Anaemia, blood transfusion practices, HIV and mortality among women of reproductive age in western Kenya

TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICIKE AND HVCIENE (1994) 88, 173-176

Anaemia, blood transfusion reproductive age in western

practic$s, Kenya

HIV and mortality

173

among women

of

J. R. Zuckerl, E. M. Lackritz’, T. K. Ruebush 1,2, A. W. Hightowerl, J. E. Adungosi3, J. B. 0. Were2 and C. C. Campbell ’ ‘Malaria Branch, Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, US Department of Health and Human Services, Atlanta, GA 30333, USA; 2Clinical Research Centre, Kenya Medical Research Institute, Nairobi, Kenya; 3Siaya District Hospital, Siaya, Kenya Abstract Severe anaemia among women in sub-Saharan Africa is frequently treated with blood transfusions. The risk of transmission of human immunodeficiency virus (HIV) through blood products has led to a re-evaluation of the indications for transfusions. Prospective surveillance of women admitted to a district hospital in western Kenya was conducted from 1 December 1990 to 31 July 1991, for haemoglobin (Hb) transfusion status, and outcome. Of the 2986 enrolled women (mean Hb IO.4 g/dL, ~~i2.6, median age 24.4 years), 6% were severely anaemic (Hb t6.0 g/dL). Severe anaemia was associated with a higher mortality rate (10.7% vs. 1.4%, odds ratio (OR)=8.2, 95% confidence interval (CI) 2.6, 34.2) compared with women with Hb 26.0 g/dL. Decreased mortality rates in hospital were observed with increasing Hb values (OR=0.43, 95% CI 0.19, 0.98), but blood transfusions did not improve survival in hospital (OR= 1.56, 95% CI 0.22, 11.03). The attributable mortality due to HIV infection and severe anaemia was 75% and 31%, respectively. Maternal/child health care services must include prevention strategies for HIV transmission and the prevention, recognition, and treatment of severe anaemia. Introduction The 2 leading causes of death among women of reproductive age in sub-Saharan Africa are complications of pregnancy and, increasingly, human immunodeficiency virus (HIV) infection (DE COCK et al., 1990). Severe anaemia is an important contributor to the morbidity and mortality associated with both pregnancy and HIV. The causes of this anaemia are multifactorial, and include Plasmodium falciparum infection, iron and folate deficiency, hookworm, and haemoglobinopathies (FLEMIKG, 1989a, 1989b). In sub-Saharan Africa current treatment guidelines for severe anaemia include the use of blood transfusions. However, the spread and intensification of the HIV Dandemic has raised concerns about the safetv of blood &transfusions in Africa. This has led to a reevaluation of the clinical indications for using blood products (WHO, 1988). We conducted an evaluation of blood transfusion uractices in a district hospital in western Kenya during 1’99% 1991. During a period of 11 months, 927 transfusions were ordered for 799 patients (LACKRITZ et al., 1993); most were for children < 15 years of age (67%), but 27% were ordered for adult women, and 6% for adult men. The high percentage of blood transfusions given to adult women raised questions regarding the indications for, and benefits of, blood transfusions in this population. This study was undertaken to describe the haematological status, blood transfusion practices, and characteristics associated with mortality in hospital among women hospital patients of reproductive age. The results provide a basis for defining circumstances when blood transfusions may affect survival in hospital, and identify factors associated with death in hospital which can lead to the development of improved hospital management strategies. Methods The study was conducted at Siaya District Hospital (SDH), a 200-bed Ministry of Health hospital in Nyanza Province in western Kenya. SDH is the primary referral centre and the only government hospital in the district, which has a population of 600 000. Surveillance of all patients admitted to the 2 adult female wards of SDH (one ward for obstetrical cases and the other for all other female admissions except tuberculosis) was conducted from 1 December 1990 to 31 July 1991. All women between the ages of 15 and 44 years had their capillary *This article is not copyright. Address for correspondence: Dr J. R. Zucker, Malaria Branch, CDC, 1600 Clifton Road, Mailstop F-12, Atlanta, GA 30333, USA.

haemoglobin level (Hb) measured and the following information collected: age, pregnancy status, admission diagnosis, whether a transfusion was ordered, and outcome of hospital admission (alive, dead, transferred, or left the hospital against medical advice). Women were selected for more intensive study if their Hb was <6.0 g/dL (defined as severe anaemia), or if they had a transfusion ordered. Women with Hb 36.0 g/dL and with a hospital in-patient number which ended with a 7 or 8 were chosen as a comparison group. The women selected for more intensive study had their reproductive history recorded, and pulse, respiratory rate, temperature and blood pressure taken at admission. If a patient was pregnant, the outcome of the pregnancy was recorded. Thick and thin blood films for malaria parasites were examined, and between 11 March and 31 July 1991 serum was taken for HIV serology. Laboratory studies Haemoglobin was measured from a capillary l-ingerprick using a Hemocue@** (Mission Viejo, CA) machine. Thick and thin blood smears were stained with 3% Giemsa for 30 min. The number of malaria parasites was determined per 300 white blood cells and parasite density was calculated assuming an average of 8000 white blood cellsimm3. HIV-l serology was done by enzyme-linked immunosorbent assay (Wellcozymea, Wellcome Laboratories, Research Triangle Park, North Carolina, USA), and all positive results were confirmed by Western blot (DuPont de Nemours, Geneva, Switzerland). Analysis Data were analysed using Epi-Info 5 and SAS statistical package computer programs. Categorical variables were analysed using frequency distributions and differences among groups were investigated using y,’ or Fisher’s exact tests, as appropriate. The Wilcoxon rank sum test was used to compare the distribution of continuous variables. Potential confounders and effect modification were adjusted for by stratified analysis and by unconditional logistic regression. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated when appropriate. Results Patient characteristics During the 8 months study period, 3466 persons were ‘*Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the US Department of Health and Human Services.

174

cc 0 300 1

; 200 n E 100 z' L , 7 '6 0 1 2 3

Haemoglobin

(g/dL)

Figure. Haemoglobin distribution of 2808 women admitted to Siaya District Hospital, Kenya, between 1 December 1990 and 31 July 1991 and for whom haemoglobin values were available.

admitted to the 2 female wards. Of these, 2986 were women of childbearing age (15-44 years of age); 95% of 1792 women admitted to the obstetrics ward and 28% of 1194 women admitted to the general female ward were pregnant. The mean age was 24.4 years (standard deviation) TSD1=6.5),and the median age was 23 years. The rangebf observed haemoglobin val&s was 0.9118.6 g/dL (Figure), with a mean Hb of 10.4 g/dL (~~=2.6); 55% of the women had Hb < 11.0 g/dL and 6% had Hb <6.0 g/dL. Pregnant women had lower Hb than non-pregnant women (mean+SD=lO.3?2.2 g/dL vs. 10.7i3.2 g/dL; P
Women with admission Hb <6.0 g/dL were compared with women in the reference group to identify factors related to severe anaemia (Table 1). Severely anaemic Table 1. Characteristics of three selected groups of women from the study population. Siaya District Hospital, Kenya: 1 December 199&31 July 1991 Haemoglobin c6.0 g/dL Number

“Standard deviations

240

150

of women

Age (years) Mean” Median Pregnant HIV positive P. falciparum No. infected Mean parasitaemia (per mm3) Mean haemoglobin WC Deaths

Transfusion ordered

26.0

(7.3)

73,1502&7Y0) 30179 (38.0%)

Comparison group 279

26.0

(7.2) 24.5 (6.5) 25 23 1351240 (56.3%) 1771279 (63.4%) 401142 (28.2%) 301173 (17.3%)

The admission diagnoses for women with Hb <6.0 g/dL included deliverv or obstetrical comnlications (83, 56%), medical diagnoses(47, 31%), gynaecological prob: lems (18, 12%), and trauma (2, 1%). Overall, women admitted with Hb <6.0 g/dL had admission vital signs that were consistent with being more ill than women with Hb 26.0 g/dL. Their mean temperatures (37.050.95”C vs. 36.8+0.79”C, P
Two hundred and forty women had a transfusion ordered and were selected for further study; 116 received the transfusion (seeTable 1). Blood transfusions were ordered for these clinical indications: severe anaemia (78, 32%), urgent operation such as ectopic pregnancy or Caesareansection (62, 26%), acute blood loss (26, ll%), or trauma (4, 2%); for the remaining 70 patients (29%), reasonsfor transfusion were not indicated. Women who had a transfusion ordered had a higher mortality rate (251240,10.4%) than women for whom a transfusion was not ordered (181933, 1.9%) (OR=5.91, 95% CI 3.04, 11.53); this difference was unchanged by adjusting for severeanaemiaor pregnancy. Among the women for whom a transfusion was ordered, those who received a transfusion were more anaemic (mean Hb 5.1 g/dL, SD=2.5) than the women who were not transfused (mean Hb 8.3 g/dL, s~=2.9) (P
301145 (20.7%)

62/235 (26.4%)

851275 (30.9%)

5314 (10933)

3442 (8175)

3694 (7960)

4.4 (1.2) 16 (10.7%)

6.8 (3.1) 25 (10.4%)

11.2 (2.1) 4 (1.4%)

in parentheses

women were older (P=O.O3, Wilcoxon rank sum test), less likely to be pregnant (OR=0.53,95% CI 0.35,0.81), and were more likely to be HIV seropositive (OR=2.92, 95% CI 1.52, 5.60) compared to women with Hb 26.0 g/dL. Women with severe anaemia were less likely to have Plasmodium falciparum parasitaemia than non-anaemic women (OR=O.SS, 95% CI 0.35, 0.96). This relationship was unaffected by pregnancy status or parity. Among women with P. falciparum parasitaemia, the mean parasite density did not differ between severely anaemic and non-anaemic women iP=O.15. Wilcoxon rank sum test).

Severely anaemic women had an 8.2 (95% CI 2.6, 34.2) increased odds of mortality in hospital compared with non-anaemic women. There were 16 deaths among 150 severely anaemic women (10.7%), compared with 4 deaths among the 279 non-anaemic reference women 11.4%). Clinical characteristics of the 20 women who died are outlined in Table 2. Of the severelv anaemic women who died, 5 were pregnant, 1 was post-partum, and 7 of the 8 for whom HIV test results were available were seropositive. All women survived the first hospital day, providing an opportunity to receive an ordered transfusion. Benefit of transfusion was examined by restricting the analysis to only severely anaemic women, in whom the greatesteffect of transfusion would be expected. Patients with severeanaemiawho received a transfusion (7 deaths among 77 women, 9.1%) demonstrated improved, but not statistically significantly so, survival in hospital compared with severely anaemic women who did not receive a transfusion (9 deaths among 71 women, 12.7%;

175 Table

2. Clinical

No.

data of study women who died Transfusion ordered/given

Clinical diagnosis

No Yes

NK

E:

E NK

2.1 4.2 4.7

Yeslno Yes/no Yeslno Yes/no NoiYes/no Yes/yes NoiYes/yes Yes/yes Yes/no Yes/yes Yes/yes Yes/yes NolYes/yes NolNo/NoiNoi-

Medical Medical Medical Medical Medical Medical h1edical Medical Medical Medical Obstetric Medical Obstetric Medical Medical Medical Medical Medical Medical Medical

43 ;I 38 ;z ! 8 9

Haemoglobin g/dL

Pregnant

:. : 5

HIV statusa

Age (years)

kb No

;:

:: 12

t;’ 28 25

:i 15

:; 18

:;

;: 28

K: No Yes No Yes No Yes Yes No No

:;

i8

:t 20

E NK NK + + f + + + +

aNK=not known, bid post-p artum.

+ =positive,

Table 3. Results of multivariate Variable Haemoglobin leveld Transfusion given Age (years) Pregnant HIV positive P. falciparum infection Temperature (“C) Pulse rate Blood pressure Systolic Diastolic

tE +

;:; 5.0 4.5 ;:; 4.7 3.9 5.2 2:; ;:; 7.7 lo:9 9.4

Days in hospital 1 s :. 2: 2: 15 1 2 14 1 fii 2: 31

- =negative. analysis of variables associated with mortality among severely anaemic women in Kenya Odds ratios (95% con!i$;E;: $tervals Model Aa 0.61 (0.39, 0.96) 0.41 (0.13, 1.32) 1.01 (O.SS, 1.08) 0.42 (0.14, 1.26) 20.03 (2.04, 197.00) 0.54 (0.15, 1.98) 1.24 (0.72, 2.12) 1.04 (1.01, 1.08) -

0.96 (0.93, 0.93 (0.88,

0.99) 0.98)

in parentheses) Model C’ 0.43 (0.19, 1.56 (0.22, -

0.98) 11.03)

20.03 (2.02, 197.00) 1.02 (0.98,

1.07)

0.94 (0.88, 0.93 (0.83,

1.01) 1.03)

“Reduced model: dependent variable=death (yes/no); independent variables=haemoglobin level, transfusion given. bExploratory model: dependent variable=death (yes/no); independent variables=haemoglobin level, transfusion given plus the following variables added individually to the model: age, pregnant, HIV positive, P. falciparum infection, admission temperature, pulse, systolic and diastolic blood pressure. ‘Final model: dependent variable=death (yes/no); independent variables=haemoglobin level, transfusion given, HIV Dositive DIUS admission Dulse, svstolic and diastolic blood pressure added individually to the model. ‘Haemogiobin value as a&cont&ous variable (g/dL). OR=0.69, 95% CI 0.21, 2.22). Further restricting the analysis to those severely anaemic women for whom a transfusion was ordered, there was a continued trend for transfusion to improve survival in hospital: 7 deaths among 77 women who were given a transfusion (9.1%) vs. 6 deaths among 26 women who were not given a transfusion (23%; OR=0.33, 95% CI 0.09, 1.36). A similar benefit of transfusion was demonstrated among severely anaemic pregnant and post-partum women: 2 deaths among 40 women who received a transfusion vs. 4 deaths among 42 women who did not receive a transfusion (OR=0.50, 95% CI 0.04, 3.76). Among full-term pregnant women who delivered, the mortality rate (3128, 10.7%) among the newborn children of severely anaemic women was higher than that (6/162, 3.7%) among newborn children of non-anaemic women (OR=3.12,95% CI 0.47, 15.64). A logistic regression model that assessed the relationship between Hb level (as a continuous variable) and receipt of transfusion showed a strong correlation of increased risk of death with decreasing Hb values. The odds ratio showed a protective effect of a blood transfusion on mortality of 0.41, but this was not statistically

significant (Table 3, model A). Each variable (transfusion given, age, pregnant, P. fulciparum infection, HIV positive, temperature, pulse rate, systolic and diastolic blood pressure) which was associated with anaemia in the univariate analysis was individually added to the 2 variable model (Hb and transfusion given). Variables that contributed to mortality were Hb, HIV status, admission pulse rate, and systolic and diastolic blood pressure (Table 3, model B). Admission vital signs (pulse, systolic and diastolic blood pressure) were no longer significant after simultaneously adjusting for Hb and HIV seropositivity (Table 3, model C). The trend for a possible benefit of transfusion was no longer demonstrated after the addition of HIV serostatus to the model. The attributable proportion of mortality due to severe anaemia was 31%, and that to HIV infection was 75% (attributable proportions may sum to over 100% due to correlation between variables). Discussion Anaemia is highly prevalent among women admitted to hospital in Siaya District; 55% of women had Hb < 11.O g/dL, which is anaemic by World Health Organiz-

176 ation/Centers for Disease Control Standards, and 6% of women were severelv anaemic (Hb <6.0 g/dL) (CDC, 1989). The public health implications are enormous; the reported health consequencesof anaemia include diminished work capacity and adverse effects on pregnancy outcome. Severelv anaemic women in SDH had an g-fold higher mortality rate than women with Hb 26.0 g/dL, and the association between Hb and death was consistent acrossall values of Hb. The contribution of severeanaemia to observed mortality was 31%, and this was not changed by receipt of transfusion. In addition, low haemoglobin level has been associated with prematurity and low birth weight, the most important predictor of infant mortality (LIEBERMAN et al., 1987; BRABIN et aZ., 1990). In SDH, newborn children of severely anaemic women had nearly a 3-fold higher mortality rate than those of non-anaemic women. Programmes to prevent, identify, and treat anaemiamust be developed to help reduce mortality associatedwith severe anaemia among women of reproductive age and their newborn infants. The prevalence of anaemia among pregnant women attending maternal/child health clinics can be reduced through combinations of iron and folate supplementation and antimalarial therapy (JACKSON& LATHAM, 1982; FLEMING et aZ., 1986; BRABIN et al., 1990). Thus, an intervention aimed at pregnant women while they are using the medical care system may be the best opportunity for them to receive treatment for anaemia. Several authors have suggestedcriteria for evaluating the use of blood transfusions in sub-Saharan Africa (TAGER et al.. 1990: ADDO-YOBO & LOVEL. 1991). An

appropriate transfusion has been defined as a’transfusion given for an acute fall in haemoglobin level, due to either bleeding or haemolysis, or for symptomatic chronic anaemia. Transfusions were considered to be avoidable if they did not meet the above criteria or if one unit or less of whole blood was given to an adult. Although there is no established criterion for transfusion at SDH, 71% of transfusions were given to women for clinical indications such as acute blood loss or urgent surgery. However, 81% of women who were transfused received only one unit of whole blood, and 50% of these units were given after the first day in hospital. If we apply the guidelines listed above, 29% of women who received a transfusion did not meet clinical criteria for transfusion, and most of the women received a transfusion that would be judged to be avoidable basedon its volume. The association between receiving a blood transfusion and improved survival in hospital while taking Hb into account consistently demonstrated a benefit, i.e. the odds ratios were below 1.00 but were never statistically significant. The small number of deaths observed in this study may have precluded demonstration of a benefit from transfusion. Alternatively, transfusions may not have been beneficial becausethe volume received was not sufficient or the transfusion was given after the patient had already survived the acute event. However, when concomitant illness, in this caseHIV infection, was taken into account, the trend for a beneficial effect of transfusion was no longer present. This highlights the need to manage a patient’s underlying illness and not just treat a consequence of that illness, such as transfusing when there is a low Hb. Seventy-five percent of the observed deaths among women of reproductive agein this hospital were attributable to HIV infection. A similar high mortality rate attributed to HIV infection among women of reproductive age has been identified in Abidjan, Cote d’Ivoire, and Tanzania (DE COCKet al., 1990; E. Urassa, personal communication). HIV infection among pregnant women has been associatedwith an increasein pregnancy-related complications and with poor birth outcome (KOONIN et al., 1989; BRADDICKet al., 1990). The striking feature of all these reports and the SDH population is that few of the HIV-associated deaths were among women who were identified as having an HIV-related iil-

nessbefore death. In summary, in a setting such as SDH the question of how to prevent the development of anaemia is more important than the question of who will benefit from transfusion. The high prevalence of anaemia must be addressed early through interventions at maternal/child health clinics before women require admission to hospital. Also, because blood transfusions are life-saving in only a small proportion of patients in this environment, they should not be routinely given. Furthermore, the high prevalence of HIV infection among women in hospital must be recognized and then addressed through prevention programmes designed to interrupt HIV transmission. Acknowledgements

This paper is published with the permission of the Director, Kenya Medical Research Institute. We thank Drs I’. M. Tukei, Virus Research Centre, Kenya and C. A. Schable, Division of HIV/AIDS, CDC, for their assistanceand laboratory support. This work was partly supported by the Global Programme on AIDS, World Health Organization. References

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