Iron deficiency in whole blood donors in a resource-poor setting: A cross-sectional study in Uganda.

BACKGROUND AND OBJECTIVE: Blood donation is known to result in iron deficiency (ID), with a higher prevalence in females. There is little published data on the frequency of ID among blood donors in resource-poor settings. We determined the prevalence of ID in blood donors in Uganda. METHODS: We conducted a descriptive cross-sectional study at the Uganda Blood Transfusion Service, Kampala from December 2021 to February 2022. A sample of 500 whole blood donors was enrolled. The evaluation included demographic characteristics, donation history, nutritional history, complete blood count, and serum ferritin. The primary outcome was the proportion of donors with serum ferritin <15 µg/L. RESULTS: The median (IQR) serum ferritin was 25 (12-47) µg/L and 89 (52-133) µg/L among female and male donors respectively. The prevalence of iron deficiency (serum ferritin <15 µg/L) among donating individuals was 11.5% (8.7-14.9), while among low haemoglobin deferrals, 61.5% (50.9-71.1). The prevalence was high among females [33.0% (27.9-38.6)] compared with males [2.5% (1.0-5.8)], but even higher among females younger than 24 years [35.4% (29.2-42.1)]. Factors associated with ID (adjusted odds ratio, 95% Cl, and significance) were; female donors (15.81, 5.17, 48.28, p < 0.001) and a high RDW (6.89, 2.99, 15.90, p < 0.001). We found a moderate correlation between serum ferritin and RDW (r = -0.419 and -0.487 for males and females respectively). CONCLUSION: Iron deficiency is common among blood donors in Uganda, affecting mostly young female donors. Considerations to adopt evidence-based strategies to prevent and manage ID among blood donors-such as serum ferritin monitoring and iron supplementation are highly recommended.

Transfusion management of severe anaemia in African children: a consensus algorithm.

The phase III Transfusion and Treatment of severe anaemia in African Children Trial (TRACT) found that conservative management of uncomplicated severe anaemia [haemoglobin (Hb) 40-60 g/l] was safe, and that transfusion volume (20 vs. 30 ml/kg whole blood equivalent) for children with severe anaemia (Hb <60 g/l) had strong but opposing effects on mortality, depending on fever status (>37·5°C). In 2020 a stakeholder meeting of paediatric and blood transfusion groups from Africa reviewed the results and additional analyses. Among all 3196 children receiving an initial transfusion there was no evidence that nutritional status, presence of shock, malaria parasite burden or sickle cell disease status influenced outcomes or modified the interaction with fever status on volume required. Fever status at the time of ordering blood was a reliable determinant of volume required for optimal outcome. Elevated heart and respiratory rates normalised irrespective of transfusion volume and without diuretics. By consensus, a transfusion management algorithm was developed, incorporating three additional measurements of Hb post-admission, alongside clinical monitoring. The proposed algorithm should help clinicians safely implement findings from TRACT. Further research should assess its implementation in routine clinical practice.

A possible role for hepcidin in the detection of iron deficiency in severely anaemic HIV-infected patients in Malawi.

INTRODUCTION: Iron deficiency is a treatable cause of severe anaemia in low-and-middle-income-countries (LMIC). Diagnosing it remains challenging as peripheral blood markers poorly reflect bone-marrow iron deficiency (BM-ID), especially in the context of HIV-infection. METHODS: Severely anaemic (haemoglobin ≤70g/l) HIV-infected adults were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. BM-ID was evaluated. Accuracy of blood markers (including hepcidin, mean corpuscular volume, mean cellular haemoglobin concentration, serum iron, serum ferritin, soluble transferrin receptor (sTfR), sTfR index, sTfR-ratio) to detect BM-ID was evaluated by ROC area under the curve (AUCROC). RESULTS: Seventy-three patients were enrolled and 35 (48.0%) had BM-ID. Although hepcidin and MCV performed best (AUCROC of 0.593 and 0.545 respectively) all markers performed poorly in identifying BM-ID (ROC<0.6). The AUCROC of hepcidin in males was 0.767 (sensitivity 80%, specificity 78%) and in women 0.490 (sensitivity 60%, specificity 61%). CONCLUSION: BM-ID deficiency was common in severely anaemic HIV-infected patients. It is an important and potential treatable contributor to severe anaemia but lack of definitive biomarkers makes it difficult to accurately assess iron status in these patients. Further investigation of the potential of hepcidin is needed, including exploration of the differences in hepcidin results between males and females.

Tranexamic acid for the prevention of postpartum bleeding in women with anaemia: study protocol for an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Postpartum haemorrhage (PPH) is responsible for about 100,000 maternal deaths every year, most of which occur in low- and middle-income countries. Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. TXA decreases blood loss in surgery and reduces death due to bleeding after trauma. When given within 3 h of birth, TXA reduces deaths due to bleeding in women with PPH. However, for many women, treatment of PPH is too late to prevent death. Over one third of pregnant women in the world are anaemic and many are severely anaemic. These women have an increased risk of PPH and suffer more severe outcomes if PPH occurs. There is an urgent need to identify a safe and effective way to reduce postpartum bleeding in anaemic women. METHODS/DESIGN: The WOMAN-2 trial is an international, multicentre, randomised, double-blind, placebo-controlled trial to quantify the effects of TXA on postpartum bleeding in women with moderate or severe anaemia. Ten thousand women with moderate or severe anaemia who have given birth vaginally will be randomised to receive 1 g of TXA or matching placebo by intravenous injection immediately (within 15 min) after the umbilical cord is cut or clamped. The primary outcome is the proportion of women with a clinical diagnosis of primary PPH. The cause of PPH will be described. Data on maternal health and wellbeing, maternal blood loss and its consequences, and other health outcomes will be collected as secondary outcomes. The main analyses will be on an 'intention-to-treat' basis, irrespective of whether the allocated treatment was received. Results will be presented as appropriate effect estimates with a measure of precision (95% confidence intervals). Subgroup analyses will be based on the severity of anaemia (moderate versus severe) and type of labour (induced or augmented versus spontaneous). A study with 10,000 patients will have over 90% power to detect a 25% relative reduction from 10 to 7.5% in PPH. The trial will be conducted in hospitals in Africa and Asia. DISCUSSION: The WOMAN-2 trial should provide reliable evidence for the effects of TXA for preventing postpartum bleeding in women with anaemia. TRIAL REGISTRATION: ISRCTN, ISRCTN62396133 . Registered on 7 December 2017; ClincalTrials.gov, ID: NCT03475342 . Registered on 23 March 2018.

Anaemia, iron deficiency and susceptibility to infection in children in sub-Saharan Africa, guideline dilemmas.

Globally, anaemia, iron deficiency and infections are responsible for a majority of the morbidity and mortality that occurs among children. As iron is essential for erythropoiesis and the human immune system, as well as a crucial element for many pathogens, these three conditions often interact. This article considers the question - have the studies conducted so far unravelled the potential complex interaction between these factors sufficiently enough to be able to develop universally applicable guidelines about iron treatment in children? It is possible, however, that the area is too complex and diverse, with many sub-populations, and that not universal, but tailor-made guidelines are needed based on some agreed principles.

Problems and Approaches for Blood Transfusion in the Developing Countries.

A safe supply of blood and the knowledge, skill, and resources for the appropriate use of blood are essential for medical services. Many problems are faced in the development of transfusion services in low- or medium-income countries (LMICs). Unfortunately, in many countries, providing safe blood is made more difficult by a lack of blood donors and the high frequency of transfusion-transmissible infections. The problems are compounded by the frequent need for urgent life-saving transfusions. This article examines the problems in supply, safety, and use of blood and how they are being addressed in LMICs, predominantly focusing on sub-Saharan Africa.

Transfusion-transmitted malaria in Ghana.

BACKGROUND: In sub-Saharan Africa, the prevalence of malaria parasitemia in blood donors varies from 0.6% to 50%. Although the burden of TTM in malaria-endemic countries is unknown, it is recommended that all donated blood is screened for malaria parasites. This study aimed to establish the incidence of TTM and identify a suitable screening test. METHODS: Pregnant women, children, and immunocompromised malaria-negative transfusion recipients in a teaching hospital in Ghana were recruited over the course of 1 year. Parasites detected in recipients within 14 days of the transfusion were genotyped and compared to parasites in the transfused blood. The presence of genotypically identical parasites in the recipient and the transfused blood confirmed transfusion-transmitted malaria. Four malaria screening tests were compared to assess their usefulness in the context of African blood banks. RESULTS: Of the 50 patients who received transfusions that were positive for Plasmodium falciparum by polymerase chain reaction (PCR), 7 recipients developed PCR-detectable parasitemia. In only 1 of the 50 recipients (2%) was the parasite identical to that in the transfused blood. The prevalence of P. falciparum malaria in transfused blood was 4.7% (21/445) by microscopy, 13.7% (60/440) by rapid diagnostic test, 18% (78/436) by PCR, and 22.2% (98/442) by enzyme immunoassay. CONCLUSIONS: Although malaria parasites are commonly detected in blood donors in malaria-endemic areas, transfusion-transmitted malaria occurs infrequently. Policies recommend screening blood donors for malaria, but none of the commonly used methods is sufficiently sensitive to be used by blood banks in malaria-endemic countries.

The microbiologic safety of umbilical cord blood transfusion for children with severe anemia in Mombasa, Kenya.

BACKGROUND: Severe anemia requiring blood transfusion is common in hospitalized young children in sub-Saharan Africa but blood is often in short supply. Umbilical cord blood may be a useful source of blood if microbiologic safety concerns can be addressed. STUDY DESIGN AND METHODS: Cord blood, donated on the labor ward at the provincial hospital in Mombasa, was cultured soon after collection (screening culture) and after a period of storage (poststorage culture). Conventional blood transfused to children at the hospital was cultured only at the time of issue (poststorage culture). Maternal sera (cord blood) and conventional blood donations were also screened for transfusion-transmitted infection. RESULTS: At poststorage culture, the overall contamination rate of cord blood was one-third that of conventional blood (13/449 vs. 38/434; odds ratio [OR], 0.31; 95% confidence interval [CI], 0.15-0.61) and for bacteria of high pathogenic potential it was half that of conventional blood (4/449 vs. 7/434; OR, 0.55; 95% CI, 0.12-2.18). Screening cultures were positive in 50% (2/4) of cord blood packs where an organism of high pathogenic potential was isolated at poststorage culture. Cord blood donors had a lower seroreactivity than conventional donors for human immunodeficiency virus (OR, 0.63; 95% CI, 0.29-1.18), hepatitis B virus (OR, 0.32; 95% CI, 0.16-0.59), and hepatitis C virus (OR, 0.20; 95% CI, 0.24-0.76). For syphilis, initial seroreactivity in cord blood donors was 3.8% compared to 1.8% in conventional blood donors (OR, 2.10; 95% CI, 1.15-3.60) but was 0.5% after retesting. CONCLUSION: With respect to bacterial contamination and seroreactivity for transfusion-transmitted infection, the safety of cord blood in Mombasa compares favorably with conventional blood. Clinical trials of cord blood transfusion are justified.

Transfusion-transmitted malaria in countries where malaria is endemic: a review of the literature from sub-Saharan Africa.

Although international policies recommend that blood for transfusion should be screened for transfusion-transmitted infections, malaria screening is not performed in most malaria-endemic countries in sub-Saharan Africa. Our literature review identified 17 relevant studies from the period 1980-2009 and indicated that the median prevalence of malaria among 33,029 blood donors was 10.2% (range, 0.7% in Kenya to 55.0% in Nigeria). Malaria screening methods, including microscopy (used in 16 of 17 studies), are either insensitive or impractical for donor screening in resource-poor countries. Even if a suitable screening method were available, rejection of malaria-positive donors would jeopardize the blood supply. Only 1 study established the prevalence of parasitemia among transfusion recipients. This review highlights the need for more evidence about the clinical impact of transfusion-transmitted malaria to justify the policy of screening for blood for malaria in areas of endemicity and for a critical analysis of the feasibility of implementing such a policy and its effect on blood supply.

Erythropoiesis in HIV-infected and uninfected Malawian children with severe anemia.

Anemia is common in HIV infection, but the pathophysiology is poorly understood. Bone marrow analysis in 329 severely anemic (hemoglobin <5 g/dl) Malawian children with (n = 40) and without (n = 289) HIV infection showed that HIV-infected children had fewer CD34(+) hematopoietic progenitors (median 10 vs. 15‰, P = 0.04) and erythroid progenitors (2.2 vs. 3.4‰, P = 0.05), but there were no differences in erythrocyte viability and maturation in later stages of erythropoiesis. Despite an HIV-associated reduction in early red cell precursors, subsequent erythropoiesis appears to proceed similarly in HIV-infected and HIV-uninfected children with severe anemia.

UK-based real-time lymphoproliferative disorder diagnostic service to improve the management of patients in Ghana.

The objective of the study was to evaluate the feasibility of a UK-based real-time service to improve the diagnosis and management of lymphoproliferative disorders (LPDs) in Ghana. Adult patients reporting to hospital with a suspected LPD, during a 1 year period, were prospectively enrolled. Bone marrow and/or lymph node biopsies were posted to the Haematology Malignancy Diagnostic Service (HMDS), Leeds, UK and underwent morphological analysis and immunophenotyping. Results were returned by e-mail. The initial diagnoses made in Ghana were compared with the final HMDS diagnoses to assess the contribution of the HMDS diagnosis to management decisions. The study was conducted at the two teaching hospitals in Ghana-Komfo Anokye, Kumasi and Korle Bu, Accra. Participants comprised 150 adult patients (>/=12 years old), 79 women, median age 46 years. Bone marrow and lymph node biopsy samples from all adults presenting with features suggestive of a LPD, at the two teaching hospitals in Ghana, over 1 year were posted to a UK LPD diagnostic centre, where immunophenotyping was performed by immunohistochemistry. Molecular analysis was performed where indicated. Diagnostic classifications were made according to international criteria. Final diagnosis was compared to the initial Ghanaian diagnosis to evaluate discrepancies; implications for alterations in treatment decisions were evaluated. Median time between taking samples and receiving e-mail results in Ghana was 15 days. Concordance between initial and final diagnoses was 32% (48 of 150). The HMDS diagnosis would have changed management in 31% (46 of 150) of patients. It is feasible to provide a UK-based service for LPD diagnosis in Africa using postal services and e-mail. This study confirmed findings from wealthy countries that a specialised haematopathology service can improve LPD diagnosis. This model of Ghana-UK collaboration provides a platform on which to build local capacity to operate an international quality diagnostic service for LPDs.

Causes of massive tropical splenomegaly in Ghana.

BACKGROUND: The causes and diagnosis of massive tropical splenomegaly are not well studied, especially with modern investigative methods. We aimed to identify features that would help local clinicians differentiate between the underlying conditions. METHODS: We collected prospective clinical and laboratory data on 221 Ghanaian patients with spleen size of at least 10 cm. We identified conditions associated with massive splenomegaly with molecular and immunological investigations as well as routine tests. Patients were assigned to diagnostic categories on the basis of these test results and predetermined criteria. FINDINGS: Hyper-reactive malarial splenomegaly (HMS; 91 patients [41%]) and B-lymphoproliferative disorders (48 [22%]) were the most common disorders associated with massive splenomegaly. Of the remaining patients, 32 (14%) had haematological disorders, and in 50 (23%) we could not identify the cause of splenomegaly. Male sex predominated in all diagnostic groups except HMS and tropical splenic lymphoma. Age less than 40 years and absolute lymphocyte count (less than 10 x 10(9)/L) were the only useful and widely available discriminators for distinguishing patients with HMS from those with lymphoproliferative disorders. INTERPRETATION: B-lymphoproliferative disorders are a previously unrecognised cause of massive tropical splenomegaly. This finding has major implications for management of massive splenomegaly. Diagnosis of the less common causes of this disorder is usually straightforward, but differentiating between B-lympho proliferative disorders and HMS can be difficult. HMS is associated with younger age, a higher proportion of women, and lower absolute lymphocyte counts than lympho proliferative disorders.