The Hemostatic Balance in HIV-Infected Patients with and without Antiretroviral Therapy: Partial Restoration with Antiretroviral Therapy

Abstract

The incidence of arterial and venous thrombosis in HIV-infected patients is increased compared to healthy controls. In this cross-sectional analysis we measured markers of endothelial cell activation, thrombin generation, fibrinolysis and anticoagulation combined with endogenous thrombin potential (ETP) and activated protein C sensitivity ratio (APCsr) as more global markers. We included 160 consecutive HIV-infected patients with a median age of 46 years (range, 27-77), of whom 92% were male, 74% Caucasian, 11% African American, 9% Hispanic, and 6% Asian. Homosexual contact was the main transmission mode. Seventy percent of patients were using combined antiretroviral therapy (cART). In 83% of patients laboratory markers outside the normal range for a non-HIV-infected population were observed. Significant lower levels of von Willebrand factor (vWF; p = 0.03), factor VIII (p < 0.0001), D-dimer (p = 0.01), and ETP (p = 0.01) were observed in HIV-infected patients on cART compared to patients not on cART. Significant lower levels of protein C (p = 0.05) and free protein S (p < 0.0001), and increased APCsr (p < 0.0001) were found in the HIV-infected patients not on cART. A single association was observed between raised levels of fibrinogen and use of a protease inhibitor (p = 0.002). No significant difference was observed in the percentage of patients with laboratory markers outside the normal range between patients using cART-regimens containing abacavir, stavudine, or didanosine and those with other nucleoside reverse transcriptase inhibitors. Although the prevalence of coagulation abnormalities was lower in HIV-infected patients using cART, a considerable proportion of HIV-infected patients on cART show endothelial cell activation and increased APCsr, suggestive of a persistent procoagulant state.

Basic Coagulation Parameters among Human Immunodeficiency Virus-Infected Adults in Gondar, Northwest Ethiopia: A Comparative Cross-Sectional Study

“…Evidence revealed that 53.5% of HIV-infected adults had circulating anticoagulants [47]. Moreover, at the low CD4 count, HIV-associated endothelial activation and liver damage are common complications [48]. Endothelial activation and liver damage cause consumption of blood clotting factors and/or abnormal production of liver-dependent clotting factors that can result in the occurrence of prolonged APTT in HIV-infected adults [7].…”

von Willebrand Factor is elevated in HIV patients with a history of thrombosis

“…It is likely that monocytes rather than T-cells are responsible for the initial immunologic response to LPS translocation, considering these cells express CD14 and TLR4, the receptors for LPS. Although markers of coagulation and immune activation are partially restored upon initiation of cART, a complete normalization fails to appear (Jong et al, 2009; Funderburg, 2014). In the SMART study, a study aimed to investigate the benefit of a CD4 guided approach on treatment (El-Sadr et al, 2006), markers of inflammation and coagulation such as IL-6, D-dimer and sCD14 were shown to be excellent predictors of atherosclerosis and mortality (Kuller et al, 2008; Sandler et al, 2011; Kelesidis et al, 2012).…”

Factor VIII concentration is greater in female than male patients with HIV infection

“…Lifering et al [19] demonstrated that increased factor VIII concentration is a marker of AIDS progression in HIV-infected patients. Moreover, factor VIII levels decrease by HAART therapy [24]. So, it could be hypothesized that HIV-infected women are more severely diseased than HIV-infected men; which is reflected by a higher plasma factor VIII concentration.…”