Hemodynamic Disorders (4) - Virchow's Triad Flashcards
Blood clot that forms in a vessel
Thrombus
Blood clot that dislodges and travels in the blood stream until it reaches a vessel that it is too large to pass through
Embolus
What does Virchow’s Triad represent?
3 things that can lead to Thrombosis (clot formation)
What 3 things in Virchow’s Triad can lead to Thrombosis?
- Endothelial Injury
- Abnormal blood flow
- Hyper-coagulability
Hypercoagulability
Increased tendency for blood to clot
What are some stimuli for Endothelial activation (injury)?
Smoking Hypercholesterolemia Toxins/inflammation Abnormal blood flow ** Injury
When the Endothelium becomes activated, it turns into a ______ state
PROthrombotic
In what 2 ways does Endothelial activation become PROthrombotic?
- DECREASED Thrombomodulin expression
2. INCREASED secretion of Plasminogen Activator INHIBITORS
Describe the normal pathway and job of the endothelium expressing Thrombomodulin
Thrombomodulin binds to Thrombin
- That complex then activates Protein C (and S)
- Proteins C and S cleave Factors Va and VIIIa to INACTIVATE them and stop clot formation
Describe what happens when the Endothelium is activated and it DOWNREGULATES Thrombomodulin
If Thrombomodulin is downregulated, it will bind less Thrombin
- That complex will then NOT activate Protein C and S
- Protein C and S then can NOT INactivate the coagulation factors Va and VIIIa
= Clot formation CONTINUES
Describe what happens when the Endothelium is activated and it SECRETES Plasminogen Activator Inhibitors
Plasminogen Activator Inhibitors INHIBIT t-PA (tissue plasminogen activator)
- If t-PA is inhibited, it cannot activate plasmin
- If plasmin is not activated it will NOT degrade fibrin and the clot
= Clot formation CONTINUES
2 types of blood flow?
Laminar (good)
Turbulent (bad)
Stasis
Slow blood flow
In what ways does Abnormal Blood Flow contribute to Thrombosis?
** Activates Endothelium
Disrupts laminar flow and prevents washout of clotting factors
Abnormal blood flow can occur in many forms. In what type of vessels is it more likely?
Dilated vessels
Where vessels bifurcate (split)
Examples of dilated vessels that lead to abnormal blood flow?
Aneurysm
Hemorrhoid
Abnormal blood flow can also occur due to obstruction or inadequate heart function. List a few specific examples.
Obstruction due to plaque
Atrial fibrillation - inadequate blood pumping
What type of disorders are involved with Hypercoagulability?
Primary and Secondary
Primary disorders that cause Hypercoagulability are caused by?
Genetics
Secondary disorders that cause Hypercoagulability are caused by?
Acquired
What is the main Primary disorder of Hypercoagulability?
Factor V Leiden Mutation
How is Factor V Leiden Mutation inherited?
Autosomal Dominant
Describe what happens with Factor V Leiden Mutation
Factor V is RESISTANT to cleavage and inactivation by Protein C
= Always more likely to clot
Primary disorders of Hypercoagulability should be considered if the patient is under what age?
40/50
What are 3 Secondary disorders that cause Hypercoagulability?
Oral Contraceptive use
Heparin-induced Thrombocytopenia
Antiphospholipid Syndrome
Oral contraceptive use increases synthesis of?
Coagulation factors
With Heparin-induced Thrombocytopenia, what must a patient come into contact with?
Unfractionated Heparin
Platelets contain alpha granules. Upon activation they release them. What is a main product that is released that is important in Heparin-induced Thrombocytopenia?
Platelet Factor 4 (PF4)
What does Unfractionated Heparin bind?
PF4
Once Unfractionated Heparin binds PF4 then what occurs?
Formation of antibodies to the complex (IgG)
Once the IgG antibodies bind to the unfractionated heparin and PF4 complex, then what occurs?
The IgG antibodies bind to Fc receptors on more platelet surfaces
Once the IgG antibodies - heparin/PF4 complex binds to Fc receptors on platelets, what are the 2 options?
- Platelet activation and aggregation (clot)
2. Macrophage removal of the platelet (thrombocytopenia)
Antibodies against plasma proteins that bind to phospholipids. The patients present with miscarriages, DVT, ect.
Antiphospholipid Antibody Syndrome
White Thrombus
ARTERIAL blood
Contains platelets, RBCs, leukocytes
Red Thrombus
VENOUS blood
Many RBCs
4 fates of a Thrombus?
Propagation and continued growth
Recanalization of the vessel
Embolization
Dissolution
For Dissolution of a Thrombus, what can be administered to speed the process if given within 6 hours of the onset?
t-PA - activates plasmin to degrade clot
Disseminated Intravascular Coagulation
Systemic activation of thrombin and widespread thrombosis
What can Disseminated Intravascular Coagulation lead to?
Severe bleeding due to depletion of the platelets being used up in all the clots forming
Endothelium dysfunction leads to decreased?
NO activity
Endothelium dysfunction causes decreased NO activity. What does this cause?
Endothelial activation
Endothelial activation increases?
Adhesion molecules
