Decreased levels or impaired function of protein S, a vitamin K-dependant physiological anticoagulant, leads to decreased degradation of factor Va and factor VIIIa and an increased propensity to venous thrombosis.

Types

There are three types of hereditary protein S deficiency:

Type I - decreased protein S activity: low levels of free protein S, normal levels of bound protein S
Type IIa - decreased protein S activity: low levels of free protein S, low levels of bound protein S
Type IIb - decreased protein S activity: normal levels of free protein S, normal levels of bound protein S

Decreased activity is present in an acquired form in vitamin K deficiency or treatment with warfarin. This generally also impairs the coagulation system itself (factors II, VII, IX and X), and therefore predisposes to bleeding rather than thrombosis. Protein S levels are also lower in pregnancy and liver disease.

Protein S deficiency is the underlying cause of a small proportion of cases of disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT) and pulmonary embolism (PE).

Hereditary PSD is an autosomal dominant condition, resulting in a 50 precent chance of passing the disease to offspring. Less than half of those diagnosed with PSD will experience thrombosis, and those who do usually are affected only from the age of the late teens onwards. A positive blood test can lead to the loss of health insurance benefits and/or employment, and the social downsides need to be balanced against the actual medical benefit of accurate diagnosis. Screening of young children is usually deferred because early testing is often inaccurate, and it is better to wait until they are old enough to decide for themselves whether they want to be tested.

Definition

Vitamin K deficiency exists when chronic failure to eat sufficient amounts of vitamin K results in a tendency for spontaneous bleeding or in prolonged and excessive bleeding with trauma or injury. Vitamin K deficiency occurs also in newborn infants, as well as in people treated with certain antibiotics. The protein in the body most affected by vitamin K deficiency is a blood-clotting protein called prothrombin.

Description

Vitamin K is a fat-soluble vitamin. The recommended dietary allowance (RDA) for vitamin K is 80 mg/day for the adult man, 65 mg/day for the adult woman, and 5 mg/day for the newborn infant. The vitamin K present in plant foods is called phylloquinone; while the form of the vitamin present in animal foods is called menaquinone. Both of these vitamins are absorbed from the diet and converted to an active form called dihydrovitamin K.

Spinach, lettuce, broccoli, brussels sprouts, and cabbage are good sources of vitamin K, containing about 8 mg vitamin K/kg food. Cow milk is also a good source of the vitamin.

A portion of the body's vitamin K is supplied by bacteria living in the intestine rather than by dietary sources.

Vitamin K plays an important role in blood clotting. Without the vitamin, even a small cut would cause continuous bleeding in the body, and death. Blood clotting is a process that begins automatically when any injury produces a tear in a blood vessel. The process of blood clotting involves a collection of molecules, which circulate continuously through the bloodstream. When an injury occurs, these molecules rapidly assemble and form the blood clot. The clotting factors are proteins, and include proteins called Factor II, Factor VII, Factor IX, and Factor X. Factor II is also called prothrombin. These proteins require vitamin K for their synthesis in the body. The blood-clotting process also requires a dozen other proteins that do not need vitamin K for their synthesis.

Causes & symptoms

Newborns are especially prone to vitamin K deficiency. A nursing-mother's milk is low in the vitamin; breast milk can supply only about 20% of the infant's requirement. Infants are born with low levels of vitamin K in their body; they do not have any vitamin K-producing bacteria in their intestines. Their digestive tracts are sterile. As a result, a form of vitamin K deficiency, called hemorrhagic disease of the newborn, may develop. This disease involves spontaneous bleeding beneath the skin or elsewhere in the infant's body, and occurs in about 1% of all infants. In rare cases, it causes death due to spontaneous bleeding in the brain.

Vitamin K deficiency in adults is rare. When it occurs, it is found in people with diseases that prevent the absorption of fat. These diseases include cystic fibrosis, celiac disease, and cholestasis. Vitamin K deficiency can exist in adults treated with antibiotics that kill the bacteria that normally live in the digestive tract. As mentioned, the intestine-bacteria supply part of our daily requirement of vitamin K. Vitamin K deficiency can result in bleeding gums, and in skin that is easily bruised.

Diagnosis

Vitamin K status is measured by the prothrombin time test. The normal prothrombin time is about 13 seconds. With vitamin K deficiency, the prothrombin time can be several minutes. The test involves taking a sample of blood, placing it in a machine called a fibrometer, and measuring the time it takes for blood-clot formation. Blood-clotting problems can also be caused by a rare genetic disease called hemophilia. Hemophilia is not related to vitamin K deficiency. Once vitamin K deficiency is suspected, further tests must be used to distinguish it from possible hemophilia. Where a bleeding disorder can be corrected by vitamin K treatment, the diagnosis of vitamin K deficiency is proven to be correct.

Treatment

Vitamin K deficiency in newborn infants is treated and prevented with a single injection of phylloquinone (5 mg). Adults with vitamin K deficiency are treated with daily oral doses of 10 mg phylloquinone for one week.

Prognosis

The prognosis for correcting vitamin K deficiency, and associated blood-clotting problems, is excellent.

Prevention

Aside from newborns and young infants, vitamin K deficiency is not a concern for the general population. Vitamin K deficiency can be prevented by assuring that the diet contains foods such as spinach, cabbage, brussels sprouts, and eggs. Soybean oil, canola oil, and olive oil are good sources of the vitamin, while corn oil and peanut oil are very poor sources.

Key Terms

Fat-soluble vitamin: Fat-soluble vitamins can be dissolved in oil or in melted fat.
Hemorrhage: Bleeding that continues for an abnormally long period of time.
Prothrombin: Prothrombin is a blood-clotting protein. Injury to a blood vessel produces a signal which triggers the conversion of prothrombin to thrombin. Thrombin is a protein which plays a central role in provoking the assembly of other proteins to form the blood clot.
Recommended Dietary Allowance (RDA): The Recommended Dietary Allowances (RDAs) are quantities of nutrients in the diet that are required to maintain good health in people. RDAs are established by the Food and Nutrition Board of the National Academy of Sciences, and may be revised every few years. A separate RDA value exists for each nutrient. The RDA values refer to the amount of nutrient expected to maintain good health in people. The actual amounts of each nutrient required to maintain good health in specific individuals differ from person to person.
Water-soluble vitamins: Water-soluble vitamins can be dissolved in water or juice.

For Your Information

Books

Brody, T. Nutritional Biochemistry. San Diego: Academic Press, Inc., 1998.
Combs, G. The Vitamins. San Diego: Academic Press, Inc.,1992.
Food and Nutrition Board. Recommended Dietary Allowances. 10th Edition. Washington, D.C.: National Academy Press, 1989.
Periodicals
Suttie, J.W. "The importance of menaquinones in human nutrition." Annual Review of Nutrition, 15 (1995): 399-417.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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Protein S deficiency