A balance between the proteins involved in coagulation and fibrinolysis is essential for hemostasis. Therefore, any change in the amount of each of these proteins, activators, and/or inhibitors of the coagulation pathway can lead to thrombosis or hypercoagulability. High concentrations of procoagulant components, such as factors XI, VIII, and IX, and low or dysfunctional fibrinogen levels are associated with an increased risk of venous thromboembolism (VTE), whether in adults or children, as early as the neonatal period. In addition, high plasma concentrations of fibrinolysis inhibitors capable of activating thrombin are independent risk factors for VTE. Moreover, other risk factors, such as non-O blood group, sickle cell disease, thalassemia intermedia and major, paroxysmal nocturnal hemoglobinuria, nephrotic syndrome, rare coagulopathies, von Willebrand factor deficiencies, malignancy, and heparin-induced thrombocytopenia, may be associated with an increased risk of thrombosis. However, it should be emphasized that their diagnostic tests are not part of the routine workup for the diagnosis of thrombophilia, but this should not be a reason to underestimate their role and importance.