Factor V deficiency, also known as Owren disease or parahemophilia, is a rare bleeding disorder that may be inherited or acquired. Dr. Paul Owren first identified the condition in Norway in 1943. The disease manifests itself similarly to other clotting factor deficiencies, with symptoms ranging from minor mucosal bleeding to severe and life-threatening hemorrhages. The severity of bleeding generally correlates with factor Va levels. However, literature reports that factor Va levels below 1% may still manifest with only mild bleeding symptoms in some individuals.

Factor V deficiency may be categorized into mild, moderate, or severe based on factor V plasma activity levels relative to the normal. Mild deficiency exceeds 10% of the normal activity level in plasma. Moderate deficiency has 1% to 10%. Severe deficiency has less than 1%. Initial laboratory values show a prolonged prothrombin time (PT) and partial thromboplastin time (aPTT) with a normal thrombin time (TT). A low plasma factor V level can confirm the diagnosis.

Plasma mixing studies help distinguish between inherited and acquired factor V deficiency. These tests assess whether the prolonged coagulation studies result from a factor deficiency or an inhibitor. Normal plasma is combined with the patient's plasma, which exhibits prolonged PT and aPTT. Improvement of these parameters after mixing suggests an inherited form, with normal plasma replacing the missing factor. Persistent PT and aPTT prolongation after mixing indicates an acquired form, as an inhibitor in the patient's plasma prevents normalization. The test is not specific to factor V deficiency.

Treatment varies based on whether factor V deficiency is inherited or acquired. In inherited cases, treatment typically involves transfusing fresh frozen plasma (FFP), which contains factor V. Mild cases may require antifibrinolytics to achieve hemostasis. In contrast, managing acquired factor V deficiency is more complex, requiring bleeding symptom control and anti-factor V autoantibody elimination. Bleeding control is achieved with transfusion of FFP, platelets, prothrombin complex concentrates, antifibrinolytics, or recombinant activating factor VII. Factor V inhibitor eradication is accomplished with immunosuppression.

Coagulation Physiology

The coagulation cascade orchestrates hemostasis through the intrinsic, extrinsic, and common pathways (see Image. Coagulation Cascade Diagram). In the intrinsic pathway, endothelial damage exposes collagen, activating factor XII. This coagulation factor catalyzes the subsequent activation of factors XI, IX, and X, culminating in thrombin generation and fibrin formation. The extrinsic pathway begins when tissue factor is released by endothelial cells, activating Factor VII and merging with the intrinsic pathway to initiate factor X activation. Factor Xa subsequently catalyzes prothrombin conversion to thrombin, promoting fibrin polymerization and stabilizing the platelet plug.

Factor V, also known as proaccelerin or labile factor, is a crucial nonenzymatic protein in the coagulation cascade. The liver produces approximately 80% of this glycoprotein, and the remaining 20% is synthesized within the α granules of platelets and megakaryocytes. Factor V circulates in plasma with a half-life of 12 to 36 hours. Either thrombin or factor Xa converts factor V to the plasma cofactor of the prothrombinase complex. The complex is composed of calcium, phospholipids, factor Va, and factor Xa and is crucial in converting prothrombin to thrombin. Thrombin then activates factor XIII and fibrin, leading to clot formation.

Factor Va is deactivated by protein C once hemostasis is achieved. Negative feedback mechanisms modulate the coagulation cascade to prevent excessive clot formation. Despite thrombin's role in clot formation, this factor activates plasminogen to plasmin, aiding fibrinolysis. Thrombin also induces antithrombin production, which inhibits thrombin and factor Xa activity. Notably, factor V is also vital in the anticoagulation pathway. Factor V coordinates with protein C to deactivate factor VIII, decreasing prothrombinase activity and, ultimately, thrombin and fibrin production. The mechanism reduces clot production. Activated protein C (APC) shifts the balance toward coagulation inhibition.