Fluidity of blood inside the vessels on one hand, and formation of thrombus just at the site of vessel injury on the other hand, is the result of an exact interactive equilibrium of multiple procoagulant and anticoagulant factors, and their activators and inhibitors.Destruction or stimulation of endothelial cells and platelets, and contact of blood and platelets with subendothelial tissues are among the main procoagulant factors. Integrity and function of endothelial cells, washing property of blood stream, fibrinolysis system (plasminogen) and thrombomodulin system, protein C and antithrombin are the most important anticoagulant factors. Dysfunction of procoagulant factors leads to bleeding tendency, whereas dysfunction of anticoagulant factors causes predisposition to the thrombosis (THROMBOPHILIA).Despite recent progresses, we can only diagnose half of hereditary THROMBOPHILIAs, among these, the factor V Leiden, antithrombin deficiency; protein C deficiency and protein S deficiency are more common. Elevation of plasma factor VIII levels has been considered as a common but weak risk factor for hereditary THROMBOPHILIA. Mutation of prothrombin G20210A which leads to elevation of prothrombin levels has the same importance as the factor VIII elevation.Presence of hereditary THROMBOPHILIA in an individual does not inevitably end up in the formation of pathologic thrombosis, for clinical presentation of thromboembolic syndromes, coincidence of one (or more) hereditary THROMBOPHILIA along with one (or more) acquired THROMBOPHILIA (such as pregnancy, immobility, surgery, OCP use) are usually evident. Individuals with hereditary THROMBOPHILIA are more prone to the recurrence of thrombosis than normal individuals, so long term use of anticoagulant drugs in such patients is recommended.Screening for hereditary THROMBOPHILIA must be considered when (I) there is not an acceptable acquired risk factor for thrombosis in history and physical examination; (2)venous thrombosis before age 40, (3) recurrent thrombosis, (4)arterial thrombosis before age 30, (5) family history of thrombosis, (6) thrombosis in unusual sites such as mesenteric or cerebral veins.

The role of inherited THROMBOPHILIAs in RPL has generated a great deal of interest. This heterogeneous group of disorders results in increased venous or arterial thrombosis. Their associations with pregnancy loss rest on both proved and hypothetical alterations in placental growth and development, particularly placental vascular development. Abnormal placental vascularization and inappropriate placental thrombosis would link these thrombophilic states to pregnancy loss. Although some thrombophilic states may be acquired, most are heritable. Those heritable THROMBOPHILIAs most often linked with reference to RPL include hyperhomocyteinemia. Activated protein C resistance associated with mutations in factor V, deficiencies in proteins C and S, mutations in the prothrombin gene promoter, mutations in prothrombin, and mutations in antithrombin III.Inherited thrombophilic mutations have been estimated to be causative in 50% of VTE during pregnancy. Approximately 40% of episodes of venous or arterial thromboembolic phenomena occur in patients carrying a heritable mutation. Associations between THROMBOPHILIAs and adverse fetal outcomes cover a range of early gestational and obstetric disorders. These disorders include isolated and recurrent, early and late spontaneous pregnancy losses, intrauterine growth restriction (IUGR), intrauterine fetal demise (IUFD). Placental abruption and pregnancy- induced hypertension (PIH). This discussion will focus on pathophysiologic mechanisms, diagnostic tesing, and treatment strategies for patients with RPL who may have an inherited or acquired predisposition to thrombosis (excluding the antiphospholipid syndrome).The basis for the association between adverse fetal outcomes and heritable THROMBOPHILIAs has focused on the mechanisms of impaired placental development and function secondary to venous or arterial thrombosis at the maternal-fetal interface.