Pathology - Coagulation and Thrombosis Flashcards
Define hemostasis
Arrest of bleeding following vascular injury (i.e. blood vessel injury)
What are the three main steps of hemostasis?
- Vasoconstriction:
surrounding endothelium and smooth muscle constricts to slow the blood flow and decrease blood loss - Platelet plug formation:
platelets adhere to the site of injury and form a temporary plug that stops blood loss - Blood clot formation:
more robust, long-lasting structure
What are the key events of primary hemostasis? What are the key events of secondary hemostasis?
Primary hemostasis:
* Vasoconstriction
* Platelet plug formation
(begins within seconds of injury, last only a few minutes)
Secondary hemostasis:
* Blood clot formation
Describe vasoconstriction (first step following vascular injury)
- Smooth muscle cells contract
- Opposed endothelial cells stick together
- Secretion of endothelin by damaged endothelium promotes vasoconstriction
It is a temporary, initial, limited response.
What forms the platelet plug?
Anucleate fragments of megakaryocytes (i.e. platelets), which start to adhere to the site of injury.
Name compounds produced by healthy endothelial cells under normal conditions that help prevent blood clot formation.
Healthy, normal endothelial cells secrete vasodilators:
* prostacyclin (prostaglandin)
* nitric oxide
These vasodilators keep the blood vessels open and prevent blood cells from sticking to blood vessel walls.
Describe the process by which platelets stick to damaged endothelial cells.
- Damaged endothelial cells have surfaces of exposed collagen and platelet-adhesion glycoprotein von Willebrand Factor
- Collagen attracts platelets, that aggregate and stick to it (and to vWF)
- These platelets become activated and “sticky”, attracting more platelets
- Platelets and endothelial cells secrete pro-coagulants which further attracts platelets and consolidates plug formation
Name 4 pro-coagulants released by platelets that promote vasoconstriction and platelet aggregation/consolidation
Tissue factor (factor III)
Thromboxane A2
ADP
Serotonin
What are the 4 steps of platelet plug formation during primary hemostasis
- Platelet Adhesion
- Activation and release of cytokines
- Platelet Aggregation
- Platelet Consolidation
What is the most common drug for preventing coagulation?
Acetylsalicylic acid - ASA (aspirin)
How is ASA use to prevent blood clotting and coagulation?
It inhibits the production and secretion of thromboxane A2 by platelets, thus preventing clotting.
What compound initiates the coagulation cascade?
Tissue factor (factor III)
What is the main component of a blood clot that differentiates it from a platelet plug?
Deposition of FIBRIN on platelet plug
What is the end result of the coagulation cascade?
Activation of thrombin (factor IIA)
Describe the key steps in clot formation (at the end of the coagulation cascade)
- Prothrombinase (enzyme), in the presence of calcium, will convert pro-thrombin to thrombin
- Activated thrombin will cleave fibrinogen, converting it to fibrin.
- Factor XIII will carry out the cross-linking of the fibrin network, forming the blood clot
What is the role of thrombin (factor IIA)?
Cleaves fibrinogen into fibrin, which forms the blood clot.
Production of small amounts of thrombin will very quickly trigger a…
positive feedback loop, which will lead to the production of large amounts of thrombin
Name 3 important coagulation factors in the coagulation cascade
- Calcium
- Phospholipids
- Plasma protein factors
What is the role of calcium in the coagulation cascade?
It is essential for many of the proteolytic steps of the coagulation cascade. It activates factors II, VII, IX, X.
Calcium activation of factors II, VII, IX, X requires … as a cofactor
Vitamin K
What is coumadin
Common anti-coagulant, blocks activation of factors II, VII, IX and X by calcium
Why do we need to do lab tests to screen activity of the coagulation cascade? PT/INR or PTT tests
These tests measure how long it takes for blood to clot and are used to monitor anticoagulation therapy.