Leg ulcers in Klinefelter's syndrome - further evidence for an involvement of plasminogen activator inhibitor-1

Abstract

An abnormality in platelet aggregability or fibrinolysis, namely elevated activity of plasminogen activator inhibitor-1 (PAI-1), has been recently documented in patients suffering from Klinefelter's syndrome associated with leg ulceration without underlying venous insufficiency. To determine whether increased PAI-1 activity is a general feature of Klinefelter's syndrome, or more specifically associated with leg ulceration, we investigated PAI-1 influencing parameters and PAI-1 activity in two groups of patients: (i) Klinefelter patients suffering from leg ulceration (n = 7); and (ii) Klinefelter patients without leg ulceration (n = 6). On analysing PAI-1 influencing parameters such as age, body mass index, triglycerides, C-reactive protein, testosterone, smoking behaviour, the presence of diabetes mellitus, and arterial hypertension, respectively, we found no statistically significant differences between the two groups. However, PAI-1 activity in group 1 was highly significantly elevated compared with that in group two patients (P < 0.005). We conclude that (i) PAI-1 activity is not elevated in Klinefelter's syndrome in general; (ii) elevation of PAI-1 activity in patients suffering from Klinefelter's syndrome does not appear to be secondary to PAI-1 influencing parameters; and (iii) elevation of PAI-1 activity may play a crucial role in the pathogenesis of leg ulceration in Klinefelter's syndrome. Therefore, a therapy for leg ulceration in Klinefelter's syndrome that aims to return the elevated PAI-1 activity to normal should be explored.

Successful Pulmonary Endarterectomy in a Patient with Klinefelter Syndrome

“…As in VTE, elevation of PAI-1 activity is also considered to play a role in the pathogenesis of (postthrombotic) leg ulceration observed in KS patients [29, 30]. Postthrombotic venous ulceration is observed in up to 13% of KS patients [31]; in fact, this may trigger suspicion on KS [32].…”

Increased activity of factor VIII coagulant associated with venous ulcer in a patient with Klinefelter's syndrome

“…Local impairment of fibrinolysis leading to the development of microthrombi may be other important factors in these thromboembolic processes 2 . Moreover, a causal relationship between venous leg ulcers and elevated levels of PAI‐1 activity in Klinefelter's syndrome has been discussed 8,9 . As Klinefelter's syndrome is known to be associated with a relative androgen deficiency a bilateral orchidectomy in rats has been shown to induce an increase in activity of coagulation factors such as PAI‐1.…”

Klinefelter’s Syndrome and Venous Thrombosis

“…12 Elevated PAI-1 levels inhibit tissue plasminogen activator (t-PA), preventing degradation of plasminogen to plasmin and predisposing to thrombosis. However, it has been found in patients with Klinefelter's syndrome with chronic leg ulcers.…”