bluuebunny/crossref_metadata_2025 huggingface dataset:
Leukapheresis and pathogenetic mechanisms in rheumatoid arthritis
Authors: Wilder Ronald L. , Malone Daniel G. , Yarboro Cheryl H. , Berkebile Carole , Haraoui Boulos , Allen Janice B. , Wahl Sharon M.
Published: February 2007

Rheumatoid Arthritis is a chronic, usually progressive inflammatory disorder of joints in which the immune system plays a central role in the pathogenesis. In its classic form, the synovial tissues from severely affected joints are densely infiltrated with HLA‐DR bearing T‐lymphocytes (primarily OKT4+/Leu3+subset) and macrophage‐like cells. Moreover, these tissues, as demonstrated by ex vivo culture, spontaneously produce high levels of a multitude of inflammatory mediators, such as collagenase, PGE2, interleukin 1 and fibroblast activating factors, indicating that the cells infiltrating the synovium are “activated”. The action of these various inflammatory mediators on different target substances or cells (collagen, fibroblasts, chondrocytes, osteoclasts, etc.) most likely produce the characteristic pattern of joint pathology. Recent data indicate that this classic form of synovitis tends to be associated with peripheral anergy and other qualitative and quantitative abnormalities in the peripheral blood mononuclear cells. Repeated leukapheresis can induce substantial, although transient, clinical improvement in patients with these classic features, probably as a consequence of disrupting T‐lymphocyte traffic.

Rheumatoid synovitis, however, is highly heterogeneous, but can be categorized into subsets. For example, a subset of patients with highly active clinical rheumatoid arthritis exists which do not exhibit the classic features of disease. Synovial tissues from this patient subset are sparsely infiltrated by T‐lymphocytes but contain mainly macrophages and fibroblasts, as well as prominent lining layer fibrin deposition. Patients with these synovial features do not appear to respond therapeutically to repeated leukapheresis. In view of the wide immunopathologic spectrum in rheumatoid arthritis, assessment of the role, if any, of leukapheresis in therapy remains unclear, but the technique does provide a powerful investigative tool.

Rheumatoid arthritis is a chronic, usually progressive, destructive disorder of joints in which effector mechanisms of the immune system appear to play a major role in its pathogenesis. Various types of apheresis have the potential to modulate immune effector mechanisms and, in theory, could have a therapeutic effect in this disorder. In this report, we present an overview of evolving concepts of the immunopathogenesis of rheumatoid arthritis and relate these concepts to our experiences with leukapheresis.
Granulocyte collection by continuous‐flow centrifugation using arteriovenous shunts
Authors: Williams Barbara M. , Clift R. A. , Buckner C. Dean , Hickman Robert O. , Sanders Jean E. , Stewart Patricia S. , Bensinger William I. , Banaji Meera , Thomas E. Donnall
Published: February 2007

Two thousand nine hundred twenty‐seven granulocyte collections were made using continuous‐flow centrifugation with the Aminco Celltrifuge I. the Fenwal Celltrifuge II. and the IBM 2997. There were 231 recipients and 246 donors. In 32 patients attempts to provide daily granulocyte transfusions from a single donor were unsuccessful owing to clotting of the silastic‐Teflon arteriovenous shunt. Repeated granulocyte donations produced severe anemia requiring red cell transfusions in all the females and most of the males who had previously donated marrow for transplantation. Granulocyte collections were similar when collected with the Celltrihge I or the IBM 2997. but collections with the Celltrifuge Il were smaller. Infusion of hydroxycthyl starch directly into whole blood as it entered the centrifuge increased granulocyte collections. Granulocyte collections decreased with increasing number of daily collections.
Peripheral blood lymphocyte numbers, lymphocyte proliferative responses in vitro, and serum immunoglobulins in regular hemapheresis donors
Authors: Braine Hayden G. , Elfenbein Gerald J. , Mellits E. David
Published: February 2007

Selected tests of lymphoid function were used to screen a population of volunteer hemapheresis donors. Testing included: 1) absolute lymphocyte numbers, and percentage of T‐cell, B‐cell, and mononuclear phagocytes, 2) serum immunoglobulins, and, 3) in vitro proliferative responses to lectin mitogens (phytohemagglutinin, concana‐valin A, and pokeweed mitogen), soluble antigens (staphylococcal filtrate, Candida, and streptococcal varidasc), and cell‐bound alloantigens (mixed lymphocyte culture). A control population of first‐time plateletpheresis donors was examined similarly. Regular donors manifested a small but statistically significant decrease in absolute lymphocyte counts (p < 0.02), and IgM (p < 0.02) compared to controls. Leukapheresis donors also manifested significant decreases in percentage of T cells (p < 0.02). These findings are qualitatively similar to changes reported following intensive lymphocytapheresis and indicate the need for conservative policies regarding donation frequency in hemapheresis programs.
Continuous‐flow techniques for platelet concentrate collection: A step toward standardization and yield predictability
Authors: Hester Jeane P. , Kellogg Robert M. , Mulzet Alfred P. , Freireich Emil J.
Published: February 2007

This study chronicles leukocyte‐ and erythrocyte‐depleted platelet concentrate collection by a dual. stage channel in which three variables: 1) donor peripheral blood platelet concentration, 2) total blood processed, and 3) collection volume were statistically correlated with platelet yield as determined by a multiple regression analysis of single variables. Platelet concentration in the final yield was related to donor precount and collection rate, and could be varied as indicated for individual applications. Total blood processed was established by procedure time, which in turn was defined by citrate‐induced calcium changes in the donor. Reduction in peripheral blood platelet concentration averaged 24% for a mean platelet yield of 3.8 × 10′. An average of 40% of transfused platelet concentrates were recovered in recipient peripheral blood 1 hr posttransfusion and were hemostatically effective, as determined by correction of bleeding time. Platelet yields and patient response were sustained during current collection procedures, verifying the principles described during the investigative period.
Cyclophosphamide‐related intravascular haemolysis during continuous‐flow plasma exchange
Authors: Wood Lucille , Jacobs Peter
Published: February 2007

The plasma of a patient being prepared for allogeneic bone marrow transplantation was found to be severely lymphocytotoxic to donor cells. Three isovolaemic plasma exchanges carried out using a continuous‐flow technique were required to reduce this titre to undetectable levels. Neither these procedures nor pretransplantation conditioning of the patient with 60 mg/kg or cyclophosphamide on two consecutive days resulted in overt haemolysis. However, a single identical plasmapheresis 12 hours after completing the second dose of the alkylating agent resulted in profound intravascular haemolysis requiring red cell transfusion. Subsequent studies in five patients receiving the same cyclophosphamide regimen demonstrated that red cell life span, when measured with radio‐chromium, was reduced from a normal of 25–35 days to a median of 11.5 days. Further studies in the same five patients carried out simultaneously demonstrated that red cell fragility, when assessed in vitro with osmotic or mechanical stress, was marginally increased but became clearly abnormal in only one individual. These doses of cyclophosphamide may result in accelerated but subclinical red cell destruction, and plasma exchange in this period may be associated with rapid intravascular haemolysis. This complication should now be added to the list of those that can occur when plasmapheresis is required in this specific clinical situation.
Platelet collection using the IBM 2997 cell separator
Authors: Bond Rodney , Wood Lucille , Jacobs Peter , Kernoff Leslie M.
Published: February 2007

Platelets were collected using the dual‐channel module on the IBM 2997 Blood Fraction Separator. We carried out 320 procedures to harvest platelets for therapeutic purposes and yielded 5.1 ± 1.5 × 1011 platelets (mean ± SD). Infusion into previously unsensitized recipients with hypomegakaryocytic thrombocytopenia achieved increments at 1 hr of 19 ± 7.3 × 109/liter/nr (mean ± SD) and at 24 hr of 15 ± 6.3 × 109/liter/nr. The only consistent donor reaction was mild hypocalcaemia. easily corrected by calcium gluconate infusion. Changes in donor packed‐cell volume and white cell count were not statistically altered (p > 0.05) but donor platelet counts fell from 216 ± 43.1 × 109/liter to 162.5 ± 41.7 × 109/liter (mean ± SD) (p < 0.01). Additional plateletphereses were carried out in seven normal volunteers, using the same technique, in order that the function of the harvested platelets could be studied. Following radiochromium labelling and reinfusion into the same donors, normal in vivo recoveries were obtained at 10 min (59.4 ± 3.4%; mean ± SD) and platelet mean life span was also normal (218 ± 12 hr; mean ± SD). Furthermore, in vitro platelet factor III availability and aggregation patterns of the harvested platelets did not differ from control values and their ultrastructural appearance was normal.
Controlled trial of plasma exchange in acute inflammatory polyradiculoneuropathy
Authors: Greenwood R. J. , Hughes R. A. C. , Bowden A. N. , Gordon N. S. , Millac P. , Davis J. Newsom , Asian S. , Chadwick D. W. , McLellan D. L. , Stott R. B.
Published: February 2007

A randomized controlled trial of exchange versus no exchange was conducted to find out whether plasma exchange would be useful in acute inflammatory polyradiculoneuropathy. It was calculated that 15 patients would be required in each group to demonstrate a worthwhile improvement in functional ability one month after completion of treatment. Treatment comprised five exchanges in 10 days (55 ml plasma/kg body weight/exchange). Both groups received normal supportive care and were followed up periodically for a year. Overall the treated group showed a slight but not significant benefit (p>0.05); at two weeks' follow‐up of patients admitted to the trial within 14 days of onset of neuropathic symptoms, p=0.07. These results do not provide grounds for recommending plasma exchange for the treatment of severe AIP.
Improved method for automated red cell exchange in sickle cell disease
Authors: Castro Oswaldo , Finke‐castro Helga , Coats Debra
Published: February 2007

An improved method for intermittent‐flow erythrocytapheresis in patients with sickle cell disease is reported. the method, a modification of the standard red cell exchange procedure for the haemonetics 30s unit, dilutes with physiologic saline the patient's blood as it flows from the draw line and before it reaches the centrifugation bowl. the blood dilution (approximately 1.6 parts saline to 1 part blood) is used only during the first two passes, when the proportion of sickle erythrocytes in the patient's blood is still high. only that amount of bowl supernatant (saline‐diluted plasma) necessary to maintain extracorporeal volume below 500 ml is returned to the patient. the method described largely prevents the clumping of sickle erythrocytes in the centrifugation bowl, a complication frequently encountered with the haemonetics 30s unit. thus, changing the bowl between passes is avoided. furthermore, the sickle red cells can be collected with the first pass and cryopreserved for possible future uses including the option of autotransfusion.
Plateletpheresis: A comparative study of six different protocols
Authors: Puig Li. , Mazzara R. , Gelabert A. , Castillo R.
Published: February 2007

Six different protocols were employed in 710 plateletpheresis employing Haemonetics 30, Fenwal CS‐3000, IBM 2997 dual stage channel, IBM 2997 single‐stage channel, and Haemonetics V‐50 „surge pump”︁ method. When Haemonetics 30 and IBM 2997 single‐stage channel procedures were used, 5.4 to 5.9 × 1011 platelets were collected with significant leukocyte contamination (10.8 to 11.6 × 109). With Fenwal CS‐3000, dual‐stage channel of IBM 2997 and Haemonetics V‐50 „surge pump”︁ there was less leukocyte contamination in concentrates (0.3 to 0.9 × 109) as well as a lower platelet yield (3.4 to 4.3 × 1011). No difference in yield was observed when plateletpheresis was performed with ACD‐A or ACD‐B employing the single‐stage channel of IBM 2997. Paraesthesias was the most frequently seen side effect in donors, with a higher incidence when using ACD‐A and IBM 2997.
Autologous transplantation with circulating hemopoietic stem cells
Authors: Zander Axel R. , Cockerill Kevin J.
Published: February 2007

Circulating stem cells exist in sufficient numbers in mouse, dog, and man to allow collection and transplantation after ablative treatment. Preclinical studies in the mouse have shown a low concentration, with a transplantation potential ratio of bone marrow to blood of 1:100. The ratio of circulating stem cells to bone marrow stem cells is more favorable in the dog (1:10‐20). Recent pilot studies carried out in different centers with 10 patients have shown that this approach is feasible in man, too. It appears that 5 × 108 mononuclear cells/kg of body weight collected by seven or eight leukapheresis procedures of about 4 hrs each is sufficient for fast hemopoietic recovery after marrow ablative treatment. Potential advantages of the use of blood stem cells over bone marrow stem cells are the decreased likelihood of contamination with malignant cells, the avoidance of general anesthesia, and the infusion of immunocompetent cells, which might hasten immunorecovery in the autologous setting.
Clinical evaluation of three types of plasmapheresis in a patient with type IIa familial hypercholesterolemia
Authors: Mimori Akio , Takahashi Koki , Mitamura Tadayuki , Kato Hirokazu , Teramoto Tamio , Komuro Issei , Honda Zenichiro , Toma Shigeto , Miyamoto Terumasa
Published: February 2007

Long‐term plasmapheresis (PP) therapy was studied in a 56‐year‐old patient with homozygous type IIa familial hypercholesterolemia also suffering from severe coronary heart disease. Three different PP techniques, plasma exchange (PE), double‐membrane‐filtration plasmapheresis (DFP), and the recently developed low‐density lipoprotein adsorbent column (adsorption plasmapheresis, adsorption PP), were used in an attempt to develop better means of managing the disease. All three techniques showed similar elimination efficiency with respect to plasma total cholesterol level. Adsorption PP with minimal supplemental plasma protein managed the circulatory status of the patient better than DFP during extracorporeal treatment. In the course of PP therapy xanthoma tuberosum markedly regressed, and the cardiac status of the patient was clearly improved.
Antibody‐mediated peripheral neuropathies associated with ARC and AIDS: Successful treatment with plasmapheresis
Authors: Kiprov Dobri , Pfaeffl Wolfgang , Parry Gareth , Lippert Randolph , Lang William , Miller Robert
Published: February 2007

Peripheral neuropathy is increasingly recognized in patients with AIDS as well as AIDS‐related complex (ARC). Thirty homosexual men with polyneuropathy were evaluated in this study. Twenty‐one had ARC and nine had AIDS. We observed three distinct clinical syndromes: distal sensorimotor polyneuropathy, chronic inflammatory demyelinating polyrediculoneuropathy (CIDP), and mononeuropathy multiplex.

Circulating antibodies to peripheral nerve tissues were found in all patients. In six patients, treatment with plasma exchange was undertaken because of severe, progressive weakness. Four patients with clinical, electoophys‐iologic, and histologic evidence of CIDP improved with plasma exchange, three regaining normal function.

These results suggest that the peripheral neuropathy associated with ARC and AIDS is immunotogically mediated and that plasma exchange is an effective treatment in a subgroup of patients with this disorder.
Predictive value of clinical, laboratory, pathologic, and treatment variables in steroid/lmmunosuppressive resistant lupus nephritis
Authors: Wallace Daniel J. , Goldfinger Dennis , Savage Gail , Nichols Sherri , Goodman David , Fichman Marshal , Stewart Morgan , Klinenberg James R.
Published: February 2007

Twenty‐seven patients with lupus nephritis and nephrotic syndrome had persistent disease activity despite an adequate trial of corticosteroids and immunosuppressive drugs; 30% were Asians, compared with 7% of our overall SLE population. Two years later, seven had a very good outcome and seven a poor outcome. Thirty clinical, pathological, laboratory, and treatment variables were analyzed in a good versus poor responder subset comparison in an effort to determine which factors were associated with favorable outcome. Administration of pulse steroids (P = .069) and a low biopsy chronicity index (P = .048) were associated with the good responder subset. Serum creatinine, biopsy class, blood pressure, complement, and anti‐DNA values at entry as well as the choice of immunosuppressive drug were not helpful in predicting outcome. All seven good responders were plasmapheresed (P = .026). Patients with refractory lupus nephritis who have a low biopsy chronicity index may benefit from the use of pulse steroids or plasmapheresis, and controlled studies are suggested.
Relief of respiratory distress with leukapheresis in a child with chronic myelocytic leukemia
Authors: Moxey‐Mims Marva M. , Luban Naomi L. C. , Bock Glenn H. , Ruley Edward J. , Preston Karen M.
Published: February 2007

Therapeutic leukapheresis of a 10‐year‐old girl with adult‐type chronic myelocytic leukemia is described. The efficiency of WBC removal was noted to improve significantly after addition of hydroxyethyl starch to the anticoagulant infusion. In fact, the percentage of white cells removed more than doubled (39% vs. 16%) when comparing procedures of similar duration, with and without the sedimenting agent. Of particular interest was the relief of the patient's respiratory distress concomitant with the decline in her leukocyte count, a finding that has not previously been documented in pediatric patients. The arterial oxygen pressure remained greater than 95 mmHg after the procedure with hydroxyethyl starch compared with 70 tnmHg after the procedures without it la addition, her respiratory rate decreased from 70 on admission to the low 20s after the final procedure. Leukapheresis with hydroxyethyl starch was shown to be a safe procedure, and the use of hydroxyethyl starch was shown to be of particular benefit for prevention of prolonged aphercsis procedures.
Treatment of hypercholesterolemia by chemical adsorption of lipoproteins
Authors: Yokoyama Shinji
Published: February 2007

Dextran sulfate (Mr 5,000) was covalently linked to porous cellulose beads, and the dissociation constant (Kd) and the maximum binding level (S) of the beads were calculated for the human plasma lipoproteins VLDL, LDL, and HDL. The S values for VLDL and LDL were 2 and 7 g cholesterol/liter of the wet beads and that for HDL was almost negligible, although the apparent Kd were all in the same order. In fact, LDL and VLDL were exclusively adsorbed by the beads from human plasma in vitro. Bound LDL was desorbed with 0.35 M Nacl. The beads were packed in a column (25‐ml) and used with polysulfone hollow fibers in experimental LDL‐apheresis for WHHL rabbits; LDL cholesterol was reduced from 500 to 200 mg/dl, while HDL, total plasma protein, and major blood cell counts did not change.

For LDL apheresis of familial hypercholesterolemia, the sorbent column, 400‐ml, was used with the polysulfone hollow fiber filter. The maximum removal of LDL + VLDL cholesterol was 6 to 8 g with a single column resulting in its reduction by 250 to 300 mg/dl after 3.5 liters plasma treatment. Adsorption was negligible with albumin, HDL, IgA, G, M, apoA‐I, A‐II, C‐II, enzymes, and electrolytes. Activated complement fragments, C3a, and Csa, were completely adsorbed. By periodic removal of LDL, an increase of HDL cholesterol was observed in some cases. In order to increase LDL removal in a single treatment and to reduce the extracorporeal circulation volume, two small columns (150 ml each) were used alternatively. The column saturated with LDL was washed with 0.7 M NaCl for regeneration while the other column was used. LDL + VLDL cholesterol decreased linearly to the treated plasma volume in semilogarithmic plot, showing that the LDL removal was optimized in mis system.
Removal of low‐density lipoproteins (LDL) and fibrinogen by precipitation with heparin at low pH: Clinical application and experience
Authors: Seidel D. , Armstrong V. W. , Schuff‐Werner P. , Eisenhauer T.
Published: February 2007

The clinical application of a new extracorporeal procedure (HELP) for the selective elimination of low‐density lipoproteins and fibrinogen by heparin precipitation at acid pH is described. Plasma, obtained by filtration of whole blood through a 0.2 μm filter is continuously mixed with an equal volume of an acetate buffer (pH 4.85) containing heparin. After removal of the precipitated heparin complex by filtration, excess heparin is adsorbed to a specially developed filter, and the dear plasma filtrate is subject to bicarbonate dialysis/ultrafiltraiion to restore physiologic pH and remove excess fluid. The calculated efficiency for the elimination of low‐density lipoproteins and fibrinogen from plasma by HELP is 100% and is therefore comparable to conventional plasmapheresis. However, the HELP system shows a high degree of specificity, with over 80% of total protein being returned to the patient. A total of over 350 treatment procedures have now been performed. Patient compliance and acceptance have been excellent, and no major complications have been observed. The system is therefore suitable for the treatment of severe hyper‐β‐lipoproteinemia; its use for the treatment of coronary heart disease is currently under investigation in a prospective multicenter study in which treatment efficiency will be controlled by coronary angiography on 45 patients treated with HELP over a period of 2 years.
Clinical uses of intravenous immune globulin: Immunoglobulin replacement therapy and treatment of autoimmune cytopenias
Authors: Sorensen Ricardo U. , Kallick Melissa O.
Published: February 2007

Intravenous immune globulin (IVIG) is indicated for IgG replacement in antibody deficiency syndromes and as immune‐regulatory therapy in some autoimmune diseases. Two case histories, illustrate both aspects of IVIG therapy.

1. Patient 1 is a 24‐year‐old male with agammaglobulinemia. He was successively treated with monthly IMIG, paternal plasma, and then over the last 5 years, IVIG. On IgG doses of 250 mg/kg q/4 weeks, IgG trough levels remained below 200 mg IgG/dl. IgG half‐life was reduced. Although asymptomatic for prolonged periods of time, he eventually developed clinically evident inflammatory bowel disease. Optimal IVIG replacement therapy requires normal IgG half‐life and adequate IgG bough levels.

2. Patient 2 is a 12‐year‐old girl with autoimmune neutropenia, recurrent skin infections, and items unresponsive to antibiotics and to steroid therapy. IVIG at a dose of 3,000 mg/IgG/kg over 3 days significantly increased her neutrophil count. Subsequently, she has required 1,000 mg/kg of IVIG q/4 weeks for maintenance. Antineutrophil autoantibodies have persisted. There is synergism of IVIG ‐with high doses of corticosteroids. The mechanism of action of IVIG seems to involve a blockage of the RES system.

IVIG therapy is safe even at high doses for most patients. However, anaphylactic reactions have been observed in IgA‐deficiem patients with IgE anti‐IgA antibodies. The full spectrum of therapeutic applications of IVIG is still being explored, for some patients self‐infusion of IVIG at home is an appealing treatment alternative.
A new approach to neocyte transfusion: Preliminary report
Authors: Kevy Sherwin V. , Jacobson May S. , Fosburg Martin , Renaud Melanie , Scanlon Anne , Carmen Raleigh , Nelson Edward
Published: February 2007

A method has been developed using phthalate oils to quality control units of young red cells (neocytes). Neocytes prepared by the NEOCEL system have a mean young red cell enrichment of 90% with only 3.4% less than 80%. Neocytes prepared in a Wood cell processor have an average enrichment of 81 % with 27% less than 75%. Based on a 12 month period, the patients as a group have received an average of 14% fewer transfusions and an 18% decrease in red cells per kg/yr as compared to frozen red cells.
Adoptive immunotherapy: Novel applications of blood cell separators
Authors: Klein Harvey G.
Published: February 2007

Animal models have demonstrated that syngeneic lymphocytes activated ex vivo and infused into animals with experimentally induced tumors can mediate tumor regression. This “adoptive immunotherapy” has been applied to patients with end‐stage malignancy refractory to standard therapy. Lymphocytes are collected with the blood cell separator, expanded in culture under the influence of cytokines such as interleukin‐2 (IL‐2), and reinfused into the patient under conditions similar to those used in the animal models. Studies from several centers using lymphokine‐activated killer (LAK) cells, involving more than 300 patients, have shown an overall response rate of greater than 15% and a complete response rate of approximately 10%. Renal cell carcinoma, melanoma, and lymphoma appear to be the cell types ?at respond best to such therapy. Toxicity in these phase 1 studies has been substantial, related primarily to high doses of intravenous IL‐2, and treatment‐related deaths have been reported. Adoptive immunotherapy using lymphocytes derived from surgically excised tumors, tumor‐infiltrating lymphocytes (TIL), is in the early stages of clinical trials, but this appears to offer a potentially more potent and specific approach than does LAK cell therapy. TIL have been shown to traffic to tumor sites and mediate tumor regression. The mechanisms of adoptive immunotherapy are poorly understood, but blood cell separators and storage technology are playing a critical role in the collection and processing of cells for these research applications.
Complete remission of paraneoplastic sensorimotor neuropathy: A case associated with small‐cell lung cancer responsive to chemotherapy, plasma exchange, and radiotherapy
Authors: Weissman David E. , Gottschall Jerome L.
Published: February 2007

A 61‐year‐old man was found to have small‐cell lung cancer following a 1‐year history of a progressive peripheral sensorimotor neuropathy. The neuropathy initially improved following chemotherapy, but subsequently progressed to the point of respiratory failure. Treatment with plasma exchange, additional chemotherapy, and radiotherapy resulted in a sustained complete tumor remission and neurologic recovery. The role of plasma exchange is unclear, but its use should be considered in cases of severe sensorimotor neuropathy unresponsive to antineoplastic treatment.
Assessment of bilirubin clearance capacity of a newly developed ion‐exchange adsorption column and its possible use as a supportive therapy in hepatorenal syndrome
Authors: Sone Jun , Saibara Toshiji , Himeno Hiromi , Yamasaki Kazuaki , Miyamoto Keiko , Maeda Takashi , Onishi Saburo , Yamamoto Yasutake , Park Keunsik , Okumiya Toshika , Sasaki Masahide
Published: February 2007

We assessed the bilirubin reduction capacity of three different types of devices in vitro: a high‐permeable membrane column for double‐filtration plasmapheresis (DFP) (Evaflux 2A, Kuraray, Japan), and non‐coated charcoal column for hemoperfusion (HP) (N‐180, Asahi Medical, Japan), and ion‐exchange columns for plasma adsorption (PA) (BR‐350, Asahi Medical, Japan, and B‐001, Kuraray, Japan). A column for DFP reduced the concentration of lowmolecular proteins effectively such as plasma bilirubin and bile acids in an albumin‐dependent manner. A charcoal column adsorbed low‐molecular substances preferentially. But in these two columns, the loss of fibrinogen is a limiting factor for determining the processing plasma volume. Ion‐exchange columns for PA adsorbed bile acids, disconjugated bilirubin, and monoconjugated bilirubin more efficiently compared with delta‐bilirubin and unconjugated bilirubin. Pretreatment of the column with heparin reduced the loss of fibrinogen to less than 10%. We applied the BR‐350 ion‐exchange column in vivo for treatment of three patients with hyperbilirubinemia. After treatment, an alcoholic hepatitis patient with the hepatorenal syndrome (HRS) recovered from acute renal failure. However, in a patient with primary biliary cirrhosis and in a patient with fulminant hepatitis, the decrease of serum bilirubin was transient and no obvious beneficial responses were noted. The capacity and ability of the BR‐350 column to adsorb plasma bilirubin was shown sufficient to treat deeply jaundiced patients, because 4 liters of the plasma of a patient with 108 mg/dl of initial total bilirubin concentration was able to be processed continuously without an obvious decrease in bilirubin adsorption capacity. Therefore, this column in combination with dialysis may be most applicable in lowering serum bilirubin concentration in the HRS.
Plateletpheresis with the COBE spectra single needle access option
Authors: McLeod Bruce C. , McKenna Rajalaxmi , Viernes Ann , Reed Susan , Owens E. Anne , Matayoshi Deborah , Moore Robert C.
Published: February 2007

A group of modifications, including a reservoir bag in the return circuit, has been devised to allow single needle plateletpheresis with the COBE Spectra. We compared the number and quality of platelets collected from 10 subjects in paired donations with single and dual needle protocols. There was no evidence of hemolysis with either protocol. Mean (±SD) platelet yields were 3.61 ± 1.47 × 1011 with two needles and 3.31 ± 1.31 × 1011 with the single needle procedure (P = .13). Mean leukocyte levels (standard manual counting chamber) were 1.0 ± 1.7 × 107 and 1.2 ± 1.0 × 107, respectively (p = .78). pH values during storage were acceptable in both groups of concentrates, and there were no significant differences between the single needle and dual needle concentrates in morphology scores or beta‐thromboglobulin levels at 0, 1, 3, or 5 days of storage. Thus the single needle modification produced platelets that were comparable in quantity and quality to those from the standard dual needle plateletpheresis protocol.
In vitro study of immunologic changes in long‐term cytapheresis donors
Authors: Prior Clive R. B. , Coghlan Patrick J. , Hall Jane M. , Jacobs Peter
Published: February 2007

Several in vitro measurements of immune function were examined retrospectively in a population of active long‐term cytapheresis donors (group I; n = 50) and the results were compared to age‐ and sex‐matched controls (group II; n = 50) who had donated only whole blood. In group I, significantly different mean absolute lymphocyte counts (P = .0025), total T‐cells (P = .0026) and T‐helper cells (P < .0001), and helper‐to‐suppressor ratios (P = .0279) were present. No differences were noted between the two groups for peripheral blood mean B‐cell count, T‐suppressor numbers, lymphocyte responsiveness to mitogens or alloantigen, and serum immunoglobulin level. The reduced mean absolute lymphocyte count in group I was due to the reduction in T‐helper cell numbers and accounted for the imbalance in the helper‐to‐suppressor ratio. These disturbances are currently unexplained and, while no clinical consequences have so far become evident, there is a need to continuously monitor the immunologic status of cytapheresis donors. It is also important to determine whether reversal of the defects occurs and, if so, over what time interval.
Concentration of bone marrow mononuclear cells using a programmable blood cell separator
Authors: Orlina Armando R. , Conant James C. , Dechristopher Phillip J. , Lin Abraham T. T.
Published: February 2007

Bone marrow was collected from adult patients with various solid tumors who consented to participate in a study of myelo‐ablative chemotherapy followed by autologous bone marrow rescue. Twenty marrow suspensions were processed by using standard Procedure 3 (PRO‐3) for lymphocytapheresis without modification. A modified Procedure 1 (M‐PRO‐1) for plateletpheresis was employed for processing 34 marrow suspensions. For PRO‐3, mononuclear cell (MNC) recovery was 68 ± 22% of the starting marrow suspension (baseline), in a concentrate volume of 234 ± 53 ml. MNC represented 59 ± 27% of the total WBC count of the concentrate. The residual volume of RBC was 49 ± 47 ml. For M‐PRO‐1, MNC recovery was 63 ± 22% of the baseline in a concentrate volume of 200 ± 8 ml. MNC comprised 94 ± 7% of the total WBC count of the concentrate. RBC contamination was 7 ± 3 ml. Hematopoietic recovery, defined as the post‐transplant days when a sustained granulocyte count of 500/μL and a platelet count of 50,000/μL were achieved, was similar in the two groups and comparable to other reports utilizing otter methods and equipment for bone marrow concentration. Personnel time was significantly reduced compared to other procedures for bone marrow concentration due to increased automation.

Although there was no significant difference in MNC recovery between the two groups (P > 0.5), M‐PRO‐1 was clearly superior to PRO‐3 because of the consistently high degree of purity of the MNC in the concentrate and minimal RBC contamination. M‐PRO‐1 is ideal in the setting of major ABO incompatible allogeneic marrow transplantation, marrow purging of malignant cells with 4‐HC, and in clinical situations where interim cryopreservation and storage of bone marrow are required.
Extracorporeal methods in lipid reduction pursuant to improvement in risk factors associated with atherosclerosis
Authors: Lobdell Donn D.
Published: February 2007

Atherosclerosis is the leading cause of death in the United States. Elevated plasma levels of low‐density lipoprotein and lipoprotein(a) [Lp(a)] and subnormal levels of high density lipoprotein are risk factors in atherosclerotic coronary heart disease. Extracorporeal methods of affecting these risk factors are reviewed. The limited information on the effects of apheresis procedures on Lp(a) is discussed and extended from a kinetic modeling approach. An estimate, made of the number of patients who could be expected to benefit from extracorporeal lipid lowering, is presented.
Severe post‐partum eclampsia: Response to plasma exchange
Authors: Stricker Raphael B. , Main Elliott K. , Kronfield Jack , Kallas Gail S. , Gerson Lauren B. , Autry Amy M. , Kiprov Dobri D.
Published: February 2007

In their severest forms, pre‐eclampsia and eclampsia may be life‐threatening complications of pregnancy. We describe a patient with severe post‐partum eclampsia characterized by seizures, deep coma, hypertension, renal insufficiency, coagulopathy, and microangiopathic hemolysis. The patient responded to treatment that included intensive plasma exchange, and she achieved full recovery. Our case supports the use of plasma exchange in patients with severe pre‐eclampsia and eclampsia. © 1992 Wiley‐Liss, Inc.
Life‐threatening reaction to staphylococcal protein A immunomodulation
Authors: Smith Roy E. , Gottschall Jerome L. , Pisciotta Anthony V.
Published: February 2007

We describe here a case of a severe, life‐threatening, serum sickness‐like reaction in a patient with refractory immune thrombocytopenia treated with protein A immunomodulation. © 1992 Wiley‐Liss, Inc.
Method for the safe and rapid pretransfusion warming of stored blood: An in vitro and in vivo evaluation of a radiofrequency (RF) instrument
Authors: Harrison G. G. , Bird A. R. , Jacobs P. , Coghlan P. , Byrne M. J. , Ozinsky J. , Besseling J. L.
Published: February 2007

Inadvertent hypothermia due to massive infusion of stored blood can be prevented by pretransfusion warming. One approach is the heating of individual packs by means of electromagnetic conduction, which is a method safely used over the last 25 years. The prototype instrument, which has now been re‐engineered, can effectively raise the temperature of a unit of blood to approximately 33°C in less than 3 minutes. Using this new model, we found, in vitro, a modest increase in free plasma haemoglobin, but this was not accompanied by any change in potassium or lactic dehydrogenase levels and the mean red cell fragility was unaltered. In vivo, the survival of autologous red cells that had been stored for 33 days and then infused as a concentrate, having a mean haematocrit of 0.60, was measured at 24 hours and 21 days. Each donor acted as his own control. In paired studies, pretransfusion radiofrequency heating was shown to have no deleterious effect when compared to measurements using the unwarmed blood pack. It is concluded that this method can be recommended as safe. © 1992 Wiley‐Liss, Inc.
Three years with a national apheresis registry
Authors: Schmitt Eberhard , Kundt Günter , Klinkmann Horst
Published: February 2007

The large number of unsolved problems in plasma exchange therapy makes an apheresis registry appear useful. The results of such an open prospective observational study from 1987 to 1989 in East Germany are presented in this paper. With 1,945 procedures in a total of 419 patients (on average 4.1 treatments per patient) about 80% of all treatments in the country were registered. Exchange volume averaged 2.7 (± 0.78) 1 or 43 (± 13.9) ml/kg body weight. Substitutes were albumin (51% of the cases), FFP (22%), and both (22%), Nephrological (25%) and neurological (23%) diagnoses prevailed among the treated diseases. Haematologic diseases (12%) were underrepresented and hepatic coma (20%) was overrepresented. Minor side effects occurred in 22% of all treatments and severe complications in 38 treatments (2%). Four fatalities probably resulted from plasmapheresis therapy. The registry permits an assessment of the treatment results and of several trends during the period of observation. © 1992 Wiley‐Liss, Inc.
Plasma exchange versus an affinity column for cholesterol reduction
Authors: Burgstaler Edwin A. , Pineda Alvaro A.
Published: February 2007

The recent introduction of low‐density lipoprotein (LDL)/very low‐density lipoprotein (VLDL) selective‐removal systems offers an alternative to plasma exchange (PE). For the last 10 years, we have treated a inale homozygous hypercholesterolemia type IIA patient with PE using 5% normal serum albumin (NSA) replacement. PE using 6% hydroxyethyl starch (HES) replacement, single dextran sulfate cellulose bead affinity column (DSAC) (Kaneka LA‐40), and double DSAC. This report compares the performance of these systems in cholesterol reduction (total, LDL + VLDL), and high‐density lipoprotein [HDL] and their effect on the total protein, albumin, and hematocrit levels. The number of procedures and average volume of plasma treated using PE‐NSA, PE‐HES, I‐DSAC, and 2‐DSAC were 113, 64, 15, 90 and 3,939, 3,270, 3,519. and 3,588 ml, respectively. The average pretreatment total cholesterol levels were baseline 864 mg/dL, PE‐NSA 606 mg/dL, PE‐HES 610 mg/dL, I‐DSAC 467 mg/dL, and 2‐DSAC 395 mg/dL with plasma reductions of 59%, S7%, 47%, and SS%, respectively. Average LDL + VLDL plasma reductions were PE‐NSA 58%, PE‐HES 59% (N = I), I‐DSAC 4670, and 2‐DSAC 56%. Average HDL plasma reductions were PE‐NSA 58%, PE‐HES 69% (N = I ), I‐DSAC 58, and 2‐DSAC 17%. The average total cholesterol and LDL + VLDL reductions were comparable for both types of PE and the 2‐DSAC system. The average HDL loss was 53% lower for the DSAC systems than for PE systems. Of the four systems compared in this study, the 2‐DSAC system offers equivalent efficiency in LDL + VLDL reductions as PE while retaining more of the beneficial HDL than PE without the use of replacement solutions. © 1992 Wiley‐Liss, Inc.
A fully automated method for mononuclear bone marrow cell concentration
Authors: Rodriguez J. M. , Carmona M. , Noguerol P. , Ruiz M. , Parody R. , Vidal F. , Perez‐Hurtado J. M. , Espigado I.
Published: February 2007

We describe our experience in processing 40 bone marrow aspirates harvested for autotransplantation from patients with several hematological diseases using the CS‐3000 blood cell separator. The bone marrow of the first 30 patients was processed by a semiautomated method, and a fully automated procedure was used for the remaining 10 cases.

Both procedures were developed in our laboratory and yielded a similar average mononuclear cell recovery of 87.78% and 86.98%, respectively, and similar nucleated cell recovery (27.39% and 27.11%). The cloning efficiency of hematopoietic progenitor cells, measured as the total CFU‐GM colony recovery in the in vitro cultures, did not differ between processed and recovered mononuclear cells. On the other hand, all the patients with transplants showed complete hematologic recovery, and the time to engraftment was similar to that described for other procedures. The automated procedure resulted in an average red cell removal of 97.81%, similar to the semiautomated procedure (94.19%), though with a narrower range (96.31–98.6% vs. 80.34–98.34%). The time taken to process a similar amount of bone marrow cell suspension was very different for each method: 1 hour for the fully automated vs. 2 1/2 hours for the semiautomated method to process 1.000 ml. Furthermore, the semiautomated procedure required the addition of homologous or irradiated plasma in a laminar air flow chamber, while the automated method is performed in a closed sterile system. We conclude that our procedure using the CS‐3000 processor is an efficient method for fully automated large‐scale processing of human bone marrow cells. © 1992 Wiley‐Liss, Inc.
Quality assurance and standards in hematopoietic progenitor processing
Authors: Bennett Sterling T. , Johnson Nancy L. , Lasky Larry C.
Published: February 2007

Bone marrow transplantation is an increasingly important therapeutic procedure. As more laboratories have become involved in the processing of hematopoietic progenitor cells from marrow or blood, it has been recognized that standards are required for hematopoietic progenitor processing, storage, and handling. Quality assurance is the process of monitoring whether laboratory procedures, equipment, and personnel fulfill their expected functions, and the aim of quality assurance is to ensure compliance with standards. Some standards for hematopoietic progenitor processing have recently been issued by professional organizations. Although these standards are not comprehensive, where applicable they should be met or exceeded. In the absence of published standards, principles of good laboratory practice should guide quality assurance programs. This article, presents concepts of quality assurance in hematopoietic progenitor processing, based on standard laboratory practice and published standards. © 1992 Wiley‐Liss, Inc.
Basic principles of the ABO and Rh blood group systems for hemapheresis practitioners
Authors: Sigmon Janice M.
Published: February 2007

Since 1901, more than 20 distinct blood group systems have been identified and characterized. Yet, the ABO System, the first described, remains the most clinically significant in blood transfusion and organ transplantation medicine. The ABO antigens are the only cellular antigens which consistently produce a potent, naturally occurring antithetical antibody which circulates in the plasma of healthy individuals. ABO antigens are expressed on most blood cells, organs, and tissues and in most body fluids. Expression of the antigens results from the interaction of several separate, but closely related genes: ABO. H. and Secretor (Se). Blood group specificity depends upon the inheritance of the ABO and H genes, and the subsequent expression of these antigens on the red blood cells. The “D” or Rh0 antigen is the most clinically significant blood group antigen next to the ABO antigens. The D antigen belongs to the Rh System, which consists of a trio of genes that are so closely linked that they are inherited as a package. The antigens are an integral part of the red blood cell membrane. They lend stability to the membrane structure when they are normal, but result in decreased red cell survival when absent. Rh antibodies are immune antibodies requiring a stimulus and can cause significant transfusion and childbearing complications if present. © 1992 Wiley‐Liss, Inc.
Evaluation of platelets collected by a new portable apheresis device
Authors: Szymanski Irma O. , Ciavarella David , Rososhansky Sarah , Napychank Paula A. , Snyder Edward M.
Published: February 2007

We studied the efficiency of platelet collection by the Mobile Collection System (MCS) using two types of experimental protocols and evaluated the effect of storage at 22°C on the platelet concentrates (PC). MCS is a new blood cell separator that combines discontinuous flow features with a new computerized operating system and can be used to harvest either full units of apheresis PC (SDP protocol) or half units of PC together with one to two units of plasma (PLP protocol). On the average, 1.98 × 1011 ± 0.46 × 1011 (mean ± SD) platelets were obtained by the PLP protocol and 3.01 × 1011 ± 0.70 × 1011 and 4.2 × 1011 ± 1.12 × 1011 by the early and later versions of the SDP protocols, respectively. The mean number of WBC per PC ranged from 3.3 to 4.7 × 108. During the storage period pH stayed above 7.0. On the average, the production of one molecule of lactate corresponded to the consumption of 0.538 molecules of glucose, indicating that less than 8% of glucose was consumed by the oxidative pathway. There were only small increases in LDH and B thromboglobulin concentrations. Furthermore, the ability of platelets to recover from osmotic shock and to aggregate following exposure to dual agonists declined only slightly during storage, indicating that both viability and function of platelets collected by the MCS were preserved during storage. © 1993 Wiley‐Liss, Inc.
Comparison of demographics and motivations of highly committed whole blood and platelet donors
Authors: Julius C. J. , Sytsma S. R.
Published: February 2007

To compare donor demographics and motivations for donation, we surveyed 159 consecutive whole blood donors (WD) and 146 consecutive plateletpheresis donors. All donors had donation experiences of at least 2 gallons (i.e., 16 previous donations). Evaluation of answers to fixed‐response and open‐ended questions revealed no difference between the two groups in age, type of wages, compensation by employer, “time off” for donation, and church or volunteer organization memberships. The two groups differed in that the platelet donor (PD) group had a higher percentage of males than females (PD group 72.6% males and 27.4% females versus WD group 59% males and 41% females [chi‐square = .01]).

PDs most often began donating platelets because they were asked (22.6%), demonstrating the importance of active recruitment. When asked why they do not donate platelet products by apheresis, highly committed WDs reported lack of time (25%), lack of knowledge (“Don't know about it,” 21%), lack of recruitment (“No one asked,” 18.5%), or lack of awareness (“Never thought about it,” 5%) as reasons.

Factors centering on time constraints, lack of knowledge or awareness about platelet donation by apheresis, and lack of active recruitment prohibit highly committed WDs from entering into plateletpheresis programs. © 1993 Wiley‐Liss, Inc.