Introduction
Deep vein thrombosis and pulmonary embolism are venous thromboembolic disorders. If a clot or a thrombus forms, it affects the blood flow through the arteries or veins. It causes serious disorders like heart attack and stroke. Antithrombotic therapy is the main treatment to prevent clot formation and growth and reduce complications arising from the clot.
What Is Venous Thromboembolism?
Venous thromboembolism refers to blood clots (thrombus) that form in the veins. The thrombus consists of fibrin and platelets. Fibrin is a protein mesh that traps red blood cells. Platelets are blood cells that form clumps and add mass to the thrombus. Fibrin and platelets are essential for the stabilization of the thrombus. Fibrin is the most important component of thrombus in veins, and platelets are important components in arteries. Arterial thrombosis causes heart attacks and strokes by blocking blood flow in the heart and brain. Deep vein thrombosis and pulmonary embolism are thromboembolic diseases.
What Is Deep Vein Thrombosis (DVT)?
Deep vein thrombosis denotes the blood clots that form in the deep veins. It is common in the deep veins of the legs. It causes leg pain and swelling and sometimes no symptoms. Blood clots form when the leg is not moved for long, either during travel or bed rests. Smoking also causes deep vein thrombosis.
Symptoms include:
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Leg pain.
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Cramps in the calf muscle region.
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Red or purple-colored skin on the legs.
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A sensation of warmth in the legs.
What Is Pulmonary Embolism?
A blood clot (thrombus) that forms in a blood vessel, breaks off, and travels to another area of the body is called an embolus. It sticks to a blood vessel and can block the blood supply to an organ. The embolus from the deep vein thrombosis blocks the pulmonary arteries and blocks the blood flow to the lungs. This is called a pulmonary embolism. It is called venous thromboembolism if deep vein thrombosis and pulmonary embolism occur together.
Symptoms include:
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Shortness of breath.
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Sharp chest pain.
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Cough with or without bloody or blood-streaked sputum.
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Dizziness.
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Excessive sweating.
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Fever.
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Discolored skin.
What Is Antithrombotic Therapy?
Antithrombotic drugs prevent the formation of blood clots, prevent the growth of old clots, and reduce the complications arising from the blood clots. Anticoagulants and antiplatelet drugs are the two classes of antithrombotic drugs. Anticoagulants slow down clot formation, thereby decreasing fibrin formation, clot formation, and growth. Antiplatelet drugs prevent platelet clumping and the formation and development of clots.
What Are the Anticoagulants Used?
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Oral Anticoagulants - Dabigatran, Rivaroxaban, Apixaban, or Edoxaban.
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Vitamin K antagonists.
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Low molecular weight Heparin.
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Newer Anticoagulants - Idraparinux, SSR 126517 (a chimeric molecule).
What Is Anticoagulant Therapy?
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The standard treatment for venous thromboembolism was the subcutaneous low molecular weight Heparin (LMWH) or Fondaparinux, followed by the oral intake of vitamin K antagonist (VKA). Administration of vitamin K antagonists requires close monitoring. Vitamin K antagonists have a delay in the onset of action. Therefore, this anticoagulation treatment is performed for at least five days. Vitamin K antagonists are effective in the prevention of recurrent thromboembolism.
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Factor Xa inhibitors block thrombin generation.
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Idraparinux binds with antithrombin in plasma and produces an anticoagulant response. It is not metabolized and excreted unchanged in the kidneys. It must be reduced in patients with renal sufficiency. The antidote is not available to reverse the activity of Idraparinux. Hence, SSR 126517 was developed.
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SSR 126517 shares similar pharmacological features to Idraparinux. It has an added biotin component that reverses the anticoagulant effects of SSR 126517 after intravenous avidin injection. Avidin is an egg white protein that binds with biotin to form a stable complex cleared by kidneys.
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Rivaroxaban is a potent and selective factor Xa inhibitor that binds to the active site of factor Xa and inhibits the prothrombinase enzyme complex. It is metabolized in the liver and contraindicated in liver disease patients.
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Apixaban is an inhibitor of factor Xa. It selectively and reversibly inhibits free factor Xa and those bound within the prothrombinase complex.
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Dabigatran etexilate inhibits the activity of thrombin, the enzyme that catalyzes the fibrinogen-to-fibrin conversion.
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The ACCP (American College of Clinical Pharmacology) guidelines of 2012 recommend anticoagulant treatment for a minimum of 3 months for all patients with deep vein thrombosis or pulmonary embolism. It should be stopped in patients with transient risk factors like surgery, trauma, immobilization, pregnancy, or hormone intake. The ACCP guidelines do not address the treatment with direct oral anticoagulants.
What Is the Treatment Modality in Specific Groups?
- Cancer Patients -Treating venous thromboembolism in cancer patients is more challenging due to the increased risk of bleeding. The American Society of Clinical Oncology (ASCO) recommends anticoagulation with LMWH over unfractionated Heparin or vitamin K antagonists for at least six months after venous thromboembolism in cancer patients.
- Pregnant Women - Venous thromboembolism is a common risk factor in pregnancy. Low molecular weight Heparins are the anticoagulants of choice because they do not cross the placenta. It should be continued for at least six weeks following delivery. It should be stopped twenty-four hours before delivery.
- Elderly Patients - Older patients are associated with an increased risk of bleeding. Therefore, all treatment regimens are the same except Dabigatran, which should be given in a reduced dose for patients aged eighty and above. For patients with an increased risk of bleeding who cannot undergo anticoagulant treatment, intermittent pneumatic compression devices or compression stockings should be used.
What Are the Limitations of Anticoagulants?
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Anticoagulants prevent the progression of the thrombus but do not remove the thrombus.
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Increased risk of bleeding.
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Deep vein thrombosis progresses to pulmonary embolism even in the presence of anticoagulants.
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Heparin therapy induces bleeding and thrombocytopenia.
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Long-term complications include post-pulmonary embolism syndrome, chronic thromboembolic pulmonary hypertension, and post-thrombotic syndrome.
Conclusion
Deep vein thrombosis and pulmonary embolism are common cardiovascular diseases in healthy people and people with medical or surgical risk factors. With a new array of anticoagulants, it is possible to treat venous thromboembolism. Healthy lifestyle changes, physical activities, stress management, weight management, and quitting smoking prevent thrombosis and also improves recovery.
