Thrombosis

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Arterial and Venous Thrombosis: Differences and Similarities

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Differentiating Thrombosis from other Diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

To view main article on venous thrombosis, click here

To view main article on arterial thrombosis, click here for myocardial thrombosis or here for ischemic stroke

Overview

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.

Pathophysiology

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:

1) Stasis

  • 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.

3) Hypercoaguability

  • Alterations in the constitution of blood (hypercoagulability): It is the propensity to develop thrombosis due to an abnormality in the system of coagulation.

These three conditions are collectively known as Virchow's triad and lead to intravascular coagulation, forming a mass of red blood cells, leukocytes, and fibrin.

Shown below is a table depicting the elements of Virchow's triad and their modern counterparts.

Virchow's Modern Notes
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.

Thrombus Formation

  • 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:

Thrombophilia

Immobilization

Trauma

Factors that serve as nidus for development stent thrombosis are:

Delayed endothelialization.

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,

Hormone replacement therapy

Advanced age

Surgery

Prolonged immobilization like hospitalization .

This video explains the process of thrombosis:

Genetics

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

Gross Pathology

  • 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".

Microscopic Pathology

  • lamination
  • Zahn line


Classification

There are two distinct forms of thrombosis:

Venous Thrombosis

Arterial Thrombosis

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:

  • Anterograde
  • Retrograde
  • Paradoxical

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.

Causes

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.

Common Causes

Causes by Organ System

Cardiovascular Antithrombin III deficiency, aortic dissection, arteritis, atheroma, atherosclerosis, atrial fibrillation, atrioventricular septal defect, cholesterol embolization, congestive heart failure, coronary artery thrombosis, deep vein thrombosis, defibrination syndrome, disseminated intravascular coagulation, Eisenmenger syndrome, elevated lipoprotein a, hypercholesterolemia, hyperlipidemia, hypertension, hypertriglyceridemia, Kawasaki disease, left ventricular failure, mesenteric venous thrombosis, obesity, Paget-Schroetter disease, pelvic vein thrombosis, peripheral vascular disease, plasminogen deficiency type I, plasminogen deficiency type II, postphlebitic syndrome, presence of a central venous catheter, stent, stroke, subclavian vein thrombosis, superficial thrombophlebitis, superior vena cava syndrome, vasculitis
Chemical/Poisoning No underlying causes
Dental No underlying causes
Dermatologic Behcet's disease, Klippel Trenaunay syndrome, vasculitis
Drug Side Effect Aflibercept, Asparaginase Erwinia chrysanthemi, asparaginase, chemotherapy, coagulation factor IX, coagulation factor XIII A-subunit, conestat alfa, desmopressin, elspar, eltrombopag, estramustine, estrogen replacement therapy, ethynodiol diacetate and ethinyl estradiol, femara, glucocorticoids, hormone replacement therapy, iodixanol, lenalidomide, letrozole, leunase, meclofenamate, oral contraceptives, pegaspargase, rapamune, romiplostim,sirolimus, tamoxifen, thalidomide, tromethamine
Ear Nose Throat Mastoiditis, superior vena cava syndrome
Endocrine Diabetes mellitus, obesity
Environmental No underlying causes
Gastroenterologic Budd-Chiari syndrome, chronic pancreatitis, hemorrhoids, hepatic vein thrombosis, inflammatory bowel disease, liver cirrhosis, liver disease, mucormycosis, obesity, pancreatic cancer, zygomycosis
Genetic Ales dysfibrinogenemia, elevated plasma fibronectin levels, factor V Leiden mutation, Marchiafava-Micheli disease, paroxysmal nocturnal hemoglobinuria
Hematologic Ales dysfibrinogenemia, antiphospholipid syndrome, antithrombin III deficiency, cavernous sinus thrombosis, decreased heparin cofactor II, decreased thrombomodulin, decreased tissue factor pathway inhibitor (TFPI), decreased tissue plasminogen activator deficiency, deep vein thrombosis, defibrination syndrome, disseminated intravascular coagulation, dysfibrinogenemia, elevated fibrinogen, elevated plasma fibronectin levels, elevated thrombin-activatable fibrinolysis inhibitor (TAFI), essential thrombocythemia, factor XII deficiency, heparin-induced thrombocytopenia, hypercoagulability syndrome, hyperviscosity syndrome, increased factor IX, increased factor VII, increased factor VIII, increased factor XI, increased plasminogen activator inhibitor-1 (PAI-1), Klippel Trenaunay syndrome, leukostasis syndrome, Marchiafava-Micheli disease, multiple myeloma, myeloproliferative disorders, Osler-Vaquez disease, Paget-Schroetter disease, paroxysmal nocturnal hemoglobinuria, pelvic vein thrombosis, plasminogen deficiency type I, plasminogen deficiency type II, polycythemia vera, polycythemia, postphlebitic syndrome, protein C deficiency, protein S deficiency, prothrombin gene mutation, sickle cell disease, sticky platelet syndrome, superior vena cava syndrome, thrombophilia, thrombotic microangiopathy, Von Willebrand factor, Waldenstrom macroglobulinemia, Wiesbaden dysfibrinogenemia
Iatrogenic No underlying causes
Infectious Disease Mastoiditis, meningococcal meningitis, mucormycosis, nipah virus encephalitis, sepsis, zygomycosis
Musculoskeletal/Orthopedic Arthroscopy, fracture, hip surgery, immobility, knee surgery, Maffucci syndrome, orthopedic surgery
Neurologic Antiphospholipid syndrome, cavernous sinus thrombosis, cerebral venous sinus thrombosis, idiopathic intracranial hypertension, meningococcal meningitis, nipah virus encephalitis, stroke, thoracic inlet syndrome, thoracic outlet syndrome
Nutritional/Metabolic Elevated lipoprotein a, glycosylphosphatidylinositol deficiency, homocystinemia, hyperhomocysteinemia, hyperlipidemia, hypertriglyceridemia, obesity
Obstetric/Gynecologic Abruptio placentae, antiphospholipid syndrome, eclampsia, leiomyoma, pre-eclampsia, pregnancy
Oncologic Cancer, leukemia, Maffucci syndrome, malignancy, multiple myeloma, myeloproliferative disorders, Osler-Vaquez disease, pancreatic cancer, paraneoplastic syndrome, polycythemia vera, superior vena cava syndrome, Waldenstrom macroglobulinemia
Ophthalmologic Retinal artery thrombosis, retinal vein thrombosis
Overdose/Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal/Electrolyte Acute kidney injury, chronic renal disease, nephrotic syndrome, renal vein thrombosis
Rheumatology/Immunology/Allergy Antiphospholipid syndrome, Behcet's disease, elevated interleukin 8, Klippel Trenaunay syndrome, polyarteritis nodosa, vasculitis
Sexual No underlying causes
Trauma Trauma
Urologic Fournier gangrene
Miscellaneous General surgery, high altitude, radiation, smoking, varicose veins

Causes in Alphabetical Order


Differential Diagnosis

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 Physical examination
Lab Findings Imaging
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
Antithrombin deficiency + + - + + + Normal
  • Normal
  • Reduces the Increase in PTT after administration of heparin
Factor V Leiden mutation + + + + + + N/A
  • N/A
  • Inactivates factor Va and factor VIIIa
Protein C deficiency + + - + + + Normal Normal / ↑
Protein S deficiency[3] + + - + + + Normal Normal / ↑
Prothrombin gene mutation + + - + + + N/A
Disseminated intravascular coagulation (DIC) + + +/- + + +
  • N/A
Antiphospholipid antibody syndrome + + +/- + + + N/A

Risk Factors

The following are the risk factors for thrombosis:

Miscellaneous

Medical

Familial

Vessel Specific Risk Factors

Arterial Thrombosis Venous Thrombosis Arterial and Venous Thrombosis
Hypertension Increasing age
Smoking Non-smoking Hereditary thrombophilia
High Cholesterol Injury, surgical trauma Reduced fibrinolytic activity
Obesity

Related Chapters


  1. 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. PMC 1989755Freely accessible. PMID 17896862. doi:10.1371/journal.pmed.0040290. 
  2. Mammen EF (1999). "Sticky platelet syndrome.". Semin Thromb Hemost. 25 (4): 361–5. PMID 10548069. doi:10.1055/s-2007-994939. 

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