Faculty of Health Sciences (ETDs)

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    HIV infection, antiretroviral therapy and the haemostasis of pregnancy
    (University of the Witwatersrand, Johannesburg, 2023-07) Schapkaitz, Elise; Libhaber, Elena; Jacobson, Barry; Büller, Harry
    The human immunodeficiency virus (HIV) epidemic affects an estimated 30% of pregnant women living in South Africa. Increasing evidence suggests that women living with HIV are at a heightened risk for venous thrombo-embolism (VTE), which is a significant contributor to maternal mortality. In addition to a higher prevalence of obstetric and venous risk factors, this increased risk of VTE has been attributed to the effects of HIV and/or its treatment. HIV is characterized by immune activation and inflammation, which promote endothelial dysfunction and activation of coagulation. This is more pronounced with untreated HIV, yet this pro-inflammatory and pro-thrombotic balance may persist with long-term suppressive antiretroviral therapy (ART). However, the extent to which ongoing inflammation disrupts maternal haemostasis and predisposes pregnant women living with HIV to its prothrombotic consequences, is currently unknown. The aims of the work presented in this thesis in women living with HIV with access to ART were firstly to identify antepartum and postpartum risk factors for VTE; secondly to assess procoagulant changes in maternal haemostasis; and thirdly to determine risks of thrombosis and bleeding associated with thromboprophylaxis for VTE prevention. An epidemiological case-control study was performed in 128 cases with pregnancy related VTE and 640 matched controls. This study found at least a two-fold increased risk for VTE among pregnant and postpartum women living with HIV. In addition, antepartum risk factors, that may explain the disproportion of VTE risk in HIV, included medical co-morbidities and chronic hypertension, while postpartum risk factors included a personal history of VTE, medical co-morbidities, systemic infection, prolonged hospital admission and postpartum haemorrhage. Opportunistic infections, ART and the degree of immunosuppression were not associated with VTE risk. A sub-study followed and investigated antiphospholipid antibodies (aPL) in 215 women with thrombosis and/or obstetric complications. In this study, 15 (13.2%) of the women with HIV were positive at baseline for one of the five criteria aPL. The prevalence of aPL was not significantly increased among women with HIV, as compared to HIV negative women. Furthermore, the aPL profiles were not significantly different between the two groups. Lupus anticoagulant (LAC) positivity, on a single occasion, was associated with thrombosis (p < 0.003). Subsequently two prospective cross-sectional studies were conducted which assessed endothelial activation as well as fibrinolysis, coagulation and platelet activation in pregnant women with HIV, in each trimester. The studies included three groups: HIV negative, HIV with virological suppression (< 50 copies/mL) and HIV with viral load (VL) of >50 copies/mL. Endothelial activation was evaluated by measuring von Willebrand factor (VWF) antigen, VWF propeptide, multimer patterns and ADAMTS-13 antigen, activity, and antibody levels. The results showed an increase in the ratio of VWF propeptide to VWF antigen in the first, second and third trimester, in the HIV virologically suppressed group (1.7 ± 0.7, 1.7 ± 0.4, 1.6 ± 0.5) and the HIV group with VL > 50 copies/mL (1.9 ± 0.9, 1.7 ± 0.9, 1.6 ± 1.1) compared to the HIV negative group (1.4 ± 0.6, 1.3 ± 0.4, 1.2 ± 0.3, p < 0.05). Virological suppression was not associated with a significant reduction in this ratio, in each trimester. In addition, increased high molecular weight multimers were observed in the HIV groups, despite only a mild reduction in ADAMTS-13 activity compared to the HIV negative group (p < 0.001). Thereafter, fibrinolytic activity was evaluated by measuring d-dimer and plasminogen activator inhibitor-1 (PAI-1). Coagulation activity was determined by measuring thrombin-antithrombin (TAT) complex concentrations, and platelet factor-4 and platelet indices, namely mean platelet volume (MPV) and platelet distribution width as a measure of platelet activation. The results showed increased log d-dimer levels in the first, second and third trimester, in the HIV virologically suppressed group (-1.2 ± 0.5, -0.9 ± 0.4, -0.5 ± 0.3) and the HIV group with VL > 50 copies/mL (- 1.1 ± 0.4, -0.7 ± 0.4, -0.5 ± 0.5) compared to the HIV negative group (-1.4 ± 0.2, -1.1 ± 0.3, -0.8 ± 0.3, p < 0.05). Additionally, log PAI-1 levels were increased in the first, second, and third trimester, in the HIV virologically suppressed group (1.0 ± 0.4, 1.3 ± 0.4, 1.5 ± 0.4) and the HIV with VL > 50 copies/mL (0.8 ± 0.5, 1.2 ± 0.4, 1.5 ± 0.3) compared to the HIV negative group (0.4 ± 0.5, 0.8 ± 0.3, 1.3 ± 0.3, p < 0.05). Virological suppression was not associated with a significant reduction in first and third trimester d-dimer and PAI-1 levels. Thrombin-antithrombin complex levels were not increased, in the HIV virologically suppressed group as compared to the HIV negative group, beyond the first trimester. With regard to platelet parameters, only log MPV measured in the third trimester was decreased in in the HIV virologically suppressed group (2.3 ± 0.1) and the HIV group with VL > 50 copies/mL (2.3 ± 0.1) compared to the HIV negative group (2.5 ± 0.2) (p < 0.001). The last study was a longitudinal study of 129 pregnant women at intermediate or high risk of VTE, who received thromboprophylaxis. Venous thrombo-embolism occurred antepartum in 1.4%, 95% confidence interval (CI) 0.04-7.7 of intermediate and 3.4%, 95% CI 0.4-11.7 of high risk pregnancies. Major, clinically relevant non-major and minor bleeding events occurred in 7.1%, 95% CI 2.4-15.9 of intermediate and 8.5%, 95% CI 2.8-18.7 of high risk pregnancies. Owing to the small number of events, this study could not assess for HIV as a predictor of thrombosis and bleeding. Thus, in conclusion, the findings described in the studies in this thesis contribute to our knowledge in pregnant women living with HIV in the following ways. Firstly, HIV emerged as a significant antepartum and postpartum risk factor for VTE. Traditional obstetric and venous risk factors were also linked to the risk of thrombosis and could be useful for identifying women with HIV, who may benefit from postpartum and/or antepartum thromboprophylaxis. Secondly, this thesis identified heightened markers of endothelial activation and impaired fibrinolysis. Markers such as the ratio of VWF propeptide to VWF antigen, d-dimer and PAI-1 may provide a biological mechanism for the increased risk of pregnancy-related VTE in in HIV. Finally, this thesis provided rates of thrombosis and bleeding in women who received thromboprophylaxis in pregnancy and the postpartum period which can be used to advise women with HIV of the associated risks.
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    Diagnosis in women suspected of pulmonary embolism at Chris Hani Baragwanath Academic Hospital – a retrospective review
    (University of the Witwatersrand, Johannesburg, 2023-11) Gqola, Siseko Mcebisi; Adam, Yasmin; Mbodi, Langanani
    Pulmonary embolism accounts for 3.6% of maternal deaths in South Africa and 9.2% of all pregnancy-related deaths in the United States. This cross-sectional descriptive study sought to identify clinical factors and investigations used in pregnant or postpartum women who presented with suspected pulmonary embolism. Pulmonary embolism (PE) is often one of the conditions that are considered in the differential diagnosis of women attending/admitted at Chris Hani Baragwanath Academic Hospital Obstetric High Care Unit. Women investigated with Computed tomography pulmonary angiogram (CTPA) and/or Ventilation/perfusion (VQ) scans from July 1, 2018, to June 30, 2019, were included. STATA version 14.2 was used for data analysis of the variables. The prevalence of PE was 9.4%. The mean age was 28.2 years (SD+-5.8). Most women, 126 (69.6%), were post-partum and 10 (7.9%) of those diagnosed and treated for PE. There were 81.7% women were delivered by caesarean section and 7.7% of them diagnosed with PE. Hundred (55.2%) women who had a CTPA or VQ scan were symptomatic, and the asymptomatic women had other clinical features suspicious of PE including persistent tachycardia of unknown cause. This was one of the indications for investigation in 159 (87.8%) women. Five (2.8%) women were diagnosed with deep vein thrombosis (DVT) on compressions ultrasound (CUS). Of the 181 scans (CTPA and VQ) done, 12 reports had features suggestive of Pulmonary Embolism. Pulmonary embolism is a rare, but severe condition. It is therefore important to diagnose and treat appropriately.
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    Management of women with hypertensive disorders in pregnancy in the immediate postpartum period: a retrospective review of practices in a busy tertiary hospital in Gauteng, South Africa
    (2024) Mashoene, Rangwato Pearl
    Background Hypertensive disorders in pregnancy (HDP) are a leading cause of maternal morbidity and mortality globally, accounting for14,8% of the total maternal deaths in South Africa. The burden of HDP continues beyond pregnancy with a third of women continuing to have persistent hypertension beyond pregnancy. Objective To describe the management and outcomes of women with hypertension in pregnancy during the immediate postpartum period. Methods This was a prospective study conducted at the postnatal ward of Chris Hani Baragwanath Hospital over 12 months on women with hypertensive disorders of pregnancy, who still required blood pressure treatment postdelivery. Post ethics approval, data were collected from patients and their files managed using REDCap® electronic data capture tools hosted by the University of the Witwatersrand. Results A total of 200 participants were included,163 (81,5%) had an abnormal blood pressure of more than the target BP of ³150/100mmHg within 24 hours of delivery and 37 (18,5%) within 48 hours at an average 3 day duration of stay for BP control. The choices of drugs for blood pressure control were not in line with the stepwise national guidelines on postpartum hypertension management, the commonest of which were Nifedipine, Enalapril, and Methyldopa. Sixty-seven participants (33,5%) still had uncontrolled blood pressure, higher than target BP at the time of discharge but less than severe hypertension of 160/110 mmHg. All discharged participants including those on 3 agents for BP were given a routine postnatal follow up at a local clinic. Conclusion The high number of patients that required treatment within 24 hours of delivery has highlighted the need for continued vigilance and enhanced postnatal care by clinicians beyond delivery. This includes strict adherence to institutional and national guidelines and protocols on the management of hypertension postdelivery and proper follow-up channels at discharge.
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    Review of the use of cervical cerclage at Charlotte Maxeke Johannesburg Academic Hospital
    (2024) Malete, N.
    Objective The aim of the study was to review the use of transvaginal cervical cerclages at Charlotte Maxeke Johannesburg Academic Hospital (CMAJH) for the period 1 June 2016 to 1 June 2017. Methods This is a retrospective review of 39 transvaginal cervical cerclages. The data collected included maternal demographic and pregnancy characteristics, previous pregnancies and outcomes, indications for the cerclages, antenatal and maternal complications, and neonatal outcomes. STATA software version 16 (Stata Corporation, USA) was used to analyse the data. Results There were 39 transvaginal cerclages, 28 (72%) of which were history-indicated (HI) and 11 (28%) ultrasound-indicated (UI). The overall live-born rate was 26/39 (67%). Seventy-one percent (20/28) and 55% (6/11) of history and ultrasound indicated cerclages culminated in livebirth respectively, however there were no statistical significance in terms of effectivity in preventing preterm birth between the two types of cerclages (p-value = 0.446>0.05). There was however higher incidence of PPROM in the ultrasound compared to the history indicated cerclage group (45.4% vs 10.7%) with a p-value= 0.05 respectively). Conclusion Transvaginal cervical cerclage remains an important intervention in the prevention of pre-term labour secondary to cervical incompetence. The use of cervical cerclage in this study resulted in a significant number of live birth rates and good neonatal outcomes regardless of the indications for the cervical cerclage.