Does Hemophilia Protect Against Atherosclerosis? A Case-Control Study

Abstract

Whether carriers of hemophilia are protected against the development of atherosclerosis is controversial. In a case-control study, the presence of atherosclerosis was assessed and quantified with echo-color Doppler of all explorable arterial districts in 50 carriers of hemophilia and in 50 age-matched control individuals. All participants submitted to echo-color Doppler of carotid and femoral axis, of brachial arteries, and of the abdominal aorta. The presence and grade of atherosclerotic plaques were assessed, as well as the intima-media thickness (IMT). At least one atherosclerotic plaque was found in six cases (12.0%) versus 15 controls (30.0%); referring to the total number of plaques, 30% of them were evaluated in patients affected by decreased coagulation while 70% in subjects with normal levels of FVIII. In all the examined districts, the mean IMT was significantly lower in patients with hemophilia than in controls. Hemophilia protects against asymptomatic atherosclerosis.

Factor VIII-von Willebrand Factor Complex Inhibits Osteoclastogenesis and Controls Cell Survival

“…OPG physically associated with the vWF is localized in the WeibelPalade bodies of endothelial cells and is rapidly secreted in response to inflammatory stimuli (24). More recently, in a casecontrol study Bilora et al (41) assessed the presence of athero-FIGURE 6. Schematic representation describing the involvement of FVIII⅐vWF complex in coagulation cascade, bone, and cancer biology.…”

Intrinsic Pathway of Coagulation and Arterial Thrombosis

“…A role for intrinsic pathway factors in arterial disease in humans is not as clear as for venous events. Severe congenital coagulopathies such as hemophilia, 40 type III von Willebrand disease, 41 or Glanzmann thrombasthenia 42 (absence or abnormality of the platelet ␣IIb/␤III integrin) do not appear to affect development of atherosclerosis, although there are suggestions that hemophilia retards arterial plaque formation somewhat in humans 43 and mice. 44 However, longitudinal studies in the Netherlands of patients with factor VIII or factor IX deficiency demonstrated a lower incidence of myocardial infarction than in controls, and an 80% reduction in mortality from coronary artery disease, suggesting factor VIII or IX deficiency may inhibit formation of thrombi at sites of plaque rupture.…”

Coronary Artery Calcification in Hemophilia A

“…[17][18][19][20][21] Srámek et al 21 and Sartori et al 20 found no differences in IMT, whereas 3 other studies [17][18][19] did show a lower IMT, fewer atherosclerotic plaques, or both in hemophilia patients. In these studies, patients were relatively young; mean age ranged from 40 to 58 years.…”

“…Moreover, comparison groups were not well chosen and, in some, not well described. [17][18][19][20][21] In addition, confounding was not accounted for in the analyses. These factors make interpretation of the results difficult.…”

“…16 Conflicting results have also been reported by studies comparing intima-media thickness (IMT) between hemophilia patients and nonhemophilic subjects. [17][18][19][20][21] This could be due to heterogeneous study populations including patients with other bleeding disorders than hemophilia, low mean ages, not well chosen or not well defined comparison populations, and variability in tests and outcome parameters.…”