Deep vein thrombosis with oral contraceptives

Lenalidomide (Revlimid) Possible birth defects (since analogue of thalidomide), neutropenia, thrombocytopenia, deep vein thrombosis, pulmonary embolism, pruritis, fatigue Dose is 10 mg orally taken with water once daily Women of childbearing age must use two forms of contraception Pregnancy test must be taken before and during use... 

A 25-year-old woman presents to the emergency department complaining of acute onset of shortness of breath and pleuritic pain. She had been in her usual state of health until 2 days prior when she noted that her left leg was swollen and red. Her only medication was oral contraceptives. Family history was significant for a history of "blood clots" in multiple members of the maternal side of her family. Physical examination demonstrates an anxious woman with stable vital signs. The left lower extremity demonstrates erythema and edema and is tender to touch. Ultrasound reveals a deep vein thrombosis in the left lower extremity chest computed tomography scan confirms the presence of pulmonary emboli. What are the likely risk factors in this woman—hereditary, acquired, or both What therapy is indicated acutely What are the long-term therapy options How long should she be treated Should this individual use oral contraceptives ... 

Data from the Leiden Thrombophilia Study have been used to construct a case-control study, based on contraceptive users who had experienced a first episode of objectively proven deep vein thrombosis (100). Patients and controls were considered thrombophilic when they had protein C deficiency, protein S deficiency, antithrombin deficiency, factor V Leiden mutation, or a prothrombin 20210 A mutation. Among healthy women, the risk of developing deep vein thrombosis was trebled in the first 6 months and doubled in the first year of contraceptive use. Among women with thrombophilia, the risk of deep vein thrombosis was increased 19-fold during the first 6 months and 11-fold (95% Cl = 2.1, 57) in the first year of use. Venous thrombosis during the first period of oral contraceptive use might actually point to the presence of an inherited clotting defect. 

Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995 346(8990) 1593-6. 

A 28-year-old woman took thalidomide 100 mg/day for Behget s disease and after 3 months developed amenorrhea (89). She took an oral contraceptive for 8 months, but then had a deep vein thrombosis in association with a factor V Leiden mutation the oral contraceptive was withdrawn and she was given warfarin. She remained amenorrheic. She had a raised serum concentration of follicle-stimulating hormone but all other laboratory tests were normal. Ultrasonography showed a normal uterus and an endometrial lining of 4 mm. The amenorrhea was attributed to thahdomide, which she decided to continue taking she remained amenorrheic. 

To conclude, the epidemiological studies on oral contraceptives and thromboembolism all point to the same direction, i.e. to an increased risk of thromboembolic disease (deep vein thrombosis, pulmonary embolism, cerebral thrombosis, myocardial infarction) in women using oral contraceptives of the combined type. Support can also be obtained from the studies on changes in the fibrinolytic system (see below). For thrombosis with rare localization, e.g. in the mesenteric vessels, epidemiological data are still lacking. It remains to be seen whether the risk of thrombosis is reduced with the new low-dose combinations. 

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