Hemostasis disorders after transfusions

Disturbances of haemostasis caused immunologically and non-immunologically were observed after transfusion of blood and blood derivatives. Transfusion of heparin blood increased the bleeding susceptibility only in case of pre-existing high-degree defects of haemostasis or if they were performed as massive or exchange transfusions. Massive transfusions with blood stored for a long time will induce complex defects. Under intensive substitution therapy of haemophilia A the so-called paradoxical bleeding will occur in spite of a high factor VIII level. These bleedings are supposed to be disturbances of the thrombocyte function and are caused by fibrin(ogen) derivatives. Post-transfusional thrombocytopenias may be brought to remission by repeated plasmapheresis. Factor specific inhibitory bodies will appear after substitution in a small percentage of haemophilic patients. 5 to 7 days after the onset of therapy an anamnestic reaction can be observed as a titre increase by leaps. Usually, the inhibitory titre will decrease to a mostly low basal value in the course of three to five months. The therapy with cyclophosphamide simultaneously started with the substitution will more frequently prevent the anamnestic reaction or reduce it. Titres with more than 5 units cannot be overcome at the beginning even by higher concentrations of preparations. The substitution therapy should be preceded by exchange transfusions or plasmapheresis of up to 25 units. With still higher titres only procedures of inhibitor-bypassing are possible with factor VIII preparations of animal origin or better with activated prothrombin complex preparations, such as FEIBA. Recent reports give evidence that permanent substitution with factor VIII concentrates at a highest dosage can eliminate the production of inhibitors completely.     

Colonic Perforation after Exchange Transfusion

Four patients are reported in whom perforation of the colon followed exchange transfusion for haemolytic disease of the newborn. This association seems to be more than coincidental, and possibly the perforation is due to a vascular accident occurring as a mechanical result of the exchange transfusion. The insidious onset of colonic perforation may be recognized early by the passage of blood per rectum. There is no place for conservative treatment, and once the diagnosis has been made treatment must include broad-spectrum antibiotics and laparotomy.     

Fetal intracardiac transfusions in patients with severe rhesus isoimmunisation

Six patients with pregnancies of 19-31 weeks'' duration showing evidence of erythroblastosis fetalis were treated with 25 fetal intracardiac blood transfusions. Complications related to the procedure occurred on five occasions in three patients. In two of the six patients the fetus died, but it was unlikely that death was related to the intracardiac transfusions.Fetal intracardiac blood transfusion may result in potentially severe complications but offers an alternative when transfusion cannot be performed into the umbilical cord.     

The Blood–Brain Barrier and Bilirubin Encephalopathy

1. The pathogenesis of bilirubin encephalopathy is multifactorial, involving the transport of bilirubin or albumin/bilirubin across the blood–brain barrier and delivering bilirubin to target neurons.2. The relative importance of the blood–brain barrier, unconjugated bilirubin levels, serum binding, and tissue susceptibility in this process is only partially understood. Even at dangerously high serum levels, bilirubin traverses the intact blood–brain barrier slowly, requiring time for encephalopathy to occur, although deposition of bilirubin can be rapid if a surge in plasma unbound bilirubin is produced by administering a drug which competes with bilirubin for binding to albumin.3. There may be maturational changes in permeability both in the fetus and postnatally which protect the brain from bilirubin.4. Disruption or partial disruption of the blood–brain barrier by disease or hypoxic ischemic injury will facilitate transport of bilirubin/albumin into brain, but the relative affinities of albumin and target neurons will determine whether the tissue bilirubin load is sufficient for toxicity to occur.     

Bilirubin uptake in vitro by the rat intestinal mucosa

Flat sheets of rat jejunum incubated in the presence of unconjugated bilirubin solutions were shown to incorporate bilirubin into the tissue.Bilirubin mucosal uptake, expressed as a function of the incubation time showed a tendency to reach a constant level within 120 min.Solutions of bilirubin in sodium taurocholate gave an incorporation of significantly greater amounts of bilirubin than those prepared with albumin.A structurally similar substance (biliverdin) inhibited bilirubin uptake in a way that suggested competitive inhibition. The results support the view that the mechanism of bilirubin uptake by the rat intestinal mucosa cannot be entirely explained by simple passive diffusion.     

双管同步换血治疗新生儿高胆红素血症的临床分析

目的:探讨外周动静脉双管同步换血术治疗新生儿高胆红素血症临床疗效。方法:回顾性分析了采用外周动静脉双管同步换血术治疗的32例高胆红素血症患儿,比较换血前后血清胆红素的变化。结果:32例患者换血前后总胆红素有明显变化,显著下降(P<0.01)。不过在治疗后出现术后感染2例,经对症处理后痊愈。结论:新生儿外周动静脉双管同步换血术治疗新生儿高胆红素血症简单、实用、安全,值得进一步推广应用。     

CRITERIA FOR BLOOD TRANSFUSIONS

A review of the use of blood transfusions used in a small community hospital over a two-year period revealed a high incidence of instances in which the clinical record did not show essential need for the procedure. Educational efforts in hospital staff meetings resulted in some improvement in this respect during the two-year period. Of single unit transfusions given during the first year, 80 per cent were deemed to have been nonessential; during the second year, 52 per cent.Methods which will reduce the use of blood except when it is essential are (1) continuation of staff education; (2) providing the staff with accurate methods of measurement of blood volume and of monitoring blood loss; (3) use of a separate blood transfusion chart in the patient''s hospital record; and (4) establishment of a hospital transfusion committee to review the criteria in all cases in which blood is transfused.     

Flurorometric study of the partition of bilirubin among blood components: basis for rapid microassays of bilirubin and bilirubin binding capacity in whole blood

Bilirubin binds to many sites in blood, the strongest binding being to a single site on albumin. Secondary sites on albumin, most sites on other plasma proteins, and sites on erythrocyte membranes have affinities for bilirubin that are at most one-hundredth as great. Bilirubin binds to hemoglobin in red cells with an effective affinity that is less than one-thousandth that of the primary albumin site. Essentially the only bilirubin present in blood which fluoresces is that bound to the primary albumin site. Almost all the other bilirubin in blood fluoresces with a yield no more than one-fiftieth as large. Quantitative fluorometry of whole blood is possible using the “front-face” technique. The concentration of bilirubin bound to the primary albumin site can be determined in this way. The albumin binding capacity of a blood specimen can be similarly assayed upon titration of the specimen with bilirubin. The nonionic detergent dodecyldimethylamine oxide (DDAO) scavenges bilirubin from all sites in blood, and, since bilirubin is fluorescent in DDAO micelles, the total blood bilirubin can be assayed fluorometrically after addition of DDAO to the specimen. This detergent method also allows facile assay of red-cell-bound bilirubin. These fluorometric assays for total blood bilirubin, albumin-bound bilirubin, and albumin binding capacity are simple and rapid and use very small volumes of blood. They should be of great value in the research on neonatal jaundice and in its clinical management.     

The blast transformation capacity and karyotypic characteristics of the T-lymphocytes in hemolytic disease of the newborn]

The blood of 6 newborn boys with haemolytic disease of newborns and of 3 healthy newborn boys was examined. In all 949 metaphase plates were analysed. In all the investigated plates the karyotype was masculine, 46,XY [correction of 46HY]. The mitotic index is lowered considerably in sick children that suggests inhibition of their cellular immunity. In these conditions, the K and L lymphocytes of donor blood, introduced in substituting blood transfusion, can interact with the sensitized erythrocytes in accordance with the type of reaction "the transplant against the host" causing the increase in the level of bilirubin after the operation. It is expedient to study the possibility of realization of substituting blood transfusion using the leucocyte-free blood.     

Inhibition of posthemorrhagic transfusion-induced gastric injury by a long-acting superoxide dismutase derivative

Although oxygen-free radicals have been postulated to play an important role in the pathogenesis of gastric mucosal injury induced by posthemorrhagic blood transfusion, direct evidence supporting this hypothesis is lacking. Superoxide dismutase (SOD) has been shown to inhibit oxygen toxicity in vitro in various types of cell injury. However, in some cases, oxidative tissue injury cannot be decreased efficiency predominantly due to its rapid elimination by renal glomerular filtration. To overcome such frustrating situations, we have synthesized a SOD derivative that circulates bound to albumin with a half-life of 6 hr. When blood was withdrawn from the rat (22 ml/kg) for 30 min followed by transfusion of the extracted blood, marked gastric mucosal lesions occurred within 30 min after transfusion. Intravenously injected SOD derivative markedly decreased gastric mucosal injury. Kinetic analysis using 125I-labeled albumin revealed that the vascular permeability of the stomach increased significantly after transfusion by a SOD derivative inhibitable mechanism. Thus, superoxide radical and/or its metabolite(s) play a critical role in the pathogenesis of posthemorrhagic transfusion-induced gastric injury.     

Intraperitoneal Blood Transfusion in African Adults with Hookworm Anaemia

Twenty-nine patients were given an intraperitoneal transfusion of blood. The procedure was found to be free of serious complications. Study of the absorption of an ⁵¹Cr-labelled cells from the peritoneum in 14 patients showed that between 35 and 100% of the blood was absorbed intact in 6 to 10 days. Intraperitoneal transfusion may be indicated as an alternative or as an addition to exchange transfusion in severe hookworm anaemia.     

Structural and functional differences between fetal and adult serum albumin

The binding of bilirubin with adult of fetal human serum albumin has been studied by steady-state fluorescence emission spectroscopy. The 1:1 complex between bilirubin and the two albumin samples shows very similar fluorescence properties, as well as essentially identical accessibility of the protein-bound bilirubin to fluorescence quenchers added to the aqueous medium. The intramolecular distance between bilirubin and the single tryptophyl residue can be estimated to be 2.4 +/- 0.2 nm for both proteins by singlet-singlet energy transfer. These findings suggest that fetal and adult human serum albumin have a very similar three-dimensional structure; the different binding capacity for bilirubin displayed by the two proteins is likely to be the consequence of small differences in the physico-chemical properties of some amino acid residues close to the bilirubin binding site, as indicated by pH-titration experiments of the intrinsic albumin fluorescence.     

Clinical use of blood,blood components and blood products.

The goal of modern transfusion therapy is to provide appropriate replacement therapy with blood components as opposed to whole blood for patients with specific hematologic deficiencies. A prerequisite of component therapy is, therefore, correct identification of the deficiency. Appropriate use of components avoids many of the hazards associated with the use of whole blood, and at the same time makes maximal use of this valuable resource. Blood components separated from whole blood soon after collection and appropriately stored can, in combination, provide all the factors present in fresh whole blood. Red cell concentrates prepared from multiple packs have a hematocrit of approximately 70%. They may be stored for up to 3 weeks at 4 degrees C and are recommended for most situations requiring red cell transfusions. Platelet concentrates, which can be stored for up to 72 hours at 22 degrees C, may be used for thrombocytopenic patients. Fresh frozen plasma, stored plasma, cryoprecipitated factor VIII, factor VIII concentrate and factor IX complex concentrate are available for the proper treatment of patients with hemorrhagic disorders due to coagulation factor deficiencies. Similarly, albumin and immune serum globulin are available for their oncotic and antibody properties respectively. Thus, the availability and appropriate use of the various blood products allows not only optimal transfusion therapy for each patient, but also fuller utilization of national blood resources.     

THE INFLUENCE OF BILIRUBIN ON OXIDATIVE PHOSPHORYLATION AND RELATED REACTIONS IN BRAIN AND LIVER MITOCHONDRIA: EFFECTS OF PROTEIN-BINDING

1. The uncoupling of oxidative phosphorylation of liver mitochondria by bilirubin does not occur in the presence of equimolar quantities of human serum albumin. With brain mitochondria, however, albumin was not protective. 2. A similar protective effect of albumin for liver, but not for brain, mitochondria was observed in studies of the effects of bilirubin on the ³²Pi-ATP exchange reaction. 3. The latent ATPase of fresh brain mitochondria is activated by Mg²⁺ but only slightly by DNP. Bilirubin increased the Mg²⁺ stimulated ATPase activity in liver mitochondria but depressed this activity in brain mitochondria. These effects were uninfluenced by protein binding. 4. Isotope studies with [¹⁴C]bilirubin demonstrated that the affinity of brain mitochondria for albumin-bound bilirubin is not greater than that of liver mitochondria. 5. The greater toxicity of protein-bound bilirubin for brain mitochondria than for liver mitochondria might be related to the greater lipid content of brain mitochondria.     

Regional cerebral blood flow in cats with cross-linked hemoglobin transfusion during focal cerebral ischemia

The beneficial effect of hemodilution on cerebral blood flow (CBF) during focal cerebral ischemia is mitigated by reduced arterial oxygen content (CaO2). In anesthetized cats subjected to permanent middle cerebral artery occlusion, the time course of regional CBF was evaluated after isovolemic exchange transfusion with either albumin or a tetrameric hemoglobin-based oxygen carrier. The transfusion started 30 min after arterial occlusion. We tested the hypothesis that bulk oxygen transport (CBF x CaO2) to ischemic tissue is increased by hemoglobin transfusion at a hematocrit of 18% compared with albumin-transfused cats at a hematocrit of 18% or control cats at a hematocrit of 30% and equivalent arterial pressure. In the nonischemic hemisphere, CBF increased selectively after albumin transfusion, and oxygen transport was similar among groups. In the ischemic cortex, albumin transfusion increased CBF, but oxygen transport was not increased above that of the control group. Hemoglobin transfusion increased both CBF and oxygen transport in the ischemic cortex above values in the control group, but the increase was delayed until 4 h of ischemia. Consequently, acute injury volume measured at 6 h of ischemia was not significantly attenuated. In contrast to the cortex, CBF in the ischemic caudate nucleus was not substantially increased by either albumin or hemoglobin transfusion. Therefore, in a large animal model of permanent focal ischemia in which transfusion starts 30 min after ischemia, tetrameric cross-linked hemoglobin transfusion can augment oxygen transport to the ischemic cortex, but the increase can be delayed and not necessarily provide protection. Moreover, an end-artery region such as the caudate nucleus is less likely to benefit from hemodilution.     

Serum bilirubin levels in breast- and formula-fed infants in the first 5 days of life.

A prospective study was conducted in a level II maternity unit to investigate the incidence of hyperbilirubinemia in healthy, term, breast-fed and formula-fed infants. Serum bilirubin levels were determined for 176 breast-red and 164 formula-fed infants in cord blood and on days 1, 2, 3 and 5 after birth. The mean total bilirubin levels were significantly higher on each postnatal day in the breast-fed infants, as was the proportion of infants with peak levels above 12 mg/dl (205 mumol/l; 28% v. 6%). The breast-fed infants also had significantly higher proportional weight losses on each postnatal day than the formula-fed infants. However, there was no correlation between the cumulative weight loss on day 3 and bilirubin levels on the same day with either feeding regimen. None of the infants required an exchange transfusion or prolonged care in hospital for hyperbilirubinemia.     

Serological and molecular analysis of ABO and Rh blood group chimeras

The serological examination, blood transfusion strategies and the molecular analysis to blood group chimera were conducted to demonstrate existent of chimera in blood group. The blood grouping of ABO or/and RhD, newborn red blood cells separated by capillary centrifugation. Aabsorption tests and DTT treated agglutination erythrocyte tests were implemented in four patients. Further molecular biological research was conducted on one patient''s sample. The results showed that for patient 1: ABO blood group was AB/B chimera, Rh blood cells contained the RhCE chimera gene; Patient 2: Rh blood cells contained the RhD chimera gene; Patient 3: ABO blood group was AB/B chimera, Rh blood cells contained the RhD chimera gene; Patient 4: ABO blood group was O/B chimera, Rh blood cells contained the RhCE chimera gene. The study suggests that the individuals categorized as chimeras are likely to be more common than existing literature reports. According to the serological tests, in the absence of a history of recent blood transfusion or disease to cause reduced antigen, the phenomena of hybrid aggregation of the ABO and Rh blood system were the main feature. In terms of transfusion strategy, the selection of ABO and Rh blood groups should be depended on the group of cells with more antigens.     

Photoactivated covalent binding of [3H]bilirubin to human serum albumin.

A one-step procedure has been developed for the preparation of [3H]bilirubin IX-alpha in good yield from unlabelled bilirubin. Irradiation of an aqueous solution of [3H]bilirubin IX-alpha in the presence of human serum albumin results in the covalent attachment of the bilirubin to the protein. Preliminary degradation studies have been carried out to locate the site of attachment of the bilirubin to the albumin.     

Separation of bilirubin species in serum and bile by high-performance reversed-phase liquid chromatography

A high-performance, reversed-phase liquid chromatographic (HPLC) procedure has been developed for the separation of at least three major bilirubin fractions in bile and four fractions in human serum. This procedure was unlike most others, in that serum was not totally deproteinized prior to injection onto the HPLC column; instead, serum was treated with an excess of sodium sulfate solution to precipitate primarily proteins larger than albumin. Injection of the filtered and diluted supernatant onto a reversed-phase column then resulted in the separation of the bilirubin species in a 24-min gradient elution run. Both the initial aqueous acidic mobile phase and the final isopropyl alcohol-based mobile phase contained 5% methoxyethanol (v/v) to facilitate elution of albumin still present in the treated sample. Bilirubin species eluting from the column were detected by absorbance at 450 nm.Results of a number of chromatographic separations of pathological sera indicated a wide variation in the relative proportions of the four bilirubin fractions observed. A correlation of the sum of the areas of the bilirubin peaks observed by HPLC was found with the total bilirubin value obtained by a standard reference procedure.     

Cost of allogeneic and autologous blood transfusion in Canada. Canadian Cost of Transfusion Study Group.

OBJECTIVE: To determine the cost, from a societal perspective, of blood transfusion in Canada. STUDY DESIGN: Cost-structure analysis. SETTING: Data were collected from eight hospitals and from six blood centres operated by the Canadian Red Cross Society in four provinces. OUTCOME MEASURES: Costs associated with four stages of transfusion-- collection, production, distribution and delivery--in 1933 were assessed. Costs were divided into the following categories; personnel, purchases, external services, overhead, donors'' time, patients'' time (for autologous transfusion), wastage and infection. RESULTS: The mean overall cost of a transfusion performed on an inpatient basis was $210 per unit of red blood cells for an allogeneic transfusion and $338 per unit of blood for an autologous transfusion. The mean cost of an allogeneic transfusion performed on an outpatient basis was $280 per unit of red blood cells. CONCLUSION: The costs determined in this study can be used in future studies comparing the cost-effectiveness of allogeneic transfusion with that of alternative methods.