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.

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.

Monoclonal IgM cold agglutinins with anti-Pr1d specificity in a patient with peripheral neuropathy.

A patient with a demyelinating sensory motor polyneuropathy secondary to IgM paraproteinaemia is reported. The paraprotein binds to the gangliosides GD1b, GT1b, GQ1b and GD3, all of which contain disialosyl groups with the sequence NeuAc alpha 2-8NeuAc alpha 2-3Gal. The paraprotein also acts as a cold agglutinin recognising the sialic-acid-dependent Pr1d antigenic determinant of the red cell membrane glycophorins. In this and in similar cases that have been reported, the coexistence of anti-Pr cold agglutinins and peripheral neuropathy suggest that they might be the causative agents of the disease.

Cold autoagglutinins with anti-Pr specificity associated with fresh varicella infection.

Cold agglutinins with the rare anti-Pr specificity were identified in an adult patient with fresh varicella infection. The antibody was of the IgM kappa type with subspecificity anti-Pr3d and caused a haemolytic episode in the patient. In the only previously reported case in which cold agglutinins were associated with varicella infection, the antibody specificity was also anti-Pr.

Platelet counting using plasma platelet concentrate samples.

Platelet counting using samples of plasma from platelet concentrates prepared for transfusion was assessed. The methods employed included a manual phase-contrast method, and counting with Coulter S Plus and Sysmex E-2500 counters. All methods were reproducible (mean CV of 4.9, 2.2 and 1.4%, respectively). However, neat samples of platelet concentrates analysed by Coulter counter were inaccurate (mean count of 863.8 x 10(9)/l compared to 1018.9 x 10(9)/l counted manually). Moreover, the Coulter platelet counts were non-linear above 900 x 10(9)/l, whereas the E-2500 platelet counts were linear to 2700 x 10(9)/l. A one-in-three pre-dilution was required to obtain accurate, linear counts with the Coulter counter, whereas the E-2500 was accurate without pre-dilution (mean count of 1030.2 x 10(9)/l compared to 1018.9 x 10(9)/l counted manually). In conclusion, the method of platelet counting may affect true platelet yields.

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.

Importance of a quality assurance scheme for factor VIII assays in quality monitoring of human plasma destined for fractionation into factor VIII concentrate.

A national quality assurance scheme has been established to monitor the validity of factor VIII assays performed by the various laboratories of the Scottish National Blood Transfusion Service engaged in collection and processing of donor plasma destined for fractionation. The results over the first 3-year period show that comparable assay values can be obtained by participating centres using a common standard, despite differences in equipment, methods or substrate chosen for the one-stage assay. The results also showed that chromogenic factor VIII assays correlated well with the one-stage method. Random factor VIII assays performed on plasma, harvested and frozen within 18 h from collection, were analysed to validate recently proposed Scottish specifications which stipulate that 70% of plasma donations destined for fractionation should contain at least 0.7 IU/ml. Plasma harvested and frozen between 8 and 18 h from collection did not meet the specified level in any of the regional centres. This nationally specified level was also not met by plasma harvested and frozen within 8 h from collection in spite of being achieved individually by three regional centres. Assays performed on large plasma pools at the Fractionation Centre suggested loss of some factor VIII during storage, transportation and thawing of plasma prior to bulk processing.

Coagulation disorder due to apparent inadvertent heparin administration.

A new competitive binding assay, which measures the concentration of heparin rather than its activity, was used to confirm the presence of a high concentration of heparin in blood samples from a patient which showed unexpected gross prolongation of thrombin time (TT) and activated partial thromboplastin time (APTT). Extrapolation of the heparin concentration enabled estimation of the likely time of administration and the probable dose given. It is possible that an error in dosage may have arisen due to the striking resemblance of vials containing different amounts of heparin marketed by different manufacturers. There is a need for the adoption by manufacturers of a standard coding scheme for vials containing different amounts of heparin (as is adhered to in the case of some drugs, e.g. warfarin), in order to pre-empt this possible source of error.

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.

Studies on the stability of VIII:C during the manufacture of a factor VIII concentrate for clinical use.

The stability of VIII:C was investigated by monitoring samples taken at different points from a routine process for the manufacture of factor VIII concentrate and by examining the stabilising influence of a number of product formulations. Loss of VIII:C over process-finishing procedures (formulation, 0.22 micron filtration, dispensing) was associated with a citrate-induced inactivation which could be prevented by controlling the ionised calcium concentration of the solution. These results were obtained using a one-stage clotting assay but were not observed using a two-stage assay. No evidence for activation was found in vitro (e.g. by FPA generation and VIII:C stability) and the yield increase suggested by the one-stage assay was supported by results from a controlled clinical evaluation.

A fatal transfusion reaction associated with blood contaminated with Pseudomonas fluorescens.

A fatal transfusion reaction due to contamination of platelet-depleted whole blood with Pseudomonas fluorescens is reported. Routine sterility testing on blood products and environmental microbiological monitoring suggested no source for the contaminating organism, as has been the case for the majority of reported incidents of this type. The value of routine sterility testing in the prevention and investigation of such incidents is discussed.