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The influence of citrate concentration on the quality of plasma obtained by automated plasmapheresis: a prospective study.

BACKGROUND: There is a need for more comprehensive work dealing with the quality of plasma collected by automated plasmapheresis using different final concentrations of citrate anticoagulant. A prospective study was performed to examine the influence of three concentrations of sodium citrate on the levels of clotting factors and markers of activated hemostasis and fibrinolysis. STUDY DESIGN AND METHODS: Fifty-one experienced plasma donors were recruited for subsequent 750-mL plasmapheresis procedures using 4-percent (wt/vol) sodium citrate. Anticoagulant-to-blood ratios of 1:16.6, 1:14.2, and 1:12.5 were used, corresponding to sodium citrate concentrations of 6 percent, 7 percent, and 8 percent (vol/vol), respectively. Between two plasmapheresis procedures, there was a washout period of 7 days. Determinations were made of the plasma levels of fibrinogen and factors V, VII, VIII, and IX, as well as antithrombin, tissue-type plasminogen activator, and several markers of activated hemostasis and fibrinolysis: activated factor VII, prothrombin splits products, D-dimers, and beta-thromboglobulin. RESULTS: The plasma samples anticoagulated with 6-percent citrate contained significantly higher levels of factors V, VIII, and IX than the samples anticoagulated with 8-percent citrate (p<0.0001, p< or =0.0001 and p = 0.009, respectively). The citrate concentration had no influence on the levels of fibrinogen, factor VII, antithrombin, or tissue-type plasminogen activator. There was no evidence that the plasma samples containing lower citrate concentrations were more prone to activation of hemostasis or fibrinolysis. CONCLUSION: A reduction in the final citrate concentration of plasma collected by automated plasmapheresis results in higher yields of factors V, VIII, and IX without activation of hemostasis. More comprehensive studies should confirm previous work dealing with the establishment of the lowest citrate concentration acceptable in plasma used as therapeutic fresh-frozen plasma or as starting material for the manufacture of plasma derivatives.

Adult↗

The impact of intensive serial plasmapheresis and iron supplementation on iron metabolism and Hb concentration in menstruating women: a prospective randomized placebo-controlled double-blind study.

BACKGROUND: Iron (Fe) depletion is common among regular whole-blood donors, but can be prevented through regular oral Fe supplementation. Little is known, however, about the Fe metabolism of donors undergoing intensive plasmapheresis. These donors lose considerable amounts of blood drawn for laboratory analyses and remaining in the disposable plastic sets. STUDY DESIGN AND METHODS: Menstruating women were enrolled in a prospective placebo- controlled double-blind study. One hundred women were randomly allocated to receive either 100 mg of elemental Fe per day or placebo over 24 weeks and asked to donate plasma at 1-week intervals. Hb was determined before each plasmapheresis. Ferritin, transferrin, and Fe concentration and reticulocyte count were measured every 4 weeks. RESULTS: Thirty donors in the placebo group and 29 receiving Fe completed the study. The total mean blood loss was 526 mL in the placebo group and 546 mL in the Fe arm (p=0.271). The number of donations with Hb values lower than 12.5 g per dL requiring prolongation of the time interval until the next plasmapheresis was significantly greater in the placebo arm. In the placebo group (n=30), ferritin levels began to decline significantly 4 weeks after entry. When the study was completed, Hb concentration and reticulocyte count also were found to be significantly lower in the placebo group than in the Fe study arm (p=0.028 and p=0.036, respectively). Hb, ferritin, and transferrin levels and reticulocyte counts did not change significantly in the Fe group during the observation period. CONCLUSION: Menstruating women undergoing regular plasmapheresis at short intervals are prone to develop Fe depletion. This can be prevented by regular Fe intake. Laboratory analyses in product plasma instead of serum gained from whole-blood samples could be an alternative to reduce blood loss.

Adult↗

Predictive value of initial histology and effect of plasmapheresis on long-term prognosis of rapidly progressive glomerulonephritis.

Intensive immunosuppressive therapy has improved the outcome of patients with rapidly progressive glomerulonephritis (RPGN), which progresses to end-stage renal failure in 90% of patients without intervention. However, it remains unclear which patients benefit most from immunosuppressive therapy and whether plasmapheresis improves long-term outcome. This prospective multicenter study randomized 39 patients with biopsy-proven RPGN (Couser type II, n = 6; pauci-immune type III, n = 33) to undergo either immunosuppressive therapy with prednisone and cyclophosphamide (n = 18) or plasmapheresis in addition to immunosuppression (n = 21). Patients were observed for a mean of 127 months or until reaching the end points of hemodialysis or death. Six of 11 patients who were initially dialysis dependent recovered renal function; however, 2 of those patients required dialysis therapy again after 10 and 105 months. Overall, 15 of 39 patients reached end-stage renal failure after a mean of 25 months, and 4 patients died before requiring hemodialysis therapy. Plasmapheresis had no significant effect on renal or patient survival in type II or pauci-immune (type III) RPGN, independently of age, sex, or serum creatinine level at the time of diagnosis. Overall, probabilities of dialysis-free survival were 0.80, 0.67, 0.55, and 0.48 after 12, 24, 60, and 120 months, respectively. Histological characteristics at the time of diagnosis predicted the effect of immunosuppression on renal outcome. All patients were dialysis dependent within 24 months if more than one third of glomeruli were totally sclerosed on the initial histological examination. Interstitial fibrosis also correlated significantly with the risk for progression to renal failure. Conversely, long-term dialysis-free survival was significantly more likely in patients with a greater number of crescents than in those with a low number of crescents. In conclusion, plasmapheresis does not add to the improvement in outcome reached by immunosuppression alone. Crescents on initial histological examination correlate with a favorable outcome. However, 90% of patients who initially have glomerular sclerosis present become dialysis dependent. Overall, approximately 50% of patients are alive and off dialysis therapy 10 years after the diagnosis of type II or type III RPGN using immunosuppression with cyclophosphamide and prednisone.

Cyclophosphamide↗

The use of plasmapheresis and immunosuppression in the treatment of pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris is an autoimmune blistering disease for which the mainstay of treatment is systemic corticosteroids and immunosuppressants. This therapy had reduced the mortality of pemphigus; however, it is associated with significant morbidity. OBJECTIVE: The objective of this study was to assess the group's experience with plasmapheresis in the treatment of pemphigus vulgaris and report on its utility. METHODS: Seven patients with severe or resistant pemphigus vulgaris underwent a series of 5 plasma exchanges over an average of 8 days. Immunosuppressive drugs were administered immediately after plasmapheresis to prevent the "rebound" flare of disease that can occur after plasmapheresis. RESULTS: Remission was induced in 4 patients, partial remission was induced in 2 patients, and 1 patient continues to have active disease. CONCLUSION: This study suggests that plasmapheresis is a useful intervention in patients with pemphigus vulgaris who are not responding to standard therapy or who require unacceptably high doses of steroids or immunosuppressants.

Adolescent↗

Plasmapheresis as part of the treatment for septic shock.

Plasmapheresis is one of the methods which has been tried in the effort to influence the course of severe sepsis with septic shock and to improve survival rates. This is a retrospective study of 17 consecutive patients with septic shock who were treated with acute plasmapheresis. Nine out of 16 patients with verified etiology suffered from infections with Gram-positive bacteria. Three (18%) of the treated patients died. The estimated mortality rate based on the patients' initial APACHE II scores was 62%. No serious side-effects of treatment were observed. This study indicates that plasmapheresis is a safe treatment for patients with septic shock and has a positive effect on survival. Prospective, randomized studies would be valuable to determine the role of plasmapheresis in the management of patients with septic shock.

Adolescent↗

Nephrogenic fibrosing dermopathy after liver transplantation successfully treated with plasmapheresis.

Nephrogenic fibrosing dermopathy (NFD) is a recently described cutaneous fibrosing disorder associated with renal dysfunction. It appears similar to scleromyxedema but with some notable exceptions, including the lack of involvement of the face and absence of plasma cells on histology, systemic involvement, and paraproteinemia. Patients can present with thickened or edematous skin with indurated papules and plaques involving the extremities and the trunk. We report the first three cases of NFD after liver transplantation successfully treated with plasmapheresis. Two patients underwent liver transplantation for hepatitis C virus-induced cirrhosis and one for hepatitis B virus-induced cirrhosis. All the patients had encephalopathy, refractory ascites, and malnutrition prior to transplantation. Like those patients with NFD, all three of our patients had renal dysfunction and required hemodialysis before and after transplantation. Two were not dependent on dialysis at the time of diagnosis, however. These patients had excellent liver allograft function, but the other patient had allograft failure secondary to recurrent hepatitis C. Immunosuppression therapy consisted of basiliximab, mycophenolate mofetil, calcineurin inhibitor, and prednisone. The patients developed "woody" skin induration of the distal extremities, erythematous papules, and contractures at 1, 2, and 120 months after transplantation. Skin biopsies resembled NFD. No paraproteinemia was evident. One to three 5-day courses of plasmapheresis resulted in moderate to marked clinical improvement. The improvement of the kidney function in two of our patients did not appear to correlate with that of the skin disorder, because the kidney function was improving at the time the diagnosis of NFD was made. In conclusion, we report the first three cases of NFD after liver transplantation. Plasmapheresis was moderately successful in resolving the skin-indurated papules, severe skin induration, and associated joint contractures. Preliminary studies (unpublished data) show that decreasing plasma levels of transforming growth factor-beta1 after plasmapheresis appear to correlate with the amelioration of this clinical condition.

Adult↗

Successful use of an enhanced immunosuppressive protocol with plasmapheresis for ABO-incompatible mismatched grafts in liver transplant recipients.

Graft and patient survival rates after transplantation of ABO-incompatible liver allografts have been poor. We used plasmapheresis and a potent immunosuppressive regimen to control hemagglutinin levels and prevent early rejection. Ten patients who had a United Network for Organ Sharing status of 4 received ABO-incompatible allografts. Quadruple immunosuppression consisted of OKT3, Cytoxan, cyclosporine, and steroid taper; prostaglandin E-1 was administrated intravenously the first week. All patients underwent perioperative plasmapheresis to maintain hemagglutinin levels < 1:16. Patient survival was 80%; graft survival was 60% at 140-505 days. The rejection rate was 90%. Three recipients (A1-->O) lost their grafts to severe rejection at 5, 12, and 30 days after transplantation. All 3 had pretransplantation hemagglutinin levels > or = 1:100. Elevated hemagglutinin levels preceded the diagnosis of severe acute cellular rejection; plasmapheresis failed to lower anti-A titers in these 3 patients. We conclude that in an urgent setting, lowering of preformed hemagglutinins via plasmapheresis in combination with quadruple induction immunosuppression allows liver transplantation across ABO barriers. In patients with high baseline levels of preformed hemagglutinins, the risk of subsequent graft loss may be increased and transplantation with an ABO-incompatible graft may serve as a lifesaving intermediate step.

ABO Blood-Group System↗

Intensive plasmapheresis as a risk factor for arteriosclerotic cardiovascular disease?

Recent studies suggest that the analogy between intensive plasmapheresis and the nephrotic syndrome with respect to plasma protein loss includes events which are generally recognized as risk factors for the development of arteriosclerotic cardiovascular disease. Experimental nephrosis and plasmapheresis alike increase the synthesis of very low density and low density lipoproteins in response to the hypoproteinemic stimulation of plasma protein synthesis. During electrophoresis, these lipoproteins move with the alpha2- and beta-globulins, and the serum levels of these fractions are often elevated in humans subjected to intensive plasmapheresis. Hyperlipoproteinemias of the alpha2- and beta-types are recognized risk factors in the genesis of arteriosclerosis. Another such factor appears to be an increased synthesis of fibrinogen. This protein enhances plasma viscosity and red cell aggregation and may play a role in myocardial infarction. Intensive plasmapheresis thus not only creates an unphysiological and partly depletional state; it is also, like the nephrotic syndrome, capable of producing surplus abnormalities of plasma constituents with a potential for delayed, insidious injury.

Arteriosclerosis↗

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

BACKGROUND AND OBJECTIVES: The safety of chronic intensive donor plasmapheresis has not been determined in large prospective studies examining dropout rates, dropout reasons and predictors of withdrawals. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adult↗

Specificity of plasmapheresis in the treatment of chronic relapsing polyneuropathy.

A 27-year-old woman with an eight year history of chronic relapsing polyneuropathy presented in her fifth relapse. Raised immune complexes prompted a trial of plasmapheresis. Remarkable clinical improvement was seen after the second exchange. Complete remission was obtained after ten treatments. Subsequently, further relapses have occurred, each responsive to plasmapheresis. The effect of plasma exchange in this patient appears to be unique as neither charcoal perfusion nor plasma infusion per se proved efficacious. The patient is currently maintained with weekly plasma exchanges, her course complicated by supervening hepatitis B antigenemia. The clearance of immune complexes observed during plasmapheresis raises the possibility that removal of a serum factor is responsible for her clinical improvement and that patients with such a factor may benefit from plasmapheresis.

Adult↗

Massive hollow fiber clotting: a distinct problem in treatment of cryoglobulinemia by membrane plasmapheresis.

Two patients with cryoglobulinemia were treated with plasmapheresis in combination with immunosuppressive therapy. One had Waldenstrom's macroglobulinemia, and the other suffered from systemic lupus erythematosus. Membrane plasmapheresis, using membrane plasma separators, was performed, and the initial plasmapheresis treatments were unsatisfactory because of clotting of hollow fibers by cryoglobulin. The plasma filtration rate and the clearance of immunoglobulins fell rapidly with the clotting of the hollow fibers. This technical difficulty was overcome by prediluting the blood with normal saline before passing it through the membrane plasma separator. The mechanism of preventing clotting of hollow fiber by saline predilution is likely to be the reduction of serum viscosity and the lowering of cryoglobulin concentration. This modification is simple and efficient and enables membrane plasmapheresis to be performed effectively in patients with cryoglobulinemia without complicated and expensive machines.

Blood Coagulation↗

Selective removal of triglyceride-rich lipoproteins by plasmapheresis in diabetic patients with severe hypertriglyceridemia.

Two diabetic patients with marked intractable hypertriglyceridemia under treatment with hemodialysis for chronic renal failure were treated by either an apolipoprotein B-dependent removal of lipoproteins using dextran sulfate cellulose column plasmapheresis or a size-dependent removal of lipoproteins using hollow-fiber filtration plasmapheresis. In one patient, a column packed with hollow fibers was used as a plasma separator and a dextran sulfate cellulose column as an adsorbent. In another patient, because the hollow-fiber column did not separate plasma from whole blood, a centrifuge-type blood cell separator was used for the plasma separation. The amounts of plasma cholesterol, triglycerides, and phospholipids removed by plasmapheresis were 30%, 33%, and 30%, respectively, when the combination of a hollow-fiber column and a dextran sulfate cellulose column was used. Corresponding values were 31%, 29%, and 27%, respectively, when the combination of the centrifuge-type blood cell separator and the hollow-fiber column was used. The efficiency of lipid removal was almost the same with both techniques. As for plasma separation, the centrifuge-type blood cell separator was more efficient than the hollow-fiber column. Some losses of albumin and platelets were observed when combination plasmapheresis using the centrifuge-type blood cell separator and the hollow-fiber column was performed. In conclusion, we prefer the centrifuge-type blood cell separator to the hollow-fiber column for plasma separation of marked hypertriglyceridemia. The second filter must be chosen for each patient according to the size of the lipoproteins.

Adult↗

Plasmapheresis for the treatment of pemphigus vulgaris and bullous pemphigoid.

Forty-two cases of pemphigus vulgaris (PV) and bullous pemphigoid (BP) were treated with plasmapheresis by one of 3 techniques: centrifugation, double filtration plasmapheresis (DFPP), or a combination of the two. Each plasmapheresis resulted in a rapid reduction in the autoantibody titer and an improvement in clinical symptoms, thereby allowing a lower dose of corticosteroid to be administered and remission to be achieved. These findings suggest that 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 due to complications, and for those who show severe clinical manifestations.

Autoantibodies↗

Outcome of collagen vascular diseases by treatment with plasmapheresis.

The outcome of collagen vascular diseases after treatment with plasmapheresis was studied in 9 patients with polyarteritis nodosa (PN), in 2 patients with Wegener's granulomatosis (WG), in 1 patient with allergic granulomatous angitis (AGA), and in 20 patients with systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). Improvement after treatment with plasmapheresis was observed in 41.7% of the patients with PN, WG, and AGA. On the other hand, with the exception of 1 patient with thrombocytopenia and 1 patient with renal failure, all of the clinical manifestations, including thrombocytopenia, central nervous system (CNS) lupus, thrombophlebitis, lung infarction, and recurrent abortions in the SLE patients with APS, improved after plasmapheresis. Plasmapheresis is thought to be an influential strategy of treatment for patients with collagen vascular diseases.

Adult↗

Plasmapheresis for removal of myeloperoxidase antineutrophil cytoplasmic antibodies: a case report.

We report on a patient with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated glomerulonephritis who had an elevated MPO-ANCA level and necrotizing crescentic glomerulonephritis on renal biopsy. She was treated by double filtration plasmapheresis and immunoadsorption plasmapheresis combined with steroid therapy and immunosuppressive agents. After plasmapheresis, the MPO-ANCA level decreased, and the cellular crescents were reduced. We conclude that plasmapheresis combined with steroid and immunosuppressive therapy may be useful to decrease the activity of MPO-ANCA associated crescentic glomerulonephritis.

Adult↗

Plasmapheresis affects responses of slowly and rapidly adapting airway receptors to pulmonary venous congestion in dogs.

1. The effects of plasmapheresis on the responses of rapidly adapting receptors (RARs) and slowly adapting receptors (SARs) of the airways to pulmonary venous congestion were examined in dogs anaesthetized with alpha-chloralose. Pulmonary venous congestion was produced in a graded manner by partial obstruction of the mitral valve sufficient to raise the mean left atrial pressure by 5, 10 and 15 mmHg. Plasmapheresis was performed by withdrawing 10% of blood volume twice. 2. Both RARs (n = 11) and SARs (n = 5) responded to pulmonary venous congestion by increasing their activities. The responses of the former were proportionately greater. 3. After plasmapheresis which reduced the concentration of plasma proteins by 12.3 +/- 1.0%, the responses of the RARs to pulmonary venous congestion were enhanced significantly. There was no significant change in the responses of SARs. 4. In another set of six RARs, the effects of graded pulmonary venous congestion were investigated twice with an interval of 45 min between the two observations. No significant differences were noted between the two responses. 5. Collection of lymph from the tracheobronchial lymph duct (n = 6) showed that after plasmapheresis, there was an increase in the control lymph flow. In addition, the lymph flow was enhanced during pulmonary venous congestion (mean left atrial pressure increased by 10 mmHg). 6. It is suggested that a natural stimulus for the excitation of the RAR is a function of the fluid fluxes in the pulmonary extravascular space.

Action Potentials↗

Plasmapheresis rapidly eliminates thyroid hormones from the circulation, but does not affect the speed of TSH recovery following prolonged suppression.

OBJECTIVE: To report an attempt to shorten the preparation interval before radioactive iodine administration using plasmapheresis in a 77-year-old woman with a history of papillary thyroid carcinoma with local recurrence and lung metastases, in whom the administration of a high dose of radioactive iodine was intended as a desperate rescue procedure. METHODS: The patient was initially started on cholestyramine. Two days later, plasmapheresis was performed. RESULTS: Plasmapheresis rapidly decreased free tri-iodothyronine (FT(3)) and free thyroxine (FT(4)). Serum FT(4) subsequently remained low, while FT(3) recovered the next day. Thyroid-stimulating hormone (TSH) reached 25 mIU/l in 14 days, which is within the time frame required to reach the target TSH level by withdrawing levothyroxine alone. CONCLUSION: Plasmapheresis is very effective in eliminating thyroid hormones from the circulation. However, it does not seem to accelerate thyrotroph recovery to a considerable extent after prolonged suppression.

Aged↗

Plasmapheresis in the management of acute severe hyperlipidemic pancreatitis: report of 5 cases.

BACKGROUND/AIM: Hyperlipidemic pancreatitis is an acute and potentially life-threatening complication of hypertriglyceridemia that can be provoked when triglyceride levels (TGL) exceed 11.3 mmol/l (1,000 mg/dl). Except for standard symptomatic treatment, plasmapheresis has been performed to rapidly reduce TGL and chylomicron levels in the blood. In 5 patients with hyperlipidemic pancreatitis, treatment with plasmapheresis was evaluated. METHODS: Five male patients who suffered from acute pancreatitis with severe primary hyperlipidemia were studied. In addition to the standard treatment, they were treated with plasmapheresis. RESULTS: Plasma exchange lowered the lipid level and TGLs in all cases. It also improved abdominal pain, the clinical state of the patients, and signs and symptoms of the disease. Complications of treatment were not encountered, none of the patients died and only 1 patient underwent surgery. Follow-up of the patients lasted 4-28 months, and recurrence of pancreatitis was not noted. CONCLUSION: Our study showed that plasmapheresis was successfully applied in patients with hyperlipidemic pancreatitis, especially to improve the acute phase of the disease.

Acute Disease↗