Pregnancies and Oral Contraceptive Therapy in Severe (Homozygons) FXII Deficiency: A Study in 12 Patients and Review of the Literature

Abstract

Twelve women with severe Factor XII (FXII) deficiency were under observation for an average period of about 16 years. During this time, these women had 19 pregnancies without any bleeding or thrombotic complications. The evaluation of the literature has shown that three patients manifested deep vein thrombosis during pregnancy. Five women also showed mild bleeding at delivery . The significance of these findings is not clear since thrombotic and bleeding complications may occur occasionally even in normal women. Five of our patients took oral contraceptive therapy during their fertile life for a variable period of time (2-10 years). No thrombosis was noted in any of these patients. From the scanty data gathered, in this respect, from the literature, it was shown that only three women with severe FXII deficiency took oral contraceptives and no thrombosis was noted. Altogether these results seem to indicate that the FXII deficiency does not play any significant role in the pathogenesis of bleeding and of thrombotic complications in pregnancy. However, the occurrence of deep vein thrombosis in 3 out of the 64 patients for whom sufficient data could be gathered indicates the need for further studies. This is more so if one considers that 3 out of the 6 cases of venous thromboses described altogether in the literature for females with severe FXII deficiency occurred during pregnancy or puerperium.

The association of a mild FXII deficiency with myocardial infarction and venous thrombosis is completely unjustified

“…The data supplied by the authors in favour of a prothrombotic role of FXII deficiency have not been confirmed with the only possible but still open, exception for DVT in patients with severe FXII deficiency occurring during pregnancy [11].…”

Fibrinolytic Defects and Recurrent Miscarriage

“…Although it has been argued that formation of microthrombi may be the pathway through which factor XII deficiency could cause miscarriage, 35 it is not yet clear whether this condition actually predisposes to thrombosis, 38,39 and both deep venous thrombosis and mild postpartum hemorrhage have been reported in a small series of pregnant women with factor XII deficiency. 40 Abnormal invasion is also a potential mechanism for miscarriage in thrombophilic disorders, but there are no studies on the effect of factor XII deficiency in placental invasiveness.…”

Relationship between Factor XII deficiency and thrombosis: the debate is still open?

“…In fact, in our article we defined this correlation at least doubtful because of the contradictory aspects emerging from the literature data, with some studies in which it is considered inexistent [3][4][5][6], except for some conditions, as correctly pointed out in the explanatory letter [7]. Nevertheless, the matter presents interesting aspects that steel need to be elucidated.…”