1. Overview
Factor II, also known as Prothrombin, is a vitamin K–dependent single-chain glycoprotein composed of 579 amino acids, with a molecular weight of approximately 72 kDa. It is synthesized in the liver and undergoes γ-carboxylation during biosynthesis. In normal plasma, prothrombin is present at a concentration of around 100 μg/mL.
Prothrombin plays a central role in the blood coagulation system. It is converted to thrombin (Factor IIa), which is essential for clot formation. Prothrombin Time (PT) is a commonly used laboratory test to assess the function of the coagulation pathway, and to maintain standardization of PT results, the International Normalized Ratio (INR) is used for uniform interpretation and monitoring.
2. Symptoms
Factor II abnormalities themselves do not present with specific symptoms unless they lead to clinical conditions. Reduced activity or deficiency of Factor II can result in bleeding tendencies, while elevated levels may predispose individuals to thrombosis. Clinical manifestations depend on the severity of deficiency or dysfunction and may include excessive bleeding, prolonged clotting time, or complications related to anticoagulant therapy.
3. Causes
Prothrombin abnormalities may arise from both inherited and acquired causes. Inherited prothrombin deficiency is rare and follows an autosomal recessive pattern. Heterozygous individuals are typically asymptomatic, whereas homozygous or compound heterozygous individuals may exhibit bleeding symptoms.
Acquired causes include liver cirrhosis, vitamin K deficiency, disseminated intravascular coagulation (DIC), and the use of anticoagulant medications such as blood thinners. Since Factor II synthesis depends on adequate liver function and vitamin K availability, any condition affecting these can impair prothrombin activity.
4. Risk Factors
Several factors increase the likelihood of abnormal Factor II activity. These include liver disease, vitamin K deficiency, prolonged use of anticoagulants, and systemic conditions such as DIC. Patients undergoing surgery, those with suspected bleeding disorders, or individuals on anticoagulant therapy are at increased risk and require close monitoring.
Prothrombin mutations are noted to be the second most common inherited thrombophilia, contributing to an increased risk of excessive clot formation due to enhanced thrombin generation.
5. Prevention and Clinical Management
Prevention and management rely on accurate diagnosis, appropriate laboratory testing, and careful monitoring. PT and INR testing are widely used as basic screening tools in suspected bleeding disorders, preoperative evaluations, antenatal care profiles, liver disease assessment, and anticoagulant therapy monitoring.
Patients are advised to avoid heparin and thrombin inhibitors at least three days prior to testing, and blood samples should not be drawn from heparinized catheters. Citrated plasma is the preferred specimen, with strict guidelines for collection, processing, storage, and transport to ensure accurate results.
Normal PT reference values typically range from 12.0 to 15.0 seconds, depending on the thromboplastin used.
The severity of Factor II deficiency is categorized based on PT and INR values, ranging from mild to very severe. During anticoagulant therapy, INR is usually maintained between 2.0 and 4.0.
PT/INR testing also holds prognostic significance, particularly in critically ill patients such as those with sepsis or septic shock, where results correlate with short-term mortality risk. Diagnostic utility further extends to differentiating congenital from acquired disorders, assessing thrombosis risk, guiding anticoagulant dosage, evaluating pregnancy-related complications, and screening family members for hereditary risk.
