Blood transfusion at the time of the First World War--practice and promise at the birth of transfusion medicine.

The centenary of the start of the First World War has stirred considerable interest in the political, social, military and human factors of the time and how they interacted to produce and sustain the material and human destruction in the 4 years of the war and beyond. Medical practice may appear distant and static and perhaps seems to have been somewhat ineffectual in the face of so much trauma and in the light of the enormous advances in medicine and surgery over the last century. However, this is an illusion of time and of course medical, surgical and psychiatric knowledge and procedures were developing rapidly at the time and the war years accelerated implementation of many important advances. Transfusion practice lay at the heart of resuscitation, and although direct transfusion from donor to recipient was still used, Geoffrey Keynes from Britain, Oswald Robertson from America and his namesake Lawrence Bruce Robertson from Canada, developed methods for indirect transfusion from donor to recipient by storing blood in bottles and also blood-banking that laid the foundation of modern transfusion medicine. This review explores the historical setting behind the development of blood transfusion up to the start of the First World War and on how they progressed during the war and afterwards. A fresh look may renew interest in how a novel medical speciality responded to the needs of war and of post-war society.

Evidence-based criteria for the care and selection of blood donors, with some comments on the relationship to blood supply, and emphasis on the management of donation-induced iron depletion.

Blood Services, which, in the UK, spend over 0.5% of the NHS budget, are generally subject to quality, regulatory, economic and political authority. As only persons in good health should give blood, Services have refined donor selection criteria and aim to base them on evidence; but they also have to balance the number of donations collected with product demand. Applying selection criteria inevitably leads to deferrals, which donors experience very negatively. Compared with successful donors, even temporary deferrals reduce return rates significantly, especially of first attenders. In order to encourage donor return and sustain supplies, selection criteria should be optimal. However, a major tool for managing patients--evidence from randomized controlled trials (RCTs)--cannot apply to donor selection, so criteria have to be defined by alternatives, such as clinical studies, epidemiology and even what experts deem to be pathophysiologically feasible. The recommended volume of blood taken from each donor at each attendance (450 mL, which was based on old studies) was increased because of greater processing losses (buffy-coat derived platelets, leucofiltration etc.). Although faint rates and donation-induced iron depletion are reduced by lowering bleeding volume and bleeding less frequently, other optimizing strategies including iron supplementation have been trialled and could be enhanced by more RCTs. Better but more complex indicators of donor iron status than one-off Hb thresholds are possible. Regulators and decision-makers must encourage more studies. This review does not consider aphaeresis donors of blood components other than red cells in detail, or the prevention of transfusion-transmitted infections.

Neutropenia and agranulocytosis in England and Wales: incidence and risk factors.

The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes. The study was conducted using data from the General Practice Research Database. All cases of idiosyncratic neutropenia or agranulocytosis were identified and the incidence was estimated. This was followed by a nested case-control study, estimating odds ratios with drug exposure from conditional logistic regression. From 1987 to 1999, 3,224 patients with idiosyncratic neutropenia (50 with agranulocytosis) were identified. The incidences of neutropenia and agranulocytosis were estimated to be 120 and 7 cases per million people per year, respectively. The adjusted odds ratios for neutropenia were 34.7 (95% confidence interval 12.0-99.7) for current users of thyroid inhibitors, 9.5 (4.4-20.8) for users of disease-modifying antirheumatic drugs, and 7.6 (4.9-11.9) for users of aminosalicylates. Other drugs with statistically significantly increased risks of neutropenia included antibacterial drugs, non-opioid analgesics, NSAIDs, antidepressants, ulcer-healing drugs, and anti-epileptics. The increase in risk of neutropenia predominantly occurred during the first months of treatment. For most drugs investigated in this study, there was no relationship to daily dose. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and mostly explained by the underlying disease state. In conclusion, the highest risks of neutropenia were generally found in patients starting treatment. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and can be mostly explained by the underlying disease state.

A study of the iron and HFE status of blood donors, including a group who failed the initial screen for anaemia.

A complete data set (age, weight, diet and recent donation history; venous blood cell count, serum ferritin and soluble transferrin receptor concentrations and transferrin saturation; HFE genotype) was obtained from 113 male and 122 female blood donors. Progressive iron depletion and deficiency - most apparent from serum concentrations of soluble transferrin receptor divided by the logarithm of ferritin concentrations (the TfR-F index) - developed in men donating up to six times in 2 years, although the serum ferritin alone was also informative; however, no prediction could be made for those iron-depleted individuals who will develop iron deficiency after donation. Iron stores in the groups of donors with 'low-normal' haemoglobin (Hb) concentrations were indistinguishable from those in donors with higher Hb values, whereas donors failing the anaemia screen had reduced stores. This supports the UK policy of accepting donations from people whose Hb concentration is up to 0. 5 g/dl below the recommended European threshold. Women eating red meat once a week sustained higher ferritin concentrations, and the iron status of first-time women donors resembled that of men donating twice each year. Homozygosity for either HFE variant allowed greater iron retention in the face of regular donation, but among heterozygotes the findings were inconclusive.

Fatal reaction to transfusion of red-cell concentrate contaminated with Serratia liquefaciens.

A 60-year-old woman undergoing surgery died from endotoxic shock and DIC after receiving a 19-day-old unit of optimal additive red-cell concentrate found contaminated with Serratia liquefaciens. No source of contamination could be found. This normally free-living organism is usually of low pathogenicity. It is a very unusual contaminant of stored donated blood, although it appears to be on the increase. When transfused, blood contaminated with S. liquefaciens always causes severe morbidity and is associated with a high death rate. This is the fifth report in the English literature.

Improved strategy for screening prospective blood donors for anaemia.

Women (568) and men (531) attending blood donation sessions in Wessex in September, 1992, were assessed for anaemia by the standard CuSO4 method on finger-prick (FP) blood samples. The haemoglobin (Hb) concentration on FP samples and on venous blood was also checked using the HemoCue. Different FP samples from the same donors revealed a wide variation on HemoCue. We recommend retaining the CuSO4 method on FP samples as the initial screen, and follow-up of apparent failures by determining the Hb concentration on venous sampling with the HemoCue. As 54% of females were found on venous samples to be below the current recommended threshold (125 g/L) for Hb concentration, we also recommend lowering the threshold to 115 g/L for women, and to 130 g/L for men. We further recommend a close re-examination of normal haematology values for adults.

Preliminary results of left heart bypass in pigs using a heparin-coated centrifugal pump.

To assess the feasibility of left ventricular assist without systemic heparinization, we used a commercially available (Sarns 3M) centrifugal pump with tubing set and cannulas, all internally precoated for the purpose of this study with heparin, to bypass the left ventricle in 12 pigs for periods of either 1 or 3 hours. There was no significant activation of clotting and there was no sign of generalized embolization. However, on postmortem studies, 5 kidneys out of 22 examined showed signs of minimal thromboembolism. This experiment shows that artificial left ventricular assist, free of systemic heparinization but using heparin precoating, is feasible and safe, at least for a short period of time.

Post-transfusion purpura following open heart surgery: management by high dose intravenous immunoglobulin infusion.

We present three cases of post-transfusion purpura (PTP) developing in the immediate post operative period after open heart surgery. All had developed platelet specific antibodies and severe anaphylactoid reactions occurred to platelet transfusion in two cases. Treatment with high dose intravenous immunoglobulin (IV IgG) led to complete recovery in two patients one of whom demonstrated a marked biphasic response pattern to therapy. The other died from congestive cardiac failure. PTP is a potentially fatal complication which may well become more frequent with increasing blood product usage.

The treatment of venous thrombosis of the upper and lower limbs with "APSAC" (p-anisoylated streptokinase-plasminogen complex).

APSAC, administered by bolus injection, has been used to treat 28 patients: 14 with ilio-femoral venous thrombosis, 6 with "spontaneous" axillary-subclavian thrombosis and eight with superior vena-caval thrombosis associated with parenteral nutrition catheter. Four of the patients with lower limb deep vein thrombosis (DVT) showed partial lysis whereas the remaining 10 showed no change. Of the patients with upper limb and/or superior caval DVT seven showed complete lysis three showed partial lysis and four showed no benefit. APSAC is an effective treatment of venous thrombosis of the upper limbs.

Successful cardiopulmonary bypass in diabetics with anaphylactoid reactions to protamine.

Two insulin dependent diabetics with previous anaphylactic like (anaphylactoid) reactions to protamine underwent successful cardiopulmonary bypass for coronary artery surgery. Platelet concentrates instead of protamine were used to neutralise their systemic heparinisation. In both cases the anaphylactoid reactions first became apparent after administration of protamine sulphate at the end of cardiac catheterisation. These cases show that adverse reactions to protamine need not be a contraindication to cardiopulmonary bypass and cardiac surgery and emphasise that this condition should be considered in all patients with a history of previous protamine exposure or one which may be associated with anaphylactoid reactions to protamine.

The therapeutic equivalence of oral and intravenous iron in renal dialysis patients.

Oral and intravenous iron were compared in patients treated with renal dialysis by a cross-over trial. Intravenous iron was given over 2 weeks as an iron dextran (equivalent to 100 mg elemental iron). Oral iron was given daily as ferrous sulphate (equivalent to 100 mg elemental iron) in a wax matrix tablet. Each treatment period lasted 26 weeks. There was no significant difference in therapeutic or unwanted effects between the treatments.