HIV-positive patients taking highly active antiretroviral therapy (HAART) who developed a thrombosis tended to be relatively young, have high levels of blood fats, and an AIDS-defining cancer, according to a retrospective United States case series published in the October 15th edition of Clinical Infectious Diseases.
It’s thought that thrombosis - the development of a clot in a blood vessel - occurs significantly more frequently in individuals taking HAART than the general population. HIV-positive patients experiencing thrombotic events appear to be younger and lack the classic risk factors of thrombosis compared to HIV-negative individuals.
Investigators wished to establish a better understanding of the frequency of, and risk factors for thrombosis in HIV-positive patients. Accordingly, they conducted a retrospective chart review of 30 HIV-positive patients attending an HIV outpatient clinic in Seattle, who developed a thrombosis between 1996, when HAART first became widely available, and 2002.
Demographic data were obtained from medical records along with risk factors for thrombosis, including smoking, family history, and the development of thromobosis before 1996. Information was also gathered on medication history, treatment and outcome.
Data were also gathered on CD4 cell count, viral load, and blood lipids at the time of thrombosis. For 24 patients, data were also available for laboratory tests conducted at the time of thrombosis to assess levels of blood proteins and anticoagulants.
The records of 29 patients were included in the investigators’ analysis. The median age was 43 years. Despite the relatively young age of the study population, several risk factors for thrombosis were common. In total 23 patients (77%) smoked, with the median duration of smoking being 22 years. A family history of thrombosis was present for twelve patients (40%), and 17 patients (57%) had high blood lipids. High blood pressure was recorded in seven patients (23%), and four patients (14%) were taking oral medicine for type II diabetes.
Thrombosis developed a median of eight years after HIV diagnosis. At the time of thrombosis the median CD4 cell count was low, but not dangerously so at 290 cells/mm3, and the median viral load was a little over 2000 copies/ml. Nine patients developing a thrombosis had an undetectable viral load.
Over half the patients were diagnosed as having AIDS, and 13 patients had cancer, the most common being Kaposi’s sarcoma.
At the time of the thrombosis diagnosis, most individuals (24, 80%) were taking HAART, with 16 individuals (53%) taking a protease inhibitor. Although over half the patients had high blood lipids, only four were taking lipid-lowering medication.
A total of 43 thrombotic events were recorded in the patients, with eight individuals experiencing more than one thrombosis. The most common site for thrombosis was the lower legs (14 patients, 33% of events), followed by the lungs (ten patients) and heart (eight individuals). A thrombosis affecting the central nervous system affected eight patients.
A detailed thrombophilia laboratory profile was available for 24 patients. In total, 50% of these patients had one or more laboratory abnormality associated with thrombosis.
Eight patients died, two deaths being directly related to the thrombotic events. A total of eleven patients were treated with long-term warfarin or low-molecular weight herapin, and a further eight patients received other anticoagulant therapy. Two patients received aspirin and four patients had a surgical intervention.
“The relatively high CD4 cell count in our thrombosis group, coupled with the variable HIV loads, suggests that thrombosis may occur over a wide range of immunologically defined HIV clinical stages,” write the investigators. However, given that most of the patients developing a thrombosis had an AIDS diagnosis, the investigators suggest that there may be “a stronger thrombosis predilection in patients with advanced HIV disease.”
Nine patients had antibodies to phospholipids. The investigators call for further examination of the association between these antibodies and the risk of thrombosis.
Malignancy, and high blood lipids are also noted by the investigators as being associated with thrombosis, and they emphasise the high levels of cigarette smoking amongst their patient group, commenting, "smoking is an important and potentially modifiable risk factor for reducing thrombosis risk."
The invesitgators note with concern that misdiagnosis delayed treatment in several patients. They conclude, “the role of antiretrovirals and other variables in promoting arterial and venous thrombosis among HIV-infected persons requires further study but is increasingly relevant as patients continue to live longer.”
Jacobson MC et al. Thrombotic complications in patients infected with HIV in the era of highly active antiretroviral therapy: a case series. Clin Infect Dis: 39: 1214-1222, 2004.