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Hematology

Factor V Deficiency

Factor V deficiency is a rare bleeding disorder that can be inherited or acquired. Factor V is a vital component of the coagulation cascade, a glycoprotein synthesized primarily in the liver and released in the bloodstream in an inactive form. Blood vessel injury activates blood clotting factors, including factor V. Activated factor V ultimately accelerates fibrinogen conversion to fibrin, the protein meshwork that reinforces the clot. Factor V deficiency disrupts this intricate clotting mechani

v1 · Reviewed Nov 7, 2026 by Automated Clinical Reviewer (Strict Verbatim v1)
  • Symptoms can range from mild mucosal bleeding to severe, life-threatening hemorrhage.
  • Life-threatening intracranial hemorrhage may also occur and often initially presents as hydrocephalus or seizures in infants, warranting an immediate workup to prevent significant morbidity and mortality.
  • Serious internal hemorrhage may also occur, and if not recognized early, mortality can reach 15% to 20%.
  • Unresponsiveness, apnea, and pulselessness are signs of cardiorespiratory arrest.
  • Prompt diagnosis of intracranial hemorrhage is vital, as untreated cases can be fatal, particularly when the etiology is unknown.
  • Diagnosis usually requires a coagulation profile and blood tests to measure the level and activity of various coagulation components, including factor V.
  • Genetic testing may also be performed in people with the inherited form to identify the specific genetic mutation responsible for the disorder and guide family planning decisions.
  • Initial laboratory evaluation shows prolonged prothrombin time and activated partial thromboplastin time (aPTT) with a normal thrombin time.
  • A low plasma factor V level confirms the diagnosis.
  • Plasma mixing studies help distinguish between inherited and acquired factor V deficiency.
  • Factor V deficiency prolongs both prothrombin time and aPTT but leaves thrombin time unaffected.
  • Factor V assays reveal reduced activity levels, with the deficiency classified as mild (>10%), moderate (1% to 10%), or severe (<1%).
  • The Bethesda assay, which measures inhibitors against a specific coagulation factor in the blood, confirms the diagnosis.
  • Sequencing DNA from peripheral blood leukocytes can identify mutations within this gene to diagnose inherited factor V deficiency.
Factor V deficiency classification
Mild factor V deficiency is identified by plasma activity greater than 10% of normal.
Factor V deficiency classification
Factor V assays reveal reduced activity levels, with the deficiency classified as mild (>10%), moderate (1% to 10%), or severe (<1%).
  • Treatment typically involves managing and preventing bleeding episodes through various strategies, including clotting factor replacement therapy using agents like fresh frozen plasma.
  • In inherited cases, treatment typically involves transfusion of fresh frozen plasma (FFP), which contains factor V.
  • Mild cases may require antifibrinolytics to achieve hemostasis.
  • FFP sustains factor V levels above 25% to 30% during bleeding episodes or invasive procedures, with higher levels required to ensure hemostasis in severe or life-threatening hemorrhages.
  • Immunosuppression may be necessary in patients with the acquired disease type.
  • Eradicating factor V inhibitor requires immunosuppression.
  • Corticosteroids, cyclophosphamide, and rituximab, alone or in combination, suppress anti–factor V autoantibody production with a 63% success rate.
  • High-dose intravenous immunoglobulin (60% success rate) and plasmapheresis (53% success rate) also reduce circulating factor V inhibitors.
  • Recombinant activated factor VII, commonly used for inhibitors in hemophilia A or B, can also manage bleeding by directly activating factor X, bypassing the requirement for factor V or other coagulation factors.
  • In acquired factor V deficiency, bleeding prevention involves treating the underlying cause, such as discontinuing inciting medications or managing conditions that trigger antibody formation.
  • Complications of factor V deficiency may occur as early as the neonatal period.
  • Although uncommon, intracranial hemorrhage poses diagnostic challenges in newborns and carries a high mortality rate.
  • Thrombotic events, while less frequent, can arise from factor V's prothrombotic effect, with reported cases including deep vein thrombosis, cerebral infarction, and limb gangrene.
  • Prompt recognition of factor V deficiency is essential to initiate treatment and prevent potentially life-threatening outcomes.
  • Coagulation parameters should be closely monitored, and appropriate blood products, including FFP, administered as needed to maintain hemostasis.
  • Regardless of etiology, patients should have regular follow-up with a hematologist and maintain prompt communication with healthcare providers in the event of bleeding.
  • review
    Factor V Deficiency. StatPearls [Internet] — Katarzyna M. Stoj, Robert B. Killeen, Joanna Pierro — StatPearls Publishing, 2025

Decision support only. Verify against local protocols and current labeling. Source: www.ncbi.nlm.nih.gov