## 8 Thromboembolic Disease  
Thromboembolic disease in HIV patients varies widely (0.19-7.63%), with a 2-10 times higher risk than the general population [61]. In a study by Malek, HIV patients had a 43% increased risk of pulmonary embolism and a 10% higher risk of deep vein thrombosis (DVT) than age-matched HIV-negative individuals. The highest risk was observed in patients aged 21 to 50 years [62]. HIV infection contributes to a prothrombotic state and endothelial dysfunction. The prothrombotic tendency is mainly due to anticoagulant factor deficiencies, particularly ProteinS deficiency. Its prevalence in HIV patients ranges from 2% to 76%, significantly higher than in the general population. However, only 12% of affected patients develop thromboembolism. Type III Protein S deficiency is most frequently observed, characterized by normal total Protein S levels but reduced free Protein S levels and decreased functional activity. This deficiency results from reduced hepatic, endothelial, and megakaryocyte synthesis due to HIV-induced damage. Elevated TNF-\(\alpha\) further inhibits Protein S production, and autoantibodies against Protein S have also been detected in HIV patients [61]. HIV infection can trigger low-grade disseminated intravascular coagulation due to prolonged immune stimulation and injury of the endothelial cells, which leads to consumption of the clotting factors and anticoagulant factors. Deficiencies of antithrombin III and Protein C are less common and are usually linked to preexisting liver disease (e.g., co-infections with Hepatitis B or C) or AIDS-related malnutrition and protein loss (due to enteropathies or nephropathies) [61]. Additionally, prolonged immune activation can trigger antiphospholipid antibody production. Lupus anticoagulant and anticardiolipin antibodies are detected in 7% to 94% of HIV patients [61]. HIV infection, along with proinflammatory cytokines, contributes to endothelial dysfunction. In response, endothelial cells increase the expression of adhesion molecules (P-selectin, E-selectin) and enhance the release of procoagulant and pro-aggregant factors (von Willebrand factor, thrombomodulin, tPA, PAI-I, fibronectin) as well as vasoconstritors (angiotensin II, endothelin-1). Additionally, tissue factor expression on monocytes is elevated due to excessive immune stimulation, further promoting arterial and venous thrombosis [61]. The risk of thromboembolism correlates with HIV disease severity. Patients with low CD4+ counts and high viral RNA loads face the greatest risk. In AIDS-stage HIV, various opportunistic infections (cytomegalovirusovirus, _Pneumocystis jirovecii, Mycobacterium avium-intracellular_) further increase the thrombotic risk [61]. HAART has substantially improved the prognosis of HIV patients. Older case reports described the occurrence of thromboembolism shortly after the initiation of therapy with protease inhibitors, in particular indinavir, raising concerns that PIs might induce endothelial dysfunction and create a procoagulant status. However, more recent analysis did not find any correlation between thrombosis occurrence and antiviral therapy, nor between its duration or the duration of HIV infection [63]. In a study by Crum-Cinaflone, 3.7% of HIV patients experienced an embolic event, with 23% of these being pulmonary embolisms. Almost all affected patients had classical thrombotic risk factors, with 59% having concurrent infections. Additionally, patients with thrombosis had lower CD4+ counts and higher viral loads and were more likely to have AIDS than those without thromboembolism [64]. The role of biomarkers in diagnosing PE among HIV patients is an area of ongoing research. Elevated D-dimer levels are commonly used to assess PE risk, but HIV infection itself can influence D-dimer concentrations due to chronic inflammation and immune activation. Further studies are needed to determine appropriate D-dimer thresholds and to explore additional biomarkers that may improve diagnostic specificity for PE in HIV-positive individuals.