Hemostasis Flashcards
Coagulation cascade diagram
Mechanisms in Medicine Coagulation Cascade Diagram
___ is the primary initiator of coagulation in vivo.
The extrinsic pathway is the primary initiator of coagulation in vivo.
Active complexes of the coagulation cascade
The many roles of vWF
- Stable binding partner of serum Factor VIII
- Binding sites for collagen and a glycoprotein complex on platelets
- Capable of ‘unwinding’ under sheer stress of bloodflow to be exposed and cut by ADAMTS13
Thrombin activates platelets by ___.
Thrombin activates platelets by cleaving the thrombin receptor on their surface.
Activated platelet image
Things that happen when platelets are activated (by thrombin, or ATP, or whatever)
- Morphology change
- Release arachadonic acid from membrane and metabolize to TxA2
- Release of dense granule contents (including more ADP)
- Release of alpha granule contents (containing proteins that contribute to hemostasis - platelet factor IV, thrombospondin, fibrinogen, and factor V)
- Expose P-selectin (normally housed within alpha granules, part of degranulation)
- Bring phosphatidylserine from the internal leaflet to the external leaflet
Zymogens of the coagulation cascade are synthesized in ___.
Zymogens of the coagulation cascade are synthesized in the liver
Basic structure and cell biology of coagulation cascade zymogens
- Signal peptide at N terminus
- Serine protease active site at C terminus
- Undergo crucial modifications at Golgi prior to release, including vitamin K-dependent carboxylation
General role of protein cofactors in the coagulation cascade
Bind to platelet and endothelial cell membranes, where they serve as docking sites for zymogens and contribute importantly to the amplification that is essential for the rapid formation of the fibrin clot.
Coagulation in a glass tube
___ is not very important for coagulation ex-vivo, such as in a glass tube, but is crucial for in-vivo coagulation.
Factor IX is not very important for coagulation ex-vivo, such as in a glass tube, but is crucial for in-vivo coagulation.
Coagulation in humans
fibrinopeptides A and B
Released from fibrinogen when it is cleaved by thrombin to form fibrin. Measurement can be useful in evaluating patients with disseminated intravascular coagulation.
Factor XIIIa
Cross-links fibrin with covalent bonds
Tissue factor pathway inhibitor (TFPI)
Synthesized in endothelial cells and is present in plasma and platelets. blocks the extrinsic coagulation pathway after its initial activation by binding first to factor Xa, then jointly binding to and inactivating VIIa/TF complexes. This shuts down the extrinsic pathway after only small amounts of Xa and thrombin are generated.
This small amount of Xa and thrombin are sufficient to activate factor VIII and factor V, enabling the intrinsic pathway to provide a burst of procoagulant activity.
Antithrombin
Most important plasma protease inhibitor in regulating hemostasis. Binds to heparin or other glycoproteins on endothelial cells and here undergoes a conformational change to reveal a site that serves as a serine protease inhibitor.
It inactivates not only thrombin but also factors VIIa, IXa, Xa, and XIa as they are carried in the blood away from the developing thrombus.
Protein C and Protein S
Work together. When activated by thrombin bound to thrombomodulin on the surface of normal endothelial cells, innactivate factors Va and VIIIa.
Undergo vitamin K–dependent carboxylation and share other structural features with factors VII, IX, X, and prothrombin
Platelet count
Platelets per microliter
Bleeding time
Make a controlled superficial incision on the forearm and monitoring the time that elapses before the bleeding stops.
As the straight vertical and diagonal lines show, in those with normal platelet function, the bleeding time is not prolonged unless the platelet count is less than 100,000 per microliter.