Overview
Congenital vitamin K-dependent coagulation factors deficiency (VKCFD), also known as combined deficiency of vitamin K-dependent clotting factors or familial multiple coagulation factor deficiency, is a rare inherited bleeding disorder characterized by reduced activity of all vitamin K-dependent coagulation factors (factors II, VII, IX, and X) as well as the natural anticoagulant proteins C, S, and Z. The condition results from defects in the vitamin K cycle, specifically mutations in the genes encoding either gamma-glutamyl carboxylase (GGCX, causing VKCFD type 1) or vitamin K epoxide reductase complex subunit 1 (VKORC1, causing VKCFD type 2). These enzymes are essential for the post-translational modification (gamma-carboxylation) of vitamin K-dependent proteins, which is required for their proper function in the coagulation cascade. The disease primarily affects the blood coagulation system but can also impact bone metabolism, since vitamin K-dependent proteins such as osteocalcin play a role in skeletal development. Clinical manifestations vary widely in severity and may present from birth or early infancy. Symptoms include easy bruising, mucocutaneous bleeding, epistaxis, gastrointestinal hemorrhage, umbilical cord bleeding, intracranial hemorrhage in severe cases, and prolonged bleeding after surgery or trauma. Some patients also exhibit skeletal abnormalities such as nasal hypoplasia, stippled epiphyses, and short stature, particularly in VKCFD type 1, reflecting impaired carboxylation of bone-related proteins. Treatment centers on oral or parenteral vitamin K supplementation, which can partially or fully correct the coagulation defect in many patients, particularly those with milder forms. The response to vitamin K therapy varies depending on the specific mutation and its effect on enzyme function. In cases of acute or severe bleeding, fresh frozen plasma or prothrombin complex concentrates may be required. Lifelong monitoring and management by a hematologist experienced in rare bleeding disorders is recommended.
Autosomal recessive
Passed on when both parents carry the same gene change; often skips generations
Neonatal
Begins at or shortly after birth (first 4 weeks)
FDA & Trial Timeline
1 eventANDEXXA: FDA approved
Coagulation factor Xa (recombinant), inactivated-zhzo is indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
1 availableTOBRADEX ST
They are also indicated in chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies.
Clinical Trials
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Specialists
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Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
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Common questions about Congenital vitamin K-dependent coagulation factors deficiency
What is Congenital vitamin K-dependent coagulation factors deficiency?
Congenital vitamin K-dependent coagulation factors deficiency (VKCFD), also known as combined deficiency of vitamin K-dependent clotting factors or familial multiple coagulation factor deficiency, is a rare inherited bleeding disorder characterized by reduced activity of all vitamin K-dependent coagulation factors (factors II, VII, IX, and X) as well as the natural anticoagulant proteins C, S, and Z. The condition results from defects in the vitamin K cycle, specifically mutations in the genes encoding either gamma-glutamyl carboxylase (GGCX, causing VKCFD type 1) or vitamin K epoxide reductas
How is Congenital vitamin K-dependent coagulation factors deficiency inherited?
Congenital vitamin K-dependent coagulation factors deficiency follows a autosomal recessive inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Congenital vitamin K-dependent coagulation factors deficiency typically begin?
Typical onset of Congenital vitamin K-dependent coagulation factors deficiency is neonatal. Age of onset can vary across affected individuals.