Vitamin K Deficiency

It is important to note that most cases of mild vitamin K deficiency are asymptomatic. The symptoms only present when there is a prolongation of prothrombin time or INR. The most common symptom of vitamin K deficiency is bleeding. The bleeding may be precipitated by minor or major trauma. Almost any organ system in the body can be involved. However, the most obvious and visible signs of bleeding are seen in the gums, urinary system (hematuria), bleeding per rectum, heavy menstrual cycle, oozing from venipuncture sites, hematoma and very easy bruisability. If the bleeding is severe, the patient may complain of dizziness, syncope, chest pain or lack of exercise tolerance (as a result of anemia). The rare patient may present with cerebral hemorrhage, which may present with lethargy, coma or stupor.

Vitamin K deficiency in infants can present with poor development of the skeleton which may reveal itself with with small facial and finger structure.

In a patient with suspected vitamin K deficiency, the following blood work is necessary:

• CBC with hemoglobin and hematocrit to assess the degree of anemia if bleeding has occurred.
• Platelet count and their function.
• Cross and type blood in case there is a need for transfusion.
• PT, INR and PTT. Patients with vitamin K deficiency tend to have an elevated PT but the PTT is normal. However, in severe cases, both parameters may be elevated.
• Most laboratorys today also measure des-gamma-carboxy prothrombin (DCP) which is a very sensitive marker for vitamin K deficiency.
• In rare cases levels of serum phylloquinone can be measured, but the results are not reliable and do depend on oral intake. In general, a low level of serum phylloquinone is indicative of low tissue stores. This value must take into account the clinical scenario.

Other laboratory values and tests that should be obtained as part of workup include:

• Liver function
• Renal function
• Urine analysis
• If bleeding is suspected in the brain, a CT scan is recommended.

General treatment

The treatment of a patient with vitamin K deficiency is vitamin K replacement. However, the treatment depends on the underlying disease and severity of bleeding episodes. If the bleeding is minor and the underlying disorder has been corrected, then observation may be prudent. In patients with severe bleeding and a coagulopathy, vitamin K can be administered intramuscularly. However, use of injections to administer vitamin K can also result in localized hematoma, which can be significant. In patients with life threatening bleeding and those who need immediate surgery, fresh frozen plasma can be administered. Depending on the severity of bleeding 6-12 units of fresh frozen plasma may be administered.

After administration of vitamin K, the prothrombin time usually starts to normalize within 12-24 hours. If the prothrombin time fails to normalize, then one should suspect the presence of significant liver disease of disseminated intravascular coagulation. In patients who are at risk for developing a hematoma with intramuscular or subcutaneous injection, then the patient can receive the oral formula. The dose of vitamin K is anywhere from 5-20 mg of vitamin K per day. The absorption of vitamin K is variable because it does require presence of bile salts in the intestine. Thus, it is important to ensure that the individual has no GI or biliary tract disorder before giving the oral formula [8].

In emergent cases where the bleeding is severe or the patient needs emergent surgery, then vitamin K can be administered as an IV drip. The rate of infusion should not exceed 1mg/ml, otherwise there is a risk of hypersensitive or anaphylactic reaction. During the infusion the patient must be connected to a cardiac monitor. CPR equipment must be at the bed side because there are reports that some patients can develop shock. When given intravenously, vitamin K can reverse the abnormal PT within 12-24 hours.

Multidisciplinary approach

When vitamin K deficiency is diagnosed, it is important to consult with a gastroenterologist, hematologist and dietician.

• The hematologist can help exclude other disorders that can present with similar features. In addition, the hematologist can help interpret the INR, PT and PTT and guide treatment. Further the hematologist can also recommend blood products in cases of severe bleeding.
• An internist can help manage the bleeding and or dosing of vitamin K.
• A gastroenterologist can help make the diagnosis of a GI disorder that may be responsible for the vitamin K deficiency.
• Intensivist to help acutely bleeding patients.
• Dietitian to help educate patients about foods that contain vitamin K.

Diet

• Patients with vitamin K deficiency do need a dietary consult as they must know which foods contain this particular vitamin. Almost any plant food can be eaten but those with the highest content of vitamin K include beans, peas, asparagus, broccoli, spinach and watercress.
• Oils recommended include canola, olive, cottonseed, soybean and safflower oil.
• Cereals such as whole wheat and oats.
• Liver is known to store vitamin K and hence a diet consisting of this meat product is recommended.

Newborns

Currently all newborns receive vitamin K injections subcutaneously at birth. In the past there was a suggestion that prophylaxis of newborns infants with vitamin K may increase the risk of malignancy, but so far no study has found a correlation.

Other uses of vitamin K

Vitamin K may increase bone mineralization and in Japan, it is routinely given to women to prevent osteoporosis. The dose of vitamin K required to prevent osteoporosis are high and vary from 40-50 mg per day.

Adverse effects of vitamin K

While vitamin K is a safe medication, it can produce a hematoma when injected subcutaneously or intramuscularly. The other side effect of concern in the risk of anaphylaxis which is believed to be due to the components of the formula. Thus, all patients who receive vitamin K parenterally need to be closely monitored and observed for at least 1-2 hours.

Blood components

There are scenarios when the patient fails to respond to vitamin K and hence fresh frozen plasma is administered. Fresh frozen plasma does contain the soluble clotting factors and is usually given intravenously. The FFP also provides volume and can help elevated the blood pressure [9].

The prognosis of individuals with vitamin K deficiency varies on its severity and age of presentation. In infants, the disorder can result in hemorrhagic disease of the newborn, which is often characterized by bleeding in the abdomen and central nervous system. This bleeding may occur within the first week after birth and can be mild to severe. There are some breast fed infants who may also develop delayed hemorrhagic disease of the newborn that may occur as late as 8 to 12 weeks after birth.

Vitamin K is also plays a critical role in bone synthesis and hence a deficiency of this vitamin can also result in osteoporosis. The vitamin plays a role in the metabolism of osteocalcin, which is an important protein that remodels and mineralizes bone [6] [7]. However, it is important to understand that vitamin K is not a substitute for vitamin D in the prevention and treatment of osteoporosis.

The majority of patients with vitamin K deficiency have an excellent prognosis if the disorder is diagnosed and promptly treated. The prognosis can worsen in patients who have severe bleeding and are not treated. In patients who require surgery in the presence of vitamin K deficiency, the prognosis is guarded and depends on the type of procedure. Patients who receive fresh frozen plasma and vitamin K prior to surgery tend to have a good prognosis but need close monitoring in the ICU.

The cause of vitamin K deficiency depends on the age of the patient.

Acute causes

• Massive blood transfusion [4]
• Disseminated intravascular coagulation (DIC)
• Chronic kidney disease and/or hemodialysis

The coagulopathy in acute vitamin K deficiency can be corrected by administering vitamin K by injection.

Infants develop vitamin K deficiency for the following reasons:

• Decreased transmission of vitamin across the placenta in utero.
• Premature liver and failure to make the coagulation factors and hence the prothrombin time or INR remains elevated.
• Lack of or low levels of vitamin K in breast milk.
• Sterile gut at birth and failure to make vitamin.

Adults

Causes of vitamin K deficiency in adults include the following:

Diet

• Vitamin K deficiency is known to occur in people with malnutrition. These individuals do not consume adequate green leafy vegetables. Within a few weeks of starting a vegetable diet, the deficiency can be reversed.
• Alcoholics may develop vitamin K deficiency from either a poor diet or liver cirrhosis.
• Long term parenteral nutrition is a cause of vitamin K deficiency if no supplement is added to the formula.
• Chronic illness where a patient is anorexic or does not eat a proper diet can lead to vitamin K deficiency. Almost any chronic disorder can lead to this medical disorder. This type of vitamin K deficiency is often seen in elderly and mentally challenged individuals.

Surgery

Anytime the terminal ileum is removed or large amount of small bowel (short bowel syndrome) resected it can lead to impairment of vitamin K absorption. Sometimes surgeon will place a T tube for bile drainage and this will divert the bile outside the body and lead to decreased ability to absorb fats.

Liver disease

Patients who have parenchymal liver disease like viral hepatitis, alcoholic liver disease, carcinoma, Wilson disease, alpha-1 antitrypsin deficiency, hemochromatosis, or amyloidosis will not be able to make vitamin K dependent coagulation factors. In these patients administering vitamin K is not helpful, in such scenarios if the patient is bleeding, then transfusion of fresh frozen plasma is needed to correct the coagulopathy.

Biliary disorders

Biliary disorders can result in failure to secrete bile salt. Bile salts are essential for absorption of fat. The inability to absorb fat results in deficiency of all fat soluble vitamins including vitamin K. Disorders of the bile duct include gallstones, strictures, cholangiocarcinoma, primary biliary cirrhosis, chronic pancreatitis and chronic cholestasis.

Gastrointestinal tract (GI) disorders that induce inflammation around the terminal ileum can affect absorption of vitamin K. These GI disorders include:

• Celiac sprue
• Crohn disease
• Ulcerative colitis
• Parasitic infestation (eg. Ascariasis)
• Bacterial overgrowth can lead to destruction of normal colonic flora, which are responsible for making vitamin K.

Systemic disorders

Conditions such as cystic fibrosis or scleroderma can lead to vitamin K deficiency.

Medications that can cause vitamin K deficiency include the following:

• Cholestyramine acts by binding to bile salts in the intestine and prevent absorption of fat soluble vitamins
• Warfarin inhibits the action of vitamin K epoxide reductase and prevents the synthesis of factors 5, 7, 9 and 10 in the liver.
• Cephalosporins the 2nd generation cephalosporins like cefoperazone and cefamandole
• Anticonvulsants
• NSAIDs (in particular salicylates) [5]
• Antituberculous drugs like isoniazid and rifampin
• Sedatives like sodium barbital
• Drug induced deficiency of vitamin K usually occurs after prolonged use of these substances.
• Supplements like vitamin E in large amounts are known to antagonize the actions of vitamin K in the liver and lead to prolonged INR.

Vitamin K deficiency is not a common disorder in adults. Most frequently it is seen in infants. In many infants who have vitamin K deficiency at birth, there may be no symptoms. Only about 1-2 % of infants present with classic hemorrhage in the brain or abdomen. In infants who are not administered vitamin K prophylaxis, delayed hemorrhage can occur which is felt to occur in about 2 cases per 10,000 live births.

Globally the rates of vitamin K deficiency do vary depending on the country. The reason is because different countries have their own criteria as to what constitutes vitamin K deficiency and how they quantify it. In Europe the prevalence appears to be the same as the USA but in Oriental countries like Thailand, the rates are at least 10-15 fold higher. The reason for the higher rates of vitamin K deficiency is thought to be related to lack of universal protocols for administering vitamin K to all newborns.

Vitamin K deficiency is also common in people who do not have an appropriate diet, like alcoholic, mentally challenged individuals and the elderly. These individuals often present to the hospital and incident blood work reveals high or prolonged INR.

Newborn infants have not yet started to make the coagulation factors at birth because of lack of vitamin K. The maternal vitamin K is usually not able to pass across the placenta during pregnancy. In addition, breast milk also contains very low levels of vitamin K; hence, breast fed infants can also develop hemorrhagic disease of the newborn. Giving large doses of vitamin K to a pregnant female is not recommended as it may lead to jaundice in the newborn. Finally, another reason why newborn infants have low levels of vitamin K is because the gut has not yet been colonized by bacteria. These microorganisms also play a role in the synthesis of vitamin K.

Because many adult patients are on warfarin to prevent blood clots, vitamin K deficiency can occur. These individuals have to be closely monitored for bleeding and their coagulation profile checked every few weeks. One of the most common causes of admission to hospitals in adults is bleeding caused by elevated levels of prothrombin time. The next group of adults who also run into bleeding problems are those with liver disease since they are unable to synthesize the coagulation factors.

Vitamin K deficiency in adults is rarely from diet as most people consume a wide range of vegetables and other meat products that contain ample amounts of vitamin K. In addition in adults there is continuous recycling of vitamin K that is excreted in the intestine. A small amount of vitamin K is also made by the colonic flora.

Vitamin K deficiency can occur for many reasons. In infancy the disorder is prevented by administering a single vitamin K injection subcutaneously. This is now the standard of care in many countries. In people who have disorders of the intestine or have difficulty with absorption, it is essential to maintain a diet that contains ample vitamin K. There are many people who are on medications to maintain an elevated prothrombin time and these people are susceptible to bleeding. To prevent complications, these individuals should regularly follow up with their healthcare provider and ensure that the blood coagulation parameters are measured on a regular basis. The PT or INR must be with therapeutic guidelines to prevent bleeding. These individuals also need to watch their diet to ensure that they are not eating foods that interact with medications and blunt its effects. Anytime a person is on an anticoagulant and has signs of bleeding, a visit to the nearest emergency room is recommended.

Vitamin K deficiency can occur in both infants and adults. In infants the cause is often due to lack of vitamin K stores, but in adults the most common cause is use of medications like the oral anticoagulants. Vitamin K is an essential fat soluble vitamin that plays a critical role in the synthesis of coagulation factors, 5, 7, 9 and 10 in the liver. The majority of people acquire their vitamin K from a diet that consists of green leafy vegetables, oils and synthesis by the colonic microorganisms. The body does not have large stores of vitamin K and hence, deficiency of this vitamin K can occur in a matter of days if there is no dietary intake of proper foods.

The most common manifestation of vitamin K deficiency is bleeding, but the intensity is variable. Infants can develop hemorrhagic diseases of the newborn characterized by bleeding in the brain and abdomen. Adults on the other hand can present with bleeding from the gums, urinary tract, intestine and easy bruising. Besides diet, a small amount of vitamin K is also made by colonic flora. Most adults with vitamin K deficiency present to the ER with bleeding as a result of anticoagulation therapy [1] [2] [3].

Daily vitamin K requirements

• For children 0-12 months: 2 mcg/day
• Children 1-8 years: 30-55 mcg/day
• Children and teens 9-18 years: 55-75/mcg day
• Women 19 years: 90 mcg/day
• Women breast feeding: 75-90 mcg/day
• Men 19 years and over: 75-150 mcg/day

The majority of vitamin K from diet is absorbed in the terminal ileum. The absorption of vitamin K depends on presence of bile salts. In addition, the villi and epithelial cells of the terminal ileum must be functioning and healthy to absorb the vitamin. If there is complete absence of vitamin K from the diet, the reserves from the liver will be depleted in 7-12 days

For patients on total parenteral nutrition (TPN), 150 mcg/d of phylloquinone is usually added to the IV nutrition formula. It is important to monitor the prothrombin time and INR on a regular basis while patients are on TPN. The reason is that the added vitamin K may counter the therapeutic effects of warfarin.

Vitamin K is an essential vitamin for the synthesis of certain clotting factors. If the body lacks vitamin K, serious bleeding can occur. Vitamin K deficiency can occur from a variety of causes. In pregnancy, the vitamin K is unable to pass through the placenta. In a newborn vitamin K also fails to pass through breast milk. Hence, all infants now receive an injection of vitamin K soon after birth. In adults, the most common case of vitamin K is use of medications. Others who can develop vitamin K deficiency include people with intestinal disease like Crohn disease or surgical removal of large amount of bowel. This prevents absorption of vitamin K.

When vitamin K deficiency develops, it can present with bruising of skin, bluish discoloration and frank blood in the urine, or stools. To prevent vitamin K deficiency it is important to eat diet that consists of green leafy vegetables and meat products like liver. Those who take medications to thin blood need close follow up with the healthcare provider to ensure that their bleeding profile is not very high otherwise bleeding can occur.

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