Vitamin K Deficiency

Vitamin K is found in green leafy vegetables and oils, such as olive, cotton seed and soya bean. Other foods rich in vitamin K are green peas and beans, watercress, asparagus, spinach, broccoli, oats and whole wheat. Vitamin K is also synthesised by colonic bacteria^[1].

• Vitamin K is an essential lipid-soluble vitamin. It is a co-factor in the synthesis of clotting factors II, VII, IX and X^[2].
• Vitamin K is also very important for bone health. Vitamin K deficiency is thought to cause impaired activation of bone matrix protein osteocalcin, and reduction of osteoblast function, resulting in impaired bone formation. However, the clinical significance of this has not yet been fully evaluated^[3].
• There is growing evidence for a role of vitamin K in vascular health^[4].

Epidemiology

Deficiency can occur in persons of any age but neonates are at risk of developing vitamin K deficiency bleeding (see the separate Vitamin K Deficiency Bleeding article). This is because of a lack of vitamin K reaching the fetus across the placenta, the low level of vitamin K in breast milk and low colonic bacterial synthesis.

Vitamin K deficiency is uncommon in otherwise healthy adults.

Risk factors

• Excessive anticoagulation with coumarins - eg, warfarin.
• Liver disease: for example, cirrhosis, malignancy, amyloidosis and Gaucher's disease decrease the synthesis of vitamin K-dependent factors.
• Malabsorption: coeliac disease, tropical sprue, Crohn's disease, ulcerative colitis, ascariasis, short bowel syndrome due to multiple abdominal surgeries, bacterial overgrowth, and chronic pancreatitis.
• Biliary tract disease: common duct obstruction due to stones and strictures, primary biliary cirrhosis, cholangiocarcinoma, and chronic cholestasis. Leads to a decrease in fat absorption and so a deficiency of fat-soluble vitamins.
• Dietary deficiency occurs in people with malnutrition, including people with alcoholism, as well as in patients undergoing long-term parenteral nutrition without vitamin K supplements.
• Drugs: colestyramine, salicylates, rifampin, isoniazid and barbiturates are some of the common drugs that are associated with vitamin K deficiency.
• Diseases with endogenously produced coagulation inhibitors (eg, lupus anticoagulant and antithrombins) and paraproteinaemias such as myeloma, may cause vitamin K deficiency.
• Miscellaneous causes include massive transfusion, disseminated intravascular coagulation, polycythaemia vera, nephrotic syndrome, cystic fibrosis, and leukaemia.

Presentation

• See the separate Vitamin K Deficiency Bleeding article for presentation in infants.
• The clinical manifestations in adults are evident only if hypoprothrombinaemia is present:
  • Bleeding is the major symptom, especially in response to minor or trivial trauma.
  • Any site can be involved, including mucosal and subcutaneous bleeding, such as epistaxis, petechiae, haematoma, gastrointestinal bleeding, menorrhagia, haematuria and bleeding from gums.

Differential diagnosis

• Vitamin K deficiency needs to be considered as a possible cause of any bleeding disorder.
• The differential diagnosis therefore includes leukaemia, disseminated intravascular coagulation, dysfibrinogenaemia, immune thrombocytopenia, scurvy, thrombotic thrombocytopenic purpura and von Willebrand's disease.

Investigations

• Bleeding time, prothrombin time and activated partial thromboplastin time are all elevated.
• The most sensitive marker is the antibody test for high level of des-gamma-carboxy prothrombin (DCP) protein in vitamin K absence (PIVKA).
• The plasma level of vitamin K can be measured.

Management

• Therapy depends on the severity of the bleeding and the underlying cause.
• In life-threatening bleeds, fresh frozen plasma (FFP) should be administered prior to vitamin K.
• Vitamin K is available as phytomenadione (vitamin K) and as the synthetic water-soluble analogue menadiol sodium diphosphate.
• Intravenous (IV) injections should be given slowly, as fast IV injection can cause bronchospasm and peripheral vascular collapse.
• Intramuscular injections may lead to severe haematoma formation at the injection site if clotting is impaired.

Infants

See the separate Vitamin K Deficiency Bleeding article.

Haemorrhage in people taking warfarin

See the separate Oral Anticoagulants article.

Prognosis

• Patients have a very good prognosis if the vitamin K deficiency is recognised early and treated appropriately.
• Morbidity correlates with severity of vitamin K deficiency, but severe bleeding can be fatal.

Prevention

• A diet rich in vitamin K - eg, green leafy vegetables and oils (such as olive, cotton seed and soya beans), green peas and beans, watercress, asparagus, spinach, broccoli, oats and whole wheat.
• Vitamin K given to neonates is very effective in preventing vitamin K deficiency bleeding.
• Menadiol sodium phosphate is a water-soluble synthetic vitamin K derivative that can be given orally to prevent vitamin K deficiency in malabsorption syndromes^[5].