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Approximately 20,000 Americans are living with hemophilia, a genetic disorder that results in excessive bleeding. About 1% of the population has von Willebrand disease, a genetic disorder in which the individual is missing an important clotting protein. Chronic liver disease, including cirrhosis, affects about 4.5 million American adults, or 1.8% of the U.S. population.
This guide provides an overview of the PT/INR test, including how it’s used to diagnose and monitor bleeding disorders and liver conditions. It also contains information on the treatments for several medical conditions that can interfere with normal blood clotting.
The purpose of the PT/INR test is to determine how much time it takes for blood plasma to clot. Although prothrombin time is measured in seconds, the result is usually reported as an international normalized ratio (INR). An abnormal PT/INR can indicate the presence of a bleeding or clotting disorder; it can also help with the diagnosis and management of liver diseases such as cirrhosis.
Dr. Joel M. Gore reports that people taking a blood-thinning drug called warfarin should have the PT/INR test performed every four weeks. Regular testing helps determine if warfarin is working properly; if the results of a PT/INR test indicate that the individual’s blood is still clotting too quickly, the dosage of warfarin can be increased accordingly. The PT/INR test should also be ordered any time an individual has unexplained bleeding or other signs that the blood isn’t clotting normally.
The PT/INR test is performed on a blood sample.
Anticoagulants, also known as blood thinners, can affect the results of this test. Because anticoagulants are used to prevent dangerous blood clots, an individual should never stop taking one of these medications without consulting a licensed medical professional. It may be necessary to stop taking aspirin and other blood thinners before having blood drawn for a PT/INR test, but only if a medical professional recommends it. It may also be necessary to stop taking vitamin C and antihistamines — medications used to treat some types of allergies — before having the PT/INR test.
Hemophilia A, hemophilia B, and von Willebrand disease are genetic disorders that prevent the blood from clotting normally.
Hemophilia A, also known as classic hemophilia, develops due to mutations in an individual’s F8 gene; this gene is involved in the production of coagulation factor VIII, a protein involved in the clotting process. Although hemophilia A can affect people of both sexes, it’s much more common in males.
The effects of hemophilia A range from mild to severe. In some people with the disorder, the main symptom is excessive bleeding following injuries or surgical procedures. At the other end of the spectrum, people with severe hemophilia A may bleed spontaneously — in other words, they bleed even if they haven’t been injured. Spontaneous bleeding can cause blood to leak into the brain, joints, and other parts of the body, resulting in serious complications.
Symptoms of hemophilia A depend on how much clotting factor VIII is missing. People with the mild form of the disorder may not have any symptoms until they are adults; they’re usually diagnosed after sustaining an injury or having a surgical procedure or dental procedure that results in excessive bleeding. In people with a severe form of hemophilia A, symptoms may be present from birth. Infants with the disorder may develop collections of blood under their scalps, or they may spontaneously bleed from the mouth. Additional symptoms of hemophilia A include joint pain, joint swelling, and excessive bleeding after a minor injury.
Hemophilia B is similar to hemophilia A, but it’s caused by a mutation in the F9 gene instead of the F8 gene. The F9 gene contains instructions for producing clotting factor IX, which is needed to help the blood clot normally. Like hemophilia A, hemophilia B is more common in males; this is because the F9 gene is located on the X chromosome. Women have two X chromosomes; if one chromosome is missing the F9 gene and the other contains a normal F9 gene, the normal gene will produce enough clotting factor IX for the blood to clot normally. In contrast, men have only one X chromosome. If a man is missing the F9 gene, he will develop hemophilia because there isn’t a second X chromosome available.
The symptoms of hemophilia B are similar to the ones produced by hemophilia A. Mild cases usually aren’t diagnosed until a person with hemophilia B has surgery or sustains an injury that results in excessive bleeding. More severe cases may cause easy bruising, bloody urine, bleeding in the gastrointestinal tract, frequent nosebleeds, joint pain and joint swelling caused by blood leaking into the joints, and spontaneous bleeding.
In healthy people, a clotting factor known as von Willebrand factor (VWF) is supposed to attach to cell fragments called platelets, causing the platelets to stick together and form a clot. People with von Willebrand disease do not have enough VWF, or the VFW they produce is abnormal in some way; as a result, people with this disease bleed excessively after injuries, dental work, and surgical procedures.
Approximately 85% of people with von Willebrand disease have type 1, about 12% have type 2, and another 3% have type 3. Type 1 is a mild form of the condition in which the individual does not have enough VWF. Type 2, which is classified according to four different subtypes, causes the individual to produce a normal amount of VWF, but the VFW doesn’t work as it should. Type 3 von Willebrand disease is characterized by little to no VWF as well as reduced levels of clotting factor VIII. Type 3 is the most severe form of von Willebrand disease.
Common symptoms of von Willebrand disease include frequent nosebleeds, easy bruising, nosebleeds that take a long time to stop, heavy menstrual bleeding, and excessive bleeding after surgery and dental procedures. Some people with von Willebrand disease also have bloody stool or urine. In the severest cases, blood can leak into the internal organs, causing serious complications.
Liver disease can interfere with normal blood clotting in several ways. First, the liver is responsible for producing the proteins involved in the clotting process; thus, any disease or injury that affects the liver can also affect the production of clotting factors. People with liver disease may also have defective platelets or faster rates of clotting within the blood vessels, resulting in either excessive bleeding or abnormal clot formation. Common liver diseases include fatty liver disease, cirrhosis, and hepatitis infections. Symptoms of liver disease include jaundice (yellowing of the skin and the white part of the eye), abdominal swelling, easy bruising, dark urine, dark stool, and swelling of the legs.
Before the PT/INR can be determined, an individual must provide a blood sample. Once the sample has been collected, it’s sent to a laboratory for analysis. To determine how long it takes blood plasma to clot, laboratory personnel add a substance called thromboplastin to the individual’s blood sample. Thromboplastin is an enzyme that triggers the clotting process. After the thromboplastin is added to the blood sample, a device called a coagulometer is used to measure the amount of time it takes for the plasma to clot.
The main treatment for hemophilia is clotting factor concentrates. These products replace the missing clotting factors in a person with hemophilia, preventing excessive bleeding and other complications. Plasma-derived factor concentrates are made from the plasma found in human blood, while recombinant factor concentrates are genetically engineered. Three other medications can also be used to treat hemophilia: desmopressin acetate, emicizumab, and epsilon aminocaproic acid.
Desmopressin acetate, sold under the brand names Stimate and DDAVP, stimulates the release of clotting factor VIII. This treatment is used in people who have mild or moderate hemophilia, and it can help eliminate the need for treatment with clotting factor concentrates. Emicizumab, sold under the brand name Hemlibra, can prevent bleeding episodes or at least reduce their frequency. It does this by replacing the function of the missing clotting factor VIII. Epsilon aminocaproic acid, marketed as Amicar, prevents blood clots from dissolving. It’s especially helpful after dental surgery, as it prevents the individual’s saliva from breaking down blood clots in the mouth.
Several treatments for hemophilia are also used for von Willebrand disease. For example, people with von Willebrand disease may take desmopressin acetate to trigger the release of VWF that has been stored in the body’s tissues. In these individuals, a desmopressin test is usually performed to determine if clotting factor VIII levels increase enough to warrant continued therapy with the drug. Desmopressin acetate is most effective for people with type 1 von Willebrand disease. Factor concentrates can also be used to replace the missing or defective VWF. Before starting therapy with factor concentrates, the individual should receive the hepatitis B vaccine. Although the risk of hepatitis B transmission via factor concentrate products is low, the vaccine provides additional protection.
In some cases, other treatments are used along with the primary treatment to reduce the risk of spontaneous bleeding. These treatments are known as adjuvant or adjunctive therapies. In people with severe von Willebrand disease, platelet concentrates may help if bleeding continues even after factor concentrates have been administered. Antifibrinolytic agents are used to reduce gastrointestinal bleeding and bleeding in other parts of the body lined with mucous membranes. Estrogen-progesterone combination products can help with heavy menstrual bleeding in women with von Willebrand disease.
The right treatment for liver disease depends on the underlying cause. Hepatitis A has no cure, so it’s important to prevent the disease by practicing safe sex, never sharing needles or razors, and practicing good hand hygiene, especially after coming into contact with blood, fecal matter, or other body fluids. About one-fourth of people with hepatitis B can be cured with pegylated interferon-alpha, a substance that fights the virus that causes hepatitis B. Hepatitis C may be treated with a combination of ribavirin and pegylated interferon, a type of chemotherapy.
Cirrhosis can’t be cured, but several treatments are used to treat the underlying cause. People with alcoholic liver disease should stop drinking immediately. If an individual suffers from alcohol addiction, inpatient or outpatient rehab may be helpful in stopping alcohol use and preventing additional liver damage. If cirrhosis develops due to nonalcoholic fatty liver disease, an overweight individual may be advised to lose weight. Engaging in regular exercise can also help prevent additional liver damage. In some cases, cirrhosis develops as the result of an autoimmune disease, which is a disease in which the immune system attacks healthy liver cells. For people with autoimmune liver disease, taking medications that suppress the immune system can reduce the risk of additional liver damage, but it won’t reverse cirrhosis.
In someone who doesn’t take warfarin or other blood-thinning medications, a normal PT ranges from 11 to 13.5 seconds.
In someone who doesn’t take warfarin or other blood-thinning medications, a normal INR ranges from 0.8 to 1.1.
It depends on the treatment goal set by an individual’s health care team, however, many people who take warfarin have an INR goal of 2.0 to 3.0.
Not necessarily. An elevated PT/INR indicates that the blood isn’t clotting fast enough, but a bleeding disorder isn’t the only reason someone’s PT/INR might be elevated. Because the liver produces many of the clotting factors involved in normal blood clotting, a condition such as hepatitis, cirrhosis, nonalcoholic fatty liver disease, or autoimmune liver disease can cause an elevated PT/INR. Vitamin K is also involved in the clotting process; therefore, a vitamin K deficiency can cause an elevated PT/INR even if no bleeding disorder is present.
Regular testing is important, as many factors affect normal blood clotting. In someone taking warfarin, a high PT/INR indicates an increased risk of bleeding; depending on the individual’s health history and other factors, it may be necessary to reduce the warfarin dosage. Conversely, a low PT/INR indicates that the blood is clotting too quickly, which can increase the risk for dangerous blood clots. In that case, it may be necessary to increase the individual’s warfarin dosage.
For more information on hemophilia, von Willebrand disease, and liver disease, along with the lab tests used to diagnose and monitor these conditions, visit these resources.
|National Hemophilia Foundation||https://www.hemophilia.org||The National Hemophilia Foundation provides information and resources for people living with hemophilia and other bleeding disorders.|
|Foundation for Women & Girls with Blood Disorders||http://www.fwgbd.org||Learn more about the special considerations associated with treating bleeding disorders in women and young girls.|
|Hemophilia Federation of America||https://www.hemophiliafed.org||The HFA engages in advocacy on behalf of Americans living with bleeding disorders.|
|American Liver Foundation||https://liverfoundation.org||Learn more about living with liver diseases such as hepatitis and cirrhosis.|
|MedlinePlus||https://medlineplus.gov||MedlinePlus offers more information on tests used in the diagnosis and management of bleeding and clotting disorders.|
|Centers for Disease Control and Prevention||https://www.cdc.gov||The CDC answers frequently asked questions about bleeding associated with vitamin K deficiency.|