E1: DVT Flashcards
Define each of the following:
Thrombosis
Thrombus
Emolus
Thrombosis - Clotting in an unbroken blood vessel - usually a vein
Thrombus - a clot
Embolus - A blood clot, air bubble, fat from broken bones, or a piece of debris transported by the bloodstream
VTE
1. Results from
2. Manifested as _____ and _____
3. Classified as _____ or ______ (define each)
4. Complications include
- results from clot formation in the venous circulation
- manifested as deep vein thrombosis (DVT) & pulmonary embolism (PE)
- classified as provoked (e.g., trauma, immobility) vs. unprovoked (unknown etiology) - alters treatment duration
- Complications – e.g. post-thrombotic syndrome & chronic thromboembolic pulmonary hypertension (CTPH)- cause disability & suffering.
Although thrombi can form in any part of the venous circulation, most begin in the ________
Locations specifically include:
most begin in the leg(s).
Locations - deep veins of the lower extremity - popliteal & larger veins above it – e.g. femoral, easily embolize, travel through right side of the heart - lodge in pulmonary artery or one of its branches
______ occurs when clotting occurs in intact vein and is rarely fatal
Deep vein thrombosis (DVT)
When do pulmonary embolisms occur?
Why do they cause necrosis and fatal circulatory collapse?
Are they fatal?
occurs when an embolus lodges in the lungs
occlude blood flow to the lung & impair gas exchange → necrosis
↓ O2 delivery to other vital organs →fatal circulatory collapse.
can result in death within mins of symptom onset
Virchow’s Triad (Name and define the 3 portions)
Endothelial damage (e.g., trauma, vascular injury, surgery, trauma, & venous catheters)
Hypercoagulability (↑ tendency of blood to clot)
Transient (drug-induced e.g., estrogen therapy, pregnancy, malignancy, etc.)
Acquired (i.e., genetic risk factors - coagulation factor abnormalities)
Activated protein C resistance - Factor V Leiden mutation (Arg to Glu substitution at 506) 3x ↑ risk of VTE
Prothrombin G20210A mutation - ↑ prothrombin levels
Venous stasis (e.g., immobility, obesity)
When does pathologic VTE occur and what happens as a result (5)
occurs in the absence of vessel wall damage
may be triggered by tissue factor (TF) brought to the clot formation site by circulating microparticles.
- An impaired blood vessel activates platelets & initiates the clotting factor cascade*.
- coagulation cascade - intrinsic, extrinsic & common pathways*
- Thrombin is activated → formation of a clot*.
- The clot may enlarge & can block the vein.
Impaired hemostasis → hypercoagulability
Initiation phase of coagulation (4)
- TF/VIIa activates limited amounts of factors IX & X
- Factor Xa + Va cleaves prothrombin (using prothrombinase) to make small amount of thrombin
- Factor IXa moves to surface of activated platelets in the growing platelet thrombus
- Tissue factor pathway inhibitor regulates TG/VIIa induced coagulation (TFPI can terminate initiation phase)
Amplification phase of coagulation (2)
- Thrombinproduced during initiation activates factors V & VIII, which bind to platelet surfaces & support the large-scalethrombingeneration occurring during the propagation phase.
- Platelet-bound factor XI is also activated bythrombinduring amplification.
Propagation phase of coagulation
- Factor VIIIa/IXa (intrinsic tenase) & prothrombinase complexes assemble on the surface of activated platelets & accelerate the generation of factor Xa & thrombin, causing a burst of thrombin production
- Thrombin generation is further supported by factor XIa bound to platelet surfaces which activates factor IX to form additional intrinsic tenase
- Thrombin then converts fibrinogen to fibrin monomers that precipitate & polymerize to form fibrin strands
- Factor XIIIa (activated by thrombin) covalently bonds these strands to form an extensive meshwork that encases the aggregated platelet thrombus and red cells to stabilize the fibrin clot
Where are antithrombotic substances secreted from and what do they control
Secreted by intact endothelium adjacent to damaged tissue to control hemostasis
What is the role of thrombomodulin and what does it prevent
Thrombomodulin modulates thrombin activity by converting protein C to its activated form (aPC)
aPC joins w/protein S to inactivate factors Va and VIIIa
This prevents coagulation reactions from spreading to uninjured vessel walls
Circulating antithrombin
What does it inhibit (2)
Inhibits thrombin and factor Xa
Heparan sulfate
Where is it secreted from
What is its effect on antithrombin activity
secreted by endothelial cells and accelerates antithrombin activity
In the process of fibrinolysis
1. Endothelial cells secrete _____ at _______ __ ______
2. t-PA binds to ________ and converts plasminogen to plasmin, which digest _______
3. PAI-1 and PAI-2 inactivate ______
4. α2-AP inactivates ______
- Endothelial cells secrete t-PA at sites of injury
- t-PA binds to fibrin & converts plasminogen to plasmin, which digests fibrin
- PAI-1 & PAI-2 inactivate t-PA
- α2-AP inactivates plasmin.
