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Warfarin Side Effects

Warfarin, a blood thinner (anticoagulant) that has been around for decades, is associated with several serious side effects and complications that can result in permanent disability, including strokes and loss of limbs, and death. While bleeding is a common side effect among all blood thinners, warfarin is also linked to severe tissue death (gangrene) and calciphylaxis (the calcification of blood vessels), a dangerous condition that can cause painful sores and permanent tissue damage, and has a high probability of death.

Even with the emergence of new-generation blood thinners on the market, warfarin (brand names Coumadin and Jantoven) is still the most widely used anticoagulant in the United States and the United Kingdom.

While the drug can be a lifesaver in patients suffering from atrial fibrillation (AFib) (an irregular, often rapid heart rate that can increase a patient’s risk of stroke, heart failure and other heart-related complications), it also has its drawbacks.

Complications include bleeding in the brain, known as a hemorrhagic stroke. Warfarin patients are required to undergo regular blood tests to monitor the drug’s effectiveness. But not doing so can result in incorrect dosages and an increased risk for excessive, potentially life-threatening bleeding in all areas of the body, including dangerous gastrointestinal (stomach) bleeding.

Warfarin, specifically in its brand-name form Coumadin, is also associated with tissue death, or gangrene, and a rare but highly deadly condition called calciphylaxis, which involves the calcification of a patient’s blood vessels, resulting in severe pain, ulcers, organ failure and full body infections (sepsis) that do not respond well to treatment.

Other serious side effects can include acute injury to the kidneys and cholesterol embolisms (or clots) that travel through the bloodstream and become lodged in various blood vessels.

Warfarin Tablet
The oldest anticoagulant is warfarin, also known as Coumadin or Jantoven.

Warfarin and Hemorrhage (Serious or Fatal Bleeding)

Major bleeding (hemorrhage) that can possibly result in death is more likely to occur within the first month of a patient using Coumadin (warfarin), according to the drug’s label. Patients are at a greater risk of experiencing this side effect if they have an elevated INR (International Normalized Ratio, a measure of how long it takes a person’s blood to clot). An INR over 4.0 can be a sign of “high-intensity anticoagulation,” putting a patient at an increased risk for major bleeding.

Other Risk Factors For Bleeding In Patients Taking Coumadin (Warfarin) Include:
  • Being 65 or older
  • Having a history of a highly variable INR measure
  • History of gastrointestinal bleeding
  • High blood pressure
  • Cerebrovascular disease (any disorder in which an area of the brain is temporarily or permanently affected by bleeding or lack of blood flow)
  • Kidney impairment
  • Certain genetic factors
  • Concurrent use of certain medicines
  • Long duration of warfarin treatment
  • Anemia (a condition in which the number of healthy red blood cells in a patient’s body is too low)

Normally, when a person bleeds, clots form to stop the flow. However, bleeding can last much longer than usual in individuals taking blood thinners, sometimes requiring emergency medical attention. Wounds and bruises may also take longer than usual to heal.

Internal bleeding can include gastrointestinal bleeding as well as bleeding in the brain. Both conditions can be fatal.

Side Effects of Internal Bleeding

Initially, internal bleeding may cause no symptoms. However, if the bleeding is chronic and/or severe, there are several signs and symptoms that can point to the problem.

Symptoms of bleeding are often associated with the specific location of the bleed. For example, bleeding in the white part of the eye called conjunctival hemorrhage, which can occur after coughing or sneezing in individuals taking blood thinners, can cause eye pain, vision changes and a red spot that can get larger over time, or may go away on its own.

On the other hand, gastrointestinal bleeding often causes little pain, but can result in sudden severe bleeding, black stool or bloody diarrhea, or vomit that is bright red or looks like coffee grounds.

Intracranial bleeding, or bleeding in the brain, can include symptoms of a stroke, such as headache, weakness, slurred speech, numbness, dizziness, and changes in or loss of vision.

Other symptoms of persistent, severe abdominal bleeding may include:
  • Weakness
  • Lightheadedness
  • Shortness of breath
  • Cold, clammy skin
  • Decreased blood pressure
  • Shock

Treatment of Internal Bleeding

The treatment of bleeding depends on where the bleeding is located, the individual circumstance of the patient, such as whether the bleeding is medicine-related, the severity of the bleeding and the stability of the patient. In patients taking blood thinners, such as warfarin, it may be necessary to administer an antidote, often in conjunction with vitamin K, to reverse the medication’s effects.

Mild cases of bleeding typically just require rest and treatment of symptoms. Rest can allow the body time to reabsorb the blood when it is a slow bleed and the cause has been identified and resolved.

In more severe cases of internal bleeding, which is often the case involving bleeding associated with blood thinners, additional treatments such as surgery may be needed. After the bleeding is stopped, treatment is directed towards stabilizing the patient’s condition and repairing any damage caused by the bleeding.

When the bleeding is significant or treatment is not readily given, the condition can cause organ failure, shock, coma and death. Serious bleeding can result in permanent damage to the body. For example, bleeding in the brain can cause stroke and long-term brain damage.

Warfarin and Tissue Necrosis (Gangrene)

Coumadin (warfarin) was also found to potentially cause necrosis, or the death of body tissue, or gangrene. Gangrene is type of tissue necrosis that occurs when the blood flow to a large area of tissue is cut off, causing the tissue to breakdown and die. This is a dangerous and potentially deadly condition. It can happen on the skin or inside the body, such as in muscles or organs.

Necrosis in patients taking warfarin can happen along with the formation of a blood clot inside of a blood vessel near the location of where the tissue death has occurred. The condition typically appears within just a few days of starting Coumadin treatment.

Blood clots can result in additional blockages or obstructions to blood flow in affected areas. There is also a possibility of a blood clot breaking apart and moving to more critical parts of the body, such as the brain or lungs.

blood vial
A blood clot, pictured above, can result in additional blockages to blood flow

Symptoms of Necrosis (Gangrene)

Symptoms of necrosis or gangrene largely depend on the location, cause and severity of the tissue damage. Sometimes, signs and symptoms of the condition may be visible, while others may only be felt by the patient.

When the skin is involved, or the gangrene is close to the skin, symptoms may include:
  • Blue or black skin color
  • Severe pain in the area
  • Loss of feeling in the affected area (numbness), following pain
  • Sores that produce a foul-smelling discharge

But, in instances where the affected area is inside of the body, patients might experience a fever and general unwell feeling. The area may also be swollen and painful. The pain associated with gangrene is often persistent and severe. Internal gangrene can also result in confusion, gas in tissues beneath the skin (gas gangrene) and low blood pressure.

Treatment of Necrosis (Gangrene)

Gangrene is a serious condition that requires emergency medical treatment, which can include surgery, antibiotics and oxygen therapy. Amputation (the removal of a limb, such as an arm or a leg) may also be necessary in more severe cases of tissue death. In general, once necrosis has occurred, it cannot be reversed.

In patients taking warfarin who are affected by tissue necrosis or gangrene the resulting damage to the tissue is permanent.

Surgical procedures aside from amputation, can be performed to find and remove dead tissue and to improve blood supply to the affected area. Sometimes, repeated operations to remove dead tissue are needed. This is called debridement. This procedure can help to improve the healing potential of the remaining healthy tissue.

One type of method of debridement is called maggot therapy, where a certain species of live maggots is used to selectively eat away only a patient’s dead tissue. Maggot debridement is found to be as good or better than conventional (often involving surgery) debridement, according to one study published by the National Institutes of Health (NIH).

The publication concludes that debridement using maggots “is more selective than surgical debridement, decreases time to healing and stay of patients in the [hospital], and may decrease the risk of major amputations.”

A patient’s recovery relies heavily on where the gangrene is located, how much gangrene there is and the patient’s overall health. In situations of necrosis where treatment is delayed, gangrene becomes extensive or the patient has other significant health conditions, death is possible.

When the patient does not die, permanent disability resulting from amputation and prolonged wound healing or the need for reconstructive surgery, such as skin grafting, can also occur.

Warfarin and Calciphylaxis (Calcification of Blood Vessels)

Calciphylaxis, or calcium uremic arteriolopathy, has been reported in patients taking Coumadin (warfarin) with or without end-stage kidney disease, according to the labeling for the blood thinner.

Calciphylaxis is a serious, often fatal, condition in which the blood vessels (veins and arteries) become blocked by a build-up of calcium in the vessel walls, preventing blood from flowing to the skin and internal organs. The lack of blood flow leads to tissue damage and resulting necrosis (death of the tissue).

Microscopic view of a blood clot
Microscopic view of a blood clot

Symptoms of Calciphylaxis

The most obvious and commonly occurring symptom of the disease is damage to the skin, which appears as ulcers (basically a hole in the skin) that can easily become infected. Lesions (any abnormal damage or change in tissue) start with tender red areas that develop into what is called a livedoid pattern, or a mottled, lace-like purplish discoloration of the skin.

Eventually, several more serious symptoms occur, including ulceration, gangrene and sepsis (a potentially life-threatening complication of an infection that affects the blood and causes inflammation, or swelling). The lower extremities of the body, such as the legs, are most likely to be affected.

Calciphylaxis can also affect fat tissue, internal organs and skeletal muscle. Resulting infections, pain and organ failure are also likely to occur as the disease progresses, typically leading to death in patients within just a few months after diagnosis.

Treatment of Calciphylaxis

Symptoms of calciphylaxis are often irreversible. Many patients do not survive longer than a few months following diagnosis, often dying from infection that spreads throughout the body and/or organ failure. The death rate in patients with calciphylaxis is as high as 60 to 80 percent, according to a study in The Journal of Clinical and Aesthetic Dermatology also published by the National Institutes of Health (NIH).

Calciphylaxis Diagnosis
Up to 80 percent of patients affected by calciphylaxis are likely to die within a few months of diagnosis.

Treatments can include medicines to reduce pain, antibiotics to treat infections, and other therapies, such as debridement (removal of dead tissue) and the surgical removal of one or more parathyroid glands, to prevent the progression and worsening of the disease.

Patients at increased risk of having fatal outcomes, are those with proximal (related) disease. Patients who survive often undergo amputations. The 1- and 5-year survival rates for patients with calciphylaxis are approximately 45 percent and 35 percent, respectively.

Warfarin’s Other Serious Side Effects and Complications

Coumadin (warfarin) is also linked to acute (sudden onset) kidney injury in patients taking the blood thinner who also have a history of kidney disease, possibly related to episodes of excessive anticoagulation and blood in the urine. Drug labeling for Coumadin recommends more frequent monitoring of anticoagulation effects in patients with impaired kidney functioning.

In addition to kidney injury, Coumadin (warfarin) is associated with an increased risk of the release of atheromatous plaque emboli, or hardened cholesterol and fat particles that can travel throughout the bloodstream becoming lodged in small blood vessels and blocking blood flow.

This condition can result in various signs and symptoms depending on where the embolization (the passage of the clot and process of obstruction) occurs. The most common symptoms include those involving the skin, gangrene of the extremities and kidney failure.

Cholesterol emboli most commonly affect the kidneys, followed by the pancreas, spleen and liver. When microemboli affect the feet, the condition is referred to as “purple toes syndrome.”

According to the drug's label, all risks associated with coumadin (warfarin) anticoagulant therapy are increased in patients with the following conditions:
  • Moderate to severe liver impairment
  • Infectious diseases or disturbances of intestinal bacteria
  • Use of an indwelling catheter
  • Moderate to severe high blood pressure
  • Eye surgery
  • Polycythemia vera (increased number of red blood cells in the bloodstream)
  • Diabetes (high blood sugar)
  • Inflammation of blood vessels
  • Deficiency in protein C-mediated anticoagulant response – a hereditary or acquired deficiency of protein C or its cofactor, protein S, has been linked to tissue necrosis

Please seek the advice of a medical professional before making health care decisions.

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Kristin Compton's background is in legal studies. She worked as a paralegal before joining Drugwatch as a writer and researcher. She was also a member of the National Association of Legal Assistants. A mother and longtime patient, she has firsthand experience of the harmful effects prescription drugs can have on women and their children. Some of her qualifications include:

  • Bachelor of Arts in Legal Studies | Pre-Law from University of West Florida
  • Past employment with The Health Law Firm and Kerrigan, Estess, Rankin, McLeod & Thompson LLC
  • Personal experience battling severe food allergies, asthma and high-risk pregnancies
Edited By

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