Vitamin K Deficiency

Vitamin K is found in green leafy vegetables and oils, such as olive, cotton seed, and soya beans.¹ 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.

• Vitamin K is an essential lipid-soluble vitamin. It is a co-factor in the synthesis of clotting factors II, VII, IX and X.
• 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.² However the clinical significance of this has not yet been fully evaluated.

• Deficiency can occur in persons of any age but neonates are at risk of developing haemorrhagic disease of the newborn. 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.
• In adults, Vitamin K deficiency is uncommon.
• In infants, Vitamin K deficiency without bleeding may occur in as many as 50% of infants younger than 5 days old.
• The classic haemorrhagic disease (presents first week of life) occurs in 0.25-1.7% of infants.
• The prevalence of late haemorrhagic disease (presents between 2 and 12 weeks old) in breast-fed infants is about 20 per 100,000 live births with no prior prophylaxis with Vitamin K.

Risk factors

• Excessive anticoagulation with Coumarins, e.g. warfarin.
• Liver disease: e.g. 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, Ascaris infection, 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 patients undergoing long-term parenteral nutrition without Vitamin K supplements.
• Drugs: Cholestyramine, cefamandole, salicylates, rifampin, isoniazid and barbiturates are some of the common drugs that are associated with Vitamin K deficiency.
• Diseases with endogenously produced coagulation inhibitors (e.g. 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.

• In infants, it causes classic haemorrhagic disease of newborns, especially with intracranial and retroperitoneal bleeding, which can occur at 1-7 days postpartum.
• Late haemorrhagic disease of newborns can occur as late as 3 months postpartum.
• Some birth defects, such as underdevelopment of the face, nose, bones, and fingers, are linked to vitamin K deficiency 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.

• 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 thrombocytopenic purpura, scurvy, thrombotic thrombocytopenia purpura and von Willebrand disease.

• 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.

• Therapy depends on the severity of the bleeding and the underlying cause.
• In life-threatening bleeds, Fresh Frozen Plasma 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 injections should be given slowly as fast intravenous injection can cause bronchospasm and peripheral vascular collapse.
• Intramuscular injections may lead to severe haematoma formation at the injection site if clotting is impaired.

• 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.

• With the consent of the mother, Vitamin K is given after birth, usually orally.
• Further doses at 1 week and again at four to six weeks of age are offered for breast-feeding babies.