Vitamin K Deficiency

Overview

Plain-Language Overview

Vitamin K deficiency is a condition where the body lacks enough vitamin K, a nutrient essential for blood clotting. Without sufficient vitamin K, the blood cannot clot properly, leading to easy bruising and excessive bleeding. This deficiency can occur due to poor diet, certain medical conditions, or the use of specific medications. Newborns are particularly at risk because they have low stores of vitamin K at birth. Treatment usually involves vitamin K supplementation to restore normal clotting function.

Clinical Definition

Vitamin K deficiency is a hematologic disorder characterized by a decreased availability of vitamin K, a fat-soluble vitamin necessary for the gamma-carboxylation of glutamic acid residues on clotting factors II, VII, IX, and X, as well as proteins C and S. This post-translational modification is essential for their calcium-binding function and subsequent activation in the coagulation cascade. Deficiency results in impaired synthesis of these functional clotting factors, leading to a bleeding diathesis. Causes include inadequate dietary intake, malabsorption syndromes such as celiac disease or cystic fibrosis, prolonged use of antibiotics that disrupt gut flora, and antagonism by vitamin K antagonists like warfarin. Neonates are particularly susceptible due to sterile intestines and low placental transfer. Clinically, patients present with mucocutaneous bleeding, easy bruising, and prolonged prothrombin time (PT). Laboratory findings typically show isolated prolongation of PT with normal or mildly prolonged activated partial thromboplastin time (aPTT). Treatment involves administration of vitamin K1 (phytonadione) to restore normal clotting factor function.

Inciting Event

Initiation of broad-spectrum antibiotics that disrupt gut microbiota.
Poor dietary intake or prolonged fasting leading to decreased vitamin K availability.
Onset of cholestatic liver disease impairing bile secretion and vitamin K absorption.
Administration of warfarin or other vitamin K antagonists.

Latency Period

Bleeding symptoms may develop within 1 to 2 weeks of vitamin K depletion in adults.
In newborns, hemorrhagic disease can present within the first week of life.

Diagnostic Delay

Mild bleeding symptoms may be attributed to other causes, delaying recognition of coagulopathy.
Lack of routine vitamin K level testing and nonspecific presentation can postpone diagnosis.

Clinical Presentation

Signs & Symptoms

Easy bruising and spontaneous bleeding.
Mucosal bleeding such as epistaxis and gingival bleeding.
Hemorrhagic events including gastrointestinal bleeding or hematuria.
In severe cases, intracranial hemorrhage may occur.

History of Present Illness

Patients often present with easy bruising, mucosal bleeding, or prolonged bleeding from minor wounds.
Newborns may show signs of intracranial hemorrhage or bleeding from the umbilical stump.
History may include recent antibiotic use, poor nutrition, or liver disease symptoms.

Past Medical History

Chronic liver disease such as cirrhosis or hepatitis.
History of malabsorption syndromes like cystic fibrosis or celiac disease.
Previous use of anticoagulants or recent antibiotic therapy.

Family History

None; vitamin K deficiency is typically acquired rather than inherited.

Physical Exam Findings

Presence of petechiae or ecchymoses indicating bleeding under the skin.
Prolonged bleeding from minor cuts or injection sites.
Possible mucosal bleeding such as gingival bleeding or epistaxis.

Diagnostic Workup

Diagnostic Criteria

Diagnosis of vitamin K deficiency is based on clinical suspicion in the presence of bleeding symptoms combined with laboratory evidence of an isolated prolonged prothrombin time (PT) that corrects with vitamin K administration. Activated partial thromboplastin time (aPTT) may be normal or mildly prolonged. Measurement of clotting factor activity shows decreased levels of vitamin K-dependent factors II, VII, IX, and X. Response to vitamin K supplementation, demonstrated by normalization of PT within 24 hours, confirms the diagnosis.

Pathophysiology

Key Mechanisms

Vitamin K deficiency impairs the gamma-carboxylation of glutamic acid residues on clotting factors II, VII, IX, and X, leading to decreased coagulation activity.
Reduced activation of vitamin K-dependent proteins results in defective blood clotting and increased bleeding risk.

Involvement	Details
Organs	Liver is the primary organ for synthesis of vitamin K-dependent clotting factors.
	Small intestine is the main site of dietary vitamin K absorption.
	Colon harbors bacteria that synthesize vitamin K2 (menaquinone).
Tissues	Liver tissue synthesizes vitamin K-dependent clotting factors essential for coagulation.
	Intestinal mucosa facilitates absorption of dietary vitamin K.
	Bone tissue requires vitamin K for activation of osteocalcin, important in bone mineralization.
Cells	Hepatocytes are responsible for synthesizing vitamin K-dependent clotting factors.
	Enterocytes absorb dietary vitamin K in the small intestine.
	Gut microbiota synthesize menaquinones (vitamin K2), contributing to vitamin K status.
Chemical Mediators	Vitamin K acts as a cofactor for gamma-glutamyl carboxylase enzyme.
	Gamma-glutamyl carboxylase catalyzes carboxylation of glutamic acid residues on clotting factors.
	Clotting factors II, VII, IX, and X require vitamin K-dependent carboxylation for activation.

Treatment

Pharmacological Treatments

Vitamin K (phytonadione)
- Mechanism: Serves as a cofactor for gamma-glutamyl carboxylase, enabling activation of clotting factors II, VII, IX, and X
- Side effects: Hypersensitivity reactions, flushing, pain at injection site
Fresh frozen plasma (FFP)
- Mechanism: Provides functional clotting factors to rapidly correct coagulopathy
- Side effects: Volume overload, allergic reactions, transfusion-related acute lung injury

Non-pharmacological Treatments

Ensure adequate dietary intake of vitamin K-rich foods such as green leafy vegetables.
Address underlying causes such as malabsorption syndromes to improve vitamin K status.
Avoid prolonged use of broad-spectrum antibiotics that disrupt gut flora responsible for vitamin K synthesis.

Prevention

Pharmacological Prevention

Prophylactic administration of vitamin K1 (phytonadione) in at-risk populations.
Use of vitamin K supplementation in patients on long-term antibiotics or with malabsorption.

Non-pharmacological Prevention

Ensuring adequate dietary intake of vitamin K–rich foods such as green leafy vegetables.
Avoidance of unnecessary prolonged use of broad-spectrum antibiotics.
Monitoring and managing underlying conditions causing malabsorption.

Outcome & Complications

Complications

Severe hemorrhage including intracranial bleeding.
Hemorrhagic shock from uncontrolled bleeding.
Anemia secondary to chronic blood loss.

Short-term Sequelae	Long-term Sequelae
Acute bleeding episodes requiring urgent intervention. Transient anemia due to blood loss.	Potential neurological deficits from intracranial hemorrhage. Chronic anemia if bleeding is recurrent and untreated.

Differential Diagnoses

Vitamin K Deficiency versus Disseminated Intravascular Coagulation (DIC)

Vitamin K Deficiency	Disseminated Intravascular Coagulation (DIC)
Normal platelet count in vitamin K deficiency	Elevated D-dimer and fibrin degradation products
Normal fibrinogen levels in vitamin K deficiency	Thrombocytopenia due to platelet consumption
Isolated prolonged PT with possible mild aPTT prolongation	Prolonged PT and aPTT with low fibrinogen levels

Vitamin K Deficiency versus Hemophilia A

Vitamin K Deficiency	Hemophilia A
Prolonged PT with possible mild aPTT prolongation	Isolated prolonged aPTT with normal PT
Deficiency of vitamin K-dependent factors II, VII, IX, X	Factor VIII deficiency confirmed by assay
Normal bleeding time unless severe deficiency	Normal bleeding time

Vitamin K Deficiency versus Liver Disease

Vitamin K Deficiency	Liver Disease
Normal liver enzymes in vitamin K deficiency	Elevated liver enzymes (AST, ALT)
Normal factor V levels since it is not vitamin K dependent	Decreased synthesis of all clotting factors including factor V
Isolated prolonged PT with or without mild aPTT prolongation	Prolonged PT and aPTT with low albumin