Large Transfusion Research Articles

Indications de la sérologie de l'hépatite C en médecine interne

A sero-epidemiological study was carried out in an Internal Medecine unit to identify high risk groups for HCV infection. Intravenous drug users, patients reported previous surgery usually requiring large blood transfusions, and alcoholic patients with cirrhosis and elevated transaminases should benefit from anti-HCV detection in priority.

Effects of prior use of non-steroidal anti-inflammatory drugs on renal function and transfusion requirements after upper gastrointestinal haemorrhage.

The possibility has been investigated that, after admission to hospital with acute upper gastrointestinal bleeding, patients who have been users of aspirin and non-aspirin non-steroidal anti-inflammatory drugs have poorer baseline renal function, a greater improvement in renal function during their hospital stay, and a larger transfusion requirement than non-users. Patients over 50 years of age admitted to public hospitals with acute upper gastrointestinal bleeding were studied. Creatinine clearance was estimated from serum creatinine and the transfusion requirement was recorded as the number of units of blood transfused on Day 1 and throughout the entire hospital stay. Data were obtained prospectively from case notes and by structured interview. Users of non-steroidal anti-inflammatory drugs were significantly older than non-users. The estimated creatinine clearance on admission to hospital declined with age. Creatinine clearance was 13.2 (95% CI 6.0 to 20.4) ml.min-1 lower in users than non-users of non-aspirin non-steroidal anti-inflammatory drugs. However, the difference was attributable to the older age of the drug users rather than to the drugs themselves. On average, the increase in creatinine clearance during hospital stay was the same in users and non-users of non-aspirin non-steroidal anti-inflammatory drugs. Prior use of aspirin had no effect on any measure of renal function. The incidence of blood transfusion was higher in older than in younger patients but neither the incidence of transfusion, nor the transfusion requirement, was different between users and non-users of non-aspirin non-steroidal anti-inflammatory drugs and aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

LEP compact 10 immunohaematology analyser overview of performance

The Compact 10 has been developed in a collaborative study between Lep Scientific and the Bristol Blood Transfusion Service. The analyser represents state of the art micro-continuous flow cytometry with advanced software support. This makes the Compact 10 the only fully automated "set and walk away" immunohaematology instrument available with the capability to perform both blood group and antibody screen. It is currently in routine operation in more than thirty major hospitals and transfusion laboratories in Europe. During 1990 it was estimated that the existing Compact 10's had grouped in excess of 5 million samples with a "group not determined" (GND) rate of less than 5%. It's size and throughput make the analyser ideally suited to both large transfusion service and hospital blood banks alike. The accuracy of testing is guaranteed by the machine readable specimen labels eliminating the chance of clerical error. The combination of advanced continuous flow and software control makes mistakes in blood group reporting impossible. The economy of the Compact 10 is outstanding. The consumption of antisera is less than <i>2%</i> of that used in established manual serological techniques. Another critical feature of the Compact 10 is its safety. The analyser's "closed system" ensures total protection of laboratory workers from the risk of infection. The combination of the Compact 10's economy, reliability, safety and efficiency make it an attractive proposition for any clinical laboratory.

A Comparison of Conductivity-Based Hematocrit Determinations With Conventional Laboratory Methods in Autologous Blood Transfusions

An investigation was made of the accuracy of a portable hematocrit measurement device (Stat-Crit) on the infusate of an autologous blood transfusion system. Baseline hematocrit values were determined by three methods on in vivo blood samples of surgical patients immediately after the start of surgery, and again on the first product of the autologous blood retrieval system. At baseline, there were no significant differences in the values determined by the Stat-Crit (33.4% +/- 6.2%, mean +/- SD) and those determined by the microcentrifuge technique (33.8% +/- 4.7%) or by the Coulter method (33.5% +/- 4.5%) (P = 0.9). In contrast, hematocrit values determined on infusate samples by the Stat-Crit (36.6% +/- 4.8%) were significantly lower than those determined by the microcentrifuge technique (51.2% +/- 5.9%) or by the Coulter method (51.6% +/- 5.8%) (P = 0.0001). This study confirms close agreement of hematocrit values derived by the conductivity of whole blood in normal samples with those determined by conventional laboratory techniques, but indicates that this method will report falsely low readings in situations where plasma has been replaced by crystalloid, as in patients who have received large transfusions of processed autologous blood.

Factors affecting survival of children after abdominal trauma in Lebanese civil war

To evaluate the risk factors affecting the survival of children with war injuries involving the abdomen, 270 children under 16 years of age with abdominal injuries during the civil war in Lebanon were studied. One hundred and ninety (70%) sustained penetrating injuries and 80 (30%) blunt trauma. The overall infection rate was 7.8%. There were 13 deaths (4.8%), 7 early and 6 late. Mortality was higher in patients with shock on admission than in those without shock (P = .009). Multiple logistic-regression analysis showed that inadequate initial treatment requiring a second laparotomy (P = .01), severe hypovolemia requiring large blood transfusions (P = .0001), and multiple intra-abdominal injuries (P = .001) were the three independent risk factors that influenced the outcome of treatment. Wound infection was associated with a higher mortality in patients with penetrating injuries (P = .0001). This study suggests that in children with war injuries involving the abdomen, multiple injuries associated with excessive bleeding led to early death and wound infection in penetrating injuries to late death.

Anaesthesia for paediatric neurosurgery and craniofacial surgery

Summary Anaesthesia for paediatric neurosurgery requires an intimate knowledge of the pathophysiology and control of raised ICP, and also of the physiology of small children. The main differences in practice between an adult and paediatric population are related to the higher metabolic rate of the child with greater oxygen demands and increased speed of development of hypoxia. The relatively large head results in much greater blood losses and the difficulties in accurate assessment of these losses common to all neurosurgery. Patients with small blood volumes may frequently require exchange transfusions and are therefore liable to the complication of massive transfusion, though in general children cope extremely well with large transfusions provided they do not become hypovolaemic, acidotic or hypoxic. Temperature control is another major factor in neurosurgery in small children because of the large surface area exposed during prolonged surgery, or even short procedures in those with poor central control. These potentially complex operations require close cooperation between the surgeon and anaesthetist, and also an anaesthetist who is confident in dealing with all aspects of anaesthesia in children, constantly alert to the mishaps which can so readily develop.

Nonoperative management of adult splenic injury due to blunt trauma: A warning

An analysis of 11 patients with splenic injury initially receiving nonoperative treatment revealed that 73 percent subsequently required surgery for delayed hemorrhage. The influence of age and the anatomic differences between the adult's spleen and child's spleen may account for the increased incidence of delayed bleeding seen in this series. Which patients might avoid surgical intervention cannot be predicted with certainty from the mechanism of injury or the lack of early physical signs and symptoms. The corresponding medical problems that often exist with the older patient may make nonoperative management, with the inherent risk of hypotension and large transfusion requirements, inappropriate. Although not advocating immediate splenectomy, we encourage early operative intervention with splenorrhaphy. Although improved diagnostic techniques will uncover a greater incidence of splenic injury, the inability to identify the nonoperative patient remains a clinical dilemma. The true role of nonoperative management of splenic injuries in the adult and the criteria for selection need to be further defined with larger prospective series. Although this approach may be useful for some patients, its application cannot be universal, and one must be willing to accept the consequences of delayed hemorrhage.

Nonoperative management of adult splenic injury due to blunt trauma: A warning

An analysis of 11 patients with splenic injury initially receiving nonoperative treatment revealed that 73 percent subsequently required surgery for delayed hemorrhage. The influence of age and the anatomic differences between the adult's spleen and child's spleen may account for the increased incidence of delayed bleeding seen in this series. Which patients might avoid surgical intervention cannot be predicted with certainty from the mechanism of injury or the lack of early physical signs and symptoms. The corresponding medical problems that often exist with the older patient may make nonoperative management, with the inherent risk of hypotension and large transfusion requirements, inappropriate. Although not advocating immediate splenectomy, we encourage early operative intervention with splenorrhaphy. Although improved diagnostic techniques will uncover a greater incidence of splenic injury, the inability to identify the nonoperative patient remains a clinical dilemma. The true role of nonoperative management of splenic injuries in the adult and the criteria for selection need to be further defined with larger prospective series. Although this approach may be useful for some patients, its application cannot be universal, and one must be willing to accept the consequences of delayed hemorrhage.

Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function.

Storage of blood can depress erythrocyte 2,3-diphosphoglycerate (DPG) levels and thereby increase oxyhemoglobin affinity and potentially decrease capillary-to-tissue oxygen transport. We measured myocardial function and metabolism in isolated rabbit hearts with fixed coronary flow under basal conditions and during isoproterenol stress at 37 and 30 degrees C, comparing high and low oxyhemoglobin affinity (OHA) erythrocytes. The high OHA state resulted from standard storage conditions, which caused depressed values of DPG and P50 (the oxygen tension at which hemoglobin is 50% saturated). The low OHA erythrocytes were initially stored and then underwent biochemical treatment to restore the DPG and P50 values to normal. The low OHA cells released more oxygen, and myocardial oxygen consumption and contractile function were increased relative to the high OHA cells during both the basal and stress states at both 37 and 30 degrees C. These observations may be relevant for patients with limited coronary flow when such patients receive large transfusions of stored blood.

Increase in plasma lipofuscin levels of stored blood.

Venous blood samples from Caucasian men, collected in citrate-phosphate-dextrose anticoagulant and stored in plastic or in glass containers for 10-, 20- and 30-day periods at 4 degrees C, showed increasing levels of plasma lipofuscin (PL) substances. These levels were measured as the intensities of the 340-nm excitation maximum and the 440-nm fluorescence maximum of PL, using a fluorescence spectrophotometer. No increase in PL level was observed in plasma samples separated before storage. These observations suggest that the free-radical activity of PL substances may confer toxic properties to stored blood used in large transfusions, and that stored blood may lose part of its osmotic, hemostatic, immunologic, and other physiologic functions as more plasma proteins are converted into lipofuscin.

Whole blood calcium activity during cardiopulmonary bypass.

Whole blood calcium activity, total plasma calcium, pH, pCO2, and plasma albumen concentrations were measured in ten patients undergoing cardiopulmonary bypass. Since calcium activity was the same before and after bypass, routine monitoring of calcium activity is only recommended when large blood transfusions are given. Depression of myocardial contractility post-bypass is rarely related to a low blood calcium activity.

Inhibitory effect of microvesicles collected from stored blood on platelet aggregation

Microvesicles extracted by ultracentrifugation from plasma of blood stored in blood bank conditions display a potent inhibitory effect on platelet aggregation. Aggregation induced by thrombin is most heavily impaired than that induced by ADP or arachidonic acid. Internalization of these microvesicles in platelets is observed by electron micrography. Since the microvesicle content of stored blood increases as a function of storing time, it could be inferred that large transfusion of blood stored for more than 15 days could induce hemostasis perturbations.

The surgical management of bleeding stress ulcers.

The series included 52 patients with acute bleeding stress ulcers of the stomach and duodenum seen at the Mayo Clinic during a 25-year period. All patients underwent operation for control of massive bleeding that was unresponsive to intensive medical therapy. All ulcers were superficial and occurred during clinically stressful circumstances. No patient had a history or findings suggestive of pre-existing peptic ulcer disease or imbibation of ulcerogenic substances. Overall operative mortality was 54%, and this rate seemed to be related to multiple factors acting together; patients with multiple predisposing stress factors and those requiring large transfusion volumes (greater than 17 total units) were at greatest risk of death. Fifty-two patients underwent 60 operative procedures for control of hemorrhage. Of the 60 procedures, 23 (38%) failed to prevent rebleeding. Of the 28 patients who died, six (21%) died of hemorrhage and five (18%) died of hemorrhage as one of many contributing factors. Of eight different procedures performed, near-total to total gastrectomy was the single procedure that was most effective in controlling hemorrhage. The authors support the selection of rapid intervention and generous extirpative surgery once intensive medical measures fail to control hemorrhage.

A safe blood transfusion procedure for immunization against major histocompatibility complex determinants in man.

A standardized procedure is proposed for deliberate immunizations against human major histocompatibility complex determinants. The data presented demonstrate its effectiveness and, by using a number of necessary precautions, this procedure has proven to be very safe. The following points are especially important: (1) exclusive utilization of regular blood donors as immunizers; (3) use of whole blood as an immunizing agent; and (3) use of small immunizing stimuli rather than large transfusions. This procedure can be recommended for the production of monospecific anti-HLA antisera and it may be useful if and when a deliberate transfusion policy for prospective kidney recipients is adopted.

Cooley anemia: High transfusion regimen and chelation therapy, results, and perspective

A tranfusion regimen aimed an maintaining hemoglobin levels above 9.5 gm/dl from the time of early diagnosis has permitted eight with Cooley anemia to liver normal, active lives, without hypersplenism or cardiac dysfunction (three to 13 years of observation). Echocardiography, however, has revealed increased thickness of the left ventricular wall. The amount of iron excreted in urine per 24 hours in response to daily administration of deferoxamine-B (20 mg/kg) was related to the estimated proportionate daily accumulation of iron from that administered by intermittent transfusion of erythocyutes, calculated from the amount of transfused RBCs The percentage of the dauily accumulated iron that was excreted after im injection of deferoxamine amounted to less than 30% in children up to five years of age; thereafter, it increased to 50%. When the same dose of the drug was given overnight by iv or sc infusion, the 24-hour excretion of iron increased threefold in the youngest and twofold in the oldest children. These data lead to the projection that deferoxamine-B, at the dose of 20 mg/kg, if given daily by im injection, may significantly reduce the iron overload and, if given daily at this dose by overnight infusion, may permit these children to approach iron balance, despite their large transfusion requirements.

The use of frozen, thawed erythrocytes in blood banking: a report of 28 months' experience in a large transfusion service.

A program of component therapy using largely frozen erythrocytes was initiated at Cook County Hospital in July 1973. Use of the three existing washing systems for routine preparation of frozen erythrocytes has shown that there are differences in the levels of free hemoglobin, hematocrit, and residual glycerol in the washed products. Adenosine triphosphate, 2,3-diphosphoglycerate, and extracellular potassium and sodium were found to be within acceptable limits. Some expired units were cultured and were found to be positive for Staphylococcus and Corynebacterium. The source of contamination has not been determined. Frozen blood, when available, has been given to all patients, regardless of age or clinical condition. The incidence of transfusion reactions has decreased from 0.57% prior to the inception of the component therapy program to 0.11% since that time. Two cases of possible posttransfusion hepatitis occurred in patients who had received non-frozen blood, and in three patients who received non-frozen erythrocytes and/or components as well as frozen blood. Although the goal of the program was the use of frozen erythrocytes exclusively, only 64% use was achieved, as sufficient quantities of blood for freezing were not available at all times.

Symptomatic neonatal plethora.

Blood volume and clinical data are reported on 8 premature and 3 full-term infants who presented with symptoms apparently due to polycythemia or hypervolemia. These cases termed 'symptomatic neonatal plethora' were caused by large placental transfusions associated with delayed clamping of the umbilical cord. Tachypnea, mild cyanosis, plethoric skin color, and neurological depression persisted on average for 30 h after birth. Chest X-rays showed mild cardiomegaly, pulmonary congestion and edema, and pleural effusions. Although the course was in general benign, phlebotomy was considered to be indicated in three infants to treat progressive clinical deterioration. The symptomatology and blood volume on these infants were compared with infants in an ongoing study with controlled time of cord clamping. Neonatal plethora must be considered as one cause of 'transient tachypnea of the newborn'.

Pulmonary edema. The water-exchanging function of the lung.

The pathogenesis of clinical pulmonary edema is considered in the light of recent physiologic and anatomic insights. Pulmonary edema is depicted as a persistent imbalance between the forces that move water into the extravascular spaces and the biologic devices for its removal. In the normal lung, intricate anatomic arrangements coupled with elaborate physiologic mechanisms maintain the gas-exchanging surfaces moist and free of excess protein. A transient excess of water in the interstitial space is associated with an increase in lymphatic flow. Should the excess rate of formation persist or increase, pulmonary edema may become manifest clinically, first as interstitial edema and then as alveolar and airway edema. The distribution of edema within the lung may be nonuniform, often favoring the central portions early in its genesis but later redistributing under the influence of gravity. A critical limitation in anatomic design is imposed by the narrow channels through which lymph passes out of the thorax into systemic veins. Accordingly, the pulmonary lymphatic system, which seems better suited to return proteins than water to the systemic circulation, may become a limiting factor in relieving pulmonary edema in states of unremitting water movement into the extravascular spaces. The anatomic and physiologic principles are then applied to current clinical enigmas, such as "shock lung," high-altitude pulmonary edema, and the edema that follows an overdose of narcotic agents, such as heroin. In "shock lung" after severe systemic hypotension, nonuniform pulmonary hypoperfusion is identified as the critical pathogenetic factor in the pulmonary edema that occurs during recovery, i.e. after systemic blood pressures have been restored to normal by large transfusions. The corresponding etiologic role for high-altitude pulmonary edema is attributed to anatomic variations in precapillary resistances in the lungs during a burst of severe pulmonary hypertension. The situation is more complicated for the pulmonary edema that follows narcotic overdosage since not only may the medication elicit severe respiratory depression, arterial hypoxemia, respiratory acidosis, and their sequelae–left ventricular failure, leakage of minute pulmonary vessels, and impaired lymphatic drainage–but the self-administered medication may be contaminated with substances that may, per se, cause minute pulmonary vessels to leak.

Studies on fibrinogen fractions isolated from human plasma by precipitation with cold ether. II. Enzymic acitivites resembling plasma kallikrein and C' I-esterase.

Mackay, Maycock, Silk and Combridge (1965) have shown that human fibrinogen preparations isolated by cold ether from freshly collected plasma (fraction HAHG, rich in Factor VIII), or from outdated plasma (fraction ETF), generate, when incubated at 37°C., traces of kinin (2–30 μmg. of bradykinin per ml. of fraction in 60 minutes). Activation of the plasminogen in the two fractions enhances the kinin formation in HAHG (30–117 μmg./ml. per 60 minutes), but not in ETF. Longer incubation did not increase the kinin yield.With larger transfusions, the amounts of kinin which develop in activated HAHG could be sufficient to produce pharmacological effects, and consequently clinical reactions (Mackay et al., 1965). However, there is no evidence that the plasminogen in transfused HAHG is activated in the body. Even if this were the case, the action of this enzyme on the kinin‐yielding substrate (kininogen) in HAHG is so slow that the resulting kinin would be destroyed in vivo by the normal blood kininase (a carboxypeptidase), before effective levels could develop. The present work suggests that the occasional reactions to transfusions (Maycock, Evans, Vallet, Combridge, Wolf, MacGibbon, French, Wallett, Dacie, Biggs, Handley and Macfarlane, 1963) could be due to the presence in HAHG and ETF of already active kalli‐krein which rapidly forms kinin by interacting with the high kininogen concentration in the recipient's plasma (cf. Fig. 1 in Mackay et al., 1965). The fractions also contain a factor capable of activating the kallikreinogen in the patient's plasma.The nature of the enzymic contaminant in HAHG and ETF, which hydrolysed p‐tosyl‐l‐arginine methyl ester (TAMe) even when the plasminogen in the two fractions had not been activated (Mackay et al., 1965), was also investigated in the present study.

Dextran and prolonged bleeding time; results of a sixty-gram, one-liter infusion given to one hundred sixty-three normal human subjects.

The effect of dextran infusions upon the bleeding time was studied in 22 women and 235 men. In 42 % of the subjects the infusion of one liter of 6 % solution of dextran measurably prolonged the bleeding time; in 8% of the subjects the bleeding time after infusion exceeded 30 minutes. The effect was maximal from three to nine hours after the infusion and was not accounted for by any demonstrable dilution or reduction of fibrinogen or thrombocytes. Comparison of dextran preparations showed that those of highest molecular weight had the most marked effect in prolonging the bleeding time. The use of dextrans as plasma expanders carries a risk of serious failure of the hemostatic mechanism and is contraindicated in patients who are known to have a tendency to bleed or who have received large transfusions of whole blood.