William G. Murphy

Screening platelet concentrates for bacterial contamination: low numbers of bacteria and slow growth in contaminated units mandate an alternative approach to product safety

Background and Objectives  We introduced 100% screening of platelets for bacterial contamination in 2005 to reduce the risk of clinical sepsis from platelet transfusion. We test all outdating units again at expiry to assess the sensitivity of the initial test.

The sex difference in haemoglobin levels in adults — Mechanisms, causes, and consequences

Men and women have different mean haemoglobin levels in health in venous blood - women have mean levels approximately 12% lower than men. A similar sex-related difference in haemoglobin levels in adult animals is found in many species of mammals, birds and reptiles, indicating that it is an important physiological phenomenon. It is probably a direct effect of sex hormones, both oestrogen and androgens, on erythropoiesis. However, since there is no difference in erythropoietin levels between the sexes, this effect most likely takes place in the kidney, rather than in the bone marrow. Oestrogens dilate and androgens constrict the renal microvasculature: dilation and vasoconstriction in vessels below 300 μm in diameter respectively increase and decrease the haematocrit in blood in arterioles, capillaries and venules, altering the oxygen delivery per unit red cell mass, and providing a mechanism for varying the red cell mass without compensatory changes in erythropoiesis.

External Financial Aid to Blood Transfusion Services in Sub-Saharan Africa: A Need for Reflection

Jean-Pierre Allain and colleagues argue that, while unintended, the foreign aid provided for blood transfusion services in sub-Saharan Africa has resulted in serious negative outcomes, which requires reflection and rethinking.

Antenatal screening for human platelet antigen-1a: results of a prospective study at a large maternity hospital in Ireland.

Objective Fetomaternal mismatch for human platelet antigen (HPA)‐1a accounts for approximately 85% of cases of neonatal alloimmune thrombocytopenia. The purpose of the study was to determine the prevalence of the HPA‐1a negative platelet phenotype in a cohort of pregnant women in Ireland, the rate of alloimmunisation to HPA‐1a in HPA‐1 mismatched pregnancies and the associated incidence of neonatal alloimmune thrombocytopenia.

Coagulase‐negative staphylococcal contamination of whole blood and its components:the effects of WBC reduction

BACKGROUND: Most bacteria present in blood components are normal skin flora, particularly Staphylococcus epidermidis and other coagulase‐negative staphylococci. Growth patterns of these bacteria and the effects of different methods of component preparation may depend on variations in behavior between different isolates of the same species.

Capillary and venous haemoglobin levels in blood donors: a 42‐month study of 36 258 paired samples

Background  EU law requires a haemoglobin of ≥ 12·5 g/dl for women or ≥ 13·5 g/dl for men at the time of donation. As capillary and venous haemoglobin values may differ in the same subject, we examined whether a capillary haemoglobin level of 12·0 g/dl for women or 13·0 g/dl for men, is equivalent to a venous haemoglobin level of ≥ 12·5 g/dl and ≥ 13·5 g/dl, respectively, to avoid unnecessary loss of blood donations.

Ebola: a call for blood transfusion strategy in sub-Saharan Africa

WHO has stated that convalescent blood or plasma is an option in the treatment of Ebola. In 1999, transfusion of locally collected convalescent blood helped decrease Ebola mortality. WHO recommends collection of convalescent plasma to treat patients in the fi ght against the Ebola outbreak. As there is an estimated 70% mortality, a randomised clinical evaluation involving 50 patients, receiving convalescent and control normal plasma, would be suffi cient to confi rm the usefulness of this approach in treatment strategies. Capacity building for the collection and testing of suffi cient convalescent blood or plasma from recovered Ebola patients is crucial. However, paradoxically, the outbreaks are occurring in the countries that have the least capability for blood and plasma collection or viral screening, and which lack infrastructure, equipment, and trained personnel. To ensure collection of safe convalescent plasma, donors must be clinically and virally free of Ebola Virus Disease (EVD) and other relevant viruses. Convalescent plasma is the preferred product, either fresh or fresh-frozen, collected by plasmapheresis with out compromising the donor’s haemoglobin level. Plasmapheresis provides large volumes (500 ml) and can usually be repeated at 2–3 day intervals. Donors selected from the same geographical area are recommended and can provide treatment for many patients. In most African countries there is a paucity of expertise, infrastructure and equipment; however, plasmapheresis equipment can be donated and training provided in-country or at regional Blood Services. Portable generators can provide power for equipment and refrigerators. The Ebola emergency shows the importance of strengthening the technical capacity and infrastructure of local transfusion systems, to respond to present and future infectious outbreaks. The importance of ensuring adequate, accessible, and safe blood—in all countries—is a global priority. Whole blood and labile blood components are now on the WHO’s Essential Medicines List (EML), emphasising the crucial role of transfusions in public health. In sub-Saharan Africa, whole blood, when available, is a life-saving product for emergency use that, together with convalescent plasma, might be the only available clinical option in the treatment of Ebola patients at present. National governments should develop sustainable local blood services for an adequate supply of safe blood as a priority. WHO’s urgent appeal, supporting the use of convalescent blood products to fight Ebola, is a timely reminder of the many World Health Assembly resolutions supporting such actions, particularly in low resource countries.

The potential of human peripheral blood derived CD34+ cells for ex vivo red blood cell production

The potential of peripheral blood derived CD34+ cells for ex vivo erythropoiesis was investigated in a stroma-free culture system using a novel strategy of daily passaging. By expanding PB-derived CD34+ cells up to 1.5 x 10(6)-fold this method achieved expansion factors previously only reported for CD34+ cells derived from more potent stem cell sources such as cord blood, bone marrow and mobilized peripheral blood. Analysis of cell surface markers showed differentiation of immature CD34+ cells to populations with 80% CD71-/GpA+ cells and up to 45% enucleated cells, indicating a significant amount of terminal maturation. Cell crowdedness was found to have decisive effects on in vitro erythropoiesis. Cell density per surface area rather than cell concentration per media volume determined cell expansion during exponential growth where more crowded cells showed reduced overall expansion. In late stage erythropoiesis, however, when cells no longer proliferating, increased cell density was seen to enhance cell viability. These results indicate that peripheral blood derived haematopoietic stem cells can be an alternative to cells sourced from bone marrow, cord blood or leukapheresis in terms of expansion potential. This provides distinct advantages in terms of availability for studies of conditions for scale-up and maturation, and may have particular clinical applications in the future.

A novel panel of protein biomarkers for predicting response to thalidomide-based therapy in newly diagnosed multiple myeloma patients

Multiple myeloma (MM) is a heterogeneous group of disorders both genotypically and phenotypically. Response to thalidomide‐based induction therapy in newly diagnosed patients varies significantly in published clinical trials. Proteomic analysis was performed on 39 newly diagnosed MM patients treated with a thalidomide‐based regimen (22 responders; 17 non‐responders) using immunodepletion, 2‐D DIGE analysis and mass spectrometry. Zinc‐α‐2‐glycoprotein (ZAG), vitamin D‐binding protein (VDB), serum amyloid‐A protein (SAA) and β‐2‐microglobulin (B2M) had statistically significant higher concentrations in non‐responders compared to responders, while haptoglobin (Hp) had a lower concentration. ELISAs were used to validate the candidate protein biomarkers using unfractionated serum from 51 newly diagnosed MM patients (29 responders; 22 non‐responders). Using logistic regression, the best possible area under the curve (AUC) was 0.96 using ZAG, VDB and SAA in combination. Leave‐one‐out‐cross‐validation (LOOCV) indicated an overall predictive accuracy of 84% with associated sensitivity and specificity values of 81.8 and 86.2%, respectively. Subsequently, 16 of 22 thalidomide‐refractory patients successfully achieved complete response or very good partial response using second‐line treatment suggesting that the biomarker profile is specific to thalidomide response rather than identifying patients with MM refractory to all therapies. Using a novel panel of predictive biomarkers, the feasibility of predicting response to thalidomide‐based therapy in previously untreated MM has been demonstrated.

Blood transfusion practice in a rural hospital in Northern Ghana, Damongo, West Gonja District

BACKGROUND: Blood transfusion in rural sub‐Saharan Africa presents special challenges. Transfusions are primarily given for emergencies—life‐threatening blood loss or anemia; blood is usually collected from family or replacement donors; and facilities to store an adequate reserve in a hospital bank are constrained. We report the everyday and organizational practices in a medium‐sized district hospital in Northern Ghana.