Blood transfusion; additional historical aspects. Part 2. The introduction of chemical anticoagulants; trials of 'Phosphate of soda'.

The pioneers of transfusion medicine around the turn of the 19th into the 20th centuries struggled with the awkward propensity of shed blood to clot. This article, a companion to a previous one (Boulton, 2013, Submitted for publication), describes in more detail how they recognised a potential for chemical anticoagulants which led to the introduction for a short period of sodium phosphate to aid blood transfusion: these cases preceded the introduction of citrate (Mollison, 2000, British Journal of Haematology, 108, 13-18).

Blood transfusion; additional historical aspects. Part 1. The birth of transfusion immunology.

The decades around the turn of the 19th into the 20th centuries covered a seminal period in the history of transfusion medicine as there was an increasing appreciation of a potential role in the management of surgical and obstetric bleeding, and also in severe non-surgical anaemias. The main obstacles to transfusing human blood were first the occasional devastating adverse reactions due, we now know, to ABO blood group incompatibility; and second the awkward propensity of shed blood to clot. This article describes in more detail how the pioneers in human transfusion immunology in the late 19th century and early 20th century learnt to recognise and avoid ABO incompatibility, and includes some hitherto obscure and rarely cited material. A companion article (Boulton, 2013, Submitted for publication) describes early attempts to find suitable anticoagulants.

A comparison of acylated streptokinase-plasminogen complex and streptokinase in healthy volunteers.

The in vivo effects on the fibrinolytic and coagulation system of infusion acylated streptokinase-plasminogen complex (BRL 26921; 5, 7 and 12 mg) or streptokinase (250,000 u) were determined in healthy male volunteers. While this dose of streptokinase resulted in depletion of plasminogen and antiplasmin, and in some cases of fibrinogen and coagulation factors V and VIII, the equivalent 7 mg dose of BRL 26921 had little effect on these parameters. 12 mg BRL 26921 had some systemic effects on the fibrinolytic system. For initial clinical studies a dose of 10 mg BRL 26021 would seem appropriate. Both drugs induced an anamnestic rise in streptokinase antibody, whereas no change in liver function tests were observed. A delayed mild febrile reaction was observed in some subjects following infusion of streptokinase or BRL 26921. Clinical, laboratory, and subjective monitoring revealed no other adverse effects with either drug.

A comparative study using immunological and biological assay of the haemostatic responses to DDAVP infusion venous occlusion and exercise in normal men.

In a group of six normal male volunteers, infusion of DDAVP, venous occlusion and exercise were shown to increase plasma levels of factor VIII and plasminogen activator, activity and antigen, to different extents and at differing rates. Any mechanisms suggested to explain release of these proteins by various stimuli should account for such differences. All three stimuli could also increase plasma levels of prostacyclin metabolites, although this was only significant for high doses of DDAVP. Other potential endothelial markers, such as fibronectin and thrombospondin, showed no specific increase after any of the stimuli.

The detection of myoglobin in urine and its distinction from normal and variant haemoglobins.

Victims of severe injuries frequently pass haemoglobin, myoglobin, or both proteins in their urine. If the kidneys of such persons are to be considered as donor material for transplantation, a pathology department may be requested to identify which of these pigments is present. If freshly passed urine is available, haemoglobinuria in the absence of myoglobinuria may be rapidly identified by spectroscopy. However, the rapid degradation of myoglobin to the met-myoglobin form will make spectroscopic recognition of this pigment in the urine unreliable. In the absence of variant haemoglobins, myoglobin may be easily distinguished from normal haemoglobin by routine electrophoresis on paper, starch gel, or cellulose acetate at alkaline pH. The electrophoretic method of choice in the presence of variant haemoglobins utilizes polyacrylamide gel at 12 g/100 ml as a supporting medium. At this concentration, the migration both of haemoglobin and its variants is sufficiently retarded to allow the easy recognition of myoglobin.

The estimation of haemoglobin A2: is visual assessment reliable?

Haemoglobin A(2) in 11 normal and 42 B thalassaemia minor subjects was estimated by simple visual assessment of the electrophoretogram. The results obtained give rise to doubts as to the reliability of this technique when used to estimate haemoglobin A(2) under normal laboratory conditions.

Clinical effects and kinetic properties of intravenous APSAC--anisoylated plasminogen-streptokinase activator complex (BRL 26921) in acute myocardial infarction.

Fifty patients with a first myocardial infarction presenting within 4 hours of the onset of symptoms were treated with intravenous anisoylated plasminogen-streptokinase activator complex (APSAC-BRL 26921). Vessel patency with good flow was documented in 88%. The left ventricular ejection fraction declined with the duration of symptoms before treatment (r = -0.53, P less than 0.001). The correlation persisted for the group with anterior infarction (r = -0.46, P less than 0.05) where the mean left ventricular ejection fraction prior to discharge from hospital was 36 +/- 9% compared to 49 +/- 7% for the group with inferior infarction. Reinfarction developed in 12% and mortality at 6 months for the whole group was 6%. A degree of systemic fibrinolysis did occur with a fall in mean plasma fibrinogen from 3.20 g/l to 1.08 g/l. A pharmacokinetic study was performed in six patients demonstrating a clearance half-life of fibrinolytic activity of 87.5 +/- 5.0 min. APSAC is an effective intravenous thrombolytic agent with a relatively long half-life of fibrinolytic activity.

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.

Exchange transfusion of whole blood in the treatment of cerebral malaria.

A case of cerebral malaria in a young British traveller, successfully treated by exchange transfusion of whole blood, is reported and the literature regarding the use of this technique in P. falciparum malaria is briefly reviewed.

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.

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.

Polymorphonuclear leucocyte transfusion in neonatal septicaemia.

In one neonatal intensive care unit during a 15 month period 6 infants developed septicaemia which was resistant to antibiotic treatment. The infants' mean gestational age and birthweight were 32.7 weeks and 1519 g respectively. Intravenous infusions of polymorphonuclear leucocytes were given. Three infants died and the remainder survived without complications. No side effects of the treatment were identified.