COAGULATION-FACTORS AND MARKERS OF ACTIVATION OF COAGULATION IN HOMOCYSTINURIA (HOCY) - A STUDY IN 2 SIBLINGS

Homocystinuria due to cystathionine-beta-synthase deficiency (CBS-def- HOCY) initially often presents with thromboembolic events. In most cas es in which coagulation factors have been analysed, a deficiency of AT -IIIc and factor VIIc has been reported, the cause of which has not be en elucidated. Activation of coagulation with consumption of coagulati on factors has been postulated as the mechanism. This paper reports a longitudinal study of two patients: patient 1 with thromboembolic dise ase and his asymptomatic sister, patient 2. Before start of therapy in patient 1, a reduction of FVIIc, other coagulation factors, and AT-II Ic was found. Markers of activation of coagulation (F1 + 2, TAT, FM, D -dimers) were elevated only in patient 1, and only at the time of thro mbotic complications. In patient 2 reduced levels of FVIIc and other c oagulation proteins, and a low borderline AT-IIIc level was found. Thu s, in the two patients, sustained activation of coagulation can be rea sonably excluded to be the cause of low levels of coagulation proteins . Vitamin therapy with 15 mg folate and 600 mg pyridoxine per day led to almost complete normalization of amino acids in urine and plasma. T hrombosis has not recurred to date. FVIIc and the other coagulation pr oteins and AT-IIIc increased in parallel with the biochemical remissio n. Direct inhibition of the activity of AT-III and coagulation factor VII and other factors by homocysteine was attempted in vitro but could not be shown at HC concentrations known to occur in the plasma of HOC Y patients. Therefore, in these patients, deficient synthesis of coagu lation factors and AT-III due to a disturbance of amino acid metabolis m is still the most probable explanation for the observed low levels.