What element do the processes of the coagulation pathway depend on? What are they antagonized by?
Depend on Ca2+
Antagonized by coumadin
What happens when thrombin encounters NORMAL endothelium?
Changes from procoagulant to anticoagulant so clotting doesn’t extend beyond site of vascular injury
What are three limiting factors of coagulation?
- Dilution - blood flow removes coag factors, which are cleared by liver
- Need for negatively charged phospholipids - as platelets are used, less of surfaces are available
- Endothelial secretion of anti-coag factors
What protein breaks down fibrin and interferes with its polymerization? What does the breakdown result in?
Plasmin - results in fibrin split products that acts as weak anti-coags
How is plasmin generated?
Catabolizing plasminogen by a factor XII-dependent pathway or tissue plasminogen activator (t-PA)
How is t-PA synthesized?
Endothelium synthesizes it
Name the massive hemorrhagic disorder associated with each:
- Rupture of aorta
- Rupture into abdomen
- Rupture of heart of aorta as a complication
- Marfan syndrome
- Aortic abdominal aneurysm
- MI
Name 3 mild bleeding tendencies.
- vWF deficiency
- Aspirin consumption
- Uremia
What is epistaxis?
Nosebleeds
What is menorrhagia?
Excessive menstruation
What bleeding defect is characteristic of hemophilia?
Hemarthrosis
What bleeding disorder can result from chronic recurrent blood loss?
Iron deficiency anemia
What is Virchow’s triad?
Factors that lead to thrombosis:
- Endothelial injury
- Abnormal flow - turbulence or stasis
- Hypercoagulability
What is the adjective to describe normal blood flow?
Laminar
What disease is associated with the following alterations in blood flow:
- Non contractile heart muscle
- Dilated atrium promoting turbulence
- Causes small vessel stasis
- Impedes blood flow in small vessels
- Acute MI
- Rheumatic mitral valve stenosis
- Hyperviscosity (polycythemia vera)
- Sickle cell
What are the two types of hypercoagulability?
Primary - genetic
Secondary - acquired
Point mutations in what gene are most common in primary hypercoagulability? Name an additional mutation as well.
Factor V gene - Leiden mutation
Leads to inactivation of protein C and loss of antithrombotic pathway
Could also be prothrombin gene mutation - increases risk of venous thrombosis
Elevated levels of what contribute to arterial and venous thrombosis? Deficiency of what can cause this?
Homocyteine
Deficiency of cystathione beta-synthetase
What common drug can lead to increased hepatic formation of coag factors?
Oral contraceptives
What are two important clinical issues involving secondary hypercoagulability?
- Heparin-induced thrombocytopenia
2. Antiphospholipid antibody syndrome
Antibodies in antiphospholipid antibody syndrome can give a false positive test for what disease?
Syphilis
4 steps in fate of a thrombus.
- Propagation - grows
- Embolization - breaks off and moves
- Dissolution - fibrinolysis
- Organization & recanalization - inflammation & repair, new lumen created
