Medication

Anticoagulants

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Anticoagulants
Last update: 21-12-2023

How else can it be called?

  • Blood thinners

  • Antithrombotic agents

  • Antiplatelets agents

  • Thrombolytics

  • Fibrinolytic drugs

What should we know?

Anticoagulants or blood thinners are medication used to prevent the formation of blood clots that could potentially block a blood vessel. They also can break down an existing clot.

The purpose of anticoagulants is the prevention of thrombosis (formation of a blood clot within a blood vessel) and embolism (a blockage-causing particle such as a blood clot or an air bubble inside a blood vessel).

A possible side effect of anticoagulants is excessive bleeding.

What are the different types of medication to prevent thrombosis?

There are three main types of antithrombotic agents:

  • Anticoagulants
  • Antiplatelet agents
  • Fibrinolytic drugs or thrombolytic agents
  1. Anticoagulants: These medications interfere with the blood clotting process by targeting specific clotting factors of the coagulation cascade.

    There are two main types of anticoagulants:

    • Parenteral Anticoagulants:

      Unfractionated heparin: Unfractionated heparin prolongs clotting time and is typically administered via subcutaneous or intravenous injection.

      Heparin, a mucopolysaccharide derived from cow lung or pig intestinal mucosa, has an average molecular weight ranging from 7,000 to 40,000. Modern standardization in IU (international units) allows for direct comparison using this measure despite the different sources to obtain it.

      There are two salts forms (calcium and sodium) that are very similar. Calcium is preferred because it can be used subcutaneously and it is less painful but both can be used intravenously. Never intramuscularly.

      Heparin is employed when immediate and short-term anticoagulation is necessary. In surgical settings to prevent venous thrombosis, a low dose of 5,000 IU is administered two hours pre-operation, followed by subsequent doses every 12 hours until discharge.

      Regular coagulation tests, specifically activated partial thromboplastin time (aPTT), are essential during heparin use.

      Upon discharge, patients often transition to oral anticoagulants.

      Low molecular weight heparins (LMWHs): They are fragments with a molecular weight between 3,500 and 6,000. They have a longer half-life and a better bioavailability compared to standard heparins.

      LMWHs has a reduced impact on inhibiting platelet aggregation. They do not replace traditional heparins but, in low-dose therapies, they are frequently used because they can be administered solely once a day subcutaneously.

      They have been gradually replacing standard heparins for their superior safety profile and the absence of the need for frequent laboratory monitoring.

      In high-dose therapies standard heparins are commonly used.

      Fondaparinux: It is a synthetic anticoagulant medication that is mainly used in Europe.

      Direct thrombin inhibitors (DTIs): Lepirudin, desirudin, bivalirudin, and argatroban are usually used in patients experiencing heparin-induced thrombocytopenia (a decrease in platelet count) as a complication of heparin therapy. These medications are particularly valuable when preventing clot formation is critical, such as after significant orthopedic surgeries (like hip replacement) or during coronary angioplasty.

    • Oral anticoagulants:

      Coumarins: Warfarin y acenocoumarol.

      They are antagonists of vitamin K.

      Regular laboratory monitoring ensures these medications achieve the desired anticoagulant effect without overextending it. The prothrombin time with INR serves as the key test, indicating the expected clotting time extension.

      Typically conducted every 3 to 4 weeks with adequate control, dosage adjustments follow: a slight increase for very low results or a decrease for excessively high readings, followed by subsequent tests.

      Long-term users of warfarin or acenocoumarol may have a coagulometer device at home. This device reads capillary blood from a finger prick, analyzing a drop of blood on a strip and automatically calculating the INR.

      Many medications and foods can interact with warfarin by increasing or decreasing its action. Examples include aspirin®, acetaminophen, various antibiotics, garlic, green tea, St. John's Wort, and vitamin E, among others.

      Dabigatran: a thrombin inhibitor.

      Rivaroxaban and apixaban: Factor Xa inhibitors.

      In these new medications, monitoring clotting time is not necessary as their effects are considerably more predictable compared to warfarin.

  2. Antiplatelet agents: Prevent blood clot formation by reducing the ability of platelets to stick together and form clots in blood vessels.

    They are primarily employed to prevent arterial embolisms, as these formations heavily involve platelets.

    There are several types of antiplatelet agents:

    • Acetylsalicylic acid (Aspirin®)

    • Thienopyridines such as clopidogrel, prasugrel, ticagrelor, and cangrelor.

      Triclopidine was the first antiplatelet agent in this group but its usage has declined due to the superior effectiveness and reduced side effects of other medications especially neutropenia (a decrease in a type of white blood cells called neutrophils).

      In high-risk scenarios, a combination of two antiplatelet drugs may be employed for a limited duration (typically Aspirin® and clopidogrel), such as in specific cases of unstable angina (chest pain indicating a potential heart attack) or when metallic prostheses (stents) need to be placed in an artery during cardiac catheterization.

    • Dipyridamole: can be combined with Aspirin® and is used to prevent strokes in individuals with transient ischemic attacks (TIA).

    • Another group of intravenously administered antiplatelet agents are Glycoprotein IIb/IIIa inhibitors like abciximab, eptifibatide, and tirofiban.

      These medications are employed, for instance, before coronary angioplasty (a procedure to unblock a coronary artery before or during a heart attack) and during high-risk unstable angina episodes that could progress to a heart attack.

    • Vorapaxar is another antiplatelet agent used in highly specific cases due to its substantial risk of life-threatening bleeding.

  3. Fibrinolytic drugs or thrombolytic agents

    The current fibrinolytics in use include streptokinase, acylated plasminogen streptokinase activator complex (anistreplase), urokinase, recombinant tissue-type plasminogen activator (rt-PA, known as alteplase or activase), along with two recombinant derivatives of rt-PA: tenecteplase and reteplase.

    Fibrinolytic therapy (or thrombolytic therapy) is an emergency treatment designed to dissolve as soon as possible blood clots that have formed within vital arteries or veins.

    They can be administered intravenously or delivered via a catheter directly into the clot.

    Their intravenous use is specifically indicated for:

    For arterial embolism and deep vein thrombosis in the legs, catheter-based clot destruction directly at the site can be employed.

    Ideally, these medications should be administered within 60 to 90 minutes of symptom onset to maximize their effectiveness.

What are the precautions and risks of medication to prevent thrombosis?

In general, anticoagulated patients receive the following recommendations:

  • Undergo regular medical and laboratory tests as advised by the doctor.
  • Cease medications only under the recommendation or your doctor, typically before procedures with a high risk of bleeding.
  • Seek immediate medical attention for any sign of abnormal bleeding: red urine, black or bloody stools, excessive menstrual bleeding, severe headache, severe abdominal pain, severe joint pain (particularly after a trauma), unexplained bruising, coughing up blood (hemoptysis), sudden vision changes, or vomiting blood.
  • Contact the doctor in case of fever, severe diarrhea, or increased bleeding from the gums (gingivorrhagia).

The main risks of anticoagulants are:

  • The main risk of Aspirin® is stomach bleeding.
  • In the case of other antiplatelet agents there could be a risk of kidney damage or easy bleeding that must be monitored.
  • Heparin use can lead to complications such as bleeding, thrombocytopenia (reduced platelet count), osteoporosis, and elevated transaminases (liver enzymes).
  • Low molecular weight heparins (LMWHs) also have these complications, but with a less frequency, which is why they are now used instead of conventional heparin. Protamine sulfate serves as an antidote for excessive bleeding caused by heparins, while there is no specific treatment for bleeding from fondaparinux, a synthetic anticoagulant.
  • Warfarin during pregnancy can result in fetal birth defects, so it should not be used during pregnancy.
  • Newer oral anticoagulants often lead to more dyspepsia (digestive discomfort) and gastrointestinal bleeding, and they cannot be used for pregnant or lactating women.
  • Fibrinolytics may trigger allergic reactions and hypotension (low blood pressure), but these reactions are easy to manage.

Active ingredients and brand names of anticoagulants

  • Anticoagulants
    • Oral anticoagulants
      • Acenocoumarol (Nicumalon)
      • Apixaban
      • Dabigatran
      • Rivaroxaban
      • Warfarin
    • Heparin and other injectable
      • Ancrod
      • Antithrombin III
      • Argatroban
      • Bivalirudin
      • Dalteparin
      • Enoxaparin
      • Fondaparinux
      • Heparin
      • Nadroparin
  • Antiplatelet agents
    • Acetylsalicylic acid
    • Dipyridamole
    • Ditazol
    • Epoprostenol
    • Sulodexide
    • Triflusal
    • Thienopyridines
      • Cangrelor
      • Clopidogrel
      • Prasugrel
      • Ticagrelor
      • Ticlopidine
    • Glycoprotein IIb/IIIa inhibitors
      • Abciximab
      • Eptifibatide
      • Tirofiban
  • Fibrinolytic drugs or thrombolytic agents
    • Abciximab
    • Alteplase
    • Anistreplase
    • Eptifibatide
    • Pamiteplase
    • Reteplasa
    • Streptokinase
    • Tenecteplasa
    • Tirofiban
    • Urokinase
Medically reviewed by Yolanda Patricia Gómez González Ph.D. on 21-12-2023

Bibliography

  • First Aid for the Basic Sciences: Organ Systems (3rd Ed) 2017, Tao Le, William L. Hwang, Vinayak Muralidhar, Jared A. White and M. Scott Moore, ISBN: 978-1-25-958704-7, Pag. 318.
  • Harrison’s, Principles of Internal medicine, 20th Edition (2018). Chapter 235: Antiplatelet, Anticoagulant, and Fibrinolytic Drugs. McGRAW-HILL EDUCATION. ISBN: 978-1259644030.
  • Mayo Clinic. Warfarin side effects: Watch for interactions. December 2023. Available on: https://www.mayoclinic.org

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