Susan Louw

The effect of initiating combined antiretroviral therapy on endothelial cell activation and coagulation markers in South African HIV-infected individuals.

An increased incidence of venous thromboembolism (VTE) is observed in human immunodeficiency virus (HIV)-infected patients. Only a limited number of studies described the effect of combined antiretroviral therapy (cART) on coagulation markers. In a prospective cohort study in cART-naive South African HIV-infected individuals the effect of initiating cART on markers of endothelial cell activation, coagulation and natural anticoagulation was studied. These markers were compared to the reference ranges for an HIV-uninfected control population recruited from hospital staff. A venous ultrasound of both legs was performed to detect asymptomatic deep venous thrombosis (DVT). A total number of 123 HIV-infected participants were included. The patients were predominantly black and severely immuno-compromised. The CD4 cell count increased and the HIV viral load decreased significantly after the initiation of cART (p<0.001). The median follow-up period was 7.2 (± 1.6) months. Laboratory testing before and after initiation of cART was completed by 86 patients. Before initiating cART significantly elevated von Willebrand factor and D-dimer levels, increased activated protein C sensitivity ratio (APCsr) and decreased total and free protein S and protein C levels were observed compared to HIV-negative controls. At follow-up all markers, except APCsr, improved towards the normal range for controls without showing complete normalisation. In a subgroup of 57 patients no asymptomatic DVT was found. Compared to the controls, abnormal levels of coagulation markers were observed in HIV-infected individuals before and after the initiation of cART. Most markers improved after starting cART, but remained significantly different from the controls, indicating a persistent disturbed haemostatic balance.

Human immunodeficiency virus infection and acute deep vein thromboses.

Abnormalities that predispose to a hypercoagulable state with an increased incidence of venous thrombosis have been described in human immunodeficiency virus (HIV) infections and are associated with an increased mortality. A recent systematic review by Klein et al concluded that further studies are essential to elucidate the link between HIV infection and deep vein thrombosis (DVT). We prospectively evaluated 24 consecutive, active people presenting with an acute DVT; 13 consented to HIV testing, revealing an HIV prevalence of 84% (95% confidence interval [CI], 0.65-1.04). In a matched healthy control group, the HIV prevalence was 4% (95% CI, 0.039-0.041). The high HIV prevalence in the DVT group that consented to testing was also significantly higher compared to that in the South African population, estimated to be 10% in 2005. Although the study numbers were low, a statistically significant increased prevalence of HIV infection was found in patients with acute DVTs.

Combination of acquired von Willebrand syndrome (AVWS) and Glanzmann thrombasthenia in monoclonal gammopathy of uncertain significance (MGUS), a case report

BackgroundAutoimmune paraphenomena, are associated with B-cell lymphoproliferative disorders, including monoclonal gammopathy of uncertain significance. These paraphenomena can rarely include acquired bleeding disorders.Case presentationThis case study reports an unusual clinical presentation of 2 acquired bleeding disorders, Acquired von Willebrand syndrome (disease) and Acquired Glanzmann’s thrombasthenia, in an elderly patient with monoclonal gammopathy of uncertain significance.ConclusionsAcquired bleeding disorders are often underdiagnosed and a high degree of clinical suspicion is required. The patient in this study demonstrated platelet aggregometry which was atypical for isolated Glanzmann’s thrombosthenia because of the severe concomitant endogenous decrease in von Willebrand factor. There was an absence of platelet aggregation to all tested agonists including ristocetin. Once the diagnosis was made, however, the patient showed a partial response to intravenous immunoglobulin confirming the immunological pathogenesis in this case. This case highlights the need to consider acquired bleeding disorders in patients with a possible predisposing factor.

Pathogenic factors associated with development of disseminated intravascular coagulopathy (DIC) in a tertiary academic hospital in South Africa

Introduction Disseminated intravascular coagulopathy (DIC) is a thrombotic microangiopathy arising from consumption of both coagulation factors and platelets. DIC is triggered by a number of clinical conditions including severe infection, trauma and obstetric complications. Early diagnosis and treatment of the underlying condition is paramount. A high clinical index of suspicion is needed to ensure that patients at risk of developing DIC are appropriately investigated. Methods In order to establish the clinical conditions most frequently associated with DIC, we reviewed all DIC screens received at a tertiary hospital in Johannesburg, South Africa over a 1 year period. Results The commonest clinical condition associated with DIC in our population was infection with 84% of patients infected with an identified pathogen. The most frequently diagnosed pathogen was HIV followed by Mycobacterium tuberculosis and other bacterial infections. In the majority of cases, bacteria were isolated from blood cultures. In 47 patients, HIV was the only pathogen which could be isolated. A relative risk ratio of 2.73 and an odds ratio of 29.97 was attributed to HIV for development of a DIC. A malignancy was present in 51 of the patients of which approximately 60% had co-existing infection. No cause could be attributed in 30 patients. Conclusion Infection was identified in the majority of the patients diagnosed with DIC in this study. HIV showed the highest relative risk ratio of all pathogens although previous studies have not suggested that HIV was strongly associated with DIC. In almost half of the HIV infected patients, there was no other pathogen isolated despite extensive investigation. This suggests that HIV has a strong association with the development of DIC, warranting further research into the relationship between HIV and disseminated microvascular thrombosis.

Evaluation of the diagnostic utility of individual parameters in the disseminated intravascular coagulation (DIC) panel for use in underresourced settings

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Conservative Management of Overanticoagulation in Patients With Low–Moderate Risk for Bleeding Complications

Despite long-standing experience with warfarin, anticoagulation clinic services are often confronted with the challenging clinical situation of patients with overanticoagulation. This requires repeat international normalized ratio (INR) monitoring and in some cases administration of vitamin K to minimize the risk of bleeding. A study was performed to determine the safety and efficacy of outpatient management in order to provide guidance on the management of patients with prolonged INRs. Patients on stable warfarin therapy for more than 1 month attending a dedicated academic hospital anticoagulation clinic who had an INR ≥5 were identified over a 1-year period. Follow-up INR results and outcomes were recorded for 30 days. One hundred and ninety-five episodes of overanticoagulation in 148 patients were identified. Patients were classified as low risk (n = 85, 57.4%) and moderate risk of bleeding (n = 63, 42.6%). The mean index INR was 7.22 (1.88). Management with low-dose oral vitamin K (n = 32, 16.4%) did not significantly result in a more rapid correction of the INR when compared to conservative management (n = 163, 83.6%; P = .103). Follow-up INR testing was performed at a mean of 11.1 (8.9) days from the index measurement. A mean of 1.6 (0.9) follow-up INR tests were performed per episode. During the 30-day follow-up, there was 1 (0.5%) episode of major bleeding and 1 (0.5%) death. The management of asymptomatic outpatients with overanticoagulation is associated with a low risk of major bleeding within 30 days. Conservative management of overanticoagulation is as effective as utilizing low-dose oral vitamin K.

The use of VTE prophylaxis in relatioN to patiEnt risk profiling (TUNE-IN) Wave 2 study

BACKGROUND The TUNE-IN (The Use of VTE prophylaxis in relatioN to patiEnt risk profiling) study evaluated venous thrombo-embolism (VTE) risk assessment and prophylaxis in private medical and surgical inpatients in Gauteng Province, South Africa. The study concluded that of the 608 patients enrolled, 54.1% were clinically evaluated to be at risk for VTE. A VTE risk assessment model (RAM), the Caprini score, increased the rate to 74.6%. OBJECTIVES TUNE-IN Wave 2, an extension of TUNE-IN, was conducted on a national level including the public sector, focusing on surgical inpatients. METHODS The study was a national, prospective, non-interventional, multisite, epidemiological disease registry enrolling 453 surgical inpatients. The perceived clinical VTE risk, VTE risk score on Caprini RAM, VTE prophylaxis and clinical details were documented during a baseline visit. A bleeding risk score was provided. RESULTS Of the cohort, 269 patients (59.4%) were assessed to be at risk for VTE before applying the RAM. All patients (100%), however, were at risk on the RAM score. Early mobilisation and assessment of the VTE risk as low were the most frequent reasons for non-prescription of prophylaxis. Only 15 patients in the private and 2 in the public sector were assessed as having a bleeding risk. Chemoprophylaxis differed between the healthcare sectors, with low-molecular-weight heparin predominating in the private sector and unfractionated heparin being prescribed only in the public sector. CONCLUSION VTE risk assessment and prophylaxis need to improve in both the public and the private sectors. A formal RAM will improve identification of patients at risk of VTE.

The utility of thrombo-elastography in the monitoring of aspirin therapy

To assess the utility of the thrombo-elastogram in monitoring of aspirin therapy 25 healthy volunteers were selected and given low-dose aspirin therapy. Thrombo-elastography and platelet aggregometry were conducted at baseline and 1 week later. After 1 week of aspirin therapy, thrombo-elastogram data failed to demonstrate a significant change in the clotting profile. Platelet aggregometry identified significant changes in the clotting profile in response to stimulation with arachidonic acid, adrenaline and ADP. We conclude that thrombo-elastography may not have utility in monitoring of response to aspirin.