Initiation Of Plasma Exchange Research Articles

Physiological changes during and outcome following ‘filtration’ based continuous plasma exchange in Guillain Barre Syndrome

Background Therapeutic plasma exchange is an extracorporeal blood purification technique designed for the removal of large molecular weight substances from plasma. It is the first line treatment in Guillain Barre Syndrome (GBS) improving outcome. Aim To study the outcome in GBS following therapeutic plasma exchange (TPE) utilizing a modified, cost saving, filtration based plasma exchange technique. Methodology and findings Consenting patients with GBS underwent TPE using a modified regime of two 48 h sessions as a cost saving strategy. The second session was conducted only if there was inadequate benefit from the first session. Nerve conduction studies confirmed the diagnosis of GBS. Results Fifteen patients were studied. One died following a cerebro-vascular accident. Of the remaining 14 patients, five showed improvement in muscle power at least by one grade in one limb within 48 h of plasma exchange. The duration of intensive care unit stay was 10 (median) days (range 4–66). Nine required mechanical ventilation for (median) 15 days (range 4–50). The mean 24 h urine output increased significantly since the initiation of plasma exchange was 6262.92 ml (SD = 8867.24, P = 0.032) at 48 h and 6474.92 ml at 72 h (SD = 6364.81, P = 0.003). The pulse rates and blood pressures were not significantly different before and after plasma exchange. Complications attributable to plasma exchange were mild; a hypersensitivity reaction and a tendency to ooze from a puncture site. Conclusion ‘Continuous’ TPE, the modified cost saving technique seems to improve the outcome of patients with Guillain Barre Syndrome with minimal complications.

Plasma exchange for acute attacks of CNS demyelination

Plasma exchange (PE) is used to treat severe episodes of CNS demyelination unresponsive to corticosteroids. Predictors of long-term response are not well known. We retrospectively reviewed the medical records of 41 patients consecutively treated by PE between January 1995 and July 2007. The primary outcome was improvement at 6 months after PE defined as decrease of >or=1 point in the Expanded Disability Status Scale (EDSS) score for patients with EDSS <or=7.5 or 1.5 points with EDSS >or=8.0 or improvement of more than 2 lines in the visual acuity chart for patients with optic neuritis (ON). Twenty-five patients (61%) were women, and the median age was 33 years (range 14-57 years). Twenty-three (56%) had multiple sclerosis, 2 (5%) had clinically isolated syndrome, 2 (5%) had Marburg disease, 7 (17%) had acute disseminated encephalomyelitis, 4 (10%) had neuromyelitis optica, 2 (5%) had idiopathic ON, and 1 (2%) had idiopathic transverse myelitis. The median EDSS score before the attack was 1.0 (range 0-6.5). At PE onset, the median EDSS score was 7.0 (range 3.0-9.5). Sixteen patients (39%) improved at discharge, and 26 (63%) improved at 6 months. In the multivariate analysis, early initiation of PE (odds ratio [OR] 6.29, 95% confidence interval [CI] 1.18-52.96) and improvement at discharge (OR 7.32, 95% CI 1.21-44.38) were significantly associated with response at 6 months. Plasma exchange (PE) was associated with clinical improvement in 63% of patients at 6 months. Early initiation of PE and improvement at discharge were predictors of this response. Twelve patients (48%) who did not improve early did so during follow-up.

Reversible oropharyngeal dysphagia secondary to cricopharyngeal sphincter achalasia in a patient with myasthenia gravis: a case report.

Bulbar weakness and fatigue resulting in dysphagia and dysarthria is common in myasthenia gravis. In chronic MG it is often assumed that these symptoms herald an exacerbation of the patient's disease and doses of cholinergic agents and immunomodulatory therapies may be increased, along with initiation of plasma exchange. A case is presented in which dysphagia was refractory to standard MG therapy, leading to the subsequent discovery of cricopharyngeal sphincter achalasia as the primary cause of the patient's symptoms rather than an assumed myasthenia gravis exacerbation. The patient's dysphagia resolved after esophageal dilatation. Cricopharyngeal sphincter achalasia is a common disorder producing dysphagia in the elderly and needs to be considered in the evaluation of a myasthenic patient with worsening dysphagia when standard myasthenia gravis therapy fails. Discussion of myasthenia gravis, cholinergic therapy and cricopharyngeal sphincter achalasia is undertaken. Clinicians are encouraged to consider non-neurologic causes of worsening dysphagia in the myasthenic patient.

Reversible oropharyngeal dysphagia secondary to cricopharyngeal sphincter achalasia in a patient with myasthenia gravis: a case report

Bulbar weakness and fatigue resulting in dysphagia and dysarthria is common in myasthenia gravis. In chronic MG it is often assumed that these symptoms herald an exacerbation of the patient's disease and doses of cholinergic agents and immunomodulatory therapies may be increased, along with initiation of plasma exchange. A case is presented in which dysphagia was refractory to standard MG therapy, leading to the subsequent discovery of cricopharyngeal sphincter achalasia as the primary cause of the patient's symptoms rather than an assumed myasthenia gravis exacerbation. The patient's dysphagia resolved after esophageal dilatation. Cricopharyngeal sphincter achalasia is a common disorder producing dysphagia in the elderly and needs to be considered in the evaluation of a myasthenic patient with worsening dysphagia when standard myasthenia gravis therapy fails. Discussion of myasthenia gravis, cholinergic therapy and cricopharyngeal sphincter achalasia is undertaken. Clinicians are encouraged to consider non-neurologic causes of worsening dysphagia in the myasthenic patient.

Alloantibody Sensitization after PLASMA Exchanges for Relapsed Thrombotic Thrombocytopenic Purpura (TTP

Deficiency of ADAMTS-13, (A Disintegrin And Metalloprotease with 8 Thrombospondin like Domains), a Von Willebrandt Factor (VWF) cleaving protease, may be congenital (Upshaw Shulman syndrome) or acquired due to inhibitory autoantibodies and leads to the syndrome of Thrombotic Thrombocytopenic Purpura. Plasma exchange (PE) therapy is efficacious in therapy of TTP as it replenishes the deficient protease and at the same time removes the inhibitory antibody responsible for the enzyme deficiency. Few data exist effect of rising ADAMTS-13 inhibitor titers on the success of TTP therapy.We report a case of a 59 yr old African American woman who was diagnosed with TTP in October 2000 when she presented with altered mental status and focal weakness in right upper extremity. Initial labs showed Hemoglobin of 5.5 gm/dl, platelet count of 21,000/mm3, LDH of 4295. Peripheral smear showed moderate schistocytes and serum haptoglobin levels were decreased, renal function was normal. The patient received a total of 6 PE with FFP along with steroids and subsequently went into remission.The patient had a relapse after 10 months. She achieved remission with 5 PE. She was started on azathiaprine as an outpatient that was continued for five months. The patient remained asymptomatic for 5 years till her next relapse in the postoperative period after elective knee replacement surgery. The hospital course was complicated by development of transfusion related acute lung injury after receiving FFP. The patient again responded to PE (total 8 sessions) and IV steroids and went into remission.Prior to initiation of PE for this third relapse, tests showed ADAMTS -13 activity level was <5% indicating severe deficiency of the enzyme; inhibitor titer was 3.2 Bethesda units (BU). Follow up testing after completion of PE and remission revealed persistently low ADAMTS 13 activity of <5% with paradoxically higher inhibitor titers of 8 BU. Repeat testing after 16 months shows ADAMTS 13 activity of <5% with inhibitor titers of 0.9 BU.CLINICAL COURSEADAMTS 13ADAMTS13 INHIBITORIMMUNOSUPRESSIONRELAPSE FREE PERIODThird RELAPSE<5%3.2 BUSTEROIDS+ PE64 MONTHSREMISSION<5%8 BUAZATHIAPRINE2 MONTHSREMISSION<5%0.9BUNONE18 MONTHSConclusion: Our patient developed rising titer of inhibitory antibodies to ADAMTS 13 post Plasma exchange during the second relapse of TTP; Pre and post plasma exchange autoantibody titers were 3.2 and 8.0 BU respectively. She was started on azathioprine after the third TTP relapse, which she took for 2 months and the therapy was then discontinued. She has remained in remission since then and repeat testing reveled ADAMTS 13 activity continues to be <5% with the inhibitor titer decreasing to 0.9 BU. We postulate that the high inhibitor titers post plasma exchange could be the result of alloantibody formation as a result of FFP transfusions and the subsequent low level (0.9BU) inhibitor detected could be related to waning of alloantibody titers in the absence of further FFP exposure. Rising antibody titers post FFP exposure after PE therapy do not preclude a successful outcome with PE therapy with FFP replacement. Further study on the significance of rising antibody titers post PE therapy is required. Epitope mapping and idiotype analysis may be helpful in future studies.

Plasma exchange combined with immunosuppressive treatment in a child with rapidly progressive IgA nephropathy

Although diffuse crescentic formation in immunoglobulin A (IgA) nephropathy, histologically characterized by extensive extracapillary proliferation, is assumed to have a poor prognosis, there has still been no established treatment because of the low prevalence of the condition, especially in pediatric patients. This paper reports on a 5-year-old boy with rapidly progressive IgA nephropathy requiring dialysis for 1 month. He had been treated with plasma exchange (PE) combined with immunosuppressive treatment, including steroids and mizoribine, because renal function deteriorated rapidly despite initial treatment with intravenous methylprednisolone pulse. The histological findings at that time revealed IgA nephropathy, with large circumferential cellular crescent formation in approximately 80% of the glomeruli. Three weeks after PE initiation, serum levels of creatinine and IgA-containing immune complexes returned to normal, and urinary protein excretion gradually decreased. The second renal biopsy taken 7 months later demonstrated mild IgA nephropathy with small fibrocellular crescents. This case report indicates that PE combined with immunosuppressive treatment may benefit children with rapidly progressive IgA nephropathy, even when extensive crescent formations are present.

Improved Clinical Outcome and ADAMTS13 Activity Following Cyclosporine Therapy in Patients with TTP.

Patients with a clinical diagnosis of TTP presenting to The Ohio State University were enrolled and treated on a prospective trial of concurrent plasma exchange (PE) and adjuvant immunosuppression.Patients: Between April 2003 and August 2004, 15 patients were entered and followed on this study. The median age was 46 years (range, 19–59), 11/15 were female, 7/15 were African American, and 9/15 were obese (body mass index >30 kg/m2). Nine patients had been previously treated for TTP.Method: All patients with TTP were treated initially with concurrent PE and corticosteroids. Daily exchanges of one plasma volume using cryosupernatant plasma were performed with concurrent prednisone at a dose of 1 mg/kg/day. PE was continued until a clinical remission was achieved as defined by: 1) normal platelet count 2) normalization of LDH for 2 consecutive determinations, and 3) improvement or stabilization of renal or neurologic abnormalities. After criteria for remission were achieved patients had 2 additional procedures performed every other day and the prednisone tapered over the next 4 weeks. Patients with exacerbations (defined as the need to reinstate PE within 30 days discontinuation) of TTP had prednisone discontinued and began oral cyclosporine (CSA) at a dose of 2–3 mg/kg/day orally concurrent with the resumption of PE. After achieving a second remission, PE was tapered as described previously and CSA was continued for a total of 6 months of therapy. Serial measurements of ADAMTS13 activity and inhibitor assays were obtained prior to the initiation of PE and at regular intervals during follow-up.Results: ADAMTS13 data is available for the first 6 patients treated with PE + prednisone. A summary of clinical outcomes and ADAMTS13 activity may be found in Table 1. Of the patients suffering exacerbations after initial therapy with PE + prednisone, ADAMTS13 data is available from the first 2 of 5 patients treated with PE + CSA and is shown in Figure 1.Clinical Responses and ADAMTS13 ActivityInhibitorRemissionExac.RelapseMed. ADAMTS13-PreMed. ADAMTS13-RemissionMed. Remission (mo)PE+Pred.5/6*14/157/152/155% (range, 2-7%)**5% (range, 2-7%)**1(range, 1-9 )PE+CSA2/2*5/50/50/5Figure 1Figure 16 (range, 3-10)* samples tested to date **median ADAMS13Conclusions: In this prospective study, no patients had significant improvement in ADAMTS13 activity despite achieving remission with PE and corticosteroids. These data showing persistently low ADAMTS13 activity at the time of remission may have contributed to the high rate of exacerbations in this group of patients. In the analysis of the first 2 patients treated with concurrent PE and CSA, there was clear and sustained improvement in ADAMTS13 activity that began after the discontinuation of PE and correlated with the clinical remission of TTP. [Display omitted]

Characteristics of 73 patients, 1984-1993, treated by plasma exchange for Guillain-Barre syndrome.

Acute Guillain-Barre syndrome (GBS) is a demyelinating polyneuropathy which responds readily to plasma exchange (PEX). According to the North American Acute GBS PEX study there is a 50% or more reduction in the recovery time if PEX is initiated early in the course of the disease. Demyelinating antibodies are usually IgM. IgA antibodies require prolonged PEX. Patients with predominant IgG antibodies have chronic inflammatory demyelinating polyneuropathy (CIDP), which requires an even longer course of PEX, over weeks to months or years. We reviewed records of 73 patients with the initial diagnosis of GBS treated with PEX. Among these patients, 55 had classic GBS, three had the Miller-Fisher variant, two had CIDP, and 13 had demyelinating-like polyneuropathies associated with other conditions including malignancy, vaccine-related myelitis, steroid-induced myopathy, polymyositis, botulism, gram-negative sepsis, Sjogren's, and AIDS. Hughes grading system was used. Patients were graded 3 to 5, with grade 3 patients being unable to walk 5 m without support, grade 4 patients being bed or chair bound, and grade 5 patients being ventilator dependent. Of 60 unassociated (GBS) demyelinating cases receiving a mean of 6.5 PEX procedures, 13 (21%) were intubated early in the treatment, with four (6%) remaining ventilator dependent post-PEX. Of 51 non-intubated patients, 15 became ambulatory post-PEX. Patients with the Miller-Fisher variant showed improvement within 6 hours of PEX initiation. We did not investigate correlation of GBS with infection; however, we did observe a rise in CMV titer among 15% of the 58 patients with acute GBS. Considering our results we believe that intensive PEX on a daily basis for a few days is necessary for severely affected individuals. We advise five to nine procedures at consultation unless early, rapid recovery occurs.

EVALUATION OF THERAPEUTIC PLASMA EXCHANGE IN 9 CASES OF POSTOPERATIVE HEPATIC FAILURE

The significance of therapeutic plasma exchange (PE) was assessed in 9 cases of postoperative hepatic failure which were treated with PE. The characteristics of survivors after PE were as follows; 1) Total bilirubin concentration was less than 15mg/dl before PE and less than 7mg/dl on the 7th day after the initiation of PE. 2) Ammonia was less than 200mg/dl before PE and fell into normal range within 7 days after PE. 3) The improvement of BCAA/AAA was achieved. 4) PT was lass than 14 seconds before PE. 5) The numbers of impaired organs were below 2. 6) Coma grade was improved. 7) The numbers treated with PE were within 5 times. When these parameters are not satisfied within 10 days after the initiation of PE, PE should not, we believe, be continued excessively.

Evidence for a beneficial effect of plasma exchange in severe active lupus nephritis

We examined the impact of plasma exchange (PE) on the long-term course of active lupus nephritis in 7 female patients (age 21–48 yr, mean 32). Before starting PE all patients had renal failure (serum creatinine 347 ± 194 μmol L ) proteinuria (6.2 ± 3.4 g/24 h) and hematuria. Renal biopsies performed before PE in 5 cases showed a membranoproliferative glomerulonephritis in 3 cases, a moderate focal and segmental glomerulonephritis in one case, and a diffuse proliferative glomerulonephritis in one case. All specimens showed active lesions. PE was carried out with the Haemonetic Model 50 blood cell separator. The volume of plasma removed (2.3–4 L per run) was replaced by human plasma-protein fraction (PPL, SRK-Hu-man). 7–135 runs (mean 36) were performed over a period of 13–1619 days (mean 359). At the time of PE all patients received prednisone in combination with azathioprine or cyclophosphamid. The course of renal failure was analyzed by plotting the reciprocal values of the serum creatinine vs time. The mean period of analysis before and after initiation of PE was 15.8 and 30.3 months, respectively. Before PE renal function was deteriorating rapidly in all 7 patients. After PE renal function improved in 3 patients, stabilized in 1 patient and deteriorated at a slower rate compared to the pre-treatment period in 2 patients. No beneficial effect of PE on renal function was observed in 1 patient. We conclude that PE combined with immunosuppressive drugs may have a favorable impact on the long time-course of lupus nephritis.

Platelet function and lipoprotein levels after plasma-exchange in patients with familial hypercholesterolaemia.

1. Repeated plasma exchange was carried out on three young patients with severe familial hypercholesterolaemia. There was a 3 week interval between each exchange. After a single exchange, plasma cholesterol, apolipoprotein B and low density lipoprotein-cholesterol levels decreased markedly, but pre-exchange levels were not achieved within 2 weeks. High density lipoprotein-cholesterol and apolipoprotein A-I levels also fell but returned to the original concentration after only 5 days. 2. Platelet aggregation and [14C]serotonin release were increased in all three patients and dropped by 20% and 13% respectively after a single plasma exchange. Platelet function in vitro returned to pre-exchange levels with similar kinetics to that observed with the low density lipoprotein concentration. On removal of 100 g of plasma cholesterol, after repeated exchanges, low density lipoprotein concentration and platelet function were significantly decreased in comparison with values before initiation of plasma exchange. In addition there was a marked regression of xanthoma in all three patients. 3. Since this procedure is instrumental in achieving a negative cholesterol balance as well as inhibiting hypersensitive platelets, it may well result in a downgrading of the atherosclerotic risk.