Why Do I Have Coagulation?
The normal hemostatic (clotting) process, i.e., coagulation, has three different phases:
- Injury to the inner (endothelial) lining of a blood vessel
- Initiation of the clotting process via complex biochemical reactions–the clotting cascade
- Clotting cessation and anti-thrombosis with removal of the clot
The ability to clot is the part of healing (hemostasis) that stops bleeding, but when the clotting process is exaggerated, thrombi (clots) can form within blood vessels. This not only interferes with the smooth flow of blood, but also risks thrombus fragmentation which can release thrombi (emboli) into the circulation.
In the venous system, these migrating clots will enter the right heart after which they’ll be sent into the pulmonary artery, threatening both lungs and life; in arteries, they can lodge downline and tissue beyond the obstruction will be deprived of oxygenated arterial blood, risking tissue ischemia, infarction, and organ death.
Thrombosis can occur in either veins or arteries, but the more susceptible are the veins, since they are a low-pressure conduit of blood flow.
- Veins: thrombosis creates a physical obstruction and if large enough will either partially or completely obstruct venous blood flow, leading to venous stasis, which alters the flow even more. Venous stasis can lead to venous ulcers and when the clots get infected, thrombophlebitis (inflamed, infected veins).
Thrombophlebitis is very painful and can affect walking, but its biggest risk is if a thrombus breaks off and travels as an embolus to the right atrium of the heart, then by way of the right ventricle to the pulmonary artery. This results in lung impairment distal to it as well as a back up of pressure in the right ventricle. This scenario, pulmonary embolus, is life-threatening.
- Arteries: in the arteries, thrombosis is associated with atherosclerosis–plaque formation which results from hypertension, smoking, obesity, dyslipidemia (abnormal cholesterol and triglyceride levels), as well as an inherited genetic predisposition. Obstruction threatens the oxygenated arterial blood flow to organs beyond the site of blockage, risking tissue and organ death. Examples include the the mesenteric artery, the carotid arteries, or the coronary arteries, resulting in tissue death of the intestines, stroke, or myocardial infarction, respectively. Such risks emphasize the importance of anticoagulation when a person has thromboembolic disease.
Any medication that interferes with the coagulation process is a double-edged sword. Anticoagulation is a balancing act between not enough anticoagulation (ineffective prevention of embolic disease) and too much anticoagulation (risk of hemorrhage). Depending on the patient’s site of thrombosis, different anticoagulants can be chosen, oral vs. parenteral (injections), short-acting vs. long-acting, and other considerations such as physician preference, expense, or patients’ tolerances.
How Is Coagulation Diagnosed?
Suspicion of a need for anticoagulation begins with a history and physical, and then tests are performed to establish a diagnosis warranting therapy.
A history can identify those with previous thrombotic episodes, risk factors (obesity, diabetes, hypertension, smoking, sedentary lifestyle), or a family history of thrombotic/atherosclerotic disease, cardiac death, or stroke.
The physical exam can elicit calf muscle tenderness (the cardinal sign of deep vein thrombosis), heart murmurs (signs of valvular heart disease), or bruits (swishing sounds in the arteries from the turbulence that obstruction creates).
Diagnostics follow two main tracts:
- Establishing the presence of thrombi in the venous or arterial system
- Evaluating the blood for hypercoagulable state
Thrombosis is confirmed with imaging studies:
- Ultrasound: Imaging via reflected sound waves is used to demonstrate the physical presence of a clot in a vein, artery, or heart chamber; Doppler imaging can examine the flow of blood. Ultrasound is most valuable in diagnosing thrombophlebitis (deep vein thrombosis).
- CT Angiography: CT is the computerized process of assembling X-rays from layered two-dimensional images, useful for angiography, especially coronary or carotid angiography.
- MRI: Also accurate in diagnosing the presence of thrombi, but less used due to expense or availability.
- Cancer screening: undiagnosed malignancies may present first with thrombosis or blood vessel obstruction, so CT, MRI, and ultrasound, while imaging for thrombi or plaques, can also screen for any anatomical distortions due to cancer.
A hypercoagulable state toward thrombosis can occur from genetics (gene mutations, antithrombin deficiency), or due to medication (estrogen), pregnancy, hyperglycemia, kidney disease, smoking, obesity, age, inflammatory bowel disease, vitamin metabolism (vitamin K), or elevated clotting factors. A hypercoagulable state is a systemic (body-wide) tendency to form clots; however, a local hypercoagulable state toward thrombosis can be limited to one area from immobility, surgery, varicose veins, malignancy, trauma, IV drug abuse, or infection.
Blood tests for hypercoagulability (“thrombophilia”) are usually individualized for each patient:
- Complete blood count (CBC): Platelet count.
- Coagulation measurements: Clotting requires both an “intrinsic” pathway and an “extrinsic” pathway that interact for the complete clotting cascade. Prothrombin time (PT–the time it takes for clotting to occur) and INR. The PT includes a measurement of the extrinsic pathway. The INR (international normalized ratio) compares a particular patient’s PT to a standard. APTT–measures the intrinsic clotting pathway.
- DNA tests: A thrombophilia panel looks for inherited protein and antithrombin deficiencies or gene mutations.
- Antiphospholipid syndrome (APS), increasing the risk of venous and arterial thromboemboli, is diagnosed from the identification of three particular antibodies seen in this condition.
- Inflammatory markers: Erythrocyte sedimentation rate (ESR) can suggest a malignancy or connective tissue disease. C-reactive protein (CRP) can identify generalized inflammatory states.
- Bleeding time: An older test which times how long blood takes to clot, is primarily used a screen for defects in coagulation and has been replaced by newer technology of platelet functional assays.
Testing During Treatment with Anticoagulants
Since there is a narrow range of therapeutic anticoagulation below which is ineffective but above which is fraught with bleeding risk, periodic blood testing using PT and INR is used to fine-tune dosing.
Management of Thrombus Disease
When thrombus disease is diagnosed, any delay in anticoagulation increases the risk of life-threatening embolization. Treatment, primarily via the use of anticoagulants (“blood thinners”), has two goals:
- Dissolve any clots that are present and inhibit a current thrombotic tendency with initial anticoagulation
- Preventing clots in the future, with long-term (maintenance) anticoagulation
Initial anticoagulation is done for up to 10 days. Medication can be from a variety of anticoagulants, among them:
- Subcutaneous heparin: Heparin increases the activity of antithrombin III, which interferes with the clotting factor, thrombin, it its role; heparin also inhibits several other clotting factors.
- Subcutaneous fondaparinux: This inhibits Factor Xa, one of the clotting factors.
After initial anticoagulation, therapeutic long-term (maintenance) anticoagulation is used. The duration of treatment depends on a patient’s risk factors for recurrence.
Since the highest risk of thrombus recurrence is in the first three months of anticoagulation, a time span which includes the transition from initial to maintenance anticoagulation, the conversion should be smooth with uninterrupted effective anticoagulation.
- Monotherapy (one agent): via oral rivaroxaban and apixaban for those who begin long-term therapy without the need for an initial coagulation period.
- Edoxaban and dabigatran orally: Are used after a five-day course of initial anticoagulation.
- Warfarin: an anti-vitamin K agent, is for patients who are not pregnant (Category “X”) and for those with kidney disease. It is used for conversion from initial therapy (subcutaneous heparin) to oral long-term therapy. Warfarin is also easily reversed, in cases of a need for surgery.
Prevention of Embolic Attacks
Prevention of embolic attacks on the lungs (venous) or other organs (arterial) is accomplished via long-term maintenance anticoagulation therapy for those already diagnosed with thrombotic disease. Even so, there are those who have recurrences of thrombosis or embolism, and their prevention can necessitate invasive procedures such as an inferior vena cava filter to catch migrating venous emboli before they get to the heart. Blockage of coronary arteries may require stenting (revascularization).
Those at risk for thromboembolic disease, whether or not they are on anticoagulants, should alter their day-to-day activities to hedge their risks:
- A strong family history of thrombosis, hypertension, or cardiovascular disease should alert someone to undergo blood tests for gene mutations before getting pregnant or beginning any hormonal medications (post-menopausal estrogen replacement or oral contraceptives). The same prevention strategy is advised for elderly patients with such a family history.
- Anti-embolic stockings should be worn for those suffering from varicosities or venous stasis/insufficiency.
- Implement a “stand goal” during office hours in sedentary clerical professions or during long air travel.
- Avoid sedentary activity or prolonged immobilization by either routine exercise and weight management or by incorporating physical therapy into convalescence during lengthy hospitalizations or recovery from surgery or bone fractures.
- Permanent anticoagulation may be indicated in those with a previous history of a thromboembolic event to prevent a recurrence.
- An inferior vena cava screen-like filter can be life-saving for those who have frequent pulmonary emboli.
- In patients who have suffered strokes or TIAs, prevention includes investigation into thrombi that might be responsible.
- Patients with atrial fibrillation, a high risk factor for arterial embolism, should be on continuous anticoagulation.
- Smokers should quit, to prevent a powerful cofactor in the smoking-hypertension-atherosclerosis vicious cycle of blood vessel damage.
- Aggressively treat any causes of secondary hypertension, such as kidney disease or hyperthyroidism.
- If on anticoagulants for prevention of thrombus recurrence, prevention also relies on compliance with scheduled, interim office visits for reevaluations and blood work.