bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological effects produced by the acute and chronic administration of hydroxyethyl starch
Authors: Mishler John Milton
Published: February 2007

Centers throughout the world have utilized various erythrocyte sedimenting macromolecules to improve the collection of neutrophils from normal donors, but in the United States, high‐molecular weight hydroxyethyl starch (HES 450/0.70) is presently the only agent approved by the Food and Drug Administration for use during leukocytapheresis. HES 450/0.70, prepared from a waxy species of either maize or sorghum, is hydrolysed by alpha‐amylase present in the bloodstream following intravenous administration. The major portion (70 to 80%) of the injected dose of HES 450/0.70 is eliminated through the kidneys; a smaller portion (20 to 30%) becomes extravasated, and a minor amount is eliminated through the gastrointestinal tract. If HES 450/0.70 is given as a single 500 ml dose, the erythrocyte sedimentation rate (ESR) will be increased and difficulties in blood typing and crossmatching may be encountered. Concentrations of most blood and plasma components will decrease, usually in direct proportion to the amount of HES 450/0.70 and other fluids administered. Determinations, both of hepatic and of renal function, will remain within normal limits, although the levels of an alpha‐amylase in plasma will become elevated. Serious bleeding complications are normally not observed when the dose of HES 450/0.70 does not exceed 1.0 to 1.5 g/kg body weight. Rarely, anaphylactoid reactions may be encountered. If HES 450/0.70 is given on more than one occasion, and especially if administered over a relatively short period of time, mild untoward effects related to expansion of the plasma volume may occur. When HES 450/0.70 is give chronically, tests of hepatic and renal function remain within normal limits, but certain tests of coagulation may become slightly prolonged. HES 450/0.70 has an excellent record of safety and is highly recommended for use during leukocytapheresis.
Membrane plasma exchange: Principles and application techniques
Authors: Samtleben Walter , Randerson David H. , Blumenstein Matthias , Habersetzer Rupert , Schmidt Baerbel , Gurland Hans J.
Published: February 2007

Membrane plasmapheresis was introduced in 1978 as a new method for performing therapeutic plasma exchange. Its principal advantages over traditional techniques include speed, ease of performance, and ready adaptability to clinical centers already performing routine extracorporeal therapy. The appearance of a membrane plasmapheresis circuit (vascular access, anticoagulation, connectology) is similar to that of hemodialysis and especially hemofiltration; the operating protocols (treatment time, filtration rates, pressures, pharmacokinetics) are quite different. Particular attention must be paid to avoiding operating conditions that lead to hemolysis.

In clinical use membrane plasma separation is as effective as centrifugal plasma exchange in removing plasma proteins. The sieving coefficients for proteins with a molecular weight (MW) ranging from 67,000 (albumin) to 2,400,000 (β‐lipoprotein) daltons are unity. An exchange of one patient plasma volume has been shown to cause a 55% reduction of the serum levels of intravascular proteins. There are no significant differences between membrane and centrifugal plasmapheresis in substitution fluid requirements (human albumin or fresh frozen plasma), indications for treatment and complications.

The next major advance in plasmapheresis technology will almost certainly be development of a “closed loop” circuit in which filtered plasma is treated to remove the offending moiety and returned to the patient. This would eliminate both the cost and the possible side effects of replacement fluid. Membrane‐based systems are already available for removing cryoglobulins or proteins with MW of at least 900,000 daltons.
Use of erythrocytapheresis in the treatment of patients with sickle cell anemia
Authors: Kleinman Steven H. , Hurvitz Carole G. , Goldfinger Dennis
Published: February 2007

We performed exchange transfusions, utilizing the technique of automated erythrocytapheresis, for the treatment of patients with sickle cell anemia. In an attempt to determine guidelines for the use of erythrocytapheresis, we studied the use of this procedure in three distinct clinical situations in nine patients with sickle cell disease. Patients with dangerous complications of sickle cell disease such as acute respiratory distress and priapism responded well to erythrocytapheresis, showing marked improvement within 24–48 hours. Patients with prolonged painful vaso‐occlusive crises showed only variable improvement after erythrocytapheresis therapy, insufficient to justify exposing the patient to the risks of the procedure. Patients treated to decrease the frequency of painful crises demonstrated no prolongation in symptom‐free intervals between crises. Therefore, erythrocytapheresis has its main value in the management of acute, dangerous complications of sickle cell disease.
The function and structure of granulocytes collected using the IBM 2997 separator
Authors: Wood Lucille , Hester Jeane P. , Jacobs Peter
Published: February 2007

The effect of oral methylprednisolone and the sedimenting agent, hydroxyethyl starch, on granulocyte recovery, morphology, and function was studied in a volunteer donor programme. Using the IBM 2997, 10 litres of whole blood were processed, with an average procedure time of 2.4 hours and a collection volume of 300 ml. Donors not receiving methylprednisolone (n = 80) had a mean total granulocyte count of 3.5 × 109/litre (range 1.6–5.3 × 109/litre) and mean granulocyte yields were 1 × 1010 (range 0.2–3.0 × 1010). Those receiving 48 mg oral methylprednisolone 6–8 hours before the procedure (n = 320) had a mean granulocyte count of 6.3 × 109/litre (range 3.2–11.4 × 109/litre) and significantly superior mean granulocyte yields of 2.0 × 10ln (0.3–6.5 × 1010) (P < 0.05). For both groups the mean packed cell volume of 0.08 litre/litre (range 0.02–0.17) and platelet contamination 1.9 × 1011 (range 0.3–5.0 × 1011). In all these procedures, hydroxyethyl starch was added to the blood entering the centrifuge channel. In none of the procedures were any untoward symptoms experienced by the donors. Light microscopy and ultrastructural studies showed no difference between control granulocytes and those collected following the addition of hydroxyethyl starch or after oral methylprednisolone. Similarly, granulocyte function measured with a random migration, chemotaxis. phagocytosis, and intracellular killing was not significantly different between control cells and those exposed to the sedimenting agent or the adrenocorticosteroids (P > 0.10). It is concluded that donor premedication with methylprednisolone significantly enhances granulocyte yields in the presence of hydroxyethyl starch and neither agent has any demonstrable effect on granulocyte morphology or function.
Erythrocyte depletion of ABO‐lncompatible bone marrow
Authors: Sniecinski I. , Henry S. , Ritchey B. , Branch D. R. , Blume K. G.
Published: February 2007

Bone marrow transplantation results in the infusion of 150 to 360 ml of erythrocytes. While this poses no problem to a recipient of marrow from an ABO‐compatible donor, it clearly represents a serious risk of intravascular hemolysis for the recipient of an ABO‐incompatible marrow. Thus, there is a need for removing incompatible erythrocytes from the marrow preparation. We removed erythrocytes from the marrow preparations by automated centrifugation. The erythrocyte‐depleted marrow (EDM) contained a mean of 5 ml erythrocytes, representing an average reduction of 98%. The mean mononuclear cell recovery was 88%, resulting in a mean infusion of 0.6 × 108 cells/Kg of recipient's body weight in a final average volume of 155 ml. EDM was infused into 22 ABO‐incompatible marrow recipients (21 patients with hematologic malignancies and one patient with aplastic anemia) without clinical evidence of hemolysis. The isohemagglutinin titers of recipients ranged from 4 to 4096 and were not lowered prior to infusion. Engraftment (i.e., recovery of peripheral leukocyte and platelet counts) and incidence of graft versus host disease were similar to those observed in recipients of ABO‐compatible marrow transplantation. Erythrocyte engraftment was significantly delayed in only one patient who had a high isohemagglutinin titer. The post‐transplantation red cell requirement was increased in EDM recipients: 9 units compared to 6 units in ABO‐compatible bone marrow transplanted patients with neither hemolysis nor interference with successful engraftment.
Visual pH monitor for medical column regeneration
Authors: Studebaker J. F. , Debroy J. A.
Published: February 2007

A flow‐through cartridge for indicating acidic and basic conditions during acid regeneration of immunoadsorption columns is described. Based on a pH dye covalently bound to polyacrylamide beads, it offers a direct visual indication of whether the pH of a column is in a range which is safe for use. The device, mounted in the waste line, may be reused several times.
Plasma exchange in six patients with advanced cancers of the head and neck
Authors: Seder Richard H. , Katz Arnold E. , Keggins John J. , Blanchard G. C. , Oh S. K. , Berman Leonard D. , Vaughan Charles W. , Hong Waun Ki , Strong M. Stuart
Published: February 2007

Six patients with advanced squamous cell cancers of the head and neck, with serum IgA ≤ 400 mg/dl and IgE ≥ 1000 IU/ml. underwent a trial of six 2‐liter plasma exchanges over a 2–3‐week period. Disease progressed in patients 1. 2. and 4. who died on days 44. 72. and 159. The tumor in patients 3 and 6 regressed significantly. repeatedly in patient 3 over each of four courses of apheresis. Tumor recurred in both patients after cessation of treatment, and they died at days 420 and 79. Patient 5. with inoperable disease, received full‐dose radiotherapy immediately following the course of apheresis. and showed complete response in the primary lesion and a major response in the extensive lymph node metastases, dying on day 421 of apparently unrelated causes. Serum IgE in the three patients experiencing tumor regression rose paradoxically during plasmapheresis. Only patient 3 had an elevated level of soluble E‐receptor suppressor factor prepheresis: the serum of patient 6 was lymphocytotoxic prepheresis but this activity decreased or disappeared during each of the exchanges studied. Controlled trials are now indicated.
Guidelines for apheresis personnel ‐ an overview
Authors: Cole Barbara
Published: February 2007

The Guidelines for Apheresis Specialists were prepared by the Standards Committee of the Society of Hemopheresis Specialists (SHS) in response to a need to safeguard donors and patients undergoing apheresis from the viewpoint of the technical staff performing the procedures. The Guidelines address technical and administrative topics not covered by instrument manufacturer's training sessions and manuals. The Guidelines contain the following objectives:

To assure that apheresis procedures are performed and supervised by qualified personnel, thereby safeguarding the donors, patients and recipients of the components harvested.

To assure that apheresis procedures are carried out in a safe, efficient and appropriate manner with minimum risk and maximum benefit.

To assure donor/patient safety and high quality component preparation through an effective quality control program.

The Guidelines are flexible, adaptable to various physical settings, applicable to different types of instruments, and useful for both therapeutic and donor hemapheresis procedures. They avoid references to issues that may be considered to interfere with internal or external policymaking bodies. In addition, they provide a base from which policies and procedures can be formulated and amended to account for advances in technology and expertise.
Plasma exchange and prednisone in acute inflammatory polyradiculoneuropathy: A controlled randomized trial
Authors: Mendell J. R. , Kissel J. T. , Kennedy M. S. , Sahenk Z. , Grinvalsky H. T. , Pittman G. L. , Kyler R. S. , Roelofs R. I. , Whitaker J. N. , Bertorini T. E.
Published: February 2007

A controlled‐randomized trial of plasma exchange combined with prednisone was compared to supportive care alone in patients with acute inflammatory polyradiculoneuropathy (AIP). The design of this study differs from other reported trials of plasma exchange in AIP because prednisone was used in the treatment group to prevent the possibility of antibody rebound. Furthermore, in this study, detailed muscle strength testing formed the principal basis for assessment of therapeutic efficacy while in the British, North American, and French studies, a functional assessment scale was used. Analysis of our data revealed no significant improvement in the treated group over the controls. The sample size, albeit small (12 treated and 13 controls), had the power (95% chance) to detect a change of two British Medical Research Council grades of strength between the groups. The difference in our results versus others (North American and French studies) probably reflects the adverse effects of prednisone on recovery in AIP. An additional consideration is that plasma exchange may have an overall modest effect on the course of AIP, less appreciated when individual muscles are tested compared to assessment by large functional categories.
Apheresis in the treatment of chronic relapsing polyneuropathy
Authors: Handelsman Harry
Published: February 2007

As a distinct inflammatory demyelinating disease, chronic relapsing polyneuropathy can be extremely debilitating and cause respiratory failure leading to death. The cause of the disorder is unknown, although evidence suggests that immune dysfunction plays some role in its pathogenesis.

Conventional treatment using steroids and immunosuppressants has been reported both as effective and ineffective in controlling the course of the disease. The rationale for apheresis, as a nonspecific therapy, is related to the removal and/or dilution of circulating cytotoxic factors, and some patients have achieved dramatic and sometimes prolonged remissions from such treatments.

Existing evidence from a large and growing number of case reports suggests that apheresis is a reasonable treatment for patients with severe or life‐threatening symptoms which fail to respond to conventional therapy. However, convincing data of its efficacy is lacking and must await the results of appropriate randomized clinical trials.
Plasmapheresis: An adjunct to medical management of severe hyperthyroidism
Authors: Braithwaite Susan S. , Brooks Marion H. , Collins Sonia , Bermes Edward W.
Published: February 2007

A woman with hyperthyroidism and myasthenia gravis developed respiratory failure in association with radiation‐induced thyroiditis. Treatment with steroids, propylthiouracil, propranolol, iodine, and plasmapheresis was associated with dramatic reduction in serum triiodothyronine (T3), serum thyroxine (T4), and thyroglobulin levels and prompt recovery of the patient. The medications that this patient received have been shown to cause an abrupt decline in serum T3 levels with little or no effect on the serum T4 concentration. The 56% decline in serum T4 observed in this patient during the first 24 hours of therapy suggests that plasmapheresis may be a useful adjunct to medical therapy in selected patients with severe hyperthyroidism.
Implementation of a semiclosed large scale counterflow centrifugal elutriation system
Authors: Gao Ino K. , Noga Stephen J. , Wagner John E. , Cremo Carol A. , Davis Janice , Donnenberg Albert D.
Published: February 2007

A semiclosed counterflow centrifugal elutriation system that minimizes the risks of contamination and cell loss is presented. A detailed description of the configuration of the system and its sterilization and assembly is provided along with examples of its application to large‐scale separation of leukapheresis buffy coat and cadaveric bone marrow. We are currently using this system to deplete lymphocytes from human bone marrow prior to use in allogeneic bone marrow transplantation. The implementation of a semiclosed system increases the safety, ease of operation, and reproduciblity of a technique that has the potential for a wide range of clinical applications.
Plasma exchange and plasma modification for the removal of anti‐red cell antibodies prior to abo‐incompatible marrow transplant
Authors: Bensinger William I. , Buckner C. Dean , Clift Reginald A. , Thomas E. Donnall
Published: February 2007

Plasma exchange (PE) is performed only rarely to remove a specific, well defined antibody. ABO incompatibility in marrow transplantation has allowed us a unique opportunity to compare the effectiveness of three apheresis procedures for removing anti‐red cell antibodies. We performed 140 marrow transplants in which a major ABO incompatibility between donor and recipient existed. To avoid a hemolytic transfusion reaction at the time of marrow infusion PE, plasma immunoadsorption (PIA) or whole‐blood immunoadsorption (WBIA) was performed a total of 243 times. PE removed a mean of 87% of intravascular IgM and 86% of intravascular IgG directed against red cell antigens. PIA removed 75% and 73% of IgM and IgG, respectively (P < .001 when compared to PE). Results for WBIA were 66% and 65%, respectively. Thus, PIA and WBIA were less efficient at removing antibody than PE. Furthermore, there were a few specific instances in which PIA or WBIA removed little or no antibody owing to differences in antibody specificity. PIA and WBIA resulted in less platelet consumption than PE. Although somewhat less effective that PE, PIA and WBIA have other advantages that can make them more desirable.
Use of autologous pregnancy plasma to treat a flare of juvenile rheumatoid arthritis: Case report and literature review
Authors: Wallace Daniel J. , Goldfinger Dennis , Klinenberg James R.
Published: February 2007

A patient with juvenile rheumatoid arthritis whose disease was in remission during pregnancy underwent third‐trimester plasmaphereses. The stored plasma was returned to her 1 year postpartum, when the disease flared, without beneficial results. The literature on the use of blood products in rheumatoid arthritis and pregnancy is reviewed.
Rapidly progressive glomerulonephritis associated with amyloidosis: Efficacy of plasma exchange
Authors: Vernier I. , Pourrat J. P. , Mignon‐Conte M. A. , Hemery M. , Dueymes J. M. , Conte J. J.
Published: February 2007

This report describes one case of rapidly progressive glomerulonephritis associated with amyloidosis in a 53‐year‐old woman with rheumatoid arthritis, successfully treated with intensive plasma exchange and immunosuppression. Amyloid deposits were present in all of 20 glomeruli in the kidney biopsy specimen and eight out of nine nonfibrosed glomeruli contained crescents. With intensive plasma exchange and immunosuppressive drugs, renal function improved, and hemodialysis was discontinued. After 2 years, renal function was stable at a moderate level of impairment, but heavy proteinuria persisted.
Benefit of a 37°C extracorporeal circuit in plasma exchange therapy for selected cases with cold agglutinin disease
Authors: Andrzejewski C. , Gault E. , Briggs M. , Silberstein L.
Published: February 2007

Plasmapheresis is commonly advocated in cold agglutinin disease with life‐threatening hemolysis. Some clinicians, however, are reluctant to use this therapy because of perceived technical problems and risks attendant with the temperature of the extracorporeal circulation. In this study we report our experience of two patients with severe life‐threatening hemolysis and in whom plasma exchange was not feasible due to red blood cell autoagglutination in the extracorporeal circuit. A method is described involving the use of blood warmers and the Fenwal CS‐3000 blood cell separator with its 37 °C centrifuge compartment. The use of plasma exchange in this manner is a safe and beneficial form of adjunctive therapy and should be considered for patients with cold agglutinin disease at risk for extracorporeal agglutination or hemolysis.
Hypercholesterolemia and atherosclerosis: Present and future therapy including LDL‐apheresis
Authors: Kottke Bruce A. , Pineda Alvaro A. , Case Marvin T. , Orsuzar Alyce M. , Brzys Karen A.
Published: February 2007

Atherosclerosis‐induced coronary heart disease remains the major cause of death and disability in industrialized countries. Hypercholesterolemia is recognized as a causative factor in the development of atherosclerosis. While the lowering of cholesterol levels as a treatment goal has met with general agreement and acceptance, the preferred methods for doing so are still open to conjecture. This literature review discusses various factors in the hypercho‐lesierolemia‐atherosclerosis link and surveys a variety of treatment protocols including diet modification, drug therapy, surgical intervention, and plasmapheresis. Evidence is accumulating to prove that the ideal hypercholes‐terolemia therapy is one that reduces LDL levels while maintaining or increasing HDL levels. Because LDL‐apheresis has this potential, this paper also reviews the various LDL‐apheresis methods, including immunoadsorp‐tion, chemical affinity,' and double‐membrane filtration.
Brief overview of the mounting evidence that atherosclerosis is both preventable and reversible
Authors: Wissler Robert W. , Vesselinovitch Dragoslava
Published: February 2007

The major life‐threatening events in advanced atherosclerosis are precipitated by the plaque. Thrombosis in the muscular arteries and rupture of the large elastic arteries usually follows rupture of the plaque's fibrous cap.

The smooth muscle cell (SMC) participates in many aspects of the atherosclerotic process: lipid uptake, synthesis of plaque components, and cell proliferation. The latter is a particularly significant aspect of the disease.

High serum cholesterol levels stimulate proliferation of arterial medial cells; low‐density lipoproteins (LDL) from hypetiipidemic plaques induce ingress and storage of cholesterol ester. These effects are inhibited by high‐denisty lipoproteins (HDL). Endothelial injury may be an important part of the patnogenesis of some atherosclerotic plaques because powerful growth factors actively stimulate SMC proliferation, even when other risk factors are absent.

Utilization of animal models of atherosclerosis, especially nonhuman primate models, has led to great progress in understanding this disease process. In controlled feeding experiments, severe atherosclerosis has been produced in rhesus monkeys by means of a high fat, high cholesterol diet. Animals then placed on a tow fat, low cholesterol diet, or given cholestyramine, or a combination of these two approaches, showed a remarkable decrease in the size of their atherosclerotic plaques.

Many cpidemologic studies, as well as more recent prospective intervention studies involving bile acid sequestrants, indicate by imaging techniques that plaque regression takes place in humans.
Treatment of hypercholesterolemia by precipitation of lipoproteins with dextran sulfate
Authors: Antwiler G. Delbert , Dau Peter C. , Lobdcll Donn D.
Published: February 2007

An on‐line continuous system for the selective precipitation of low‐density lipoproteins (LDL) and very low‐density lipoproteins (VLDL) has been devised and tested. This system conserves high‐density lipoproteins (HDL) and other plasma macromolecules. LDL and VLDL are precipitated from plasma using 10–35 mg/dl dextran sulfate (Mr 5,000) in the presence of 55 mM calcium with a reduced concentration of monovalent cations. The plasma is obtained by membrane filtration of whole Wood using the COBE Gentryr̀ TPE System (Cobe Laboratories Inc, Lakewood, Co.). The precipitated LDL plus VLDL is removed by filtration, and the electrolytes are restored by dialysis. The plasma minus LDL plus VLDL is then returned to the patient.

Four patients with heterozygous familial hypercholesterolemia (type II) were treated 70 times. The mean pretreatment serum cholesterol was 383 mg/dl. The mean reductions in plasma components were: LDL plus VLDL 63%; HDL 27%; fibrinogen 19%; albumin 15%; IgG 20%; IgA 19%; IgM 25%; C3 30%; and C4 27%. The cholesterol returned to near normal values in approximately 2 weeks after each treatment.

Four normal volunteers were each treated one time. These individuals had a mean pretreatment serum cholesterol of 201 mg/dl. The mean reduction in plasma components were: LDL plus VLDL 70%; HDL 27%; fibrinogen 24%; albumin 14%; IgG 18%; IgA 17%; IgM 20%; C3 27%; C4 22%; C3 proactivator 12%; alpha1‐antitrypsin 17%; ceruloplasma 17%; transferin 18%; alpha2‐macroglobulin 17%; and orosomucoid 13%.

It is our conclusion that dextran sulfate precipitation is an effective on‐line means of selectively removing LDL plus VLDL from plasma while conserving HDL and other plasma macromolecules. The capacity of the system is limited only to the size of the filter (currently estimated at over 30 gm of cholesterol). The reduction of LDL plus VLDL is limited only by the quantity of plasma processed while the reduction in the other plasma components is virtually independent of plasma volume processed.
Apheresis techniques in lymphokine‐activated killer cell production
Authors: Sniecinski Irena , Sentinella Kim , Margolin Kim , Mills Bonnie
Published: February 2007

Adoptive transfer of autologous lymphokine‐activated killer cells (LAK) in conjunction with recombinant interleu‐kin‐2 (rIL‐2) has been reported to produce significant regression in metastatic disease in patients with advanced cancer. In an effort to confirm the results reported by the Surgery Branch of the National Cancer Institute, the same IL‐2/LAK regimen was used in cancer patients at six extramural cancer centers.

In this report we will review our experience with mononuclear cell removal from the blood of cancer patients using apheresis technology and extracorporeal handling of these cells to generate a selective, highly cytotoxic cell population.
Plateletpheresis concentrates produced in 30 minutes along with plasma and packed red cells: Preliminary results
Authors: Valbonesi Mauro , Frisoni Roberto , Capra Carlo , Lercari Giuseppe , Fella Mauro , Pittaluga Pierantonio
Published: February 2007

Centrifugal devices for donor plasmapheresis that collect platelets as a by‐product have recently been introduced. The platelet yield ranges from 1.2 to 2 × 1011 per collection, and the collection time exceeds 50 minutes. An attempt to increase yields and to reduce the procedure time was carried out at our center, taking advantage of the Dideco Eccentriplate (Dideco spa. Mirandola, Italy). Within 30 minutes, 510 ml of plasma were collected along with 3.3 × 1011 platelets. The shift of donors from whole blood to plasma and platelet donation generated a progressive decrease in red‐cell availability. In order to maintain plasma and platelet production without affecting the erythrocyte production, a technique was developed that allows the collection of 3.68 × 1011 platelets, 250 ml of plasma, and 225 ml of packed red blood cells with a hematocrit of 66.5%. The mean procedure time was 31.6 minutes; 2,671 ml of blood were processed at flow rates of 85–100 ml/minute. The cellular cross contamination of the platelet concentrates was 1.76 × 108(leukocytes) and 2.23 × 108 (erythrocytes). Although me procedure was carried out in a selected group of donors, the technical experience has strongly modified our procedure for platelet and plasma collection.
Staphyiococcal carriage and infection in myasthenia gravis patients receiving therapeutic apheresis
Authors: Johnson Richard B. , Muder Robert R. , Kominos Spyros O. , Nasca Thomas J.
Published: February 2007

Populations exposed to repetitive needle puncture (such as hemodialysis patients, insulin‐dependent diabetics, and parenteral drug abusers) are at increased risk for nasal carriage of Stophylococcus aurais. These groups appear to have increased susceptibility to serious staphylococcal infection as well. We performed a microbiologie survey on a group of patients receiving regular, long‐term therapeutic apheresis for my asthenia gravis (MG), and compared the rate of nasal staphylococcal carriage with that found in control groups of MG patients not receiving apheresis and ambulatory general medical patients without known risk factors for staphylococcal carriage. Medical records were reviewed for episodes of significant staphyiococcal infection occurring since commencement of apheresis. Nasal S. aurais carriage was found in 9/29 (31%) apheresis patients, 8/30 (27%) MG controls, and 8/30 (27%) general medical controls. No significant difference in frequency of apheresis was noted between carriers and noncarriers. A single episode of S. aureus bacteremia occurred in 95 patient‐years of apheresis therapy. We conclude that therapeutic apberesis for MG does not increase the risk of staphylococcal carriage, and mat serious infection is infrequent.
LAK cell generation in normal subjects: Ficoll‐Hypaque vs. light spin purification
Authors: Burgstaler Edwin , van Haelst Carol , Pineda Alvaro A. , Homburger Henry A. , Gonchoroff Nick J. , Kovach John S.
Published: February 2007

Research in adoptive immunotherapy such as lymphokine‐activated killer cell (LAK) generation requires a large number of mononuclear cells (MNCs). The original procedure for generation of LAK cells used a Ficoll‐Hypaque (FH) purification of the MNCs collected by a blood separator to remove granulocytes, platelets, and red blood cells. Since the Fenwal CS 3000 blood separator produces MNCs with reduced granulocyte contamination, it is possible that FH purification could be replaced by a light centrifuge spin (LS) purification. We report on a study comparing the MNC recovery, platelet and red cell removal, purification time, in vitro LAK cytotoxicity, and phenotypic characterization of the lymphocytes, collected by FH purification vs. LS purification by using the CS 3000. Six donors were leukapheresed with the CS 3000 using a shortened LAK Cell procedure. Following an LS (3 minutes at 1,000 rpm), the MNC collection was divided into two equal aliquots, one aliquot purified by FH and the other aliquot purified by LS. Both aliquots were then washed, cultured for 5 days in IL‐2, and harvested with the CS 3000. Our findings suggest the LS purification resulted in improved 1) postpurification MNC recovery (89% vs. 60%), 2) purification time (54 minutes vs. 129 minutes), and 3) LAK cell generation by phenotype. LS purification was similar to FH purification in 1) platelet removal and 2) in vitro LAK cytotoxicty. We found the LS superior to FH when considering efficiency, economics, simplicity, and LAK cell genration and comparable in platelet removal and in vitro LAK cytotoxicity.
Counterflow centrifugation apheresis for the collection of autologous peripheral blood stem cells from patients with malignancies: A comparison with a standard centrifugation apheresis procedure
Authors: Schouten Harry C. , Kessinger Anne , Smith Douglas M. , Landmark James D. , Wigton Robert S. , Weisenburger Dennis D. , Armitage James O.
Published: February 2007

Two apheresis methods used to collect hematopoietic stem cells from peripheral blood were compared in eight patients with a variety of malignancies. The standard lymphocyte collection method was alternated with the counterflow centrifugation or lymphocyte surge protocol. The number of clonogenic cells (CFU‐GM and BFU‐E), the red cell volume, and the number of mononuclear cells in each collection were assessed as well as the changes in circulating leukocytes, platelets, and blood hemoglobin produced by each apheresis procedure. There was no statistically significant difference found in the number of clonogenic cells collected with either method, but the number of mononuclear cells collected with the standard procedure was significantly higher (P = 0.001). The red cell volume collected with the standard procedure was significantly higher, (P = 0.0001), but corrected for the number of mononuclear cells the difference was not significant. The counterflow centrifugation apheresis produced significantly less thrombocytopenia (P = 0.005). The counterflow centrifugation apheresis procedure used collected fewer mononuclear cells than the standard procedure, however, with less red cell contamination but a comparable number of CFU‐GM and BFU‐E in four hour apheresis procedures. Each collection method resulted in a comparable amount of anaemia and leukopenia but the lymphocyte surge method produced less thrombocytopenia following the collection.
Alpha‐ and gamma‐tocopherol in Plasma, red blood cells, and platelets during plasma exchange
Authors: Van Doormaal Jasper J. , Tijhuis Gerard J. , Zwertbroek Rolf , Muskiet Frits A. J. , Velvis Herman J. R. , Sibinga Cees Th. Smit , Doorenbos Hieronymus
Published: February 2007

The effect of a rapid reduction of plasma lipoproteins on the alpha‐ and gamma‐tocopherol levels in plasma, erythrocytes, and platelets was studied. Sixteen successive plasma exchange procedures performed weekly in an adult with heterozygous familial hypercholesterolemia were evaluated. Plasma exchange was done by intermittent flow centrifugation, exchanging one plasma volume against a 4% human albumin solution. Plasma exchange reduced in plasma alpha‐tocopherol from 41.5 ± 8.9 to 23.6 ± 4.8 μmol/L and gamma‐tocopherol from 4.9 ± 4.1 to 2.4 ± 2.1 μmol/L, without changing their ratios to total lipids. It diminished alpha‐tocopherol in platelets from 12.97 ± 4.37 to 10.03 ± 1.78 μmol/1015 cells and gamma‐tocopherol from 1.43 ± 0.55 to 1.06 ± 0.41 μmol/1013 cells, but did not affect erythrocyte tocopherols. The total amount removed per procedure was 47.57 ± 13.65 μmol for alpha‐tocopherol and 4.70 ± 3.59 μmol for gamma‐tocopherol. Plasma exchange increased the number of erythrocytes from 3.67 ± 0.10.1012 to 4.05 ± 0.13.1012 cells/L, without affecting their volume. Platelet count did not change, but mean platelet volume decreased from 7.7 ± 0.5 to 6.9 ± 0.5 fl and platelet distribution width from 15.1 ± 0.4 to 14.9 ± 0.5. Thus, plasma exchange reduces plasma alpha‐ and gamma‐tocopherol to the same extent as total lipids, and decreases these tocopherols in circulating platelets, along with a reduction in platelet size and, compared to the change in erythrocyte count, a fall of platelet number. The total amount of both tocopherols removed per procedure equals the recommended dietary allowances of 5–11 days for men and 7–14 days for women, assuming an effective absorption of 20–40%. This suggests the need for vitamin E supplementation during long‐term plasma exchange treatment.
Clinical studies on adequate dosage of heparin during immunoadsorption with membrane plasmapheresis
Authors: Hosokawa Shinichi , Oyamaguchi Atsushi , Yoshida Osamu
Published: February 2007

Heparin has been used as an anticoagulant during hemodialysis and plasmapheresis. Recently, immunoadsorption with membrane plasmapheresis (IAP) has been used for treatment of myasthenia gravis and multiple sclerosis. Ten patients were examined. Plasma heparin levels were studied before IAP, 30 minutes, 60 minutes, 90 minutes, and 120 minutes after the start of IAP, and at the end of IAP. Prothrombin time, activated partial thromboplastin time (APTT), bleeding time, plasma fibrinogen levels, fibrin degradation products, and complete blood count were measured pre‐ and post‐IAP. In general, plasma heparin levels lower than 1 IU/ml during plasmapheresis are adequate. The dosage of 40 IU/kg/hr of heparin administered during IAP resulted in plasma heparin levels lower than 1 IU/ml. APTT pre‐IAP (36.8 ± 3.4 sec) were nearly one‐half values of APTT post‐IAP (6.2 ± 9.70 sec).

In conclusion, 40 IU per kg of the body weight per hour is an acceptable dose of heparin during IAP.
Therapeutic plasmapheresis and protein A immunoadsorption in Malignancy: A brief review
Authors: Nand Sucha , Molokie Robert
Published: February 2007

Plasmapheresis is being used with considerable frequency in the management of malignant and non‐malignant disorders. More recently, staphylococcal Protein A immunoadsorption has been employed in similar clinical situations. In patients with malignancy, plasmapheresis has been shown to produce alterations in plasma proteins, decrease circulating immune complexes, remove “specific” and “non‐specific” blocking factors, change immune reactivity, and affect monocyte function. Partial responses have been reported in a small number of patients with carcinoma of lung, colon, and breast following plasmapheresis. In addition, there are reports of favorable responses in patients with melanoma, head and neck tumors, lymphomas, leukemias, and Kaposi's sarcoma in acquired immune deficiency. All these responses were partial and brief, and the treatment did not alter the course of the disease. Plasmapheresis has been useful in the management of hyperviscosity and occasionally of paraneoplastic syndromes. It may also have a role in the treatment of thrombotic thrombocytopenic purpura associated with mitomycin‐C therapy. Protein A immunoadsorption, by which circulating immune complexes are selectively removed, can activate the complement system, increase blastogenic responses, and increase the natural killer cell activity. It has been shown to produce partial responses in breast and colon cancer, as well as Kaposi's sarcoma in acquired immune deficiency. It may have a useful role to play in the management of mitomycin‐C‐associated thrombotic thrombocytopenic purpura. Both plasmapheresis and Protein A immunoadsorption should be considered investigational interventions at this time. Toxicity of plasmapheresis, though uncommon, can be serious and may rarely be fatal. Toxicity of Protein A immunoadsorption is mild, consisting mainly of influenza‐like symptoms and rash.
Application of a new LDL apheresis system using two dextran sulfate cellulose columns in combination with an automatic column‐regenerating unit and a blood cell separator
Authors: Knisel W. , Müller M. , Besenthal I. , Nicuolo A. Di , Rebstock M. , Risler T. , Eggstein M.
Published: February 2007

Extracorporeal procedures for selective removal of low‐density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column‐regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous‐flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57‐year‐old male with drug‐resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4–5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A‐I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug‐resistant familial hypercholesterolemia without or with concomitant hypertri‐lyceridemia.
Plasma exchange and vincristine in the treatment of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura associated with bone marrow transplantation
Authors: Silva Victor A. , Frei‐Lahr Debra , Brown Randy A. , Herzig Geoffrey P.
Published: February 2007

Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) is a rare and often fatal complication of bone marrow transplantation (BMT). In this study, we report eight such cases (seven allo and one auto) treated with plasma exchanges (PE), vincristine (six patients), and discontinuation of cyclosporin A (in allo BMT). This complication occurred in 6.3% of 112 allogeneic BMT and in 0.7% of 146 autologous BMT. In seven patients, the BMT preparatory regimens consisted of cyclophosphamide, etoposide, and total‐body irradiation (TBI). Among the eight patients with HUS/TTP, one allogeneic BMT patient with reversible renal failure, but without central nervous system (CNS) involvement, or systemic mycotic infection, responded completely and is without evidence of disease for a period of >3.5 years. Three patients showed hematologic improvement, and four did not respond. The median duration of survival was 17 days. Six of the seven deaths occurred in a setting of systemic infection, progressive renal failure, and worsening of graft‐versus‐host reaction. In spite of hematologic improvement to PE and vincristine, BMT patients in whom HUS/TTP developed usually succumbed to complications.
Efficacy and safety of fenwal cs‐3000 plateletpheresis performed at a rapid donor blood flow rate: Rapid plateletpheresis with fenwal cs‐3000
Authors: Strauss Ronald G. , Ludwig Gerald A. , Randels M. Joleen , Winegarden Diane C.
Published: February 2007

Results of 3,214 plateletpheresis procedures, using the Fenwal CS‐3000 cell separator, were reviewed to determine the effects on performance when the donor blood flow rate was increased by 30% (i.e., to 65 ml/min instead of 50 ml/min). Ninety‐two percent (2,962 of 3,214) of procedures completed the rapid flow protocol, and results were compared with those reported by others using the more conventional blood flow rates of 32–55 ml/min. When the rapid flow procedure was used, mean platelet yields (4.07 × 1011) and leukocyte contamination (2.65 × 108) were satisfactory, and major donor reactions were infrequent (0.6% of procedures). Thus, CS‐3000 plateletpheresis can be performed at a relatively rapid, donor blood flow rate of 65 ml/min to shorten the procedure and make it more appealing to donors.
Selective absorption of anti‐DNA antibodies and their idiotype‐positive cells in vitro using an anti‐idiotypic antibody‐affinity column: Possible application to plasma exchange
Authors: Harata Naoko , Sasaki Takeshi , Shibata Shinobu , Kameoka Junichi , Hirabayashi Yasuhiko , Osaki Hirofumi , Tamate Eiichi , Yoshinaga Kaoru
Published: February 2007

We examined the possibility of using affinity columns coupled with anti‐idiotype (Id) antibodies to selectively remove nephritogenic anti‐DNA antibodies in order to determine their possible application to therapeutic plasmapheresis. Monoclonal anti‐Id antibodies termed D1E2 or 1F5 were directed to idiotypes of human anti‐single‐stranded and anti‐double‐stranded DNA antibodies. The mixture of D1E2‐ and 1F5‐coupled Sepharose absorbed 26 to 92% of human anti‐DNA antibodies in sera. The affinity columns were also effective in removing anti‐DNA idiotype‐positive cells from the blood samples of patients, especially those with active lupus nephritis. Thus, an anti‐idiotypic antibody‐coupled affinity column could, in theory, serve as a tool for selective plasma exchange in the therapy of autoimmune diseases.
Plasmapheresis and subsequent pulse cyclophosphamide versus pulse cyclophosphamide alone in severe lupus: Design of the LPSG trial
Authors: Clark William F. , Dau Peter C. , Euler Hans H. , Guillevin Loïc , Hasford Joerg , Heer Andreas H. , Jones J. Verrier , Kashgarian Michael , Knatterud Genell , Lockwood C. Martin , Pusey Charles D. , Rifle Gérard , Robinson John A. , Schroeder Johann O. , Tan Eng M. , Wallace Daniel J. , Weiner Steven R.
Published: February 2007

A group of clinics are collaborating in the Lupus Plasmapheresis Study Group (LPSG) to investigate whether repeated plasmapheresis prior to pulse cyclophosphamide improves the therapeutical results in severe systemic lupus erythematosus (SLE). The underlying rationale is the hypothesis that plasmapheresis 1) eliminates pathogenic autoantibodies and immune complexes and 2) induces compensatory lymphocyte activation via feedback mechanisms between circulating antibodies and their respective clones (“antibody rebound”). It should be possible to utilize this enhanced activity for increased clonal deletion if pulse cyclophosphamide is applied shortly after plasmapheresis. Accordingly, in a randomized study, the LPSG will be comparing the repeated application of pulse cyclophosphamide alone with a treatment involving repeated plasmapheresis prior to the cyclophosphamide pulses in severe SLE. A third arm of the study will be gathering experience with a more intensified procedure. This overview summarizes the most important details of the planned study.
Concurrent comparison of the cobe spectra and fenwal CS3000 for the collection of peripheral blood mononuclear cells for autologous peripheral stem cell transplantation
Authors: Padley Doug , Strauss Ronald G. , Wieland Martha , Randels M. Joleen
Published: February 2007

Hematopoietic stem cells, collected by leukapheresis from peripheral blood, can be used as an alternative to autologous bone marrow transplantation following high‐dose chemotherapy as treatment of several malignancies. We compared the ability of the Cobe Spectra and the Fenwal CS3000 to collect peripheral blood mononuclear cells (MNC) for autologous peripheral blood stem cell transplantation. Ten patients experienced repeated leukapheresis (10 L blood processed per procedure) using both instruments. Procedures were alternated between the two until a total of 7 × 108 MNC/kg was collected. Data from 61 Spectra and 50 CS3000 collections were analyzed. The yield (mean per procedure) of nucleated cells (NC) and MNC was higher (P < .005) with the Spectra (0.77 × 1010 NC and 0.54 × 1010 MNC) than with the CS3000 (0.59 × 1010 NC and 0.40 × 1010 MNC). However, colony forming units (CFU‐GM) were not different (P > .05) for Spectra (0.92 × 104) and Fenwal (0.65 × 104) collections. Platelet contamination was lower (P < .001) with the Spectra (2.2 × 1011) than the CS3000 (5.0 × 1011). This correlated with a higher patient blood platelet count immediately following Spectra collections (117 × 109/L) versus the CS3000 (86 × 109/L). Using the methods described, the Spectra product contained greater yields of NC and MNC with less platelet contamination than did the CS3000.
Plateletpheresis with the new fresenius AS 104 blood cell separator
Authors: Valbonesi M. , Frisoni R. , Fella M. , Capra C. , Malfanti L. , Ferrari M. , Zia S. , Florio G. , Nickel H.
Published: February 2007

Among the many blood cell separators introduced into the international market in these last few years, the Fresenius AS 104 represents an advanced and safe thrombocytapheresis machine whose development took advantage of extensive worldwide experience with blood cell separation. Nonetheless the AS 104 has generated most interest in West Germany and most, if not all, the studies published on its platelet collection efficiency have been carried out in that country. It is normally reported that from 2.7 to 3.5 × 1011 platelets can be collected in approximately 80 minutes. Since these results could not be duplicated routinely in our hemapheresis unit, we set up a study by modifying the standard procedure. It was possible to reduce the procedure time and to collect platelet concentrates containing more than 4 × 1011 cells on a routine basis by using the following procedure: ACD‐A/blood ratio 1:10; Interface position 6:2; blood flow rate always exceeding 65 mL/min; rpm 1750; cell collection from 4 to 7 mL/min; volume of blood processed 3.6 L followed by the rinsing of the system with 200 ml of saline; extraction of the content of the secondary separation chamber by the action of the plasma pump working at 20 mL/min for 2 min. With this procedure the platelet yield in 34 collections exceeded 3.1 × 1011 and averaged 4.06 × 1011. The procedure time was reduced to 56.5 minutes with a mean blood flow rate of 62.3 mL/min. The leukocyte and erythrocyte contamination of the products were in the range of 1 × 107 and 1 × 108 respectively. By the methods of counting employed, leukocyte contamination was too low to be determined in 25 preparations. Only two minor citrate reactions were recorded.