Thrombosis and Hemorrhage Flashcards
What are the main regulators of hemostasis
Anticoagulant proteins
Endothelial cells
Fibrinolysis
Who contributes the most to anticoagulation
Antithrombin (80%)
What does antithrombin degrade
II, IX, X
plasmin & kallikrein
What stimulates antithrombin
Heparin & family
Where does heparin live
On the endothelial cells
Protein C contributes to……
Anticoagulation
How is protein C activated
-Circulating in blood
-Complex between thrombin and thrombomodulin
-Binds to a receptor on the epithelium
-Then activates protein C
How does protein C contribute to anticoagulation
Once activated –>
Inactivates V and VIII
How do epithelial cells contribute to anticoagulation
HEALTHY endothelial cells release granules that inhibit platelet aggregation
Pro-fibrinolytic ‘carpet’
What enzyme makes fibrinolysis possible
plasmin
How is plasmin activated
Plasminogen (zymogen) activated by t-PA and u-PA
What makes the vessel itself anticoagulative
Glycocalyx ‘carpet’
Sheds when there is an injury to the vessel wall
What determines the severity of a thrombis
Alternative routes available
Needs of the cells in the occluded areas
How fast did it happed (was there time for angiogenesis to occur)
How do neutrophils contribute to immunothrombosis
Spit out nucleus –> proteins kick off coag cascade
Neutrophil extracellular traps can activate platelets
How do monocytes contribute to immunothrombosis
Upregulate tissue factor
Bleb off membranes (high in TF)
Is DIC a primary or secondary process
Secondary (always!)
What is DIC (generally)
disseminated intravascular coagulation
Unregulated, unlocalized, inappropriate clotting
Is DIC thrombotic or hemorrhagic
Both. Starts as thrombotic, but uses up the platelets so becomes hemorrhagic
Why is DIC hard to diagnose
Clots can dissolve prior to necropsy because they’re so small
Coag tests are designed to measure a delay in clotting not the other way around
How can you diagnose DIC
Measure the breakdown products (D-dimer)
How are thrombocytopenia and bleeding related
A severe thrombocytopenia CAUSES bleeding—not the the other way around
How are liver disease/damage and bleeding related
Liver not working –> no coag factors being produced or carboxylated
What are the general causes of bleeding
Defects in primary hemostasis - platelet # or function, vWF issues, drugs, thrombocytopenia
Defects in secondary hemostasis - trauma, toxins, vessel wall damage
