Faculty of Laboratory Medicine

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    EFFECTS OF HYPERHAEMOLYSIS ON FETOMATERNAL OUTCOMES IN PREGNANT WOMEN WITH SICKLE CELL DISEASE
    (ASARE EUGENIA VICKY NAA KWARLEY, 2021-09-30) ASARE, EUGENIA VICKY NAA KWARLEY
    Background: Sickle cell disease (SCD) is a public health problem in sub-Saharan Africa. Recent improvement in healthcare has ensured significant increase in survival and increased chance of getting pregnant. Chronic haemolysis is a feature of SCD; haemolysis has been linked to chronic uncompensated anaemia, pulmonary hypertension, chronic leg ulcers, priapism, renal impairment, acute vaso-occlusion, venous thromboembolism and death in SCD. Hyperhaemolysis occurs in stressful conditions, and pregnancy can be stressful. Pregnancy in SCD, can be life-threatening and may be associated with poor fetomaternal outcome. Few studies, have looked at hyperhaemolysis during pregnancy and its association with fetomaternal outcome. Methodology: A prospective cohort study with 25 pregnant women with SCD, and their 2 sets of matched controls (23 pregnant women without SCD; 25 non-pregnant women with SCD) was conducted at the Obstetrics department, Korle-Bu Teaching Hospital, and the adult sickle cell clinic, Ghana Institute of Clinical Genetics, Korle-Bu. The pregnant women with and without SCD were matched for gestational age (±2weeks) and enrolled during the second trimester. Most pregnant women presenting to the clinic for their booking visit are unsure of the date of their last menstrual period. As such, the gestational age is determined by an obstetrics scan. During the second trimester an obstetrics scan gives an error margin of 10 to 14 days; hence there will be no difference in the gestational age match using ±2weeks. The SCD group (pregnant/non-pregnant) were matched for age (±2years) and phenotype. The age match was based on convenience. All pregnant women with and without SCD were followed up prospectively till six weeks postpartum. The non-pregnant women with SCD had only baseline samples drawn. The primary outcome of the study was to determine the association between hyperhaemolysis and fetomaternal outcome in pregnant women with SCD using selected markers of haemolysis- haemoglobin, absolute reticulocyte count, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), serum bilirubin and urobilinogen. The maternal outcomes were acute pain, ACS and anaemia. The fetal outcomes were spontaneous abortion, intrauterine fetal death (IUFD), preterm birth and low birthweight. Data was extracted using Excel and analysed by the use of means, standard deviation, analysis of variance and logistic regression using STATA corps version 14. Results: The mean age of the study participants was 30.3 ± 5.3 years. The mean gestational age at enrollment for the pregnant women with and without SCD was 19.4 ± 3.7 weeks. There were 13 acute pain episodes in nine pregnant women with SCD with a pain incidence rate of 1.23 events per patient- years. There was no admission for ACS during the study period. Using the criteria for defining hyperhaemolysis, only one patient each had a drop in Hb ≥20% from baseline at 28 and 36 weeks’ gestation and six weeks postpartum; with no corresponding 25% increase in reticulocyte count and an increase in LDH, indirect bilirubin and AST. There were no significant differences in the concentrations of the haemolytic markers during study follow-up. Compared to the pregnant women without SCD, the pregnant women with SCD had more caesarean deliveries [4(19.0%) vrs 18(72.0%);p=0.01]; preterm births [5(27.8%) vrs 10(41.7%);p=0.35], low birthweight babies [3(16.7%) vrs 7(29.2%); p=0.74] and IUFD [0 (0.0%) vrs 2 (8.0%)] respectively. Conclusion: This study did not demonstrate hyperhaemolysis in pregnant women with SCD; hence no association between hyperhaemolysis and fetomaternal outcome could be determined. There was no difference in steady state laboratory parameters of the selected markers of haemolysis between the SCD cohorts (both pregnant and non-pregnant).
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    FACTOR VIII INHIBITOR STATUS OF HAEMOPHILIA A PATIENTS AT THE KORLE-BU TEACHING HOSPITAL
    (Ghana College of Physicians and Surgeons, 2023-03-31) AWUKU, NANA AGYEIWAH
    Background: Haemophilia is an inherited bleeding disorder resulting from mutations in the Factor VIII (FVIII), Factor IX (FIX) or Factor XI (FXI) gene. These mutations give rise to Haemophilia A, B or C respectively. Haemophilia A and B clinically manifest as bleeding into joints, soft tissues, and muscles spontaneously or after minor trauma whilst Haemophilia C is commonly associated with mucosal bleeding which is usually provoked. Recombinant factor replacement is the mainstay of treatment for Haemophilia A, with inhibitor formation remaining the major challenge in the treatment with factor concentrate. General Aim: This study determined the factor VIII inhibitor status among patients with Haemophilia A at the Korle-Bu Teaching Hospital Methods: Cross-sectional study involving all haemophilia A patients attending both adult and paediatric clinics at Korle-Bu Teaching Hospital (KBTH). Patients were recruited after giving informed consent or assent and or parental permission where appropriate. A data extraction form was used to extract clinical data from the patient’s medical records/folder.4.5mls of blood was taken for measuring residual FVIII activity and inhibitor assay using Bethesda Assay. Statistical analysis was done using STATA version 14. Results: All eighty-one (81) participants were male with 70.4%, 14.8%, 14.8% having severe, moderate, and mild disease respectively. The mean age of participants was 17.1 years (±13.5). Majority (93.8%) of participants had received some form of therapy which included recombinant FVIII concentrate, plasma derived FVIII concentrate, cryoprecipitate and emicizumab. A small number (6.2%) of participants had never been exposed to any form of therapy. Prevalence of inhibitors in this study was found to be 11.1% with 85.7% (n=6) having low titre inhibitors and 14.3% (n=1) having high titre inhibitors. All inhibitor positive participants were on on-demand therapy with majority (85.7%) having severe disease. Inhibitor positive participants had had higher bleeding episodes in the past year 2.14 (p=0.286). Most (57.1%) of the inhibitor positive participants had received only recombinant factor concentrate and 42.9% had received both recombinant and plasma derived concentrates (p=0.211). xiv Bleeding from the oral cavity was the commonest presentation at diagnosis (32.1%) followed by joint swelling and pain (21.0%). Almost half (46.9%) presented with spontaneous bleeding at diagnosis and 53.1% had provoked bleeding out of which 60% was trauma related and 40% from surgical/medical procedure. A small percentage (6.2%) of participants were on prophylactic therapy. Conclusion: This study reported prevalence of FVIII inhibitor in haemophilia A patients to be 11.1% with majority of participants classified as severe haemophilia A. There is the need for education and increased awareness for early diagnosis and prevention of complications of haemophilia A; especially the development of inhibitors in Ghana to enable institution of appropriate therapy.