and blood coagulation, and biochemical cardiovascular risk markers, were determined at baseline and at every 15th donation. We also collected statements from donors who dropped out of the plasmapheresis programme about their reasons for withdrawal. Dropouts were predominantly related to socioeconomic (n = 34) or medical reasons not related to plasma donations (n = 8). Three donors had to drop out when their TSP levels fell below threshold for the third time within a 5-week period. At baseline, donors had significantly lower TSP, albumin, IgG, Hb and ferritin levels than gender-matched and age-matched non-donor controls. However, subsequent intensive plasmapheresis over 3 years did not impair the individuals' ability to donate plasma. TSP, IgG, Hb, ferritin, transferrin, cardiovascular risk markers and parameters of blood coagulation did not change significantly during the observation period. The reasons why donors cease to participate in intensive plasmapheresis programmes are predominantly not directly related to the plasma donation itself.

Characteristics and Prognosis of Chinese Patients with Anti-Glomerular Basement Membrane Disease

Background: Patients with anti-glomerular basement membrane (GBM) disease were predominantly reported in Caucasian population and reports from Chinese were lacking. The general picture of Chinese patients with anti-GBM disease was still unclear. This study is to investigate the characteristics and prognosis of Chinese patients with anti-GBM disease. Methods: Data from 105 patients with anti-GBM disease diagnosed in our hospital, between 1997 and 2002, were analyzed retrospectively. All the 105 sera were screened by enzyme-linked immunosorbent assay (ELISA) using highly purified bovine α(IV)NC1 as solid phase ligands. Clinical and pathological data of 69 patients with complete clinical remission (n = 5), partial remission (n = 10), and treatment failure (n = 54) were compared and the prognostic factors were evaluated. Results: Patients increased chronologically and three quarters of the 105 patients were diagnosed in the last 3 years. Most of the patients were between 20 and 29 years (n = 31) and a smaller second peak was found in patients over 60 years. 25/105 (24%) were also ANCA-positive. Patients with both anti-GBM antibodies and ANCA positive were elder (50 ± 19 vs. 34 ± 15 years, p < 0.01) and female predominant (15/25 vs. 16/80, p < 0.05). 56/97 (58%) patients presented as Goodpasture syndrome, 40/97 (41%) patients presented as rapidly progressive glomerulonephritis and one patient had pulmonary hemorrhage only. The following factors predict poor prognosis: (1) serum creatinine more than 600 µmol/l on diagnosis (p < 0.01); (2) oliguria or anuria on diagnosis (p < 0.01); (3) a high percentage (>85%) of glomeruli had crescents (p < 0.01), and (4) renal involvement before pulmonary hemorrhage (p < 0.05). Patients with serum creatinine over 600 µmol/l on diagnosis had higher levels of anti-GBM antibodies (106 ± 48% vs. 73 ± 40%, p < 0.01). Intensive plasma exchange therapy predicts a better prognosis in the patients with serum creatinine less than 600 µmol/l (p < 0.05). Conclusions: Anti-GBM disease is not rare in China and behaves similarly to elsewhere. Early diagnosis and intensive plasmapheresis might be the most promising approaches to improve the outcome.

Incidence and outcome of antiglomerular basement membrane disease in Chinese.

Antiglomerular basement membrane (anti-GBM) disease is an uncommon disease, especially among Asian population. Many reports and studies on this condition in the Caucasian population are available, but little information exists on anti-GBM disease in Asians. To study the incidence and clinical characteristics of anti-GBM disease among Chinese patients, we reviewed our experience of anti-GBM disease in our hospital (Queen Mary Hospital, Hong Kong) from 1992 to 2003. All patients who were admitted for acute renal impairment, which was caused by crescentic glomerulonephritis associated with linear immunoglobulin G (IgG) staining on immunofluorescence, were included in the analysis. Serum anti-GBM antibodies were detected by either enzyme-linked immunofluorescence or indirect immunofluorescence. Ten patients were treated for anti-GBM disease during this 11-year period, yielding an incidence of approximately 0.6 cases per million population per year. In this cohort, anti-GBM disease predominantly affected older patients (mean age: 58.6 +/- 21.7 years). Eight patients were aged between 60 and 80 years and there was a female preponderance (M:F = 2:8). The 1-year renal and patient survival was 15% (95% CI 0-40%) and 70% (95% CI 42-98%), respectively. Most patients presented with non-specific symptoms as well as impaired renal function. Detection of anti-GBM antibody provided a good screening test for the disease. Antiglomerular basement membrane antibodies were not detected in two patients. All but two patients received steroid, cyclophosphamide and intensive plasmapheresis therapy. Haemoptysis occurred in four patients (40%), and usually lagged behind the renal presentation and commencement of treatment. Six patients required long-term dialysis after the acute disease. Three patients died from the disease, two died from pulmonary complications and one died suddenly after a partial recovery of renal function. Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long-term preservation of renal function after the initial attack is unusual.

Full neurologic recovery after fulminant thrombotic thrombocytopenic purpura with status epilepticus

Thrombotic thrombocytopenic purpura (TTP) is an ischemic vasculopathy frequently associated with neurological dysfunction including seizures. However, status epilepticus (SE) has rarely been reported in this condition. We report on a 70-year-old woman with fulminant TTP who developed convulsive SE despite high therapeutic serum levels of phenytoin and phenobarbital. Her electroencephalogram (EEG) was characterized by bilateral independent periodic lateralizing epileptiform discharges (BIPLEDs) propagating into clinical and electrographic seizures. She recovered completely after intensive plasmapheresis and treatment with pentobarbital induced coma for 5 days. This case illustrates that aggressive treatment with pentobarbital and plasmapheresis may prevent permanent neurologic deficits when TTP is complicated by SE and that periodic lateralizing epileptiform discharges (PLEDs) in this syndrome can be the manifestation of a reversible ischemic insult.

Unusual antibody titer in a severe case of rhesus incompatibility

Unusual antibody titer in a severe case of rhesus incompatibility

Treatment of pemphigus with intravenous immunoglobulin

Background: Intravenous immunoglobulin (IVIg) has recently been advocated as a treatment for pemphigus, but the results of published studies are in conflict. This study was conducted to re-examine the effectiveness of IVIg for the immediate control of active disease and to study the mechanisms of its action. Methods: Six patients with active pemphigus vulgaris unresponsive to conventional therapy with high doses of corticosteroids were treated with IVIg (400 mg/kg per day for 5 days) and concurrently given cyclophosphamide (100-150 mg/d). The primary end points were healing of skin lesions and changes in the level of intercellular antibodies and steroid dose. Results: New lesions ceased to form within 1 week of initiating IVIg therapy, and within 2 weeks the extent of existing skin lesions was reduced by 80% or more in all but one patient. Within 3 weeks, steroid doses were reduced by an average of 41%. The improvement was more rapid than that in patients previously treated with similar doses of steroids and cytotoxic agents at the same institution. Clinical improvement was associated with a rapid decline in pemphigus antibodies whose levels decreased by 72% within 1 week of initiation of IVIg therapy. The rapidity and extent of this decline were similar to those achieved with intensive plasmapheresis. The decline was not due to blocking the synthesis or the immunologic activity of intercellular antibodies by IVIg, suggesting that it resulted from increased immunoglobulin catabolism. Conclusions: These results indicate that IVIg can effectively and rapidly control active pemphigus unresponsive to conventional therapy and suggest that the mechanism of its action is decreasing serum levels of intercellular antibodies. (J Am Acad Dermatol 2002;47:358-63.)