Preserved erythrocytes undergo several changes during storage, collectively referred to as the storage lesion, which reduce the effectiveness of stored erythrocytes following transfusion. This review describes the mechanisms leading to these changes, so far as they are known, and discusses the relationship of the changes to one another and how they contribute to the diminished function of stored erythrocytes.
The belief that lymphocytes and autoantibodies that react with antigens of the host necessarily lead to autoimmune disease has given way to the now well-recognized finding that self-reactivity occurs regularly in healthy individuals. Autoreactivity to major histocompatibility complex products is even necessary, to generate an immune response against non-self antigens (Zinkernagel-Doherty phenomenon). Although self-recognition is a prerequisite for autoimmune disease, it is not sufficient grounds for clinically manifest autoaggression, and currently, major research effort is dedicated to a better understanding of the downregulating factors of physiological autoimmunity. Both cellular and humoral mechanisms participate in the control of autoimmunity. First, as an advance post, the T lymphocyte receptor for antigens already is part of signal resistance: Clonespecific proliferation with suppression of uninvolved T lymphocytes is a major consequence of its activation. The study of B lymphocyte downregulation is more difficult, because these cells may become activated through a larger variety of pathways (antigen-dependent or independent) than T lymphocytes, including T helper cells, polyclqnal B cell activator sub-
The symposium “Haemapheresis” was held on 10 September 1987 in Dordrecht, The Netherlands, celebrating the 10th anniversary of the Blood Bank “Zuid-West Nederland”. Various aspects of donor and of therapeutic apheresis were discussed.
The aim of this study was to evaluate the QuickVue® RSV Test Kit (QUIDEL Corp, CA, USA) as a screening tool for respiratory syncytial virus in children with acute respiratory disease in comparison with the indirect immunofluorescence assay as gold standard. In Brazil, rapid antigen detection tests for respiratory syncytial virus are not routinely utilized as a diagnostic tool, except for the diagnosis of dengue and influenza.The authors retrospectively analyzed 486 nasopharyngeal aspirate samples from children under age 5 with acute respiratory infection, between December 2013 and August 2014, the samples were analyzed by indirect immunofluorescence assay and QuickVue® RSV Test kit. Samples with discordant results were analyzed by real time PCR and nucleotide sequencing.From 313 positive samples by immunofluorescence assays, 282 (90%) were also positive by the rapid antigen detection test, two were positive only by rapid antigen detection test, 33 were positive only by immunofluorescence assays, and 171 were positive by both methods. The 35 samples with discordant results were analyzed by real time PCR; the two samples positive only by rapid antigen detection test and the five positive only by immunofluorescence assays were also positive by real time PCR. There was no relation between the negativity by QuickVue® RSV Test and viral load or specific strain. The QuickVue® RSV Test showed sensitivity of 90%, specificity of 98.8%, predictive positive value of 99.3%, and negative predictive value of 94.6%, with accuracy of 93.2% and agreement κ index of 0.85 in comparison to immunofluorescence assay.This study demonstrated that the QuickVue® RSV Test Kit can be effective in early detection of Respiratory syncytial virus in nasopharyngeal aspirate and is reliable for use as a diagnostic tool in pediatrics.Avaliar o teste QuickVue® RSV Test Kit (QUIDEL Corp, CA, EUA) para o diagnóstico rápido do vírus sincicial respiratório em crianças com doença respiratória aguda, comparando-o com a imunofluorescência indireta como padrão ouro. Visto que, no Brasil, testes rápidos para detecção de antígenos para vírus sincicial respiratório não são rotineiramente utilizados como ferramenta de diagnóstico, exceto para Dengue e Influenza.Um total de 486 amostras de aspirado de nasofaringe de crianças menores de 5 anos com doença respiratória aguda, coletadas entre dezembro de 2013 e agosto de 2014, foram analisadas por imunofluorescência e pelo teste QuickVue®. Amostras com resultados discordantes entre os métodos foram submetidas a PCR em tempo real e sequenciamento.Das 313 amostras positivas por IFI, 282 foram positivas no teste rápido (90%), 2 amostras foram positivas apenas no teste rápido (0.6%), 33 apenas na imunofluorescência (10.5%) e 171 foram negativas em ambos os métodos. As 35 amostras com resultados discordantes foram testadas por PCR em tempo real, sendo que duas que foram positivas apenas no teste rápido e 5 apenas na imunofluorescência confirmaram-se positivas. Não houve relação entre a ausência de positividade no teste QuickVue® com a carga ou com a cepa viral. O teste QuickVue® mostrou sensibilidade de 90.1%, especificidade 98.9%, valor preditivo positivo 99.3%, valor preditivo negativo de 94.6%, acurácia de 93.2% e índice κ de concordância de 0.85 em comparação à imunofluorescência.Nosso estudo demonstrou que o teste QuickVue® RSV pode ser efetivo na detecção precoce do vírus sincicial respiratório em amostras de aspirado de nasofaringe e é confiável como uma ferramenta de diagnósticos em pediatria.
Elevation of blood cholesterol, low-density lipoproteins (LDL) and apolipoprotein B (apoB) are hallmarks of familial hypercholesterolemia (FH), a genetic condition caused by the defective functioning of the cellular receptor for apoB-100 in LDL. ApoB-100 is also present in lipoprotein(a) (Lp(a)). In this lipoprotein, apoB-100 is linked to a plasminogen-like protein called apo(a). By direct comparison of the Lp(a) and apoB plasma concentrations in 28 affected and 31 unaffected members of seven families carrying the FH trait and without history of coronary artery disease, we reached the conclusion that LDL receptor activity is not a major determinant of the Lp(a) plasma levels in these subjects. This suggests that the molecular determinants for catabolism of Lp(a) are not the same as those for LDL. Consistent with this view is our observation that the turnover rate of Lp(a) and of LDL apoB, calculated from their rate of reappearance in plasma following Lp(a)/LDL apheresis, differ greatly.
We studied serum lipids during and shortly after a single plasma exchange (PE) on seven separate occasions in four patients, and during long-term treatment by regular PE in three patients with heterozygous familial hypercholesterolemia. Also, a comparison was made for efficacy in lipid and apolipoprotein removal between long-term weekly PE therapy and three consecutive weekly low-density lipoprotein (LDL) filtration procedures in one patient. PE was done by intermittentflow centrifugation (IFC) with Haemonetics V50 apparatus, exchanging one plasma volume. LDL filtration consisted of a cascade PE, in which the plasma was separated by IFC and the LDL fraction was subsequently removed by membrane filtration over a polyalcohol filter (Evaflux®). From the results, we concluded that (1) LDL cholesterol is reduced about 50% by both methods; (2) after PE, high-density lipoprotein (HDL) cholesterol does not increase during the first two hours, but rises thereafter faster than LDL cholesterol and can reach baseline within three days; (3) by LDL filtration, HDL cholesterol decreases about 30% less than LDL cholesterol and tends to increase above the starting levels found during weekly PE treatment; (4) the reductions in LDL and HDL cholesterol are larger than those in apolipoprotein B and A-I, respectively, in both methods; and (5) connection of the LDL filter device to the Haemonetics V50 system simplifies the cascade procedure, resulting in a single needle approach and avoidance of hemolysis in the primary plasma separation.
The morphologic alterations of progressive posterior uveitis observed in the chorioid, retina, and subsequently in the vascular system are generally controlled by hemorheologic and/or anti-inflammatory/ immunosuppressive drug therapy. Plasma exchange therapy using 5% serum albumin or serum preserve also appears to be indicated if these conventional treatments do not suffice and if side effects of the drugs applied limit their efficacy, as has been shown from the experience of 22 patients treated. The mechanisms discussed are: elimination of an underlying pathogenic substance, immunomodulatory effects of the plasma exchange fluids, and an improvement of the blood rheology. Further work needs to be done to evaluate the different variables under consideration.
The extent and degree of coronary atherosclerosis may be assessed by indirect parameters and by direct angiographic measurements. Determinations of the hemodynamic significance and properties of coronary stenoses by classical fluid dynamics, and semi-quantitative evaluation of regional hypoperfusion or abnormalities of metabolism and of regional contractile performance are indirect parameters, that do not provide precise information on progression or regression of coronary atherosclerosis. To obtain reliable and reproducible angiographic measurements of coronary stenoses, angiographic pitfalls (film exposure and processing as well as distance of the patient to x-ray tube and image intensifier must be constant, pincushion distortion must be compensated for, standard reference must be used), physiological variables (respiratory and cardiac cycle and coronary vascular tone must be identical on repeat films, slitlike stenoses must be visualized in different projections), and problems with the measurement procedure itself (reproducibility is important, inter- and intra-observer variability must be minimized, stenosis dynamics and plaque volume can only be quantitated by a computer system) have to be overcome or be compensated for. Using a standardized angiographic protocol, we were able to follow progression and regression in a cohort of 10 patients with familial hypercholesterolemia IIa, who were successfully treated with long-term specific LDL-cholesterol immunoabsorption (LDL-apheresis), that favorably influenced the long-term atherosclerotic activity in the coronary arteries of these patients.
Cytapheresis of progenitor cells and immature granulocytes was employed in the initial management of a pregnant patient with Chronic Myelogenous Leukemia (CML). A semicontinuousflow blood cell separator was used; no sedimenting agents were applied. Over a period of 16 weeks the patient underwent 15 therapeutic Cytapheresis. Mean efficiency for CFU-GM was 72% and for mature granulocytes 8%. Hb loss per session was equivalent to 80 mL of whole blood and transfusion was unnecessary.
A middle-aged female with posttransfusion purpura (PTP), serologically proven to be associated with anti-PLAI antibody was treated successfully with high-dose intravenous immunoglobulin (IVIG). Normalization of the Platelet Associated IgG-antibody (PAIgG) correlated with peak platelet count on day 6 of therapy. Anti-PLAI antibody was detectable until week 5 of the follow-up period. Impaired pre-therapy lymphocyte transformation with Phytohemagglutinin (PHA) corrected with the disappearance of the Anti-PLAI antibody.
We used the Fenwal CS-3000 cell separator to harvest units of neocytes for transfusion in patients with chronic hemolytic anemia. Neocyte enrichment was evaluated by reticulocyte count. These units were contaminated by a large number of leukocytes. In order to minimize immunization to HLA-antigens, these cells could be eliminated by an additional freeze-thaw-wash procedure. To determine the clinical effectiveness, four patients were transfused with neocyte concentrates over a period of six months. This study fails to show a significant benefit of neocyte transfusion, although there was a trend in terms of transfusion requirement.
Loiasis is endemic in the tropical rain forest of Central and some parts of West Africa and is transmitted by the insect vector Chrysops silacea and Chrysops dimidiata. Loa loa infestation causes local inflammation due to migrating adult worms in the subcutis (Calabar swelling) and in the conjunctivae (eye worm). The diagnosis is made by the demonstration of circulating blood microfilariae, the larvae of the adult worms. Since the density of the microfilariae is very low, they can only be identified by concentration methods, such as hemofiltration. During treatment with the specific antiparasitic drug (diethylcarbamazine, DEC), side effects such as allergic reactions due to the rapid disruption of circulating microfilariae may occur. Those symptoms are aggravated in patients with a high number of larvae, leading to meningo-encephalomyelitis or even death.1
Autoimmune thrombocytopenia, ITP, is a bleeding tendency in which antiplatelet antibodies cause severe thrombocytopenia. In children there is an 80% chance that platelet counts will return to normal levels within 6 to 12 months. Therefore treatment is directed at maintaining a safe platelet count until spontaneous improvement occurs. Adults have a worse natural history and a high percent undergo splenectomy within 3 months of diagnosis. The 10 to 20% of patients not responding to splenectomy are the hard ones to treat and have many alternative therapies, none of which have been proven to be curative and all of which have at least some drawbacks.
Prior to 1980 the drug therapy of hereditary hypercholesterolaemia was, as compared to nowadays standards, rather limited. There was virtually no effective therapy for homozygous patients, though plasma exchange introduced in France and Britain, demonstrated the use-fullness of the introduction of apheresis techniques. Parallel to the improvement of cholesterol lowering drug therapy for heterozygous patients, apheresis was developed as therapeutic affinity chromatography since 1980 at the university of Cologne for both homozygous and therapy refractory heterozygous patients. This development was named LDL-Apheresis based on the specificity for the removal of Apoprotein B bound cholesterol, the capacity due to the development of a repetitive cycling technique and the economy determined from the reuse of affinity chromatography columns for each single patient. The capacity of the system allowed for the introduction of new standards of post-treatment values such as 100 mg/dl total cholesterol or alternatively 50 mg/dl LDL-cholesterol and if cholesterol lowering drugs can also applied for a limited extent the rebound can be also slowed down. After 33 years of experience with seven homozygotes and 32 heterozygotes without treatment alternative, we found that in addition to the improvement of the quality of live the extension of live expectancy are the real proof of a therapeutic success as compared to other diagnostic procedures. The average live expectancy of our seven homozygous patients is 45.6 years; our oldest heterozygous patient is 81 years. There are no comparable long term data at present available neither from studies using drugs nor from subsequently developed apheresis techniques which also removed LDL-cholesterol together with plasma constituents not participating in the development of atherosclerosis. Also two homozygous patients giving birth to four children without complication support our concept of aggressive cholesterol lowering therapy being without major side effects (3–4% minor undesired reactions).
The normal circulating platelet probably exists in a state of minimal activation and low metabolic rate. The combined effects of continuous exposure to inhibitors (such as prostacyclin from the endothelial wallId) and the relative absence of agonists (such as thrombin), as well as contact with the nonthrombogenic endothelial surface, all work to limit activation. As a result, the platelet disc shape is maintained and there may be little accumulation of surface “opsonizing” molecules (such as IgG4) which might promote platelet clearance. Also, platelet surface glycoproteins are left intact and foster continued circulation. The collection, preparation, and storage of platelets for transfusion exposes these cells to an activating environment. Initially, the whole blood containing plasma and platelets is swept along an un-anticoagulated, foreign surface (the tubing) generating thrombins and consuming soluble phase Factor VIII.6 The platelets are then pelleted into close cell contact in the presence of low ionized calcium; an environment which promotes activation through the thromboxane
The best apheretic approach to myasthenia gravis is the selective removal of antiacetylcholine receptor antibodies (antiAchR-Ab) from plasma. A new tryptophan-linked polyvinyl-alcohol gel recently reported to be able to adsorb IgG autoantibodies semiselectively from plasma was investigated in vitro. A consistent reduction of antiAchR-Ab ranging from 76% to 100% was observed in all plasma samples tested. Various degrees of reduction of other immunoglobulins were noted. The regeneration of the immunocolumn did not reduce the efficiency in autoantibody removal. Further in vitro and in vivo investigations are needed to confirm the clinical usefulness of this promising apheretic approach to myasthenia gravis.
