Hemostasis Flashcards
Define Hemostasis
Process preventing blood loss while maintaining blood flow
How do platelets adhere to the ECM exposed at the site of vascular injury?
wall expose ECM, endothelial cells produce VWF - which binds to the GPIb on platelets.
also binds onto integrin alpha beta, and collagen.
Ca signal from adhesioni, which causes big shape change. ADP and TXA2 released. ADP causes GpIIb-IIIa to bind fibrinogen and grab onto other platelets with the same receptor - clot.
What is the role of Von Willebrand factor?
On endothelial cells and from platelets. Binds to GPIb on platelets to grab. also binds to factor VIII - prolongs half life of VIII.
What is the role of Glycoprotein Ib?
It binds to VWF on the endothelial cells.
What is the pathophysiology of Von Willebrand Dz?
Less VWprotein/function. this means they also have reduced Factor VIII. Nosebleeds/dental work wont stop bleeding. Managed with Desmopressin - inc levels of VWF and VIII
Describe morphological changes associated with Platelet activation. What sorts of compounds are secreted?
The activated platelets grow long processes and secrete ADP and TXA2.
ADP causes GpIIb-IIIa to bind to fibrinogen.
Explain the process of Platelet aggregation.
aggregation signals?
GpIIb-GpIIa?
Fibrinogen?
Platelets have GpIb receptors on surface, when exposed to VWF they are activated. Then they change shape and Negatively charged phospholipids are directed to the cell membrane. they secrete ADP and TXA2, which cause the GpIIb-IIIa receptors on their surface to bind to fibrinogen and attach to other platelets.
What is the importance of Vitamin K in the coagulation cascade?
How does warfarin function in inhibiting?
It manages Factor X, IX, VII, and II
Vitamin K converts Glutamate to Gamma carboxy glutamate
Warfarin binds to Vitamin K epoxide reductase, so used Vit K cant be reconverted into the good kind again.
Outline the activation of thrombin
The negatively charged phospholipids on Platelets draw in the Calcium, which is bound to Gamma carboxy glutamate. (clotting factors are being drawn to site of injury)
Outline the activation of thrombin
The negatively charged phospholipids on Platelets draw in the Calcium, which is bound to Gamma carboxy glutamate. (clotting factors are being drawn to site of injury)
Tissue factor is exposed at the site of vascular damage. In the presence of Ca, it binds factor VII to VIIa and produces IXa also. VIIa then activates factor X. Factor Xa slowly cleaves prothrombin to thrombin. Then thrombin activates factors V, VIII
Factor Va, Xa, and Ca work to cleave more Prothrombin to Thrombin. Factors VIIIa and IXa form a complex to amplify activation of more Factor Xa. which speeds the process.
Thrombin also produces factor XIa, which acivates more IXa, which goes onto make more Xa.
Outline the physiology of Hemophilia A
and Hemophilia B
A: X linked. #1, Factor VIII def.
B: Factor IX def. Queen Victoria.
How does thrombin, via thrombomodulin, Protein C, and Protein S function in anticoagulation?
anticoagulation
thrombin both drives and inhibits coag
Thrombomodulin changes thrombin to one that can make active protein C - which makes Protein S. which forms a complex that degrades factor VIII and factor V. The necessary arm of the coagulation cascade.
What is ‘Factor V Leiden’ and what are its consequences?
Pt mutation. V resistant to proteolysis. Harder time shutting off coagulation and increased risk of hypercoagulation.
What is meant by ‘serpins’
and ‘Tissue Factor Pathway Inhibitor’ (TFPI)?
Serine Protease Inhibitors: AT3 is an inhibitor of thrombin. also binds heparin to inhibit additional clotting factors
TFPI made by endothelial cells - inhibis signalling from tissue factor arm. also inhibits factor Xa.
How is fibrinolysis achieved?
How does streptokinase help?
Plasmin degrades fibrin. Plasminogen has high affinity for fibrin. tPa is made by endothelial cells and circulates and localizes to plasmin. Fibrin binds tPa adn Plasminogen. tPa activates to plasmin. then degrades fibrin. tPa gets released and shut off by alpha 2 antiplasmin and alpha 2 macroglobulin.
Streptokinase is another way to turn on plasminogen. Produced by streptococci - used clinically
