We report an incidence of VTE of 0.54%, comparable to what has been reported in the literature.6–8
Klein et al3
systematically reviewed the literature on the epidemiology of VTE among patients with HIV infection. The 10 studies reviewed varied greatly in quality. The largest, a multisite US study, reported results from medical record abstraction on 42,935 patients between 1990 and 1998 and found an incidence of DVT of 0.26%.9
A high-quality study using Veterans Affairs hospital administrative data reported a 2% incidence of DVT, PE, phlebitis, and thrombophlebitis in the 13,549 studied men.9
Another study looking at PE among 3792 patients admitted to an HIV service between 1993 and 1997 documented an incidence of 0.26%.10
These studies had varying rigor regarding the requirements for objective documentation of thrombosis, and most were restricted to identifying thromboses diagnosed in inpatients. We suspect that the use of administrative data may have overestimated the incidence rate in some studies. Despite their limitations, the incidences are fairly comparable across studies and are around 1%, a rate approximately 10 times what would be expected in a population of comparable age without HIV.
In several of the studies described previously, investigators sought to identify risk factors for VTE in this population, noting that the population of patients with HIV/AIDS has a disproportionately high prevalence of many of the traditional risks for VTE, including frequent hospitalization.11,12
In our cohort, independent risks for VTE included age, hospitalization in the past 3 months, recent central venous catheter use, and a CD4 count <500 cells/mm3
Several groups have aimed to identify unique risk factors for VTE among patients with HIV/AIDS. In a large study by Sullivan et al,13
age older than 45 years, cytomegalovirus infection, other opportunistic illness, hospitalization, and use of megestrol acetate or indinavir were identified as risks for VTE. Similar to our findings, Saif et al14
found a higher prevalence of thrombosis in patients with CD4 counts <200 cells/mm3
relative to patients with higher CD4 counts. Many other hypotheses about thrombotic risk factors in this population have been proposed, including activation of endothelial cells from infections such as cytomegalovirus, herpes, and possibly HIV itself or formation of thrombotic microparticles from platelets or CD4 lymphocytes as a consequence of HIV infection.15
Alterations in natural anticoagulant proteins have been observed in patients with HIV; most commonly reported is a reduction in protein S.15–18
Much has been reported on the prevalence of antiphospholipid (APL) antibodies in this population, as reviewed in detail by Uthman and Gharavi.19
The prevalence of lupus anticoagulants has been estimated as high as 53% to 70% and that of anticardiolipin antibodies as high as 44% to 90%. Despite these associations, the clinical relevance of these antibodies is unclear.19,20
Although a prospective study in which risk factors can be identified before the event is optimal, there are several strengths to our study. We were able to nest this case-control study in an existing cohort established in 1990. With this study design, data were collected without knowledge of the outcome of interest. An additional strength of this study is that we verified each case of VTE by medical record review. We demonstrated that the use of administrative data from ICD-9-CM codes alone may be risky in this population; the specificity was low in our cohort. As with any case-control study, there are limitations, including the variable length of time between the laboratory measures, particularly CD4 cell count and HIV RNA level, and the outcome. The choice of controls can also strongly affect the estimates in a case-control study, and matching on duration of enrollment in the cohort eliminated this as a variable that we could investigate. We consider the results of this study to be hypothesis generating, because the CIs surrounding our ORs are wide and should be more thoroughly investigated prospectively.
Future studies should involve further clarification of the risks for VTE in this population. The rate is 10 times higher that what would be expected in the general population and is expected to increase as this population ages. Mechanistic work is essential to identify the common pathway to thrombosis in this population, which originates from these rather disparate risk factors. With this understanding, appropriate prophylactic measures can be instituted, which may include universal VTE prophylaxis with heparin or low-molecular-weight heparin on hospitalization or possibly anti-inflammatory or antiplatelet agents for high-risk outpatients. The mortality from PE is high, and the morbidity from DVT is great. With the tremendous recent gains in life expectancy for patients with HIV/AIDS, addressing the threat of VTE is increasingly appropriate.