The Power of Your Choice
Your choice of the IHTC Pharmacy Program directly supports your IHTC team and patient services, and activities provided to the hemophilia community. The IHTC Pharmacy Program provides savings to you and your health insurance plan.
Every patient has the right to choose their clotting factor pharmacy provider. The IHTC supports your right of choice and will assist you in making an informed decision.
Treatment of Blood Clots
Once a patient is diagnosed with a blood clot, blood thinners (also called anticoagulants) are used to reduce the ability of the blood to clot. Depending on the type and location of the blood clot, a person will often be treated with a blood thinner for approximately 3 to 6 months, but sometimes the person will need to take the treatment for the rest of their life. The total length of treatment depends on other conditions, such as a “triggering” event (the condition that caused the blood clot), the severity of the clot, patient age, and family history. Identified underlying risk factors, such as an abnormality in a coagulation factor, also affect length of treatment. The length of blood thinning therapy is based on clinically proven evidence as well as individual factors.
Blood thinners can cause serious bleeding and should only be taken under the direction of a health care provider.
Commonly used blood thinners include the following:
|Commonly Used Anticoagulants*|
|Oral Anticoagulants||Injectable Anticoagulants||Intravenous (IV) Anticoagulants|
|Unfractionated heparin (UFH)|
|*Not a comprehensive list of all anticoagulants|
Warfarin (Coumadin®, Jantoven®)
Warfarin is most commonly taken by mouth in tablet form. Warfarin affects clotting by interfering with the vitamin K pathway. The vitamin K pathway is involved in producing several clotting factors, including factors II, VII, IX, and X. All of these clotting factors are needed for normal clot formation. Interference of the vitamin K pathway leads to a reduction in the function of the clotting factors, which in turn reduces the ability to form a stable clot. This results in a blood thinning effect.
Each person may need a different dose of warfarin. In addition, warfarin interacts with many different medications and is also affected by the daily vitamin K content in a person’s diet (green leafy vegetables contain vitamin K). View IHTC’s section on Food Interactions with Warfarin for a review of the diet considerations for warfarin therapy.
Frequent monitoring (weekly to monthly) may be needed to make sure that the warfarin dose is safe and effective. Warfarin commonly requires 3 to 7 days to produce an adequate blood thinning effect. Therefore, patients started on warfarin therapy need some form of heparin for additional coverage to assure adequate anticoagulation. This therapy is called “bridging anticoagulation.”
Anticoagulation with warfarin is monitored with laboratory (INR) testing. The International Normalized Ratio (INR) is a standardized measurement indicating how long it takes the blood to clot on warfarin compared to someone not on warfarin. The frequency of INR testing varies per person and depends on how stable the INR values are and other conditions that vary per person. Warfarin should not be used during pregnancy, as it could cause birth defects.
Dabigatran is a medication used to slow and inhibit the formation of blood clots. It is called a direct thrombin inhibitor and prevents blood clots by blocking thrombin, a very important protein involved in blood clotting. Dabigatran is a tablet taken twice a day by mouth (oral). It does not need laboratory monitoring because it has a predictable anticoagulant effect in people with normal kidney function. It does not require bridging with heparin, and is fully active within 2-3 hours of taking the first dose. It does not interact with most common medications or foods like warfarin does. However, there are certain medications that may affect the way dabigatran works, so it may not be an appropriate option for everyone, including people with kidney problems or liver disease. Dabigatran is not for use in people with prosthetic heart valves.
Rivaroxaban is a once-a-day oral blood thinning medication used to treat and/or prevent blood clots by turning off a specific clotting protein (factor Xa) in the blood. When it is used to treat a new blood clot, it is taken twice a day for 3 weeks, before switching to once a day. Like dabigatran, it does not require laboratory monitoring because it has a predictable anticoagulant affect. It does not require bridging with heparin, and is fully active within 2-4 hours of taking the first dose. It does not interact with most common medications or foods like warfarin does. There are certain medications that may affect the way rivaroxaban works, so it may not be an appropriate option for everyone, including people with kidney problems or liver disease. The use of rivaroxaban is not recommended in people with prosthetic heart valves.
Apixaban is an oral blood thinning medication used to treat and/or prevent blood clots that works like rivaroxaban by turning off a specific clotting protein (factor Xa) in the blood. It is a tablet taken by mouth twice a day. Apixaban does not require laboratory monitoring it has a predictable anticoagulant affect. It does not require bridging with heparin, and is fully active within 3-4 hours of taking the first dose. It does not interact with most common medications or foods like warfarin does. However, there are certain medications that could interact with apixaban and increase the risk for bleeding. As with all blood thinners, this medication should only be taken under the supervision of your doctor.
Enoxaparin (Lovenox®), Dalteparin (Fragmin®)
The low molecular weight heparin (LMWH) category of blood thinners includes medicines such as enoxaparin and dalteparin. Enoxaparin was approved by the FDA in 1993 and dalteparin in 1994. LMWH injectable anticoagulant blood thinners are used for both the treatment and prevention of clots. They are produced by chemically breaking down heparin into smaller-sized molecules. Unlike heparin, the effect of LMWHs does not always need to be monitored with blood tests. LMWHs prevent blood clots from forming by binding to a natural anticoagulant called antithrombin, which is then able to rapidly block the action of two of the 12 clot-promoting proteins in the blood (factors Xa and IIa [thrombin]). Factors Xa and IIa are necessary for blood to clot. LMWHs are administered via subcutaneous (under the skin) injection once or twice per day. Laboratory monitoring by a blood test can measure the inhibitory activity of the clotting protein (called an anti-FXa assay). LMWHs do not cross the placenta and are therefore used commonly during pregnancy for the prevention of clotting complications. Since the effective blood thinning action of LMWHs occurs within 2 to 3 doses, it is also used as a “bridging” therapy when a patient is started on an oral (taken by mouth) blood thinner such as warfarin.
Fondaparinux is a synthetic blood thinner, acting similarly to a LMWH. It blocks the clotting activity of a blood clotting protein (factor X), and is administered via a subcutaneous injection (under the skin) once daily. Laboratory monitoring with a blood test can measure the inhibitory activity of the clotting protein (called an anti-FXa assay). Fondaparinux can be used to prevent blood clots, treat new blood clots, and as bridging therapy for a patient starting warfarin. It can also be used as an alternative to warfarin in patients who have had a recurrent blood clot in spite of therapeutic warfarin.
Intravenous (IV) Anticoagulants
Unfractionated Heparin (UFH)
UFH’s major blood thinning effect is through inactivation of thrombin (factor IIa) and activated factor X (FXa), in the presence of a natural blood thinner called antithrombin (AT). UFH can be given intravenously as a continuous infusion in the hospital setting, or under the skin (subcutaneously) as bolus dosing. A specific blood test called an activated partial thromboplastin time (aPTT) can measure the effectiveness of UFH in thinning the blood. UFH is often used in the setting of an acutely ill patient in the hospital who is bedridden or is having major surgery. It can be used in the treatment of a heart attack, stroke, deep vein thrombosis, or pulmonary embolus. As with all blood thinners, heparin is not without its side effects, and is associated with an increased risk of low platelets, bleeding events and bone weakening/loss.
Argatroban is called a direct thrombin inhibitor because it stops the action of a clotting protein called thrombin. It prevents blood clots by binding to thrombin and blocking its blood clotting activity. Argatroban is used as anticoagulant therapy in patients with heparin-induced thrombocytopenia. It can be given intravenously only in the hospital setting.
Bivalirudin (Angiomax, Angiox®)
Bivalirudin stops blood clotting by directly inhibiting the activation of thrombin. It is called a direct thrombin inhibitor and prevents blood clots by inhibiting both free and clot-bound thrombin and thrombin-induced platelet aggregation. It is often used as an anticoagulant in patients undergoing coronary artery stent placement who cannot take heparin-based anticoagulants due to a previous reaction. It can be given intravenously only in the hospital setting.
Long-Term Management of Blood Clots and Clotting Disorders
Management of an inherited blood clotting disorder involves the treatment of acute clotting events, prevention of clots in people who do not have symptoms (called primary prophylaxis), and prevention of a recurrence of a clot (called secondary prophylaxis). In general, clotting episodes do not occur in a continuous fashion except in persons who have a specific gene alteration for proteins C or S. Lifelong prevention therapy, therefore, should not be considered for people who do not have symptoms and who are not exposed to risk factors. Such prevention therapy is considered impractical for many reasons, including:
- Cost of lifelong blood thinning therapy and associated monitoring
- Adherence to therapy (ability of person to take medicines as prescribed)
- Lack of documented target blood thinning levels in this setting, and
- Long-term risk of bleeding associated with blood thinning therapy
Currently, there is no accurate way to identify affected individuals who have no symptoms but who will develop a clot. However, these individuals should take preventive measures when they are in situations that place them at increased risk for clots. Co-existing risk factors for development of clots include the following:
- Oral contraceptives, pregnancy, time period after labor and delivery
- Hormone replacement therapy
- Congestive heart failure
- Increasing age
- Chronic inflammatory states
- Air travel
For more detailed information on many of these risk factors, see the IHTC’s webpage on Acquired Causes of Blood Clots.
Hirsh J, et al. Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol. 2001;21:1094-1096.
Crowther M, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome N Engl J Med. 2003;349:1133-1138.