Plasmapheresis Procedures Research Articles

Plasmapheresis as preconditioning protocol in an extremely high titer ABO incompatible renal transplant (ABOiRTx) case: A new prospect for chronic kidney disease patients in India

The biggest hurdle in renal transplantation is the ABO blood group system. But recently ABO incompatible renal transplants have been performed using plasmapheresis (PP) as a part of the preconditioning protocol. In the present study, the objective of PP along with immunosuppression was to bring down the antibody titer of the patient to ⩽16 during the transplant and keep it low, around 32, until post-operative 4–14weeks. The patient (O Negative) had his mother (B Positive) as the ABO non-identical donor. The PP was performed with an apheresis equipment Com.Tec (Fresenius Kabi, Germany) to lower the anti-B antibody titer in the recipient. An Antihuman globulin (AHG) titer was performed for anti-B antibody following the departmental standard operating procedure. A total of 11 plasmapheresis procedures was performed preoperatively and four procedures were performed post-operatively to maintain the titer of the anti-B antibody at or below the desired level. The baseline anti-B antibody titer in the recipient was 512. The baseline titer came down to 8 after the end of the 11th procedure. Post-operatively we performed four plasmapheresis procedures to keep the titer at 32. During the post-operative follow up the titer has been maintained at 32 and the serum creatinine level has been maintained at approximately 1.0mg/dl and other parameters relevant to graft function were within normal limits. Our case could be the first reported case from India in which we used a plasmapheresis procedure as a part of preconditioning protocol instead of using an immunoadsorption column. Furthermore, it could be one of the few ABOiRTx cases, which has been performed at an isoagglutinin titer of 512 using plasma exchange as part of a preconditioning regime.

Comparison of Plasmapheresis and Molecular Adsorbent Recirculating System Efficacy in Graft Failure After Living Donor Liver Transplantation

IntroductionLiver transplantation may result in graft failure, requiring time and supportive treatment for regeneration of the graft. The aim of this study was to compare the laboratory parameter changes after single-session molecular adsorbent recirculating system (MARS) and plasmapheresis procedures among living donor liver transplantation patients experiencing graft failure. Patients and MethodWe analyzed retrospectively the results in 45 liver transplantation patients treated with plasmapheresis and/or MARS between June 2011 and July 2012: (plasmapheresis, n = 17; MARS, n = 15; MARS + plasmapheresis, n = 13). When cadaveric donor cases (n = 11) were excluded, the remaining 34 included patients, underwent. MARS (n = 18) or plasmapheresis (n = 16) at the first session. FindingsBoth groups were similar in age, sex, and body mass index features. The MARS group displayed significantly higher levels of international normalized ratio, blood urea nitrogen, and Model for End-stage Liver Disease score. The plasmapheresis cohort, displayed significantly higher levels of initial direct bilirubin and gamma glutamyl transferase (P < .05). The plasmapheresis group showed a significant decrease in GGT after treatment (P < .05). ResultsAn initial MARS session provided significantly greater decrease in renal function associated with graft failure after living donor liver transplantation.

Powikłania u chorych leczonych metodą plazmaferezy na oddziale intensywnej terapii

Plasmapheresis is one of the methods of extracorporeal blood purification involving the removal of inflammatory mediators and antibodies. The procedure is used in a variety of conditions, including autoimmune diseases. The aim of the present study was to analyse the incidence of plasmapheresis-related complications in patients treated in the intensive care unit (ICU). The analysis involved 370 plasmapheresis procedures in 54 patients. The data were collected from patients' medical records, including procedure protocols. The most common diseases treated with plasmapheresis included: myasthenia gravis (33.3%), Guillain-Barre syndrome (14%), Lyell's syndrome (9.3%), systemic lupus erythematosus (7.4%), and thrombotic thromcytopenic purpura (7.4%). The adverse side effects observed most frequently during plasma filtration were: fall in arterial blood pressure (8.4% of all procedures), arrhythmias (3.5%), sensations of cold with temporarily elevated temperature and paresthesias (1.1%, each). In most cases the symptoms were mild and transient. Severe and life-threatening episodes, i.e. shock, fall in arterial blood pressure requiring pressor amines, persistent arrhythmias and haemolysis, developed in 2.16% of procedures. Plasmapheresis can be considered a relatively safe method of treatment of ICU patients. Continuous observation and proper monitoring of patients provided by highly trained medical personnel are essential for its safety.

Perioperative Therapeutic Plasmapheresis

Perioperative Therapeutic Plasmapheresis

Development of an automated plasmapheresis procedure for the harvest of equine plasma in accordance with current good manufacturing practice

To develop a high-speed, continuous-flow, automated plasmapheresis procedure for the high-volume harvest of equine plasma in accordance with current good manufacturing practice. 143 horses (predominantly draft breeds) between 3 and 10 years of age at the time of purchase. Adaptations were made to automated plasmapheresis instruments and sterile disposable collection sets, which allowed for dual-instrument, continuous-flow operation. Donor horses were connected to the apparatus via 2 catheters (1 inserted in each jugular vein). The instruments removed whole blood from donors, fractionated the blood, diverted plasma to collection bags, and simultaneously returned concentrated cells to the donors. Plasmapheresis was performed on donor horses at 14-day intervals with a maximum of 22 mL of plasma/kg of donor body weight harvested during each plasmapheresis procedure. During a 5-year period, 3,240 plasmapheresis procedures were performed and > 50,000 L of sterile equine plasma was harvested in accordance with current good manufacturing practice. Donors typically remained calm during the plasmapheresis procedures and tolerated the procedures well. The high-volume and frequent plasma harvest did not result in sustained hypoproteinemia in donor horses. Adverse events associated with the automated plasmapheresis technique were infrequent, and the recurrence of adverse events was minimized by making minor adjustments to the procedure. The automated plasmapheresis procedure described in this report can be used to safely harvest equine plasma or to perform therapeutic plasmapheresis in horses.

Effects of serial harvest of plasma on total plasma protein and total immunoglobulin G concentrations in donor horses involved in a plasmapheresis program

To determine the effects of intensive serial plasmapheresis on total plasma protein and total IgG concentrations in donor horses involved in a plasmapheresis program. 18 horses (13 mares and 5 geldings; 13 Belgians, 3 Percherons, 1 Standardbred, and 1 warmblood) ranging from 7 to 14 years of age (mean ± SD, 10 ± 3 years) and weighing 822 ± 128 kg. Horses from which 22 mL of plasma/kg of donor body weight was harvested at 14-day intervals for a minimum of 8 consecutive plasmapheresis donations were retrospectively selected for use in the evaluation. Automated plasmapheresis procedures were performed by use of 2 modified plasmapheresis instruments/donor horse. Plasma samples were obtained at each donation and used for determination of total protein and total IgG concentrations. Total plasma protein concentrations were determined via refractometry. A commercially available ELISA was used to determine total equine IgG concentrations. The 18 donor horses were used in 8 to 19 serial donations (mean ± SD, 13 ± 3 donations) during the study. Donor horses had significant decreases in both plasma protein and IgG concentrations over the study period. Serial plasmapheresis procedures caused significant decreases in both plasma protein and IgG concentrations in donor horses; however, decreases were not physiologically relevant. Performing plasmapheresis in horses in accordance with the evaluated automated plasmapheresis procedures did not result in a critical decrease in total plasma protein or total IgG concentrations.

The role of plasmapheresis in the multimodal treatment of anti‐Pr cold agglutinin disease

The blood bank received a hemolyzed specimen (see left figure, left tube, preplasmapheresis specimen) from a 56-year-old male with marked anemia (Hb, 5.1 g/dL), fatigue, tachycardia, and a strong cold antibody reactive with all panel cells. He was treated for cold agglutinin disease with steroids, IVIG, rituximab, cyclophosphamide, and transfusion through a blood warmer with mild improvement. Unfortunately, the patient remained transfusion dependent with a decreasing but still elevated LDH. An extensive investigation to rule out malignancy was performed but revealed only lymphadenopathy, mild splenomegaly, and erythroid hyperplasia on marrow biopsy. The cold antibody was nonreactive with enzyme-treated RBCs and was identified as anti-Pr. The DAT was weakly positive (RBC-bound C3). The antibody was reactive at 30°C and very weakly reactive at 37°C. The antibody was predominantly IgM, but microscopic reactivity remained in DTT-treated serum, suggesting a minor component of IgG. The titer was abnormal but not extremely high (128 at 4°C). Pr is present on almost all human RBCs and carried on oligosaccharide side chains attached to RBC membrane-borne glycophorins 1 (majority on glycophorin A). A new explanation for the pathophysiology of hemolysis caused by this antibody in a context of unimpressive serologic results was described by Brain and colleagues 2 and Garratty 3 and involves antibody-induced aggregation of glycophorin A causing destabilization of the RBC membrane phospholipid bilayer, leading to an increase in cation permeability. The patient's room was kept as close to 37°C as possible. To hasten recovery and transition to outpatient treatment, plasmapheresis was initiated to further facilitate removal of the cold antibody. The cold agglutinin disease was treated and hemolysis stabilized by the use of a multimodal approach to therapy, including immunosuppressant medications, IVIG, RBC transfusion, and plasmapheresis: acute hemolysis resolved (see left figure, right tube, postplasmapheresis specimen) and the decrease in LDH accelerated (see figure, right, hospital time course). After two plasmapheresis procedures the patient was discharged with a Hb of 6.9 g/dL but continued to receive weekly outpatient transfusions. This case illustrates the lack of correlation between the relatively benign serology related to anti-Pr and the severity of hemolytic anemia. Plasmapheresis can play an important role in the multimodal treatment of cold agglutinin disease and the transition to outpatient treatment.

Plasma Exchange for Heparin-Induced Thrombocytopenia: Is There Enough Evidence?

Plasma Exchange for Heparin-Induced Thrombocytopenia: Is There Enough Evidence?

Plasmapheresis-induced Clinical Improvement in a Patient with Steroid-Resistant Nephrotic Syndrome Due to Podocin (NPHS2) Gene Station

Podocin mutations (NPHS2 gene) are mostly responsible for steroid-resistant nephrotic syndrome (SRNS) of childhood onset. Patients with NPHS2 gene mutations do not respond to corticoids and other immunosuppressive agents; partial remission can be rarely induced by cyclosporin A. We present a boy, where SRNS was diagnosed within first year of life. By the age of 15 years, proteinuria reached 9000 mg/24 h, cholesterolemia 15 mmol/L, albuminemia 19.6 g/L, in spite of combined therapy with cyclosporine A, methylprednisolone, enalapril and losartan. At that time a combined heterozygous form of two NPHS2 gene mutations (p.R138Q and p.V290M) was diagnosed, methylprednisolone was discontinued and patient underwent ten plasmapheresis procedures. This resulted in clinical improvement (proteinuria 3000 mg/24 h, S-cholesterol 6 mmol/L, albumin 30g/L) lasting for three years. In conclusion, plasmapheresis can result in clinical improvement and stabilization of SRNS caused by podocine mutation, before renal replacement therapy is initiated.

Recurrence of Nephrotic Proteinuria in Children With Focal Segmental Glomerulosclerosis After Renal Transplantation Treated With Plasmapheresis and Immunoadsorption: Case Reports

Idiopathic focal segmental glomerulosclerosis (FSGS) is believed to be caused by a circulating permeability factor. FSGS recurrence is common after transplantation. The treatment is still a matter of debate; plasmapheresis (PE) and immunoadsorption (IA) are often used. We report on PE and IA in the treatment of two children with recurrent nephrotic proteinuria. Patient 1 was a 16-year-old girl who had recurrence of nephrotic proteinuria on the first day after transplantation (proteinuria-19 g/d). Primary immunosuppressive therapy was changed to high-dose cyclosporine and cyclophosphamide; plasmapheresis was started on day 4. Altogether we performed 53 PE and 38 IA procedures. During the first month, PE procedures were performed with no more than a 2-day interval between sessions, and the girl achieved partial remission (proteinuria 3 g/d). PE was then stopped. After 2 months, a relapse of heavy proteinuria occurred. This relapse was successfully treated again with intensified PE treatment. After achieving remission, a chronic PE regimen was started (PE once a week), similar to the previous series. The child remained in partial remission. Seven months after renal transplantation, she was switched from PE to IA, because of severe hypoproteinemia. Graft biopsy performed at 4 months showed effacement of the foot processes. At the present time she has a good graft function and 3 g/d proteinuria. Patient 2 was a 13-year-old girl with FSGS since 9 years. On the second day after renal transplantation she developed nephrotic proteinuria (proteinuria-14 g/d), which was treated with 39 PE and 16 IA treatments. She went into complete remission on the intensified PE regimen, had one relapse, and was switched to chronic IA. Graft biopsy performed at 2 weeks after transplantation showed effacement of the foot processes. At the present time she has good graft function and low proteinuria (0.3 g/d). In conclusion, intensified PE or IA treatments induced remission of recurrent nephrotic range proteinuria. Chronic PE or IA can maintain patients with frequent relapses in long-term remission.

A Controlled Study of Double Filtration Plasmapheresis in the Treatment of Active Rheumatoid Arthritis

Double-filtration plasmapheresis with a plasma fractionator pore size of 20 nm should selectively remove large molecular weight substances like rheumatoid factor and IgM. This was proposed to be more likely to be helpful for rheumatoid arthritis than standard plasma exchange. To evaluate the efficacy of double-filtration plasmapheresis (DFPP) in the treatment of patients with active rheumatoid arthritis. Eighty-two patients were randomly assigned, 42 to the DFPP group and 40 to the no-DFPP group. All patients received sulfasalazine (0.75 g 3 times daily) plus methotrexate (10 mg orally once weekly). All patients had been on stable doses for more than 3 months. DFPP was performed once a week for 2 to 3 sessions. A total of 121 plasmapheresis procedures were performed in 42 patients. Control patients did not receive sham DFPP. The efficacy measures recorded 1 day after the final treatment and every month in follow-up for 4 to 22 months included the American College of Rheumatology (ACR) 20%, 50%, and 70% improvement criteria (ACR20, ACR50, and ACR70), the Health Assessment Questionnaire estimate of disability and the disease activity index. Patients in the DFPP group had ACR20, ACR 50, and ACR70 improvements immediately after the last treatment of 100%, 92.9%, and 81.0%, when compared with the patients in no-DFPP group 17.5%, 0%, and 0% (P < 0.001). Significant change from baseline was observed in Health Assessment Questionnaire scores in the DFPP group, but not in the no-DFPP group (P < 0.001). The changes from baseline in the disease activity scores were significantly greater than in the no-DFPP group (P < 0.001). Improvements were maintained during follow-up of 7 to 22 months. This open trial showed that DFPP therapy significantly altered the signs and symptoms of active rheumatoid arthritis. There were increases in physical function and improvement in quality of life. This is proposed as an approach that merits further investigation.

Light‐chain removal by plasmapheresis in myeloma‐associated renal failure

Although plasmapheresis has been recommended to reverse nephrotoxic elevations of serum free light chains (sFLCs), there are scant published data on removal of sFLC measured with modern assays. sFLC levels were recorded in two patients with myeloma-associated renal failure receiving multiple plasmapheresis procedures. In one patient, presenting with acute renal failure 8 months after diagnosis of kappa-LC myeloma, 16 plasmapheresis procedures neither reduced sFLC levels (percent removal ranging from -70% to +40%) nor improved renal function. In another patient who presented with leukemic immunoglobulin A-lambda myeloma and acute renal failure, sFLC decreased by 30 to 60 percent after each plasmapheresis procedure, but rebounded within 5 to 10 hours. Renal failure occurred despite plasmapheresis, and hemodialysis was required. In both patients, plasmapheresis failed to effectively lower sFLC levels. The results provide initial biologic data supporting the conclusions of a recent randomized multicenter clinical trial in which plasmapheresis was an ineffective adjunct to chemotherapy for myeloma-associated acute renal failure.

Therapeutic plasmapheresis as a bridge to liver transplantation in fulminant Wilson disease

Wilson disease is an autosomal recessive disorder of copper metabolism that leads to the accumulation of copper mainly in the liver, cornea, brain, and kidney. Rarely, Wilson disease can present as fulminant hepatic failure with direct antiglobulin test-negative hemolytic anemia and renal failure. In the absence of liver transplantation, this disease is uniformly fatal because medical therapy is ineffective. This report describes the successful use of plasmapheresis for a patient with fulminant Wilson disease as a bridge to transplantation. Five daily therapeutic plasmapheresis procedures using fresh frozen plasma as a replacement fluid were performed over 6 days. Serum copper, urinary copper excretion, and hemolysis were significantly reduced and renal function improved. The patient's clinical status improved and she remained clinically stable until a liver transplant was possible. Plasmapheresis can be a successful medical treatment in fulminant Wilson disease and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.

Acquired lysosomal storage caused by frequent plasmapheresis procedures with hydroxyethyl starch

Hydroxyethyl starch (HES) solutions have largely replaced conventional plasma expanders such as human albumin and colloidal fluids. Only a few side effects have been reported and mainly concern pruritus or blood coagulation disorders. Excessive HES exposure can result in diffuse tissue storage and accumulation with foamy appearing macrophages which produce the enzyme chitotriosidase (CT). In case of massive tissue storage, this enzyme activity can reach levels comparable to those of Gaucher disease. In this single-center retrospective analysis of 11 consecutive patients receiving large amounts of HES for chronic plasmapheresis, plasma CT activity was investigated. Five patients receiving chronic intermittent plasmapheresis with conventional plasma expanders served as controls. Plasma CT activity was measured and plotted against creatinine clearance. Where available, marrow aspirate was analyzed with light microscopy to detect foamy macrophages. One patient developed a lysosomal storage disease and was examined extensively. Conventional plasma expanders did not alter plasma CT activity. In patients with impaired renal function, frequent plasma replacement with HES resulted in an increase in plasma CT activity. In the patient with the acquired lysosomal storage disease, massive tissue infiltration with activated foamy macrophages was observed. The phagocytic capacity in this patient, however, did not seem to be altered. Patients with impaired renal function receiving large amounts of HES exhibit an increase in plasma CT activity. Because excessive HES exposure can result in an acquired lysosomal storage disease, this should be avoided in chronic plasmapheresis procedures.

Complications of double‐filtration plasmapheresis

Double-filtration plasmapheresis (DFP) removes high-molecular-weight molecules semiselectively, thereby minimizing albumin loss, but with subsequent need for fluid substitution. The purpose of this study was to establish the overall incidence of complications during DFP and to analyze the possible contributory factors. From November 1993 to October 2003, a total of 2502 plasmapheresis procedures were performed during 515 courses of plasmapheresis in 335 patients. The medical and technical records for these patients were reviewed. The overall frequency of complications was 67.5 percent per patient, 60.0 percent per course, and 26.3 percent per procedure. The rate of major complications was 18.2 percent of patients, 13.2 percent of courses, and 2.7 percent of procedures. Hemolysis, the most common complication of DFP, occurred in 20 percent of patients. A total of 83 (3.3%) episodes of hypotension were documented in 63 patients. Vascular-access-related complications constituted approximately 17 percent of the total. There was one documented episode of clinically overt bleeding from laboratory coagulopathy necessitating infusion of fresh plasma to stop bleeding. There was no allergic reaction or mortality associated with the DFP procedures. The per-patient frequency of hypotension was higher in cases of chronic inflammatory neuropathy (35.1%) compared to the other illness categories (15.4%-17.3%), with marginal significance demonstrated (p = 0.0611). The safety of DFP treatment has been confirmed by this study. High-risk patients should be monitored carefully during treatment to minimize the occurrence of complications.

Plasmapheresis in neurological diseases. Experience in 140 procedures in 47 patients

Plasmapheresis can be useful in myasthenia gravis, Guillain Barré syndrome and chronic demyelinating inflammatory polyradiculoneuritis. To report our experience with plasmapheresis in patients with neurological diseases. Retrospective review of plasmapheresis procedures done between 1995 and 2001, in a public hospital. Indications criteria, clinical results and technical yield were analyzed. One hundred fifty nine procedures were reviewed. One hundred forty (88%) were indicated for neurological diseases (44% for Guillain Barré syndrome and 29% for myasthenia gravis). Clinical improvement or eventual complications were avoided in 70% of patients with Guillain Barré syndrome and 100% of patients with myasthenia gravis. Hypotension in 10% and paresthesias in 7% were observed. All complications were successfully controlled with crystalloid or fresh plasma infusions or citrate management. In 11 cases, the procedure was interrupted due to obstruction of the venous access, that was peripheral in eight of these. The most common difficulties of the procedure were delay in performing it in 50% of patients and insufficient exchange volumes in 30%. Plasmapheresis was safe and useful in patients with myasthenia gravis and Guillain Barré syndrome. The drawbacks of the procedure are its costs and requirement of special equipment.

Assessment of complement activation during membrane‐based plasmapheresis procedures

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.

Extracorporeal blood volume of donors during automated intermittent-flow plasmapheresis and its relevance to the prevention of circulatory reactions.

Intermittent-flow plasmapheresis often involves a large extracorporeal blood volume of the donor during the procedure with the concomitant risk of circulatory reactions. Guidelines governing donor recruitment often apply an arbitrary threshold of 15 percent of the donors' blood volume not to be exceeded during hemapheresis procedures. No data demonstrating the suitability of this approach exist. The blood volumes of 1204 plasmapheresis donors were calculated with different formulae that utilized either body weight or body surface area. Extracorporeal blood volumes of these donors were determined for a commonly used intermittent-flow plasmapheresis machine known to result in a large extracorporeal blood volume. A validated model was employed that calculated the fluid volume shifts occurring during the procedure. The records of all plasmapheresis procedures of these donors were retrospectively reviewed for circulatory reactions. The median extracorporeal volumes ranged from 14 to 17 percent of the blood volume at a donor Hct level of 0.40 to 0.48 L per L for men and from 17 to 20 percent at a Hct level of 0.36 to 0.44 L per L for women. In more than 60 percent of male and more than 90 percent of female donors, extracorporeal volumes exceeded 15 percent of the blood volume during plasmapheresis. In this subgroup, 65 percent of male and 75 percent of female donors never presented with any signs of circulatory reactions. Application of an arbitrary threshold of 15 percent of the donors' blood volume not to be exceeded during hemapheresis procedures is expected to lead to an unjustified deferral rate in plasmapheresis donors.

Volunteer donor apheresis.

Volunteer donor apheresis has evolved from early plasmapheresis procedures that collected single components into technically advanced multicomponent procedures that can produce combinations of red blood cells, platelets, and plasma units. Blood collection and utilization is increasing annually in the United States. The number of apheresis procedures is also increasing such that single donor platelet transfusions now exceed platelet concentrates from random donors. Donor qualifications for apheresis vary from those of whole blood. Depending on the procedure, the donor weight, donation interval, and platelet count must be taken into consideration. Adverse effects of apheresis are well known and fortunately occur in only a very small percentage of donors. The recruitment of volunteer donors is one of the most challenging aspects of a successful apheresis program. As multicomponent apheresis becomes more commonplace, it is important for collection centers to analyze the best methods to recruit and collect donors.

Bradykinin production during donor plasmapheresis procedures

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. 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. 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. 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.