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Highly successful living donor kidney transplantation after conversion to negative of a previously positive flow-cytometry cross-match by pretransplant plasmapheresis.

Between July 2001 and November 2003, 16 patients with a positive flow-cytometry crossmatch to their potential living donor for kidney transplant were treated with desensitization protocol based on plasmapheresis and low-dose IVIg starting 1 week before the scheduled transplant. Twelve patients (75%) converted to negative crossmatch and were successfully transplanted. Immunosuppression consisted of induction with thymoglobulin, tacrolimus, mycophenolate mofetil, and steroids. Plasmapheresis and IVIg were continued on alternate days for the first postoperative week. The 1-year patient and graft survival was 100%. The rate of acute rejection was 41% (16% cellular and 25% humoral). All of the rejection episodes resolved with treatment. Combination of plasmapheresis and IVIg allows successful conversion from positive to negative flow-cytometry crossmatch in 75% of cases; after conversion, kidney transplant can be carried out with a high rate of success.

Adult↗

Combined therapy of deoxyspergualin and plasmapheresis: a useful treatment for antibody-mediated acute rejection after kidney transplantation.

Antibody-mediated acute rejection (AbAR) is one of the primary causes of graft impairment in kidney transplant recipients. Deoxyspergualin (DSG), which displays an antiproliferative action against antigen-stimulated B cells inhibiting antibody production, may be effective to rescue AbAR in combination with plasmapheresis by suppressing antibody production and elimination. In the present study, we report our experience with DSG/plasmapheresis therapy for the treatment of AbAR. Five kidney transplant patients experienced a steroid-resistant acute rejection requiring dialysis followed by an AbAR that was confirmed by biopsy and flow cytometry crossmatch (FCXM) results. DSG was administration at 3 mg/kg per day for 10 days with plasmapheresis reduce antidonor antibody. Treatment outcome, effectiveness, and adverse events were examined; in two cases sequential FCXM examinations were performed to evaluate antibody status. All five patients received DSG/plasmapheresis therapy. The number of plasmapheresis treatments ranged from 1 to 9 according to treatment outcomes. Four patients recovered graft function following treatment; whereas one showed no response to the treatment, and the graft was lost. No serious side effects or infections were observed during or after treatment. Monitoring of sequential FCXM correlated with the clinical course. AbAR shows a worse prognosis than cellular rejection. It is refractory to conventional antirejection therapy. In the present study, DSG/plasmapheresis therapy was effective in four of five patients (80%) with AbAR. It may be considered the first choice of treatment for cases of acute humoral rejection.

Acute Disease↗

Antibody-dependent cell-mediated cytotoxicity against melanoma cells induced by plasmapheresis.

Patients with disseminated melanoma were treated by repeated plasmapheresis using a continuous-flow blood-cell separator, as part of a study to investigate methods of removing factors from tissue fluids which block cell-mediated immunity. Using 51Cr release cytotoxic assays, it was found that plasmapheresis resulted in removal of serum blocking activity. Post-plasmapheresis sera taken from several patients also increased cell-mediated cytotoxicity by induction of antibody-dependent cell-mediated killing. This effect may have resulted from removal or alteration of circulating immune complexes in the serum. It is not known whether cytotoxic activity induced in this way improves the patient's immune response against their tumours. However, the procedure is well tolerated and these preliminary in-vitro results indicate that this form of therapy could act as an adjunct to other forms of treatment of advanced melanoma.

Antigen-Antibody Complex↗

Intensive antenatal plasmapheresis in severe rhesus isoimmunisation.

Intensive antenatal plasmapheresis can significantly lower Rh-antibody levels in the blood of mothers carrying babies severely affected with rhesus haemolytic disease. Twenty-seven out of forty-four mothers were successfully delivered of babies that survived, after being treated with a combination of plasmapheresis and intrauterine transfusions. A further 52 mothers were treated by plasmapheresis along. When severe disease developed as an early stage in pregnancy the results were rather poor, but excellent results were obtained when severe disease developed relatively late in pregnancy. No serious complications were encountered in the mothers or babies.

Blood Transfusion, Intrauterine↗

Plasmapheresis in the management of acute systemic lupus erythematosus?

Eight patients with systemic lupus erythematosus (S.L.E.) have been treated with plasmapheresis. In four patients in whom immunochemical studies indicated high levels of circulating immune complexes, the removal of 5-8 litres of plasma weekly produced a striking clinical and immunochemical improvement. The four other patients, with only minor complement disturbances and no direct evidence of circulating immune complexes, could not be shown to benefit from plasmapheresis and one patient in this group died of cerebral lupus despite intensive treatment with cytotoxic drugs. It is concluded that plasmapheresis may be of value as an adjuvant to the treatment of acute S.L.E.

Acute Disease↗

Current status of plasmapheresis in toxicology.

Although the elimination of specific toxins by the removal of all plasma constituents is a crude approach, further refinements of the technique should permit safer and more selective detoxification in the future. Currently the mainstay of treatment of intoxicated patients remains careful, aggressive, supportive care. Plasmapheresis should be considered as yet an unproven, hazardous form of therapy for the treatment of intoxication. Its main role should be confined to a research setting in which investigators attempt to develop more advanced and potentially useful apheresis techniques. Membrane plasmapheresis with subsequent on-line treatment of the plasma by sorbent may remove specific plasma solutes. The plasma may be perfused back to the patient without the need to use replacement fluids, thus avoiding many of the side effects of conventional exchange. Bile acids have been removed by circulating plasma over charcoal-coated glass beads, and several toxic substances were shown to be absorbed by perfusion over amberlite resin columns. Another productive area for future research includes the use of plasma exchange therapy for the treatment of acute endogenous intoxications. Recent examples include the treatment of severe preeclampsia, extensive rhabdomyolysis, and life-threatening bleeding in a hemophiliac with inhibitors to clotting factors. Although plasmapheresis in the management of intoxications is still an experimental technique, it may open the door to the treatment of previously intractable syndromes, both medical and toxicologic.

Adult↗

The AIDS epidemic and commercial plasmapheresis.

In 1986 an epidemic of HIV infection among paid plasma donors was identified in Mexico; paid donors were iatrogenically infected in a plasmapheresis center. These paid donors sold both plasma and blood: they provided one-third of blood consumed in 1986. This led to infection of blood recipients, mainly women of childbearing age. Blood transfusion is the leading cause of AIDS in women in Mexico. The male:female ratio decreased from 30:1 in 1986 to 5:1 1990; that coincided with the increase of transfusion-associated AIDS cases. Mexico prohibited the blood trade in 1987, ending the epidemic in paid donors and recipients. latrogenic infection of paid donors in plasmapheresis facilities could help to explain the explosive AIDS epidemic in central Africa and Haiti in the 1980s. There is a temporal and geographical coincidence in the early eighties between that AIDS epidemic, high numbers of hepatitis B asymptomatic carriers and an increased production of serum inactivated hepatitis B vaccine. Plasmapheresis facilities in these developing countries may have taken advantage of the high prevalence of hepatitis B asymptomatic carriers in their populations to obtain plasma for exportation through brokers to developed countries where the vaccine and other plasma products were manufactured. This hypothesis is relevant to establishing preventive policies and warrants further investigation.

Acquired Immunodeficiency Syndrome↗

Intraoperative use of platelet-plasmapheresis in vascular surgery.

STUDY OBJECTIVE: To determine, in a pilot study, whether pheresis of plasma and platelets before surgical blood loss, with reinfusion of the autologous plasma and platelets after completion of the aortic reconstruction, will result in decreased bleeding and decreased transfusion of allogenic blood components in patients undergoing elective aortic reconstruction. DESIGN: Randomized study. SETTING: University medical center. INTERVENTIONS: Patients were randomized to perioperative (acute) platelet plasmapheresis (APP group) versus conventional blood component therapy (control group). In the APP group, blood was withdrawn after induction of anesthesia, to sequester approximately 300 mL of platelet rich plasma (PRP); platelet poor plasma (PPP) and red blood cells (RBC) were sequestered as well. An autotransfusion device was used to collect and re-infuse autologous RBC during the course of the operation in both groups. After completion of the aortic reconstruction, autologous PRP and PPP were re-infused in the APP group. Blood loss, volume of blood component transfusions, and preoperative and postoperative hemoglobin (Hb), hematocrit (Hct), platelet, international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were recorded. MEASUREMENTS AND MAIN RESULTS: There was no difference between groups in demographics, preoperative laboratory values, or surgical procedures, although more patients were treated for aneurysms (73% vs. 60%) and fewer for occlusive disease (20% vs. 40%) in the control versus APP group. Also, there were no differences between the control and APP groups in duration of operation, blood loss, volume of colloid infused, or volume of allogenic RBC and plasma transfused. Patients in the APP group received a greater volume of crystalloid solution (9.1 +/- 3.4 L vs. 6.8 +/- 3.0 L; p = 0.002), but fewer units of allogenic platelets than the control group (0.7 +/- 1.0 units vs. 0.2 +/- 0.4 units; p < 0.04). There were no differences in postoperative Hb, Hct, INR, aPTT, or fibrinogen. The platelet count was lower in the APP group than in the control group (123 +/- 40 x 10(3)/mm(3) vs. 182 +/- 51 x 10(3)/mm(3); p = 0.004). CONCLUSIONS: Perioperative platelet plasmapheresis led to fewer allogenic platelet transfusions in patients undergoing elective aortic reconstruction. However, there was no decrease in blood loss and no reduction in transfusion of allogenic RBC or plasma. Perioperative platelet plasmapheresis is not recommended for routine use in elective aortic reconstruction.

Aged↗

Plasmapheresis with intravenous immunoglobulin G is effective in patients with elevated panel reactive antibody prior to cardiac transplantation.

BACKGROUND: Patients with a PRA >10% are considered to be at greater risk for the development of not only acute cellular and humoral rejection but also increased mortality when compared to nonsensitized patients following transplantation. All patients with a PRA >10% at our institution are treated with plasmapheresis and intravenous immunoglobulin G immediately prior to cardiac transplantation. METHODS: Sixteen (Group 1) of 118 patients awaiting cardiac transplantation were found to be sensitized. These patients underwent plasmapheresis followed by 20 gm of intravenous immunoglobulin G (IVIG) immediately prior to cardiac transplantation. Group 1 was compared to the remaining 102 patients with a PRA <10% (Group 2). RESULTS: Despite more patients in Group 1 having a positive crossmatch, pulmonary hypertension, and requiring mechanical circulatory support, there was no statistically significant difference in length of stay or mortality at a mean follow-up of 21.6+/-15.0 months. There was no difference in the occurrence of mild, moderate or severe cellular rejection or humoral rejection in these sensitized patients when compared to Group 2. CONCLUSIONS: Pretransplant plasmapheresis followed by intravenous immunoglobulin G may be an effective therapy that obviates the need for a prospective crossmatch and allows sensitized patients to undergo cardiac transplantation. There is no increase in the post transplant length of stay, occurrence of rejection or short term mortality. Long term follow up is necessary to evaluate whether there is a difference in the development of late rejection, transplant vasculopathy and survival.

Adult↗

Plasmapheresis therapy in pemphigus vulgaris and bullous pemphigoid.

Blistering dermatitises are characterized by the presence of blisters that begin owing to acantholysis (intraepidermic blister) such as pemphigus vulgaris (PV) or owing to dermoepidermic detachment (subepidermic blister) such as bullous pemphigoid (BP). Both diseases are autoimmune pathologies characterized by the presence of autoantibodies against specific adhesion molecules of the skin and mucous membranes. PV, in which oral lesions are always present, has a progressive course that, if the disease is not treated, nearly always brings to death from sepsis within a few years. In BP, oral lesions are rare and the disease, that is most frequent in older individuals, has a chronic course with spontaneous remissions. Systemic corticosteroids and immunosuppressants are the mainstay of treatment of these two diseases. Although this therapy had reduced the mortality of the two pathologies it is associated with serious side effects. To reduce the corticosteroids dose and to improve the symptomatology in resistant therapy cases, we treated five patients with several procedures of plasma exchange. Four patients were affected by BP and one by PV. Their disease severity at onset of plasmapheresis ranged from mild to severe. One of 5 patients suffered a plasmapheresis side effect. All patients responded with complete remission of symptomatology and had a prednisone dosage reduction until 70%. Plasmapheresis is an effective treatment for PV and BP patients who have been unresponsive to conventional therapy, for those for whom conventional drugs are contraindicated, for those who show severe clinical manifestations and for those who need high doses of corticosteroids and immunosuppressants to keep the disease under control.

Aged↗

Phenytoin removal by plasmapheresis in thrombotic thrombocytopenic purpura.

Phenytoin removal was followed in a patient undergoing plasmapheresis for thrombotic thrombocytopenic purpura. It was determined that 10% of total body phenytoin was removed with each two plasma volume exchanges, which is two to four times that reported with hemodialysis or peritoneal dialysis. During each 4- to 5-hr apheresis, serum phenytoin levels fell an average of 3.2 micrograms/ml and the phenytoin clearance by plasmapheresis was 21.9 +/- 2.1 ml/min (equal to the patient's endogenous clearance of 20.8 ml/min). Adjustment in drug doses were necessary such that, at steady state, the patient required 600 mg/day phenytoin to maintain therapeutic serum levels. These data indicate that plasmapheresis can clear the body of a significant amount of phenytoin and that increased doses may be required to maintain serum phenytoin levels. The potential use of apheresis in phenytoin overdose warrants further examination.

Adult↗

Failure of plasmapheresis, corticosteroids and thionamides to ameliorate a case of protracted amiodarone-induced thyroiditis.

We report a case of amiodarone-induced thyrotoxicosis of protracted duration, unresponsive to conventional thionamide therapy, with therapy limited by severe adverse drug reactions. Other treatment modalities included high dose corticosteroids, plasmapheresis, lithium and perchlorate. Temporary amelioration was achieved following plasmapheresis; however, this and other measures were unsuccessful in controlling the thyrotoxicosis, which deteriorated to thyroid storm. Histopathologically, a degenerative, inflammatory thyroiditis was evident. We discuss the limitations of conventional drug therapy and the lack of a sustained response to plasmapheresis. The failure of high doses steroids to alter the course of illness and to completely suppress the thyroidal inflammatory process is highlighted. A potential role for renal and hepatic impairment in the observed protracted course of amiodarone-induced thyrotoxicosis is suggested.

Amiodarone↗

Bradykinin production during donor plasmapheresis procedures.

BACKGROUND AND OBJECTIVES: Extracorporeal circuits made of artificial substances may induce blood cells and humoral activation. Negatively charged surfaces may activate Factor XII and the prekallikrein-kinin cascade, resulting in bradykinin (BK) production. BK has been considered to be involved in severe hypotensive reactions occurring during therapeutic apheresis in patients taking angiotensin-converting enzyme (ACE) inhibitors or in those receiving platelet transfusion. In this study we investigated BK production during donor plasmapheresis procedures. PATIENTS AND METHODS: Eighteen volunteer donors entered the study protocol. Nine of them were taking ACE inhibitors. Their blood pressure (BP) was monitored both pre- and post-apheresis, and BK determination was carried out using a competitive enzyme immunoassay (EIA), in plasma samples collected both during and at completion of the procedure. In addition, a limited number of thawed plasma units were checked for BK. RESULTS: No side-effects were observed during the procedures. However, donors taking ACE inhibitors showed a higher variation of their systolic BP compared to those who were not taking ACE inhibitors, while diastolic BP percentage variations did not differ significantly between the two groups. The BK concentration was considerably higher in donors taking ACE inhibitors: 183 +/- 26 versus 82 +/- 6 ng/ml (P < 0.0001) after the first collection cycle and 142 +/- 20 versus 65 +/- 11 ng/ml (P < 0.0001) in the final samples. BK was also detected, at a lower concentration (15 ng/ml), in one out of four thawed plasma units obtained from donors taking ACE inhibitors and at 1 ng/ml in one out of two thawed plasma units from the control group. CONCLUSION: Donors taking ACE inhibitors and undergoing plasmapheresis showed higher levels of BK compared to the control group. Furthermore, the detection of BK in plasma units after a freeze-thaw procedure might explain the sudden hypotensive reaction occurring during therapeutic plasma exchange when plasmapheresis units are adopted as substitution fluids. Further investigations are needed to assess the real clinical importance of the presence of BK in plasma units.

Adult↗

Plasmapheresis-related hypotension.

Hypotension is an uncommon complication of procedures involving extracorporeal circulation, including plasmapheresis. From November 1993 to March 1999, we treated 139 patients who underwent a total of 1,137 sessions of double filtration plasmapheresis (DFP). Hypotension was defined as a systolic blood pressure (BP) < 80 mm Hg or any decrease of systolic BP with systemic reactions. A total of 17 (1.5%) episodes of hypotension were documented in 15 patients during the study period. Hypotensive episodes occurred in 2.3% of patients with inflammatory neuropathy, 1.2% of patients with myasthenia gravis, and 1.2% of patients with all other medical diseases. Involvement of the autonomic nerve system (ANS) and a low baseline BP were associated with the occurrence of hypotension. Eight (47%) of 17 episodes were symptomatic and 2 were complicated with seizure. Patients with symptomatic hypotension had a higher level of systolic BP prior to DFP and a larger drop of systolic BP and pulse rate during hypotensive attacks compared to asymptomatic patients. Most hypotensive episodes were resolved briefly after intravenous infusion of saline within 30 min. Eight (47%) of the hypotensive episodes occurred during the first session of DFP treatment. Twelve (71%) of 17 episodes occurred during the last half period of treatment; 6 of them were noted during the terminating stage of DFP. In conclusion, in this series plasmapheresis-related hypotension occurred in 1.5% of DFP sessions and had a higher prevalence in patients with ANS instability and low BP. Extra caution in monitoring BP during DFP therapy is warranted in these vulnerable patients, especially during the termination phase of the first DFP session.

Adult↗

Miller Fisher syndrome with central involvement: successful treatment with plasmapheresis.

Miller Fisher syndrome is characterized by external ophthalmoplegia, ataxia, and areflexia. Most researchers favor a peripheral origin while others suggest a brainstem inflammatory lesion or a combination of central and peripheral demyelination. We report 2 cases of Miller Fisher syndrome with the typical triad of ataxia, areflexia, and ophthalmoplegia. Strong clinical evidence of central involvement included initial drowsiness, bilateral Babinski sign, and quadriparesis. Evoked potential studies showed prolongation of central conduction time. Plasmapheresis was performed to relieve respiratory failure in Patient 1 and to shorten the duration of nasogastric tube feeding due to severe bulbar palsy in Patient 2. Significant improvement of electrophysiologic parameters was recorded after plasmapheresis. Abnormal evoked potentials, together with clinical evidence of central nervous system abnormalities, support the hypothesis that there is a combination of peripheral and central involvement in Miller Fisher syndrome in our patients. Plasmapheresis is highly effective in relieving the profound neurological deficits of this atypical syndrome.

Adult↗

The six year experience of plasmapheresis in patients with myasthenia gravis.

Plasmapheresis (PP) effectively removes autoantibodies in various autoimmune diseases. The use of PP in the treatment of myasthenia gravis (MG) has been widely accepted since the 1970s. The treatment protocol, however, has not been standardized. For the last 6 years, we collected a total of 94 MG patients, 38 males and 56 females aged 14-80 years, who received 175 courses of PP treatment for a total of 823 sessions. The methods we used were double filtration plasmapheresis (DF), immunoadsorption plasmapheresis (IA), and plasma exchange (PE). There were 167 courses of DF, 6 courses of IA, and 2 courses of PE. Each course of treatment consists of 4 to 5 sessions of apheresis. The processed volume of plasma is 1 calculated plasma volume. All patients tolerated PP well although 2.3% of them experienced hypotension. Our experiences are summarized as follows. Both DF and IA effectively ameliorate symptoms and signs of MG. IA removes acetylcholine receptor antibody more effectively than DF does, but clinical effects between these 2 methods are similar. A daily schedule seems more effective than an alternate daily schedule. The optimal number of PP sessions for each course is 4. The factors correlating with better clinical response are high MG score, nonthymoma patients, younger age at onset, and higher removal rate for immunoglobulin G.

Adolescent↗

The effectiveness of intravenous human immunoglobulin treatment after plasmapheresis in restoring serum immunoglobulin levels: a preliminary study.

This study was performed to examine the effects of intravenous human immunoglobulin (IVIG) on the level of serum immunoglobulin G (IgG) and its subclasses after plasmapheresis in patients with autoimmune disorders. Twenty-nine patients with predominantly rheumatoid arthritis were enrolled in this study. The plasmapheresis was performed by the use of double-filtration plasmapheresis (DFPP). Immediately after DFPP, IVIG (2.5 g, 50 ml) was intravenously administered. The treatment with IVIG had almost no effect on subjective and objective symptoms. Immediately after DFPP, the total of serum IgG was decreased by approximately 40%. After 24 h, the total of serum IgG recovered to 16% reduction in IVIG-treated patients whereas it remained at 32% reduction in nontreated patients. The beneficial effect of IVIG was significantly observed in patients who had shown 1,000-1,800 mg/dl IgG in their sera. After DFPP, IgG subclasses were decreased without change in the ratio of subclasses. Twenty percent to 30% of IgG subclasses were supplemented by the treatment with IVIG without change in the ratio of subclasses. These results suggested that the treatment with IVIG at minimal amount was safe and effective to supplement IgG for hypogammaglobulinemia after DFPP.

Adult↗

Plasmapheresis in immunologically mediated polyneuropathies.

One of the most common uses of therapeutic plasmapheresis is for the treatment of immunologically mediated polyneuropathies. This paper discusses the use of plasmapheresis in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, polyneuropathies associated with paraproteins, lower motor neuron syndromes, and polyneuropathies associated with HIV. As the pathogenesis of immunologically mediated polyneuropathies becomes better understood, newer therapies for these syndromes will evolve: however, therapeutic plasmapheresis is likely to continue to play a central role in the treatment of many of these diseases.

HIV Infections↗