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 decrease the ability of the blood to clot. The commonly used blood thinners include:
- Unfractionated heparin (UFH)
- Low molecular weight heparin (LMWH)
- Warfarin (Coumadin®)
Unfractionated Heparin (UFH)
UFH’s major blood thinning effect is through inactivation of thrombin and activated factor X (FXa). This process also needs the presence of a natural anticoagulant called antithrombin (AT). By inactivating thrombin, UFH not only prevents fibrin formation but also blocks thrombin from activating platelets and factors V and VIII.1
UFH is usually the treatment of choice immediately after a blood clot has been diagnosed, but can also be used to prevent a blood clot. It can be given intravenously as a continuous infusion or under the skin (subcutaneously). The APTT test is used to measure the effectiveness of UFH. To achieve an adequate blood thinning effect, the APTT value is kept between 60 and 80 seconds. Frequent monitoring is required to maintain the blood thinning effectiveness of UFH. Specific treatment charts are available to guide UFH dose adjustments. After the initial treatment, the blood thinner may be changed to a low molecular weight heparin or warfarin (Coumadin®) for continued therapy.
Low Molecular Weight Heparin (LMWH)
The LMWH category of blood thinners includes medicines such as enoxaparin (Lovenox®) and tinzaparin (Innohep®). LMWH is used for both the treatment and prevention of clots. It is made from UFH. LMWH is administered via subcutaneous (under the skin) injection once or twice per day. Laboratory monitoring of blood levels is not always required. In special patient populations, including children or pregnant women. LMWH is monitored by measurement of an anti-FXa assay. Specific treatment recommendations are available. LMWH is used commonly during pregnancy for the prevention of clotting complications. Since the effective blood thinning action of LMWH 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 (Coumadin®), as these oral agents require several days (~5-7 days) to reach an adequate blood thinning level.
Warfarin (Coumadin®) 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 generate thrombin. This results in a blood thinning effect. Each person may require a different dose of Coumadin. In addition, Coumadin has interactions with medications and is also affected by the daily vitamin K content in a person’s diet (green leafy vegetables contain vitamin K). So frequent monitoring is needed to make sure that the Coumadin dose is safe and effective. View IHTC’s section on food interactions with Coumadin® for a review of the diet considerations for Coumadin therapy.
Coumadin is by far the most commonly used blood thinner as it is administered orally (by mouth). Coumadin commonly requires 3 to 7 days to produce an adequate blood thinning effect. Therefore, patients started on Coumadin therapy need some form of heparin for additional coverage to assure adequate anticoagulation. This therapy is called “bridging anticoagulation.” Anticoagulation with Coumadin is monitored with INR testing. The frequency of INR monitoring varies per person and depends on how stable the INR values are and other conditions that vary per person. Monitoring may be needed weekly to monthly.
After a DVT, a person will often be treated with a blood thinner such as Coumadin for approximately 6 months. The total length of treatment for a clotting episode depends on other conditions, such as a “triggering” event, the severity of the clot, patient age, and identified underlying risk factors such as an abnormality in a coagulation factor. The length of blood thinning therapy is based on clinically proven evidence as well as individual factors. Coumadin should not be used during pregnancy.
Treatment of Antiphospholipid Antibody Syndrome (APS)
Patients who persistently test positive for either a lupus anticoagulant or anticardioplipin antibodies (ACA) and have a clotting history appear to be at increased risk for recurrent clotting events (~50% over a 5-year period). Treatment is reserved for patients who have clinical evidence of antiphospholipid antibody syndrome (APS). If a person initially experiences a clotting event in a vein (venous clot), any recurrences after that event tend to also occur in a vein. The intensity of oral blood thinning therapy needed to prevent recurrence of a venous clot (for example, keeping the INR between 2 and 3) remains controversial. In general, patients with APS should be treated more aggressively with oral blood thinners (high intensity) with an INR goal of 2.5 to 3.5.2 Treatment is not required for patients with temporary anticardiolipin antibodies or a lupus anticoagulant.
The following table lists many of the anticoagulants that are currently available.
|HALF-LIFE||PRIMARY EXCRETION MODE||ANTI-
|ANTICOAGULATION MONITORING||REVERSAL AGENTS*|
|VITAMIN K ANTAGONIST|
|Warfarin (Coumadin®)||42 hours||Liver||Inhibits vitamin K
Factor II, VII, IX, X
|Loading dose: 0.2
|Loading dose: 5-10
|Unfractionated Heparin||90 minutes (range: 1-2 hours)||Majority reticuloen-dothelial
system (faster clearance); Liver
|Anti-thrombin mediated inhibition of thrombin & factor Xa||Loading dose:
50-75 U/kg, IV
50-75 IU/kg, IV
|APTTMay also use:
|Low Molecular Weight Heparin: Enoxaparin (Lovenox®), Dalteparin (Fragmin®), Tinzaparin (Innohep®)||Single dose: 4.5 hours
Repeat dosing: 7 hours
|Renal||Anti-thrombin mediated inhibition of factor Xa||< 2 months: 1.5-2
|1 mg/kg/dose, SC,
q12 hr; 1.5 mg/kg daily, SC
monitoring requiredAnti-factor Xa
(heparin level) using
drug specific curve
of factor Xa
|< 50 kg: 5 mg,
50-100 kg: 7.5 mg,
>100 kg: 10 mg
|DIRECT THROMBIN INHIBITORS|
|Bivalirudin: (Angiomax®)||25 minutes||Enzymatic cleavage||Direct inhibition of thrombin||Loading dose:
0.25 mg/kg, IV
Loading dose: 0.75 mg/kg,
1.75 mg/kg/hr, IV
|APTT, TCT, ACT||Desmopressin
|Argatroban®||40-50 minutes||Biliary, Liver||Direct inhibition
65-250 mg/kg, IV
|Loading dose: None
|80 minutes||Renal||Direct inhibition
|Loading dose: Not
Ecarin clotting time,
|* Reversal Agents: Table includes agents that do not have an indication for reversal of antithrombotic agents.|
Treatment of Heparin-Induced Thrombocytopenia (HIT)
Medicines called direct thrombin inhibitors are specifically licensed for treatment of heparin-induced thrombocytopenia (HIT). Examples of these types of blood thinners include lepirudin (Refludan®), and Argatroban®. In addition, the only low molecular weight heparin that can be used in people with HIT is danaparoid (Orgaran®). Other LMWHs are not suitable blood thinners in people who have confirmed HIT.
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.