Depending on the size and the location of the clot, this may lead to sudden-onset shortness of breath, chest pain, palpitations and may be complicated by collapse, shock and cardiac arrest.Venous thrombosis may also occur in more unusual places: in the veins of the brain, liver (portal vein thrombosis and hepatic vein thrombosis), mesenteric vein, kidney (renal vein thrombosis) and the veins of the arms. Whether thrombophilia also increases the risk of arterial thrombosis (which is the underlying cause of heart attacks and strokes) is less well established.Thrombophilia has been linked to recurrent miscarriage, and possibly various complications of pregnancy such as intrauterine growth restriction, stillbirth, severe pre-eclampsia and abruptio placentae.Protein C deficiency may cause purpura fulminans, a severe clotting disorder in the newborn that leads to both tissue death and bleeding into the skin and other organs. The condition has also been described in adults. Protein C and protein S deficiency have also been associated with an increased risk of skin necrosis on commencing anticoagulant treatment with warfarin or related drugs. Causes
Thrombophilia can be congenital or acquired. Congenital thrombophilia refers to inborn conditions (and usually hereditary, in which case "hereditary thrombophilia" may be used) that increase the tendency to develop thrombosis, while, on the other hand, acquired thrombophilia refers to conditions that arise later in life. Congenital
The most common types of congenital thrombophilia are those that arise as a result of overactivity of coagulation factors. They are relatively mild, and are therefore classified as "type II" defects.
Furthermore, particular cancer treatments (such as the use of central venous catheters for chemotherapy) may increase the risk of thrombosis further.Nephrotic syndrome, in which protein from the bloodstream is released into the urine due to kidney diseases, can predispose to thrombosis; this is particularly the case in more severe cases (as indicated by blood levels of albumin below 25 g/L) and if the syndrome is caused by the condition membranous nephropathy. Inflammatory bowel disease (ulcerative colitis and Crohns disease) predispose to thrombosis, particularly when the disease is active. Various mechanisms have been proposed.Pregnancy is associated with an increased risk of thrombosis of 2- to 7-fold. This probably results from a physiological hypercoagulability in pregnancy that protects against postpartum hemorrhage. This hypercoagulability in turn is likely related to the high levels of estradiol and progesterone that occur during pregnancy.Estrogens, when used in combined hormonal birth control and in menopausal hormone therapy (in combination with progestogens), have been associated with a 2- to 6-fold increased risk of venous thrombosis. The risk depends on the types of hormones used, the dose of estrogen, and the presence of other thrombophilic risk factors. Various mechanisms, such as deficiency of protein S and tissue factor pathway inhibitor, are said to be responsible.Obesity has long been regarded as a risk factor for venous thrombosis. It more than doubles the risk in numerous studies, particularly in combination with the use of oral contraceptives or in the period after surgery. Various coagulation abnormalities have been described in the obese.