Cardiovascular risk in patients with hemophilia

Abstract

Patients with hemophilia, who have a lifelong hypocoagulability, seem to have a lower cardiovascular mortality than the general population. Nevertheless, the prevalence of cardiovascular risk factors in patients with hemophilia is as prevalent as in the general population, and hypertension is even more common. Furthermore, hemophiliacs have the same degree of atherosclerosis as the general population. The reduced cardiovascular mortality may be explained by reduced thrombus formation resulting from hypocoagulability. On the other hand, hemophilia, which is associated with reduced thrombin generation, may also increase atherosclerotic plaque stability, as has been shown in mice. Because treatment of these events is extremely challenging in patients with increased bleeding tendency, detection and aggressive treatment of risk factors is mandatory.

Arterial and Venous Thrombosis in Haemophilia Patients: Experiences from a Danish Haemophilia Centre

“…Eight patients had ≥2 risk factors. The prevalence of CVD risk factors in PWH is reported to be similar to that of the general population, and hypertension is found by some authors to be even more prevalent in PWH [9]. This is in agreement with our study, since hypertension was seen in 8 of 9 patients with CVD in our population.…”

“…The prevalence of cardiovascular disease (CVD) in PWH has been investigated in several studies [1,2,3,4,5,6,7] and varies from <2% to 20% between studies, depending on age and the severity of the haemophilia. Thus, it is difficult to estimate the exact magnitude of the problem; however, there is agreement that CVD occurs in PWH, especially in older patients or those with ≥1 CVD risk factors, and it can pose a serious problem [8,9]. Anti-thrombotic treatment in haemophilia is a particular problem.…”

Adult haemophilia A patients with inhibitors: successful immune tolerance induction with a single FVIII/VWF product

“…Management with bypassing agents of older haemophilia A patients with inhibitors is further complicated in the presence of age-related comorbidities [1][2][3], not only due to the high costs, but also bypassing agents have a potential risk for adverse thrombotic events [4]. Immune tolerance induction (ITI) treatment protocols are currently the recommended intervention for this serious complication in any age group.…”

“…Consequently, health care professionals within comprehensive care centres are seeing more older PWH, who are presenting with age-related comorbidities [2]. It is recognized that PWH, as with the general population, acquire risk factors for cardiovascular disease (CVD) with advancing age [3]. While haemophilia may offer some protection against acute cardiovascular events, this is mainly seen in severe haemophilia [4].…”

Upstream versus downstream thrombin inhibition

“…Activated factor XI drives factor IX conversion and subsequent downstream intrinsic coagulation. Excess factor XI (activity) is a risk factor for VTE, and absence of factor XI may provide some protection against ischemic stroke [58]. For all these reasons, targeting factor XI may provide a reasonably effective antithrombotic therapy, perhaps with less bleeding tendency as compared to more centrally acting anticoagulants.…”