What Is Hemostasis & Thrombosis?
Hemostasis is clotting, a part of the healing process, and it can be exaggerated, which leads to thrombosis, or impaired, leading to bleeding/hemorrhage.
The hemostatic process is an interaction among three different phases:
- Injury to the inner (endothelial) lining of a blood vessel
- Initiation of the clotting process via the overlap of two different complex biochemical reactions; the clotting cascade
- Clotting cessation and anti-thrombosis with removal of the clot
In thrombosis–abnormal clot occurrence–hemostasis has the disadvantage of reacting or overreacting to endothelial injury. When clot formation occurs, it can lead to two major developments:
- Thrombosis: The clot can grow to a size that causes obstruction of blood flow through the vessel.
- Thromboembolic disease (embolism): The clot can break off and be pushed by the force of blood flow until it lodges in a distal vessel
Thrombosis can occur in either veins or arteries, but the more vulnerable are the veins, since they are a low-pressure conduit of blood flow.
Alterations in blood flow, endothelial injury, and hypercoagulable changes in the clotting process provoke thrombus formation in veins. This is a mass effect, 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 (inflammatory veins). Thrombophlebitis is very painful and can affect walking, but its biggest risk is if a thrombus breaks off and travels as an embolus.
In the arteries, thrombosis is associated with plaque formation which results from hypertension, smoking, obesity, and dyslipidemia (abnormal cholesterol and triglyceride levels). Obstruction threatens the arterial blood flow to organs, their perfusion, and their oxygenation, which jeopardizes their tissue survival. An example is in the coronary arteries, where obstruction to blood flow can lead to cardiac cell death (ischemia and infarction).
When a clot partially or completely breaks away from its thrombotic bed, it can migrate with blood flow, in the veins, upward toward the right side of the heart; in the arteries, distally to the end-organs perfused by the respective artery.
In veins, all blood flow is directed toward the right atrium of the heart, which by way of the right ventricle enters the pulmonary artery with deoxygenated blood going to the lungs to exchange its carbon dioxide for oxygen. A traveling clot can enter the pulmonary artery and result in lung impairment distal to it as well as back up pressure to the right ventricle. Dyspnea can be severe enough to cause death, the biggest fear with pulmonary emboli.
In arteries, whatever tissue is perfused with a particular artery will be deprived of oxygenated blood and suffer hypoxia, risking tissue and organ death. If this were to involve the mesenteric artery, the intestines could die; if in the carotid arteries, stroke ensues; if in the coronary arteries, a heart attack can occur. Any thrombus in the arterial circulation can put one at risk, even thrombi (plural) in the left atrium that break off during atrial fibrillation.
Diagnosis of Hemostasis and Thrombosis
A history and physical begins any diagnostic process, and thrombotic disease is no exception. Painful calf muscles may not require imaging to diagnose thrombophlebitis, but more information is better than less information, and when there is any doubt or when the severity of thrombotic disease needs to be assessed, there are two general approaches toward evaluation:
- Establishing the presence of thrombi in the venous or arterial system
- Evaluating the blood for hypercoagulable state
Thrombosis is confirmed with imaging studies:
- Ultrasound: Sound waves that can demonstrate the physical presence of a clot in a vein or artery but also evaluate the compromise of blood flow using Doppler technology. This is best used in thrombophlebitis (vein thrombosis)
- CT Angiography: CT is the process of assembling X-rays into layered 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
A hypercoagulable state toward thrombosis can be one that affects coagulation and the likelihood of thrombus formation systemically, as with general clotting tendencies that are present from genetics (gene mutations, antithrombin deficiency), medication (estrogen), pregnancy, kidney disease, smoking, obesity, age, inflammatory bowel disease, vitamin metabolism (vitamin K), or elevated clotting factors.
Locally, a 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, but are useful in persons who have already suffered a thrombus or who have a family history of venous thromboembolism:
- Complete blood count, platelet count, and routine coagulation studies (PT and INR, aPTT)
- Inheritable thrombophilia panel: Gene mutations, protein deficiencies, and antithrombin deficiency
- Tests for hidden malignancy
- Antiphospholipid syndrome: Increasing the risk of venous and arterial thromboemboli
- Inflammatory markers such as erythrocyte sedimentation rate (ESR): Can suggest a malignancy or connective tissue disease
- Bleeding time: An older test which times how long blood takes to clot in a test tube. It is primarily used a screen for defects in coagulation
Anticoagulation Tests During Treatment
Once anticoagulation is begun for thrombotic disease, the manipulation of the clotting process is assessed via blood tests that determine how much slower the clotting process occurs:
- PT: Prothrombin time measures the time for plasma to clot when exposed to tissue factor.
- INR: The international normalized ratio is a PT ratio applied to a world-wide standard and measures how well the PT is affected by anticoagulants. It is expressed in the multiples of decreased speeds from normal clotting. The therapeutic goal for anticoagulation is an INR of 2-3 (ideally, 2.5). Because it is an international standard, it is especially useful for travelers.
- APTT: activated partial thromboplastin time measures the time for plasma to clot after exposure to contact factors.
Management for Hemostasis and Thrombosis
Once a thrombus is identified, attempts at dissolving it as well as preventing more should be made. Treatment aimed at these two goals is primarily in the medical use of anticoagulant therapy (“blood thinners”).
Initial anticoagulation is instituted upon diagnosis, and any delay in the initial anticoagulation increases the risk of life-threatening embolization. After initial treatment, therapeutic long-term (maintenance) anticoagulation is used. The duration of treatment depends on risk factors for recurrence.
Initial anticoagulation is done for up to 10 days. Medication can be from a variety of anticoagulants, among them:
- Subcutaneous heparin
- Subcutaneous fondaparinux
The conversion from initial to long-term anticoagulation should be smooth, with no drops or interruptions, as the highest risk of recurrence in in the first three months of 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 and for those with kidney disease. It is used in the conversion from the heparin used in initial therapy to oral long-term therapy. Warfarin is also easily reversed, in cases of the need for surgery. It is contraindicated in pregnancy (Category “X”).
Prevention of Hemostasis and Thrombosis
Besides continuous anticoagulation therapy for those at risk for recurrence of thrombosis or embolism, prevention of blood clots (thrombosis) is via altering those aspects of day-to-day life that add risk to their formation:
- A strong family history of thrombosis: Should alert someone to undergo tests for gene mutations (blood tests) before getting pregnant or beginning any hormonal medications (post-menopausal estrogen replacement or oral contraceptives).
- Avoid prolonged immobilization: By either altering a sedentary lifestyle to include routine exercise and weight management, or by incorporating physical therapy into convalescence during lengthy hospitalizations or recovery from surgery or bone fractures.
- Implement a “stand goal”: During office hours in clerical professions or during long air travel. Several smart watches use reminders for this.
- Use anti-embolic stockings for varicose veins: For those suffering from varicosities or venous stasis/insufficiency.
- A previous history of thromboembolic event: should prompt consideration for permanent anticoagulation. Rarely, inserting a inferior vena cava screen-like filter can be life-saving for those who have frequent pulmonary emboli.
- Patients with cognitive changes: Require investigation into thrombi that might be responsible for transient ischemic attacks (TIAs) or strokes; the diagnosis of arterial thrombosis can be life-saving.
- Patients with atrial fibrillation: A high risk factor for arterial embolism, should be on continuous anticoagulation.
- Smoking cessation.