eMedicine Specialties > Endocrinology > Metabolic Disorders

Vitamin K Deficiency

Author: Pankaj Patel, MD, Fellow, Department of Gastroenterology, Winthrop University Hospital and SUNY-Stony Brook
Coauthor(s): Mageda Mikhail, MD, Assistant Professor, Department of Medicine, Division of Endocrinology, State University of New York at Stony Brook
Contributor Information and Disclosures

Updated: Dec 18, 2008

Introduction

Background

Vitamin K (VK), an essential, lipid-soluble vitamin that plays a vital role in the production of coagulation proteins, is found in green, leafy vegetables and in oils, such as soybean, cottonseed, canola, and olive oils.¹ VK is also synthesized by colonic bacteria. The 3 main types of VK are K-1, which is derived from plants; K-2, menaquinone, which is produced by the intestinal flora; and K-3, which is a synthetic, water-soluble form used for treatment.

VK deficiency can occur in persons of any age. Infants are at higher risk for hemorrhagic disease of newborn, caused by a lack of VK reaching the fetus across the placenta, the low level of VK in breast milk, and low colonic bacterial synthesis.^2,3,4 However, a large amount of VK given to a pregnant patient can lead to jaundice in a newborn. In adults, VK deficiency is uncommon due to the intake of a wide variety of vegetables and other foods; the recycling ability of VK, which helps to conserve the body's supply; and adequate gut flora to produce VK.

Pathophysiology

Vitamin K (VK) acts as a cofactor; it is needed for the conversion of 10-12 glutamic acid residue on the NH2-terminal of the precursor coagulation proteins into the action form of gamma-carboxyglutamic acid (which occurs via VK-dependent gamma-glutamyl carboxylase).^5,6,7 This essential reaction allows the VK-dependent proteins to bind to surface phospholipids through calcium ion channel – mediated binding, in order to start the normal antithrombotic process. The exact mechanism by which VK functions as cofactor with the carboxylase is not fully understood. In addition to the coagulation factors, bone matrix proteins, specifically osteocalcin, undergo similar gamma carboxylation with calcium that requires VK; therefore, osteoporosis is associated with VK deficiency.⁸

If a healthy person is subject to a complete dietary absence of VK, his/her VK reserve is adequate for 1 week. Because diet is the main source of VK, an adult's daily requirement has been estimated at 100-200 mcg/d. About 80-85% of VK is absorbed mainly in the terminal ileum into the lymphatic system; therefore, bile salts and normal fat absorption, as well as normal villi of the ileum, are necessary for the effective uptake of VK.

The characteristics of VK deficiency vary according to the age of onset. In infants, it causes hemorrhagic disease of newborn, resulting especially in intracranial and retroperitoneal bleeding, which can occur at 1-7 days postpartum. The low transmission of VK across the placenta, liver prematurity with the prothrombin synthesis, lack of VK in breast milk, and the sterile gut in neonates account for VK deficiency in infants.^2,3,4,9 Late hemorrhagic disease of newborn can occur as late as 3 months postpartum.

In adults, low dietary intake of VK due to chronic illness, malnutrition, alcoholism, multiple abdominal surgeries, long-term parenteral nutrition, malabsorption, cholestatic disease, parenchymal liver disease, cystic fibrosis, inflammatory bowel disease, and drugs (eg, antibiotics [cephalosporin], Coumadin, salicylates, anticonvulsants, certain sulfa drugs) are some of the common causes of VK deficiency.^9,10 Because 2 main sources of VK exist, neither dietary deficiency nor gut sterilization produces significant coagulopathy in a healthy person.

Frequency

United States

The prevalence of vitamin K (VK) deficiency varies by geographic region.³ In infants, VK deficiency without bleeding may occur in as many as 50% of infants younger than 5 days old. The classic hemorrhagic disease occurs in 0.25-1.7% of infants. The prevalence of late hemorrhagic disease in breastfed infants is about 20 cases per 100,000 live births with no prior VK prophylaxis.

International

Internationally, the incidence of vitamin K deficiency is similar to that in the United States.

Mortality/Morbidity

Morbidity correlates with the severity of vitamin K deficiency; severe bleeding can be fatal.

Race

There is no race predilection for vitamin K deficiency.

Sex

Vitamin K deficiency occurs with equal frequency in males and females.

Age

Vitamin K deficiency can occur in any age group, but it is encountered most often in infancy.

Clinical

History

The clinical manifestations of vitamin K deficiency are evident only if hypoprothrombinemia is present. Bleeding is the major symptom, especially in response to minor or trivial trauma. Any site can be involved, so manifestations can include mucosal and subcutaneous bleeding, such as epistaxis, hematoma, gastrointestinal bleeding, menorrhagia, hematuria, gum bleeding, and oozing from venipuncture sites. Easy bruisability also is observed.¹¹

Physical

Ecchymosis, petechiae, hematomas, and oozing of blood at surgical or puncture sites are observed. In infants, some birth defects, such as underdevelopment of the face, nose, bones, and fingers, are linked to a vitamin K – deficient state.

Causes

• Parenchymal liver diseases, such as cirrhosis secondary to viral hepatitis, alcohol intake, and other infiltrative diseases; hepatic malignancy; amyloidosis; Gaucher disease; and others decrease the synthesis of vitamin K (VK)–dependent factors. Therefore, supplementation with VK is not effective unless a patient has severe bleeding and fresh frozen plasma (FFP) is administered in addition to correct the coagulopathy.
• Malabsorption syndrome affects VK absorption in the ileum. Celiac sprue, tropical sprue, Crohn disease, ulcerative colitis, Ascaris infection, bacterial overgrowth, chronic pancreatitis, and short bowel syndrome resulting from multiple abdominal surgeries can be involved in lack of absorption of VK (which can be corrected with VK supplementation).¹²
• Biliary diseases, such as common duct obstruction due to stones and strictures, primary biliary cirrhosis, cholangiocarcinoma, and chronic cholestasis, cause maldigestion of fat; the decrease in fat absorption leads to a deficiency of fat-soluble vitamins.⁴ In addition, surgery and T-tube drainage of the bile duct can lead to a VK-deficient state.
• Dietary deficiency occurs in people with malnutrition, including people with alcoholism, as well as patients undergoing long-term parenteral nutrition without VK supplements. A large amount of vitamin E can antagonize VK and prolong the prothrombin time (PT).
• Various drugs, such as cholestyramine, bind to bile acids, thus preventing fat-soluble vitamin absorption. Coumadin blocks the effect of VK epoxide reductase and VK reductase, thereby inducing an intracellular deficiency. Cefamandole, cefoperazone, salicylates, hydantoins, rifampin, isoniazid, and barbiturates are some of the common drugs that are associated with VK deficiency, but the mechanism is unknown.
• Disease with endogenously produced coagulation inhibitors, such as lupus anticoagulant and antithrombins, and paraproteinemias, ie, multiple myeloma, may cause a VK-deficient state.
• Miscellaneous causes include massive transfusion, disseminated intravascular coagulation (DIC), polycythemia vera, nephrotic syndrome, cystic fibrosis, and leukemia.

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