Browsing by Author "Louw, Susan"

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    Overview of the Haematological effects of COVID19 infection
    Wiggill, Tracey M.; Mayne, Elizabeth S.; Vaughan, Jenifer L.; Louw, Susan
    From its early origins, COVID-19 has spread extensively and was declared a global pandemic by the World Health Organization in March of 2020. Although initially thought to be predominantly a respiratory infection, more recent evidence points to a multisystem systemic disease which is associated with numerous haematological and immunological disturbances in addition to its other effects. Here we review the current knowledge on the haematological effects of COVID-19.
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    The relationship between HIV infection and acute deep vein thromboses.
    (2012-01-17) Louw, Susan
    Objective: HIV infection is a global pandemic with approximately 37 million adults infected worldwide.1 Numerous abnormalities predisposing to a hypercoagulable state have been described in patients with HIV infection and include deficiencies of antithrombotic proteins and the presence of procoagulants. The abnormalities have been described to correlate with the degree of HIV associated immunosuppression as well as with the presence of concomitant infections and / or neoplastic disorders. The conclusion of several studies2-3 has been that although evidence pointed towards a relationship between HIV infection and venous thrombotic disease, more studies were indicated to further elucidate this link. The majority of studies reporting on the documented prothrombotic abnormalities in HIV infection were conducted in first world cohorts. The objective of the study was to determine the prevalence of underlying HIV infection in patients presenting with acute deep vein thrombosis (DVT) without the presence of traditional risk factors for DVT. This prevalence was compared to the HIV prevalence in a sex, age and race matched control group without symptomatic DVT. In addition, the possible pathophysiological mechanisms for DVT development in this cohort are detailed. Methods: Consecutive adult patients presenting to the Charlotte Maxeke hospital casualty with lower limb acute deep vein thrombosis (DVT) were invited to participate in the study. Voluntary HIV testing of the participants were performed after counselling and consent with appropriate referral for further management if HIV result was positive. A record review was performed and information regarding the presence of commonly encountered traditional risk factors for the development of DVTs. The control group was an age, sex and race matched cohort to establish the prevalence of HIV infection in a matched population without symptomatic DVTs. A review of the literature to identify the possible underlying causative factors linking HIV and DVT was conducted. Results: The HIV prevalence in the DVT group who consented to HIV testing and who had no traditional risk factor for DVT development (22 patients) was 81% (95% CI 0.67 - 0.96). The HIV prevalence in a matched control group without symptomatic DVTs was found to be 4% (95% CI 0.039 – 0.041). All the DVT patients who consented to HIV testing were active, community integrated members of the society. The average CD4 cell count of the HIV positive patients with acute DVTs was 247 /mm3. Two of the HIV positive patients with DVTs were on ART (anti-retroviral therapy) and 4 were also diagnosed with pulmonary tuberculosis. Traditional DVT risk factors identified in the HIV infected DVT cohort other than tuberculosis were immobilisation and carcinoma. Conclusion: A prothrombotic state is present in HIV infected individuals giving rise to an increased prevalence of thrombotic complications with potentially fatal consequences. The risk of DVTs in the general population is 0.10 % a year2 but the current and other studies indicate that the prevalence in HIV positive patients is significantly increased. From this thesis it is clear that there is no available evidence evaluating thromboprophylaxis specifically in HIV-infected individuals. The available thrombosis treatment guidelines lack recommendations in this growing sub-population. Important treatment decisions are therefore left to medical attendants without clear guidelines. HIV infection in the ARV era is a chronic disease with a clearly prothrombotic tendency. Future studies and guidelines should further define the thrombotic risk in the HIV infected population and direct treatment and prophylaxis.
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    The changing face of thrombotic thrombocytopenic purpura: the pathophysiological role of endotheliitis and complement activation in the development of human immunodeficiency virus associated thrombotic thrombocytopenic purpura
    (2024) Louw, Susan
    Introduction- Human Immunodeficiency virus (HIV) is a described risk factor for secondary thrombotic thrombocytopenic purpura (TTP) (HIV-TTP). The pathogenesis of this thrombotic microangiopathy (TMA) is however still unclear. The micro-thrombotic process in TTP is related to excess ultra-large von Willebrand Factor (ULVWF) multimers produced by the endothelial cells. Autoantibodies to the VWF cleaving protease, adisintegrin-and-metalloproteinase-with-thrombospondin-motifs 13 (ADAMTS-13), are postulated to be pivotal in initiating HIV-TTP. Inflammation and complement activation with resultant endothelial dysfunction and excessive release of ULVWF multimers have been implicated in other forms of TMA. These pathophysiological processes were investigated to assess the contribution to the development of HIV-TTP. Methods- Data were collected from patients presenting with HIV-TTP in an observational cohort study to delineate the routine presenting laboratory parameters and treatment outcomes. The published literature was reviewed to ascertain the documented prevalence, postulated pathogenesis and treatment outcomes of patients with HIV-TTP. An investigational study was performed in patients (n=35) presenting with HIV-TTP. In this study, patient samples were analysed for levels of endothelial activation markers (soluble intracellular adhesion molecule [sICAM] and soluble vascular adhesion molecule [sVCAM]), inflammatory cytokines (tumour necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]), and complement components C3 and 4 and complement Factor H (CFH), an inhibitor of the complement pathway. Published studies were also reviewed to define the baseline biomarker levels of endothelial dysfunction and coagulation activation in people living with HIV (PLWH) without TTP to serve as points of reference. Data were collected from 2 patient cohorts with HIV infection with either disseminated intravascular coagulation (DIC) or with HIV-TTP to assess the utility of scoring systems. Results- In contrast to published literature which suggests that the prevalence of HIV-TTP is declining, this TMA is prevalent in South African PLWH in Johannesburg with heterogeneous clinical and laboratory presentation. Conventional scoring systems specifically the PLASMIC (reduced platelet count, red blood cell haemolysis, absence of cancer, no history of transplantation, reduced red blood cell volume, preservation of the international normalised ratio and creatinine) score, developed for detection of other acquired forms of TTP, performed inconsistently in the 35 patients assessed with considerable overlap with other TMAs, notably disseminated intravascular coagulation (DIC). ADAMTS-13 levels were undetectable in all patients and all patients had anti-ADAMTS-13 antibodies. The clinical presentation was, however, atypical. To delineate intermediate pathophysiological markers, the complement system, proinflammatory system and coagulation system, as well as markers of endothelial activation were analysed before and after therapeutic plasma exchange (TPE). Complement components C3 and -4 were consistently at the lower limit of the normal reference range in HIV-TTP patients at presentation. The complement regulatory protein, complement Factor H, was increased. Patients with HIV-TTP had significantly increased levels of proinflammatory cytokines when compared with published results in PLWH without comorbidities. Endothelial activation markers, sICAM and sVCAM, were also significantly increased in the HIV-TTP cohort. Importantly, D-dimer levels were also raised in this cohort of patients. Conclusions- HIV-TTP remains a cause of HIV-related morbidity and mortality in South African patients. This study reports the findings on 35 PLWH who presented to hospitals in Johannesburg with suspected TTP. The clinical presentation was inconsistent with other secondary forms of TTP i.e., minimal evidence of systemic organ dysfunction. All patients presented with schistocytosis, evidence of haemolysis and thrombocytopaenia and all had low ADAMTS-13 activity levels at presentation with detectable antiADAMTS-13 antibodies. Biomarkers of endothelial dysfunction, proinflammatory cytokine levels and markers of coagulation were all significantly increased suggesting that the pathophysiology involves complementary proinflammatory pathways which directly impact secretion of VWF from a compromised endothelium. Activation of the coagulation system, as reflected by increased D-dimer levels, specifically suggests that there may be overlap in the pathophysiology of HIV-TTP and HIV-associated DIC. A potential strategy for differentiation of these disorders with modification of scoring systems is suggested. This study provides compelling evidence of the role of the endothelium in HIV-TTP. Future directions will include validation of the biomarkers described here in more extensive cohorts as well as investigation of these biomarkers in management of these patients.