Factor II Deficiency

In the blood coagulation cascade, prothrombin is cleaved by factor Xa to form thrombin, an active serine protease. This proteolytic reaction occurs on the phospholipid surfaces of platelets and requires calcium. Thrombin is responsible for inducing platelet aggregation and activating several other mediators in the coagulation cascade. It converts fibrinogen to fibrin, which then polymerizes to form a clot around platelet aggregates. Thrombin also converts factor XIII to factor XIIIa, an enzyme that cross-links and stabilizes fibrin polymers.

The prothrombotic effects of thrombin are ultimately suppressed by the binding of thrombin to thrombomodulin on endothelial cell surfaces to form a complex that activates protein C. Protein C then degrades factors Va and VIIIa to inhibit the coagulation cascade. Thrombin also has cytokine and growth-factor functions, inducing mitosis and chemotaxis in cell lines, including smooth muscle, fibroblasts, endothelial cells, and mononuclear phagocytes. Decreased levels or a dysfunctional structure of factor II can lead to absent or defective clot formation and dysfunctional platelet aggregation. Thus, thrombin functions not only in the clotting cascade, but also as a cytokine and growth factor capable of inducing mitosis and chemotaxis in several different cell lines. Several specific missense mutations of the prothrombin gene have been documented. These single amino acid substitutions can cause hypoprothrombinemia and/or dysprothrombinemia. In fact, most hypoprothrombinemia-associated mutations are missense ones.

Acquired factor II deficiency has several possible etiologies. Because prothrombin is synthesized almost exclusively in the liver, severe liver disease can have a dramatic impact on prothrombin levels. Vitamin K deficiency can also result in decreased prothrombin levels. Vitamin K is produced in the gut by enteric flora, and levels can be affected by intestinal malabsorption, bile duct obstruction, or antibiotic administration. Vitamin K deficiency can be iatrogenically induced by the administration of propylthiouracil or vitamin K antagonists such as warfarin. Vitamin K deficiency can also be seen in neonates. Finally, acquired factor II deficiency can sometimes be observed in patients with lupus anticoagulant. These patients can develop specific prothrombin autoantibodies that form a complex with prothrombin and cause excessive clearance of prothrombin from the body. This condition, sometimes referred to as "lupus anticoagulant hypoprothrombinemia syndrome," is most often seen with systemic lupus erythematosus (SLE).

The lupus anticoagulant hypoprothrombinemia syndrome may also occur in individuals without SLE. Bleeding attibuted to acquired hypoprothrombinemia caused by antiphospholipid antibodies may follow acute adenovirus gastroenteritis and mycoplasma pneumonia. The lupus anticoagulant hypoprothrombinemia syndrome is associated with a high mortality.

History

Patients with a factor II deficiency may report a family history of bleeding disorders. They may also report a history of the following symptoms:

• Prolonged bleeding following circumcision
• Postpartum bleeding
• Easy bruising
• Umbilical cord stump bleeding at birth
• Intracranial bleeding
• Epistaxis
• Menorrhagia
• Prolonged postsurgical bleeding
• Melena
• Bleeding gums
• Soft-tissue hemorrhages

Laboratory Studies

Clotting factor assay results in patients with factor II deficiency are as follows:

• In hypoprothrombinemia, functional and antigenic levels of factor II are decreased
• In dysprothrombinemia, functional levels are decreased; antigenic levels are within reference ranges or are slightly decreased
• In isolated factor II deficiency, assays of other clotting factors should reveal normal levels
• In factor II deficiency due to liver disease, vitamin K deficiency, or vitamin K antagonist use, assays of other clotting factors reveal a decrease in the level of all vitamin K–dependent factors (ie, factor II, factor VII, factor IX, factor X, protein C)

Coagulation study results in patients with factor II deficiency are as follows:

• Prothrombin time (PT) is prolonged
• Activated partial thromboplastin time (aPTT) is prolonged
• Bleeding time is within reference ranges

Treatment

Treatment options include the following:

• Infusion of fresh frozen plasma (FFP) is usually sufficient to treat most cases of bleeding; a loading intravenous (IV) dose of 15-20 mL/kg is administered, followed by a maintenance dose of 3-6 mL/kg IV q12-24 h
• Plasma exchange transfusion may be used to increase factor II levels before surgery
• Prothrombin complex concentrates (PCCs) have also been used to increase factor II levels ^[45] ; PCCs contain factors II, VII, IX, and X, along with protein C; however, PCCs should be used judiciously because of the risk of thromboembolic complications
• Vitamin K administration may be useful in patients with acquired factor II deficiency

Source :

http://emedicine.medscape.com/article/209742-medication#2

http://emedicine.medscape.com/article/209742-overview#a5