EXAM #1: THROMBOSIS Flashcards
What is the definition of thrombosis?
Pathological blood clotting in an uninjured blood vessel or exaggerated clotting in response to minimal injury
Outline Virchow’s Triad.
These are the major factors that predispose one to thrombosis:
1) Endothelial injury
2) Blood stasis or turbulence to blood flow
3) Blood hypercoaguability
What are the anti-platelet effects of the endothelium?
- Non-activated platelets do NOT adhere to the endothelium
- PGI2 and NO produced by the endothelium prevent platelet activation
What are the anti-coagulant properties of the endothelium?
- Heparin like molecule activates anti-thrombin III
- Thrombomodulin binds thrombin to activate Protein C
What are the fibrinolytic properties of the endothelium?
Endothelium synthesizes t-PA
What are the prothrombic properties of the endothelium?
- vWF
- TF
- Plasminogen activator inhibitors (PAI)
Describe the mechanism of action of ASA.
ASA prevents platelet activation and release
List the contents of the dense granules.
ATP ADP Ca++ Histamine Epi
List the contents of the alpha granules.
P-selectin Fibrinogen Fibronectin Factor V VIII PDGF TGF-a
Outline the process that leads to the development of the primary platelet plug.
1) vWF and Gp1b causes platelet adherence
2) Ca++ mediates secretion of granules
3) GpIIb/IIIa binds fibrin
What is a major predisposing factor for thrombosis? Why?
Endothelial dysfuction–loss of endothelium will expose the ECM and activate platelets and thrombosis
What is the effect of blood turbulence on the endothelium?
Turbulence enhances endothelial injury
What is the effect of stasis on the endothelium?
Enhances venous thrombosis
What are the combined effects of blood stasis and turbulence of flow?
- Platelets are brought close to endothelium
- Clotting factors accumualte
- Clotting factor inhibitors are blocked
- Endothelial activation occurs
What happens to vWF under shear stress?
Unfolding i.e. the faster blood flows, the STICKIER it gets
What are the primary causes of hypercoaguability?
- Factor V Leiden
- Antithrombin III deficiency
- Protein C/S deficiency
- Prothrombin gene mutation
What are the secondary causes of hypercoaguability?
- Anti-phospholipid Syndrome
- Lupus
- Stasis
- Cancer
- Nephrotic syndrome
- Contraceptive pills
- Smoking
What is Heparin-Induced Thrombocytopenia (HIT)?
- Heparin therapy
- Heparin antibodies binding platelets and activate them
What is Antiphospholipid Syndrome?
Antibodies to phospholipids
What is the difference between a superficial and deep venous thrombosis?
Superficial= rarely embolize but can be quite painful
Deep= more frequently embolize
**Note that only 50% of patients will have a symptomatic DVT b/c of collateral circulation
What is DIC?
Disseminated Intravascular Coagulation
- Sudden fibrin thrombi in microcirculation
- Leads to circulatory insufficiency
Paradoxically CONSUMES platelets and clotting factors, increasing risk of bleeding
Outline the fates of a thrombus.
1) Propagation
2) Embolization
3) Lysis
4) Organization and recanalization
What is the second most common medical complication?
DVT
What is the most common cause of preventable death in hospital?
PE
What are the risks and complications associated with a VTE?
- Increased risk for recurrent VTE
- Post-thrombotic syndrome
What are the different types of PEs?
1) Small= silent
2) Medium= pulmonary infarct with acute respiratory and cardiac symptoms
3) Large= right heart failure and collapse
4) Massive= sudden death
What is a paradoxical embolus?
Venous embolus passing the arterial circulation through a septal defect, causing an arterial embolism
What tissue is the most vulnerable to hypoxia?
Neurons (can only handle 3-4 minutes of anoxia)
How much is the relative risk of thrombophlia increased with a homozygous Factor V Leiden Deficiency?
80x
**vs. 7x in heterozygous
How much does oral contraception increase the risk for thrombosis?
3.7x
How much does Factor V Leiden Deficiency + oral contraception increase the risk for thrombosis?
34.7x
How do you evaluate the clotting state of a patient?
- PT, PTT, TT, Fibrinogen
- Assess clotting factors
When do you further evaluate a patient with a clot of a patient that presents with a family history of clotting?
- Young patient
- Family history
- Thrombosis in absence of known risk factors
- Recurrent miscarriage
- Warfarin-induced skin necrosis
- Neonatal pupura fulminans
What is a factor that you would normally further evaluate, which you no longer do?
MTHFR
