Thrombosis****** Flashcards
Definition of thrombosis
Thrombosis refers to the formation of a thrombus. A thrombis is an aggregate of coagulated blood containing platelets, fibrin and entrapped cellular elements attached to vascular endothelium, within the vascular lumen that occur during life.
Virchow’s Triad
The three factors involved in the initiation of thrombosis:
- Endothelial injury
- Hypercoagulability
- _Abnormal blood flow _
__In normal blood vessels mild endothelial injury occurs with normal wear and tear on the vessels. Therefore the greatest risk factors are alterations in blood flow and hypercoagulability.
Endothelial cells functions
- Anti-platelet function (remain intact, PGI2 and NO impede Plt adhesion and aggregation, along with adenosine diphosphatase which degrades ADP),
- anticoagulant (heparin like molecules, antithrombin III, thrombomodulin, tissue factor pathway inhibitor)
- fibrinolytic properties (tissue plasminogen activator, that produces plasmin, that cleaves fibrin) that balance pro-coagulant factors.
Thrombophilia
This is a congenital or acquired predisposition to thrombosis. Suspect n young patients, FHx of thrombosis, unusual site from thrombosis or in females with recurrent miscarriage.
Venous thrombosis
Usually forms as an initial platelet fibrin head, usually attached to a valve. A column of static blood forms downstream which coagulates. Turbulence as blood enters form the next tributary causes repeptition of the cycle. The thrombis can therefore extend a long distance up the vessel, yet only be attached loosly at one point.
What factors predispose to venous thrombosis.
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Statis is the most important factor in venous thrombosis. Venous statis is associated with:
- Immobility - prolonged bed rest, during surgery, long distance air travel, advaced age, HF, oedema, pelvic obstruction, following AMI or trauma.
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Hypercoagulability
- __Acquired hypercoagulable states
- Genetic predisposition
- Changes in the vessel wall: inflammation of the vessel wall.
Acquired hypercoagulable states
Associated with:
- Pregnancy
- Oral contraceptive pill, hormone replacement therapy
- Malignancy (paraneoplastic syndrome)
- Antiphospholipid antibody syndrome - recurrent thrombosis, miscarriage, cardiac valve vegetations, thrombocytopenia associated with antibodies directed against plasma proteins boung to anionic phospholipids.
- Secondary antiphospholipid syndrome - seen in association with SLE.
- Associated with an increase APTT but paradoxically present with increased risk of thromosis.
- Increased platelets (thrombocythaemia) for example follofing haemorrhage or surgery. Polycythaemia.
Congenital hypercoagulability
Genetic predisposition occurs with:
- *Factor V Leiden:** *variant of factor V which is resistant to inactivation by protein C; and less commonly prothrombin mutation
- *Increased factors VIII, IX, XI or fibrinogen *
- *Less commonly deficiency in: *antithrombin, protein C and protein S
Outcomes of venous thrombosis
Venosu thrombi are almost always occlusive and cause congestion and oedema. The main risk from venous thrombosis is pulmonary thromboembolism.
Arterial thrombosis contributing factors
- Endothelial injury: is the most important factor, usually as the result of atherosclerosis.
The initiating event may be either a direct result of impaired endothelial function, disruption of the damaged endothelium or plaque rupture.
- Turbulent flow contributes to both the formation of atheroma and of thrombosis on the surface of atheroma.
Other causes of arterial thrombi are vasculitis. This occurs in areas of high flow (ie abdominal aorta) where alternating layers of platelets, fibrin and RBC are laid down (lines of Zahn). For lamination to occur the layers must be tightly adherent and therefore laminated thrombi rarely embolise.
What determines the presence of ischaemia with arterial thrombi?
The majority of arterial thrombi (except in large vessels) are occlusive. Whether ischaemia occurs depends on the presence of collateral circulation.
Microvascular thrombi
Formation of thrombi in microvascular beds. Most commonly seen in association with major illness (gram negative sepsis, secondary to major haemorrhage, amniotic fluid embolism and neoplasms) and is referred to as disseminated intravascular coagulation. The clinical symptoms reflect ischaemic damage to major organs as well as a consumptive coagulopathy as fibrin and platelets are used up.
Ebolism definition
Embolism refers to the blockage of vessels by material that has originated elsewhere in the body and travelled in the blood.
Venous thromboembolism
Alsmot always originate from the deep veins of the lower limbs. The thrombus propagates and part or all of it may detach. They travel through the venous system until the calibre of the vessels becomes too small, almost always in the pulmonary circulation. Small emboli may be clinically silent, whereas large emboli may be fatal, causing pulmonary infarction or obstruction to right ventricular flow.
VQ mismatch may be seen with nuclear isotope scanning or blockage may be seen with CT pulmonary angiogrphy.
Arterial thromboembolism
As with VTE, thrombi may detach and impact in downstream small vessels. Common sites of arterial thromboembolism are:
- The brain (thrombi originating from the heart associated with atrial fibrillation or post AMI and carotid artery)
- The heart (thrombi originating in the coronary circuation lodging distally)
- Aorta and it’s branches (mesenteric and renal vascular beds and the distal vessels of the lower limbs).
