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PubMed2003

[Blood substitutes--current evidence].

The aim to find an artificial substitute for human blood has failed in the past 70 years and will most probably fail in the following future. Genomics, proteomics and posttranslational research have revealed that blood is our most complex and highly coordinated organ. Plasma substitutes can only promote a single function of plasma: the blood volume replacement. The even more complex coordination of the intraerythrocytic hemoglobin functions based on the allosteric structural changes induced by binding of O2, CO2 and NO can not be replaced safely by artificial oxygen carriers. Cell-free haemoglobin binds NO, which under physiological conditions coordinates O2 supply with the respiratory cycle and vasomotor function. The binding of NO to haemoglobin results in hypertonic crisis and in increase of leukocyte adherence and platelet aggregation. These complications may have a fatal outcome.

Blood Substitutes↗
PubMedDate not supplied

[Successful treatment of patients with thrombotic thrombocytopenic purpura].

The paper presents the case of a 23 years old patient diagnosed with thrombotic thrombocytopenic purpura on the basis of increased body temperature, thrombocytopenia, microangoipathic hemolytic anemia, renal function disorders and a rapid development of coma after the epileptic seizure of Jacsonian type. The treatment included the therapy with antithrombocytic drugs such as lysin acetysalicylate, dipridamol, methylprednisolon, and other symptomatic and substitutional therapies. Fifteen therapeutic plasmaphereses were made with the replacement of 33.150 ml of plasma substituted with albumin and freshly frozen plasma (20.080 ml totally). The applied therapy gradually improved patient's neurologic finding. The patient was discharged from the hospital with normal neurological finding and magnetic resonance of the brain. In the conclusion we emphasize the importance of therapeutic replacement of plasma with the infusion of freshly frozen plasma, antithrombocytic therapy and the application of corticosteroids in the treatment of thrombotic thrombocytopenic purpura.

Adult↗
PubMed2000

Reduction of the antigenicity of factor VIII toward complex inhibitory antibody plasmas using multiply-substituted hybrid human/porcine factor VIII molecules.

Factor VIII (fVIII) circulates as a heavy chain/light chain (A1-A2-B/ap-A3-C1-C2) heterodimer. The 41-residue light chain activation peptide, ap, is cleaved from fVIII during proteolytic activation by thrombin or factor Xa. We constructed 7 active recombinant hybrid B-domainless human/porcine fVIII molecules that contained combinations of porcine sequence replacements within the A2, ap-A3, and C2 domains. The cross-reactivity of 23 high-titer inhibitory antibodies between human fVIII and the hybrids was inversely related to the degree of porcine substitution. In all plasmas, the substitution of all 3 regions yielded cross-reactivities that were not significantly different from those of porcine fVIII. To differentiate between inhibitor binding to the ap region and the A3 domain, we constructed 2 additional hybrids that contained porcine A2 and C2 domain substitutions and either porcine A3 or porcine ap substitutions. The porcine ap segment was less antigenic than the human ap segment in several plasmas that had activity against the ap-A3 region. This indicates that some inhibitor plasmas contain antibodies directed against the fVIII ap segment in addition to A2, A3, and C2 domain epitopes identified in previous studies. Substitution of porcine sequences within the A2, A3, C2, and ap regions of human fVIII is necessary and sufficient to achieve a maximal reduction in antigenicity relative to porcine fVIII with respect to most inhibitory antibody plasmas. (Blood. 2000;95:564-568)

Animals↗
PubMed1981

Effects of increased plasma viscosity and red blood cell aggregation on blood viscosity in vivo.

The effects of increased plasma viscosity and induced red blood cell (RBC) aggregation on apparent viscosity of blood in vivo in the skeletal muscle of the dog were studied. Apparent viscosity in vivo was determined in the isolated and vasodilated calf muscles of one hindlimb by comparing pressure-flow relationships for RBC suspensions with pressure-flow relationships for a Newtonian solution of known viscosity. RBC suspensions of increased plasma viscosity with and without RBC aggregation were obtained by substituting plasma with isoviscous solutions of high- and low-molecular-weight dextran in saline. Hematocrits of the suspensions were adjusted to either 45 or 60%. The viscosities of the suspensions in vitro were determined in a Wells-Brookfield viscometer. Apparent viscosity of blood in vivo was found to be mainly dependent on the viscosity of plasma. RBC aggregation had no significant influence on the viscosity in vivo.

Animals↗
PubMed2002

Hemoglobin-based oxygen carriers do not alter platelet functions: study of three chemically modified hemoglobin solutions.

OBJECTIVE: Chemically modified hemoglobins are being developed as potential oxygen-carrying blood substitutes (HBOCs). Clinical and preclinical data demonstrate the vasoactive properties of HBOCs by trapping of nitric oxide, which is also known to have platelet inhibitory activities properties. This study evaluated the effects of three structurally different HBOCs (Hb-Dex-BTC, alphaalpha-Hb, and o-raffinose-poly-Hb) on platelet functions in vitro to compare to those elicited by plasma substitutes, such as hydroxyethylstarch. DESIGN: Platelet activation state was assessed using platelet-rich plasma diluted to 20% (v/v) with the different solutions, by main measuring glycoproteins (GPIb, GPIIb/IIIa, and P-selectin) using flow cytometry. Aggregation was assessed by impedance aggregometry on whole blood hemodiluted to 20% (v/v) with the solutions. SETTING: Biological hematology department of the university hospital of Nancy-Brabois. PATIENTS AND PARTICIPANTS: Ten healthy volunteers consent and informed of the study who denied taking any drugs at the time of the experiment. MEASUREMENTS AND RESULTS: None of these solutions induced activation nor modified reactivity of platelets as measured by the surface expression of glycoproteins GPIb, GPIIb/IIIa, and P-selectin. Moreover, none of these solutions induced platelet aggregation when added alone, nor modified the aggregation patterns of platelets induced by collagen (0.5 microg/ml) and thrombin receptor agonist peptide (12.5 microM). CONCLUSIONS: The three tested structurally different HBOCs, as with hydroxyethylstarch, did not alter platelet functions in vitro.

Blood Platelets↗
PubMed1980

A blood component program for the treatment of surgical haemorrhage and its potential for national supplies of albumin and factor VIII.

For medical as well as logistic reasons, the importance of blood component therapy is rapidly increasing. The use of red cell concentrates in conjunction with an appropriate plasma substitute for the treatment of surgical haemorrhage "liberates" substantial quantities of plasma for the fractionation to derivatives, among which albumin and factor VIII are particularly needed. The experience obtained in Berne with the application of this principle is presented and its implications for the coverage of national demands for albumin and factor VIII are discussed.

Blood Transfusion↗
PubMed2000

Apheresis registry in France: indications, techniques, and complications. French Registry Study Group.

The French Registry for Plasma Exchange (PE) was set up in 1985. For 13 years it has allowed for the analysis of the techniques used, along with the indications and complications. After a decrease in the number of participating centers due to the heaviness of the data collection mode, the telematic network created in 1991 led to a new increase in participants from 26 in 1990 to 69 in 1998. Follow-up shows a slight fall in activity since some protocols ended, while the neurological pathologies remain the most frequent indicators. The important modifications observed over the years are the increase of the centrifugation technique, the development of plasma treatment, and the plasma substitution by an association of albumin-pentastarch. The French Registry for plasma exchange is the largest data base dealing with therapeutic hemapheresis. The registry set-up through the internet is the first step toward an international data base.

Blood Component Removal↗
PubMed1986

Effectiveness of treatment of children with hypogammaglobulinemia: comparison of fresh plasma and intravenous immunoglobulin preparation.

Eight children aged 2 to 16 years who were diagnosed as having primary humoral immunodeficiency were treated with fresh plasma substitution, during the first 2 years. Subsequently these children and 5 other children with primary humoral immunodeficiency (ID) were treated during the next 10 months with intravenous preparation of IgG. Eight children received doses of 500 mg/kg body weight (group A), while five children received doses of 150 mg/kg (group B) at monthly intervals. After five months of this therapy the average increase of IgG concentration was in group A--395 mg/dl, while in group B--100 mg/dl, the difference being statistically significant. Substitution therapy with intravenous IgG was more effective than therapy with fresh plasma and caused appreciable clinical improvement. Only in one out of 130 cases of intravenous injections mild post-transfusion reaction was observed.

Adolescent↗
PubMed1986

Therapeutic plasmapheresis and plasma exchange.

Plasma exchange is a process in which large volumes of plasma, usually equivalent to one plasma volume, are exchanged with donor plasma or a plasma substitute. This permits the removal of antibody, immune complexes, inflammatory mediators, paraproteins, drugs, toxins, and other plasma constituents. Plasma exchange may also have an effect on the immune system by enhancing the function of the reticuloendothelial system, removing blocking antibody, increasing clearance of tumor cells, and making lymphocytes more vulnerable to immunosuppressive drugs. Over 100 diseases have been treated with plasma exchange with variable success. Results of controlled studies are less dramatic than those of earlier uncontrolled case reports. Reports of complications and even death have tempered initial enthusiasm. Now, over a decade since the initial promising reports began to appear in the literature, the role of plasma exchange remains undefined.

Amyotrophic Lateral Sclerosis↗
PubMed1988

Hemoglobin: a lifesaver and an oxidant. How to tip the balance.

Hemoglobin solutions were assessed in terms of their ability to promote lipid peroxidation, which was quantitated by measuring the formation of thiobarbituric acid reactive substances (TBARS) under specified conditions in murine brain homogenates. Solutions designed for use in acute treatment of hypovolemic shock and trauma should incorporate ingredients specifically aimed at decreasing oxygen and lipid radical mediated injury occurring secondary to ischemia and reperfusion. A number of strategies aimed at decreasing the oxidant effect of hemoglobin solutions and other blood and plasma substitutes have been evaluated. These include use of the naturally occurring anti-oxidants in human plasma, specifically transferrin and ceruloplasmin. Similarly, certain iron chelators, such as deferoxamine (Desferal, Ciba-Geigy), effectively prevent molecular and cellular damage caused by iron catalyzed formation of oxygen derived radicals.

Animals↗
PubMed1982

Effect of plasma exchange on blood viscosity and cerebral blood flow.

The effects of plasma exchange using a low viscosity plasma substitute on blood viscosity and cerebral blood flow were investigated in eight subjects with normal cerebral vasculature. Plasma exchange resulted in significant reductions in plasma viscosity, whole blood viscosity, globulin and fibrinogen concentration without affecting packed cell volume. The reduction in whole blood viscosity was more pronounced at low shear rates suggesting an additional effect on red cell aggregation. Despite the fall in viscosity there was no significant change in cerebral blood flow. The results support the metabolic theory of autoregulation. Although changes in blood viscosity appear not to alter the level of cerebral blood flow under these circumstances, plasma exchange could still be of benefit in the management of acute cerebrovascular disease.

Adult↗
PubMedDate not supplied

[Content of free amino acids in rabbit tissues as affected by adrenalectomy and administration of hydrocortisone and ACTH].

Adrenalectomy is accompanied by a decreased content of free amino acids in muscules and blood plasma by an increased content of certain amino acids in the liver. A single injection of hydrocortisone to adrenalectomized animals increases the content of amino acids in muscles and lowers their total content in the liver; a single injection of ACTH lowers the total content of amino acids in the liver and blood plasma "Substitutive therapy" by hydrocortisone essentially increases the content of amino acids in the liver, muscles and blood plasma. Under conditions of the experiment the least changes in the content of amino acids were found in the brain tissue.

Adrenalectomy↗
PubMed1994

[Hemorheologic changes in preoperative hemodilution during total hip replacement. Randomized study comparing hydroxyethyl starch 200,000/0.62 (HES) and a dextran 60,000].

Hemodilution can be used to save blood transfusion during total hip replacement. We have carried out a randomized study to compare the hemorheological effects of two plasma substitutes: a hydroxyethylstarch 200,000/0.62 versus a dextran 60,000. Twenty-two patients were hemodiluted with 20 mk/kg of either substitute, just after the spinal anesthesia. Whereas the hematocrit have fallen by 30% in the two groups, significant differences are observed about hemorheological parameters. The plasma viscosity express a greater increase at hour 4 in the dextran group. The whole blood viscosities are more increased in the dextran group at hour 4 and 24. The erythrocyte aggregation is decreased in the HES group at hour 4 and 24, but is increased in the dextran group. The fibrinogen is more increased in the dextran group at day 7. In spite of similar hemodilutions, the two substitutes express different hemorheological effects with a favourable role of HES on erythrocyte aggregation and blood viscosities. This can improve the microcirculation and decrease the activation of the endothelial cells, reducing the inflammatory reaction.

Adult↗
PubMed1987

Blood substitution and complement activation.

Complement activation was studied in 45 patients undergoing total hip arthroplasty under epidural anesthesia. The patients were randomly allocated to three groups. In Group I blood loss was replaced with microaggregate-poor erythrocyte concentrate (SAGM-ERC) plus 3% dextran-60 as plasma substitute, and postoperative analgesia was maintained with intramuscular ketobemidone. In Group II blood loss was replaced as in Group I, but epidural anesthesia was prolonged 12 h postoperatively and kept at a level of T4 with 0.5% bupivacaine. In Group III blood loss was replaced with non-frozen stored plasma plus SAGM-ERC, and postoperative analgesia was maintained with ketobemidone as in Group I. All groups received pre- and postoperative thrombo-prophylaxis with dextran. The plasma concentration of C3a-des-arginine (C3a-desArg) was measured by radioimmunoassay preoperatively, immediately after operation and 3, 6 and 18 h postoperatively. No significant differences in plasma C3 and C4 were found between the groups. C3a-desArg was significantly (P less than 0.01) increased up to 6 h postoperatively in Group III compared with both the preoperative value and Groups I and II. It is demonstrated that infusion of plasma can enhance or initiate endogenous complement activation. Blood component therapy with SAGM-ERC and 3% dextran-60, on the other hand, did not significantly increase the plasma level of C3a-desArg irrespective of the type of postoperative analgesia.

Aged↗
PubMed2003

Comparison of various dimethylsulphoxide-containing solutions for cryopreservation of leucoreduced platelet concentrates.

BACKGROUND AND OBJECTIVES: Leucoreduced platelet concentrates (LR-PCs) can be stored at 20-24 degrees C for 5-7 days. When LR-PCs are cryopreserved they can be stored for several years. For cryopreservation to become applicable in blood-bank practice, an off-the-shelf cryoprotectant is needed that can be added to the LR-PC in a sterile manner. For this, we varied the composition of the cryopreservation medium and studied various parameters of cryopreserved LR-PCs for up to 24 h after thawing at room temperature. MATERIALS AND METHODS: LR-PCs in plasma or Composol were concentrated and divided into 2 units. To each unit, an equal part of 10% dimethylsulfoxide (DMSO) in plasma, Composol with or without 5% albumin, or GPO (pasteurized plasma-protein solution) was added. Freezing occurred at 1 degrees C/min and LR-PCs were placed in the vapour phase of nitrogen. LR-PCs were thawed at 37 degrees C and stored at room temperature. LR-PCs were tested for morphology, platelet recovery, swirling effect, and activation antigens at various time-points thereafter. RESULTS: LR-PCs in 100%, 65% and 50% plasma supplemented with Composol showed good morphology scores (>250), limited CD62P expression (<35%), low CD63 expression (<20%) and a swirling effect of about 2, at 24 h after thawing. At the same time-point, platelet recovery was >80% under all conditions and CD42b expression varied between 70 and 85%. Results of LR-PCs in 15% plasma and Composol, with or without plasma substitutes, were not acceptable at 24 h after thawing, i.e. the morphology score was <200 and the CD62P expression was >40%. CONCLUSIONS: A minimum of 50% plasma in the cryopreserved LR-PC is necessary to maintain an acceptable in vitro quality of platelets up to 24 h after thawing. Composol is a good candidate for using to prepare an off-the-shelf cryoprotectant.

Blood Platelets↗