In tropical countries such as Nigeria, where factor VIII (FVIII) is scarce, severe pain due to musculoskeletal bleeding complications, leading to frequent opioid prescription, is not uncommon in poorly managed people with haemophilia (PWH). The relationship between opioid use and dependence is intensively studied in other painful diseases, such as cancer and rheumatoid arthritis, but surprisingly little is known about opioid dependence in haemophilia. We hypothesise that the risk of opioid dependence among PWH in tropical countries like Nigeria is multi-factorial, encompassing demographic (age), clinical (haemophilia severity and chronic arthropathy) and biological (ABO blood groups and haemoglobin (Hb) phenotypes) factors that may directly or indirectly increase incidence of bleeding and/or pain.
To determine the prevalence of opioid dependence and relative risks (RR) associated with age, haemophilia severity, chronic arthropathy, ABO blood groups and Hb phenotypes, and to elucidate the pathophysiological roles of each risk factor in the development of opioid dependence among haemophilia-A patients in five hospitals in northern Nigeria.
A retrospective review of the medical records of 88 PWH seen between 1996 and 2012 was used to collate data on age, sex, haemophilia severity, painful chronic haemophilic arthropathy, ABO blood group, haemoglobin phenotypes, presence or absence of opioid dependence, and the types of opioids on which the patients were dependent. The prevalence of opioid dependence among the cohort was expressed as a percentage. The frequency of each putative risk factor for opioid dependence in patients with and without opioid dependence were compared using Fisher’s exact test; RR associated with each risk factor was determined by regression analysis. P<0.05 was taken as significant.
Of the 88 PWH studied,15 (17%) were shown to be opioid-dependent. Compared with PWH who were not opioid-dependent, this group had higher frequencies of severe haemophilia (86.7% vs. 49.3%: RR= 5.2, p=0.02), survival to adulthood (73.3% vs. 12.3%: RR= 9.5, p=0.0001), chronic arthropathy in one or more joints (86.7% vs. 21.9%: RR= 13.2, p=0.0004), blood group-O (80% vs. 49.3%: RR= 3.3, p=0.04), and HbAA phenotype (86.7% vs. 54.8%: RR= 4.3, p=0.04).
Prevalence of opioid dependence among PWH treated at five hospitals in northern Nigeria was 17% during the study period. Significant risk factors were directly or indirectly associated with increased rates of bleeding and/or pain, which can only be prevented or treated through optimal application of FVIII. There is a need for the Nigerian government to establish standard haemophilia care centres with adequate FVIII for optimal prophylaxis and treatment in order to minimise painful complications, thereby helping to prevent undue opioid use and dependence.
Haematuria is not uncommon in people with haemophilia and is mainly caused by spontaneous haemorrhage or trauma. The frequency and clinical significance of urinary schistosomiasis in the aetiology of haematuria among haemophiliacs in schistosomiasis endemic countries such as Nigeria have not been previously studied. We retrospectively analysed the clinical and laboratory data of 45 haemophiliacs with haematuria in Nigeria with the aim of determining the frequency of urinary schistosomiasis and other causes of haematuria among haemophiliacs, the haematological profiles of haemophiliacs with haematuria and the severity of schistosomal haematuria relative to non-schistosomal haematuria. Haematuria was due to spontaneous haemorrhage in 23 (51.1%) patients, trauma in 14 (31.1%) patients and schistosomiasis in 8 (17.8%) patients. There were no significant differences in mean values of haematological parameters between patients with spontaneous and traumatic haematuria. However, compared to patients with spontaneous and traumatic haematuria, patients with schistosomal haematuria had significantly lower mean Hb concentration (8.5 vs.11 and 11.5g/dL; p<0.05) and significantly higher mean eosinophil count (0.42 vs. 0.21 and 0.2×109/L; p<0.05). This study revealed that schistosomiasis was responsible for 17.8% of cases of haematuria in northern Nigerian haemophiliacs. Schistosomal haematuria was severe and caused significant anaemia in contradistinction to spontaneous and traumatic haematuria that were mild and did not cause significant anaemia. A superimposed pro-haemorrhagic host-parasite relationship was responsible for the severe haematuria seen in haemophiliacs with schistosomiasis, a situation that would potential increase their risk of iron deficiency and its attendant consequences including childhood cognitive impairment. Haemophiliacs with haematuria in schistosomiasis endemic countries should be investigated by urinalysis for early detection and treatment. Haemophiliacs who present with haematuria in association with eosinophilia should evoke the strongest clinical suspicion for schistosomiasis. Parents of haemophiliacs should be counseled on how to protect their children from exposures to infected waters.
We predicted that haemophilia would create a prohaemorrhagic host-parasite relationship, which would make haemophiliacs very vulnerable to haemorrhagic effects of intestinal helminths in tropical countries like Nigeria. If our prediction is correct, the frequency and risks of gastrointestinal haemorrhage and iron deficiency will be higher among haemophiliacs infected by helminths in comparison with uninfected haemophiliacs. Frequency of gastrointestinal haemorrhages and iron deficiency among haemophiliacs with and without intestinal helminth infections were retrospectively obtained and analysed, and their relative risk determined by regression analysis. Haemophiliacs with intestinal helminths had significantly higher frequencies of gastrointestinal haemorrhage (73.3% vs. 18.5%, p<0.05) and iron deficiency (60% vs. 22.2%, p<0.05) in comparison with haemophiliacs without intestinal helminths. Haemophiliacs with intestinal helminths had significantly elevated relative risks (RR) of gastrointestinal haemorrhage (RR=3.4, CI95%: 2.4- 4.3, p=0.007) and iron deficiency (RR=2.5, CI95%: 1.7-3.3, p=0.009). These results showed that helminth infections were associated with increased risks of gastrointestinal haemorrhage and iron deficiency in haemophiliacs. This is thought to be due to a pro-haemorrhagic host-parasite relationship resulting from host haemostatic abnormality, coupled with the concurrent manipulation of the host haemostatic system by anticoagulants produced by some of the parasites. Haemophiliacs in tropical countries should be regularly screened and treated for intestinal helminths.
Haemophilia A is an X-linked recessive disorder associated with deficiency of coagulation factor VIII and lifelong bleeding diathesis. Sickle cell trait (SCT) is the heterozygous state for the sickle β-globin gene. The frequency of SCT is up to 30% in Africa, wherein it confers survival advantage by providing resistance against severe malaria. SCT does not cause vaso-occlusive crisis, but is associated with high risk of venous thromboembolism as variously reported in the literature. We consider SCT as a hypercoagulable prothrombotic state and hypothesise that coinheritance of SCT may ameliorate the clinical phenotype of severe haemophilia. We conducted a retrospective analysis of frequencies of spontaneous bleeding among severe haemophiliacs with SCT (Hb AS phenotype) and their counterparts with normal Hb phenotype (Hb AA phenotype) in order to determine the possible ameliorating effect of SCT on spontaneous bleeding rates in severe haemophilia A. If our hypothesis is correct, severe haemophiliacs with SCT will have lower frequencies of spontaneous bleeding than their counterparts with normal Hb phenotype. Our results revealed that severe haemophiliacs with normal Hb phenotype had significantly higher mean annual bleeding episodes per patient in comparison with their counterparts with SCT (45±7 vs 31±5, p=0.033), suggesting that severe haemophiliacs with SCT had lower frequencies of spontaneous bleeding episodes. The result of this study indicates that coinheritance of SCT in patients with severe haemophilia may be associated with reduced frequency of spontaneous bleeding, which may imply better overall prognosis. However, the study has important limitations, which include its retrospective nature and the very low number of subjects. The findings should therefore be validated by a larger and prospective study.
Scarcity of FVIII concentrate compels caregivers in poor countries to use multiple transfusions of fresh whole blood (FWB), fresh frozen plasma and cryoprecipitate for managing haemophilia A. FWB is the most frequently transfused blood product due to ease of production and its ability to simultaneously stop active bleeding and treat anaemia. Iron deficiency anaemia is common among haemophiliacs in poor tropical countries such as Nigeria, due to the combined effects of bleeding, malnutrition, and haemorrhagic parasitic diseases. Multiple FWB transfusion is usually initiated at local sub-tertiary hospitals before eventual referral to tertiary hospitals. The Nigerian blood transfusion service is underdeveloped, donor screening is rudimentary and transfusion safety is poor. The prevalence of transfusion transmissible viral infections (TTVIs), including HIV, and hepatitis B and C viruses (HBV and HCV), is therefore predicted to be high among Nigerian haemophiliacs.
To determine prevalence and pattern of TTVIs (HIV, HBV, HCV infections) among paediatric haemophiliacs who have received multiple FWB transfusions in Nigeria.
Materials and methods
Retrospective analyses of demographic and clinical data, disease severity, number of previous transfusions of FWB, and prevalence and pattern of TTVIs (HIV, HBV and HCV infections) of newly referred haemophiliacs as seen in five tertiary hospitals in northern Nigeria. Prevalence rates of TTVIs were expressed as percentages. Comparisons of parameters (age, disease severity and number of previous transfusions) between patients with and without TTVIs were performed using Students t-test for mean values and Fisher’s exact test for percentages, with p-values of less than 0.05 taken as significant.
Of 97haemophiliacs studied, 24 (24.7%) were infected with TTVIs. The pattern and frequencies of TTVIs among the infected patients revealed HBV infection in 10 (41.7%), HIV-1 infection in five (20.8%), HCV infection in four (16.7%), HBV and HIV co-infection in three (12.5%), and HBV and HCV co-infection in two (8.3%). In comparison with haemophiliacs without TTVIs, haemophiliacs with TTVIs had a significantly lower mean age (4.9 vs. 7.8; p=0.007); a higher proportion of severe disease (62.5% vs. 26%; p=0.009), and a higher mean number of transfusions per patient (27.5 vs. 15.3; p=0.006).
The prevalence of TTVIs among haemophiliacs in Nigeria is high, and the risk is correlated with disease severity and number of previous transfusions. There is need for the national transfusion service to be upgraded and for standard haemophilia care centres with an adequate supply of FVIII concentrates for optimal care to be set up. Haemophilia healthcare providers in Nigeria can minimise multiple transfusions by incorporating regular screening and treatment of haemorrhagic parasitic diseases, iron supplementation, and the use of pharmacological agents in the standard of care for haemophilia.