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.

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“…The volume of the ejaculate is usually lower than in controls, even though the mean ultrasonographic prostate volume has been reported to be normal [Kamischke et al, 2003], whereas no data are available about the volume of the seminal vesicles, the main source of seminal fluid. Osteoporosis has been reported in 25% of patients [Foresta et al, 1983] and varicose veins in up to a third of patients [Zollner et al, 1997]. The clinical (increased waist and blood pressure) and biochemical (reduced glucose tolerance, high triglycerides and low HDL cholesterol) features of the metabolic syndrome are often present in Klinefelter patients, with low testosterone levels now well recognized as a risk factor for the syndrome [Bojesen et al, 2006b].…”

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“…Hence, chromosomal aberrations are known for "Klinefelter syndrome" characterised by the presence of an additional X-chromosome. In Klinefelter patients, the incidence of varicosis and thrombosis is significantly increased, and about 13% of these patients develop venous ulcers, due to a post-thrombotic syndrome caused by high levels of the fibrinolysis inhibitor PAI-1 and diminished fibrinolysis [14][15][16].…”

A case report of Klinefelter’s syndrome hiding behind pulmonary embolism

“…The patient didn't receive placement of vena caval filter ( Figures 5A-5C). synthesis and testosterone levels (11). The testosterone level of our patient was 0.01 ng/ml suggesting severe hypogonadism which probably reflecting increased fibrinolytic tendencies due to increased PAI-1 synthesis.…”