Site of Thrombosis
Differentiating Thrombosis from other Diseases
Thrombosis On the Web
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Thrombosis is the formation of a thrombus (medical term for a clot) inside a blood vessel. This can dislodge from the site it was formed and can move along the flow of blood to distant places in the body. A piece of thrombus that is transported in this way is called an embolus (plural emboli). This process of formation an emboli, from a thrombus is called thromboembolism. The term was coined in 1848 by Rudolph Carl Virchow.
The most important sites of thrombosis formation, based on their frequency and clinical effect are coronary arteries and deep veins of the legs. Former, the most important site of arterial thrombosis and latter the most important site of venous thrombosis.
The major pathophysiological mechanisms leading to thrombus formation are similar and overlap in both arterial and venous thrombosis. Rudolf Virchow noted several factors involved in the generation of thrombus, which are as follows:
- Alterations in blood flow (stasis): Blood flows throughout the circulatory system, without significantly stopping or slowing any where. In certain pathological conditions where the blood flow slows down or stops, it causes:
- Increase in platelet to endothelium contact
- Decrease the dilution of clotting factors
- This increases the risk of clot formation and form microthrombi, which further grow and propagate.
2) Endothelial Injury
- Injury to the vascular endothelium: Intrinsic or secondary to external trauma (eg, catheterization) can cause intimal damage and stimulates clot formation. See Coagulation.
- Alterations in the constitution of blood (hypercoagulability): It is the propensity to develop thrombosis due to an abnormality in the system of coagulation.
Shown below is a table depicting the elements of Virchow's triad and their modern counterparts.
|Phenomena of interrupted blood-flow||"Stasis" or "venous stasis"||The first category, alterations in normal blood flow, refers to several situations. These include turbulence, stasis, mitral stenosis, and varicose veins. The equivalence of Virchow's version and the modern version has been disputed.|
|Phenomena associated with irritation of the vessel and its vicinity||"Endothelial injury" or "vessel wall injury"||The second category, injuries and/or trauma to endothelium includes damage to the veins arising from shear stress or hypertension.|
|Phenomena of blood-coagulation||"Hypercoagulability"||The last category, alterations in the constitution of blood, has numerous possible risk factors such as hyperviscosity, deficiency of antithrombin III, nephrotic syndrome, changes after severe trauma or burn, disseminated cancer, late pregnancy and delivery, race, age, whether the patient is a smoker, and obesity. All of these risk factors lead to hypercoagulability.|
- The processes triggering thrombosis and, often, perpetuating the thrombus may be distinct in arterial and venous thrombosis.
- Usually there is a balance between the coagulation and fibrinolysis systems in order to not having abnormal thrombosis in the body.
- Factors that increase the risk for a homeostatic imbalance include:
- An insult to homeostatic balance can expose the sub-endothelium and lead to the collection of various coagulation factors. Accumulation of coagulation factors can lead to the formation of a thrombus of red blood cells, leukocytes, and fibrin.
- A thrombus is characteristically found to first develop in the calf veins and progressively grow in the direction of blood flow (leading to the heart).
- An exceedingly extensive thrombosis in deep veins can extend well into the iliac veins or the inferior vena cava.
- Atherosclerosis is a miss balance between lipids and the hemostasis system which caused clot in arteries. By occluding the artery myocardial infarction, stroke could happen .
- Thrombosis can happen in both Bare Metal Stent (BMS) and Drug Eluting Stent (DES).
Factors that serve as nidus for development stent thrombosis are:
Inflammatory response to the stent material.
Hypersensitivity reaction around the stent material in DES serving as nidus for ST.
- Pregnancy increases risk of having thrombosis in both veins and arteries because of hypercoagulate state .
- Acquired risk factors for thrombosis are:
Oral contraceptive use,
Prolonged immobilization like hospitalization .
This video explains the process of thrombosis:
Genetic factors that play roles in causing thrombosis :
- Non-O blood groups
- Factor V Leiden mutation
- Prothrombin G20210A gene variants
- Polymorphisms in factors IX17 or XI
- Dull appearance.
- Zahn line from platelets and fibrin with layers of RBCs in pulmonary venous thromboembolism.
- Gross picture of thrombosis is different in live and dead person.
In live person it is gray and firm.
In dead person it is dark purple or yellow elastic called "chicken fat".
- Zahn line
There are two distinct forms of thrombosis:
- Deep venous thrombosis (with or without pulmonary embolism; together classified as venous thromboembolism/VTE)
- Portal vein thrombosis
- Renal vein thrombosis
- hepatic vein thrombosis (Budd-Chiari syndrome)
- Paget-Schroetter disease
- Cerebral venous sinus thrombosis
- Thoracic outlet syndrome (the cause of most Subclavian vein thrombosis unrelated to trauma)
Classification of Embolism Based on Direction of Blood Flow
If a bacterial infection is present at the site of thrombosis, the thrombus may break down, spreading particles of infected material throughout the circulatory system (pyemia, septic embolus) and setting up metastatic abscesses wherever they come to rest.
Without an infection, the thrombus may become detached and enter circulation as an embolus, finally lodging in and completely obstructing a blood vessel (an infarction). The effects of an infarction depend on where it occurs.
The pathway of the embolism can be one of three types:
In anterograde embolism, the movement of emboli is in the direction of blood flow. In retrograde embolism, however, the emboli move in opposition to the blood flow direction; this is usually significant only in blood vessels with low pressure (veins) or with emboli of high weight. In paradoxical embolism, also known as crossed embolism, an embolus from the veins crosses to the arterial blood system. This is generally found only with heart problems such as septal defects between the atria or ventricles.
Thrombosis is caused by abnormalities in one or more of the following (Virchow's triad): the composition of the blood (hypercoagulability or thrombophilia), quality of the vessel wall (endothelial cell injury), and/or nature of the blood flow (stasis, turbulence)
Life Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.
Causes by Organ System
Causes in Alphabetical Order
General Differential Diagnosis of Clotting Disorders (Thrombophilia) Leading to Thrombosis
The following disorders might lead to thrombus formation in the coronary, pulmonary and peripheral circulation. The should be differentiated from each other:
|Diseases||Clinical manifestations||Para-clinical findings||Gold standard||Additional findings|
|Symptoms of DVT||Symptoms of Pulmonary Embolism||Symptoms of Myocardial Infarction||Tenderness in extremities||Edema in extremities||Warmth in extremities||PT||aPTT||Doppler ultrasound||Chest CT scan|
|Factor V Leiden mutation||+||+||+||+||+||+||N/A||↑||
|Protein C deficiency||+||+||-||+||+||+||Normal||Normal / ↑|
|Protein S deficiency||+||+||-||+||+||+||Normal||Normal / ↑||
|Prothrombin gene mutation||+||+||-||+||+||+||↑||N/A|
|Disseminated intravascular coagulation (DIC)||+||+||+/-||+||+||+||↑||↑||
|Antiphospholipid antibody syndrome||+||+||+/-||+||+||+||N/A||↑|
The following are the risk factors for thrombosis:
Vessel Specific Risk Factors
|Arterial Thrombosis||Venous Thrombosis||Arterial and Venous Thrombosis|
|High Cholesterol||Injury, surgical trauma||Reduced fibrinolytic activity|
- Deep vein thrombosis
- Pulmonary embolism
- Congestive heart failure and thrombosis
- Kuipers S, Cannegieter SC, Middeldorp S, Robyn L, Büller HR, Rosendaal FR (2007). "The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organisations". PLoS Med. 4 (9): e290. doi:10.1371/journal.pmed.0040290. PMC 1989755. PMID 17896862.
- Mammen EF (1999). "Sticky platelet syndrome". Semin Thromb Hemost. 25 (4): 361–5. doi:10.1055/s-2007-994939. PMID 10548069.