The increased fibrinolytic activity during HCs use appears to be induced by the estrogen component and may be the result of an enhanced down-regulation of fibrinolysis ^{(26,51,82,90)}.

Compared to second generation, the use of third generation oral contraceptives has been associated with an increased risk of venous thrombosis, especially in women with the factor V Leiden mutation ^(87,91).

These HCs induce a decrease in factor V,  whereas the levels of all other coagulant factors increased.

Several studies demonstrate that many progestins markedly potentiate the vascular procoagulant effects of thrombin by increasing the availability of membrane thrombin receptors in the smooth muscle and this effect seems linked to their glucocorticoid-like-activity ⁽⁵⁹⁾.

When the women used POP (progestin-only pill), a differential effect from DSG and LNG was only found for factor IX.

While, in women at high risk of VTE (previous documented history of deep vein thrombosis or pulmonary embolism,  carriers of a congenital or acquired thrombophilia or history   of   a   severe/fatal   venous   thrombosis   in   a   first-degree   family member) chlormadinone acetare (17a hydroxyprogesterone derivative) only, used at antigonadotropic doses during 18-20 cycles, was not associated with a significant increase in the risk of VTE ⁽⁷⁸⁾.

In carriers of the factor V Leiden mutation, DSG- containing oral contraceptives induce more pronunced changes in factor V and in factor VII compared with LNG. Comparing DSG and LNG only,exclusively for factor V a differential effect was found. 

It appears that DSG-containing oral contraceptives have a more pronunced effect on the coagulation system than LNG-containing oral contraceptives which may explained by a less effective compensation   of   the   thrombotic   effect   of   ethinylestradiol   by   desogestrel ^{(51,61,87,91,92)}. 

When compared to COCs containing LNG or norethisterone, these containing desogestrel or gestodene present a two-fold greater risk of VTE.

For COCs containing cyproterone acetate, the risk is four-fold greater, while there are no or insufficient data for those containing norgestimate, chlormadinone acetate or drospirenone ^{(86,88,91,92)}.

Deep venous thrombosis with pulmonary embolus is a rare complication of oral contraceptives, which generally occurs in adult   women   and   becomes   more   common   with   increasing   age ^(87,90).

Nevertheless, these complication are believed to be less common with low-dose oral contraceptives than with high doses, a case of thromboembolism with a life-threatening pulmonary embolism in an adolescent on low dose triphasic oral contraceptives has been reported ⁽⁷³⁾.

In the development of these thrombotic events, secondary hypercoagulable states may have an important relief. However, these are complex clinical conditions associated with an increased risk of thrombosis in which the exact patho physiology is still poorly understood ⁽⁹⁴⁾.

With regard to the contraceptive patch, the available data suggest that the risk of VTE is similar to that observed with COCs. In the last years, several studies found a relatively moderate risk of non fatal venous thromboembolism in the contraceptive patch (ethinylestradiol/  norelgestromin)  users.  Despite this,  the contraceptive patch may be an appropriate option for many women.