TRANSFUSION PRACTICE Blood utilization at a national referral hospital in sub-Saharan Africa Elissa K. Butler,1 Heather Hume,2,3 Isaac Birungi,4 Brenda Ainomugisha,2 Ruth Namazzi,2 Henry Ddungu,2,5 Isaac Kajja,2 Susan Nabadda,6 and Jeffrey McCullough1

BACKGROUND: A safe and adequate supply of blood is critical to improving health care systems in subSaharan Africa, where little is known about the current use of blood. The aim of this study was to comprehensively describe the use of blood at a tertiary care hospital to inform future efforts to strengthen blood programs in resource-limited settings. STUDY DESIGN AND METHODS: Data were collected from blood bank documentation for all units issued at Mulago Hospital Complex in Kampala, Uganda, from mid-January to mid-April 2014. RESULTS: A total of 6330 units (69% whole blood, 32% red blood cells, 6% platelets, 2% plasma) were issued over the 3-month study period to 3662 unique patients. Transfusion recipients were 58% female and median age was 27 years (interquartile range [IQR], 14–41). Median pretransfusion hemoglobin was 5.6 g/dL (IQR, 4.0–7.2 g/ dL, n 5 1090). Strikingly, cancer was the top indication for transfusion (33.5%), followed by pregnancy-related complications (12.4%) and sickle cell disease (6.9%). CONCLUSION: This study provides a comprehensive picture of blood use at a national referral hospital in subSaharan Africa. Noncommunicable diseases, particularly oncologic conditions, represent a large proportion of demand for transfusion services.

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orldwide, one in four people are affected by anemia. Sub-Saharan Africa is disproportionately affected, where two-thirds of preschool-age children and half of all women have anemia.1 Iron deficiency, blood loss due to heavy menstruation or obstetric hemorrhage, malaria, parasitic infections, micronutrient deficiencies, and hemoglobinopathies are some of the most common causes of anemia in sub-Saharan Africa.2-7 Anemia has significant associated morbidity and mortality, particularly in young children and pregnant women.4,7-10 Blood transfusion effectively reduces morbidity and mortality in the setting of acute severe anemia. A safe and

ABBREVIATIONS: IQR 5 interquartile range; UBTS 5 Uganda Blood Transfusion Services; UCI 5 Uganda Cancer Institute; UHI 5 Uganda Heart Institute. From the 1University of Minnesota Medical School, Minneapolis, Minnesota; the 2School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; the Centre Hospitalier Universitaire Sainte-Justine, University of

3

Montreal, Montreal, Quebec, Canada; and 4Global Health Uganda; the 5Uganda Cancer Institute; and the 6Mulago Hospital, Kampala, Uganda Address reprint requests to: Jeffrey McCullough, Laboratory Medicine and Pathology, MMC 609, D185 Mayo Building, 420 Delaware Street SE, Minneapolis, MN 55455; e-mail: [email protected]. This work was supported by the Transfusion Medicine Research Fund of the Department of Pathology and Laboratory Medicine, University of Minnesota, Minneapolis, Minnesota, and in part by the Doris Duke Charitable Foundation through a grant supporting the Doris Duke International Clinical Research Fellows Program at University of Minnesota. EKB is a Doris Duke International Clinical Research Fellow. Received for publication August 26, 2014;

revision

received October 2, 2014; and accepted October 2, 2014. doi:10.1111/trf.13010 C 2015 AABB V

TRANSFUSION 2015;55;1058–1066 1058 TRANSFUSION Volume 55, May 2015

BLOOD UTILIZATION IN SUB-SAHARAN AFRICA

TABLE 1. Summary of studies on blood use in sub-Saharan Africa Number of transfusions

Age and sex distribution

Major diagnoses

Rural district

927

67% C, 27% W, 6% M

46% malaria, 13% pregnancy complications

Malawi

Rural district

104

65% C, 26% W, 8% M

57% malaria, 17% pregnancy complications

2010

Uganda

Regional referral

2777

Joubert et al.23

2013

South Africa

Tertiary university

55

Adults only; median age 36; 58% W, 42% M

64% symptomatic anemia, 33% perioperative

Arewa25

2009

Nigeria

Tertiary

682

33% C, 67% adults

26% severe anemia, 20% acute bleeding, 18% surgery

Reference

Year

Country

Lackritz et al.22

1993

Kenya

Bugge et al.21

2013

Natukunda et al.24

Type of hospital

Median age: 19 years, F:M 5 1.3

33% malaria, 19% other infections, 17% pregnancy complications

C 5 children; M 5 adult men; W 5 adult women.

consistent supply of blood is critical to improving health care systems in sub-Saharan Africa.11-13 Worldwide, approximately 107 million units of blood are collected annually, almost half of which are collected in high-income countries, despite only representing 15% of the world’s population. The median blood donation rate in high-income countries is 39 donations per 1000 population compared to four donations per 1000 in low-income countries.11 Uganda collects approximately 5.6 units per 1000 population.14 It is estimated that the demand for blood far outweighs the supply in sub-Saharan Africa.5 Approximately 25% of maternal mortality and 40% of mortality in children with malaria could be due to shortage of blood.10,15,16 With limited supply of blood, it is imperative to maximize clinical benefit for each unit of blood.17 However, there are little data on the current utilization of available blood in hospitals in sub-Saharan Africa. Most reports are general estimates of blood utilization, with little concrete data to support them.11,18 It is estimated that up to 65% of blood transfusions are given to children under 5 years of age. The most commonly stated indications for transfusion include severe childhood anemia due to malaria, obstetric hemorrhage, trauma, and surgery.5,12,18-20 Table 1 summarizes the few studies that have collected more detailed data on utilization of transfusion services in sub-Saharan Africa.21-25 Only three studies have looked at blood use at a tertiary care facility and none fully describe blood use at a tertiary care facility in sub-Saharan Africa. These studies had relatively small sample sizes, were conducted over a short period of time, or had a limited scope. The aim of this study was to comprehensively describe the utilization of blood at a tertiary care hospital in sub-Saharan Africa.

MATERIALS AND METHODS Study setting Mulago Hospital is a tertiary care, national referral, and teaching hospital in Kampala, Uganda. The hospital has

approximately 1500 beds and offers services in all major medical specialties. The Uganda Cancer Institute (UCI) and the Uganda Heart Institute (UHI), which are semiautonomous organizations, also make up part of the Mulago Hospital Complex and offer specialized care in oncology and cardiology and cardiovascular surgery, respectively. Mulago Hospital Complex has four laboratories where blood is issued for transfusion: the main hospital blood bank and the hematology laboratories in the acute care unit (pediatric medical emergency ward), UCI, and UHI. Uganda Blood Transfusion Services (UBTS), the national organization responsible for blood collection, testing, and distribution, supplies all four laboratories. Of all blood distributed in Uganda, approximately 12% goes to Mulago Hospital (personal communication with UBTS personnel). UBTS distributes whole blood, red blood cells (RBCs), fresh-frozen plasma (FFP), and platelets (PLTs). RBCs are produced from 1 unit of whole blood by removing the plasma and then resuspending in an additive solution to give a volume of approximately 450 mL. This is then divided into three smaller units of 150 mL each, intended to be used in pediatric patients. For this study, one instance of transfusion was counted as one transfusion of RBCs, whether an adult received three small packs or a child received one small pack. PLTs are derived from a single unit of whole blood using the PLT-rich plasma method. There is no pooling of PLT units. Each unit of PLTs was counted as a separate transfusion. A child typically receives 1 to 2 units and an adult 2 to 4 units at a time, depending on availability.

Data collection Data were collected from laboratory records prospectively over a 12-week period from mid-January to mid-April 2014. This period was chosen to account for seasonal variation in malaria diagnoses. Historically, January and February are dry months and March and April are rainy months in Uganda. For each unit issued from one of the four Mulago Hospital laboratories during the study period, Volume 55, May 2015 TRANSFUSION 1059

BUTLER ET AL.

TABLE 2. Distribution of blood product type among children, adult women, and adult men* Blood product type

Children (n 5 1479)

Adult women (n 5 2859)

Adult men (n 5 1868)

Overall (n 5 6330)

Whole blood RBCs PLTs FFP Unknown

329 (22.2) 955 (64.6) 136 (9.2) 37 (2.5) 22 (1.5)

2084 (72.9) 564 (19.7) 120 (4.2) 74 (2.6) 17 (0.6)

1335 (71.5) 419 (22.4) 74 (4.0) 19 (1.0) 1 (1.1)

3808 (60.2) 1970 (31.1) 349 (5.5) 132 (2.1) 71 (1.1)

* Data are reported as number of units (%).

quent transfusions. If a specific clinical diagnosis was not listed, a general diagnosis was assigned based on the hospital ward. For example, patients on the solid tumor ward at UCI were given the diagnosis of solid tumor.

Statistical analysis

Fig. 1. Age distribution of individuals at Mulago Hospital

Data were analyzed using computer software (Excel 2011, Microsoft Corp., Redmond, WA; and SPSS Statistics 22.0, IBM Corp., Armonk, NY). Continuous data are summarized with means, medians, standard deviations, and interquartile ranges (IQRs). Categorical data are summarized with frequencies and percentages. The t test and one-way analysis of variance were used to compare mean Hb among sample subgroups.

receiving transfusions from January to April 2014 (n 5 2890).

Ethical considerations the study team recorded all available information from the transfusion request form and the unit issue logbook, including age, sex, hospital ward, clinical diagnosis, hemoglobin (Hb) concentration, PLT count, type of blood product, patient ABO group and RhD type, unit ABO group and RhD type, date of request, and date of issue. If a unit was listed in the issue book but did not have an accompanying request form, all available data from the issue book were recorded. If an exact age was not documented, adult or child was documented, if known. If a Hb value was not listed on the request form, the study team made attempts to determine the Hb value. At the main hospital laboratory, the hematology analyzer used to determine Hb concentration was not in service (due to shortage of reagents or malfunction) for 10 of the 12 weeks during the study period. For 1 week, the study team recorded any available Hb values directly from the laboratory reports. At the acute care unit, the study team recorded Hb values directly from the laboratory book, when available. The UCI and the UHI generally have more complete documentation, so no attempts were made to find Hb values not listed on the request forms. PLT levels were rarely recorded on the transfusion request forms (likely because there is no designated place on the form) and no attempts were made to attain this value directly from the hematology laboratory. Subsequent transfusions for an individual are documented on the initial request form, so transfusion number was recorded for any subse1060 TRANSFUSION Volume 55, May 2015

The Makerere University College of Health Sciences School of Medicine Research and Ethics Committee provided ethical approval. The University of Minnesota Institutional Review Board approved exempt status. This study involved access only to blood bank records and no patient identifying data were collected.

RESULTS Transfusion demographics During the 3-month study period, a total of 3662 unique patients received a total of 6330 transfusions. Table 2 shows the distribution of product types among adults and children. The majority of units were issued from the main blood bank (66.4%), followed by the UCI (22.7%), acute care unit (9.2%), and the UHI (1.7%). Of transfusion recipients with a specific age available, the median age was 27.0 years (IQR, 13.5–41.5 years; n 5 2890). Fourteen percent (399/2890) were under the age of 5 years and 29.1% (840/2890) were under the age of 18 years. The age distribution of individuals receiving transfusions is bimodal with peaks in children less than 5 years and in young adults between 20 and 30 years (Fig. 1). A specific age was unavailable for 21% (733/3662) of transfusion recipients, however either “adult” or “child” is generally recorded. Overall, 73% (2617/3570) were adults and 27% (953/3570) were children and 57.6% (2101/3650) of individuals were

BLOOD UTILIZATION IN SUB-SAHARAN AFRICA

Fig. 2. Distribution of transfusions by hospital ward. Numbers represent the total number of transfusions for each ward type. OB/GYN 5 obstetrics and gynecology.

TABLE 3. Distribution of clinical diagnoses among children, adult women, and adult men* Clinical diagnoses

Children† (n 5 1479)

Adult women (n 5 2859)

Adult men (n 5 1868)

Overall (n 5 6330)

UCI cancer Pregnancy-related complications Non-UCI cancer Sickle cell disease Nontrauma, noncancer surgery HIV infection‡ Trauma Gynecologic disorders§ Kidney disease (non-HIV) Acute, nontraumatic bleedingk Malaria Anemia of unknown cause Diabetes Burn Sepsis Other medical Unknown¶

324 (21.9) 9 (0.6) 81 (5.5) 338 (22.9) 150 (10.1) 17 (1.1) 50 (3.4) 11 (0.7) 6 (0.4) 9 (0.6) 78 (5.3) 46 (3.1) 1 (0.1) 42 (2.8) 25 (1.7) 87 (5.9) 205 (13.9)

418 (14.6) 778 (27.2) 436 (15.3) 60 (2.1) 88 (3.1) 202 (7.1) 60 (2.1) 274 (9.6) 70 (2.4) 11 (0.4) 19 (0.7) 40 (1.4) 48 (1.7) 18 (0.6) 20 (0.7) 96 (3.4) 221 (7.7)

590 (31.6)

1407 (22. 2) 788 (12.4) 715 (11.3) 437 (6.9) 395 (6.2) 350 (5.5) 340 (5.4) 285 (4.5) 211 (3.3) 130 (2.1) 125 (2.0) 117 (1.8) 95 (1.5) 82 (1.3) 61 (1.0) 246 (3.9) 546 (8.6)

193 (10.3) 38 (2.0) 154 (8.2) 131 (7.0) 222 (11.9) 134 (7.2) 109 (5.8) 28 (1.5) 31 (1.7) 45 (2.4) 19 (1.0) 16 (0.9) 61 (3.3) 97 (5.2)

* Data are reported as number of transfusions in each diagnosis category (%). † Defined as less than 18 years old. ‡ Includes complications of HIV such as zidovudine (AZT) toxicity, opportunistic infections, HIV-associated malignancies, and HIV-associated kidney disease. § Noncancer. k Predominantly gastrointestinal bleeding. ¶ Request form listed “severe anemia” or was left blank.

female. In the pediatric population, 45.7% (435/950) were female, and in adults, 62.5% (1634/2616) were female.

gery wards accounted for almost half of units issued. The acute care unit (pediatric triage) and the pediatric hematology ward used 74% of blood issued to pediatric wards.

Ward distribution Obstetrics and gynecology wards, medicine wards, and the UCI evenly shared two-thirds of units issued for transfusion, followed by surgical, pediatric, and emergency wards (Fig. 2). More specifically, the lymphoma treatment center (at UCI), obstetric and gynecologic emergency, labor and delivery, and adult hematology wards were the top users of blood products, accounting for 35% of blood issued. Among surgical wards, general and orthopedic sur-

Clinical diagnoses A clinical diagnosis was available for 5784 of the 6330 units issued (Table 3). Overall, cancer was the most common clinical diagnosis (1668/6330). Of cancer diagnoses, leukemia and lymphoma made up 45.6% (761/1668), gynecologic tumors 16.4% (273/1668), and other solid tumors 38.0% (634/1668). Pregnancy-related complications were the second most common diagnosis (788/6330) with Volume 55, May 2015 TRANSFUSION 1061

BUTLER ET AL.

Fig. 3. Proportion of diagnoses in children, adult women, and adult men. For each diagnosis, the proportion of children, adult women, and adult men is shown. Exact numbers are given in Table 3.

postpartum hemorrhage making up 32.9% (259/788); abortion (intended or unintended) 15.9% (125/788); preeclampsia, eclampsia, or HELLP syndrome 13.3% (105/788); and ruptured uterus 10.4% (82/788). If units issued from UCI are not included in the analysis, pregnancy-related complications becomes the top reason for transfusion and cancer (not treated at UCI) is the second most common indication for transfusion. Overall, nonobstetric, noncommunicable diseases made up 68% (4309/6330) of clinical indications for transfusions. Children less than 18 years of age received 23% of all transfusions (1479/6330). For pediatric patients, cancer remained the top diagnosis, but sickle cell disease and malaria rose to the second and fourth most common diagnoses, respectively. Of cancer diagnoses in children, leukemia and lymphoma make up 83% (337/405) of diagnoses. Children were overrepresented in the distribution of sickle cell disease, malaria, and burn diagnoses (Fig. 3). In children less than 5 years of age, sickle cell disease is the top diagnosis (25.5%, 128/502) followed by nontrauma, noncancer surgery (15.5%, 78/502). The majority of surgery performed in this age group is for correction of congenital malformations (70.5%, 55/78). For adult women, cancer and pregnancy-related complications are the top diagnoses, followed by gynecologic conditions and human immunodeficiency virus (HIV). For adult men, cancer and trauma are the top diagnoses. Adult men account for the majority of trauma, gastrointestinal bleeding, and kidney disease diagnoses (Fig. 3). Seasonal variation in malaria diagnosis was not observed. The proportion of malaria diagnoses across the 3 months of data collection did not significantly change (Month 1, 2.6%; Month 2, 1.9%; Month 3, 1.2%). Even when examining only diagnoses in children, the proportion of malaria diagnoses actually decreased in Month 3, 1062 TRANSFUSION Volume 55, May 2015

which was the beginning of rainy season (Month 1, 6.5%; Month 2, 5.2%; Month 3, 3.6%).

Hb concentrations Overall, for those with Hb concentration available, the mean Hb concentration was 5.9 g/dL (95% confidence interval [CI], 5.7-6.1 g/dL; n 5 1090). Figure 4 shows the distribution of Hb levels among children, adult women, and adult men (Fig. 4A) and among hospital ward types (Fig. 4B). Children had significantly lower mean Hb levels than adults (Table 4), but there was no difference between men and women. Pediatric, medical, and emergency wards had significantly lower mean Hb levels than wards at the Cancer Institute and obstetric and gynecologic wards. Surgical wards had a significantly higher mean Hb level compared to all other types of wards. Patients on public wards had significantly lower pretransfusion Hb levels than patients on private wards.

Plasma and PLT transfusions Six percent (349/6330) of units issued were PLTs. The vast majority of PLTs went to patients with cancer (74.8%, 261/ 349), followed by pregnancy-related complications (4.3%, 15/349) and HIV (3.7%, 13/349). PLT count from request forms was only available for nine transfusions and median PLT count was 21 3 109/L (IQR, 9 3 109-33 3 109/L). Two percent (132/6330) of units issued were FFP. The top three diagnoses for plasma were pregnancy-related complications (38.6%, 51/132), cancer (24.2% 32/132), and burns (9.8%, 13/132).

Transfusion documentation A specific clinical diagnosis was not documented on transfusion request forms in 30% (1895/6330) of cases. A

BLOOD UTILIZATION IN SUB-SAHARAN AFRICA

Fig. 4. Distribution of Hb levels by age and sex (A) and by type of hospital ward (B). Each bin represents the range of Hb levels from n.0 to n.9 (e.g., 4 5 4.0 to 4.9). Bin labeled 14 represents all Hb levels of 14.0 or more. OB/GYN 5 obstetrics and gynecology.

TABLE 4. Comparison of Hb levels among subgroups Subgroup Age Adults Children Sex Women Men Ward type Pediatric Emergency Medical Cancer Institute OB/GYN Surgical Ward type Public Private

Number

% Tested

Mean (g/dL)

95% CI (g/dL)

p value

658 422

13.9 28.5

6.2 5.4

6.0-6.3 5.2-5.7

Blood utilization at a national referral hospital in sub-Saharan Africa.

A safe and adequate supply of blood is critical to improving health care systems in sub-Saharan Africa, where little is known about the current use of...
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