Pathophysiology of Hemostasis Flashcards
When there is a break in the endothelium what forms the inital plug?
platelets that are circulating in the bood
What comes in after the platelet plug and creates a network to hold them all together?
fibrin
They have a natural affinity for each other to form a fibrin strand
Fibrin has a natural affinity for each other. How do we stop them from binding to each other while they are cicrulating in the blood?
fibrinogen, cap that covers a binding site
How does your body know when to convert fibrinogen into fibrin?
thrombin
is activated from its inactive form called prothrombin
Name the steps in the clotting factors in the intrinsic pathway.
8
12-11-9 and 8-10 and 5-2(thrombin)- 1(fibrin)
2 and 1 are part of both pathways and not necessarily part of each pathway
Each factor in the clotting casacde is not becoming one or the other. What is it doing?
One factor is activating the next factor. So factor 12 activates factor 11 to become factor 11a
Name the steps in the clotting factors in the extrinsic pathway
factor 3 (tissue factor)-7-10 and 5
What is the pathway that get activated first by the inital injury?
the extrinsic pathway
Which pathway gets most of the clotting work done?
the intrinsic pathway
What are the proteins that are secreted by the endothelium and the proteins that are newly exposed called?
tissue factor or factor3
What gets the intrinsic workhorse going in the first place?
thrombin (2) that was slightly activated by the extrinsic pathway
What factors does thrombin activate?
5
5, 7, 8, 11, 13
Whats the end goal of the clotting casade?
create fibin strands
and to connect all the fibrin strands that are made.
How are all the fibrin strands connected together?
factor 13 creates crosslinks that connect all the fibrin strands that are created
How do we stop the clotting system when we need it to?
2
negative feedback loop that is regulated by thrombin
- Thrombin helps create plasmin which act directly on the mesh networks of the fibin strands and breaks them apart.
- Thrombin stimulates the production of antithrombin which decreases the amount of thrombin produced from prothrombin and impede the production of activated 10a from 10.
What does antithrombin do?
2
decreases the amount of thrombin that prothrombin is making and impede the activatoion of 10a from 10
What are the three processes through which hemostasis is regulated?
3
- vascular spasm
- platelet plug formation
- coagulation
Describe the first step in hemostasis, vasoconstriction?
3
- direct injury
- chemical messengers from endothelial cells and platelets
- initiation of the pain reflex
What are the chemical messengers secreted from endothelial cells platelets?
Whats the most potent?
Thromboxane A2,
serotonin,
endothelin I(most potent)
What is primary hemostasis?
Describe the steps in the process?
3
Platelet plug formation
- injury to vascular endothelium
- VWF is released
- Proteins on platelets bind with fibrinogen causing platelets to adhere
Describe the effectivness of platelet plug formation?
quick temporary solution that lasts 12-24 hrs
describe the structure of a platelet?
3
A glycoprotein, Glycosaminoglycans
Coagulation proteins
will an outter cell membrane and no nucleus
Which glycoproteins bind to bridge platelets toegther?
GPIIb/IIIa binds fibrinogen
Whats the lifespan of a platelet and where are they made?
8-12 days
Bone marrow
What enzymes do platelets conatin?
5
serotonin, calcium, ADP, PDGF, thromboxane A2
What is the production of platelets regulated by and where does it come from?4
thrombopoietin from liver, kidney, smooth muscle, bone marrow
What does an activated platelet look like?
inactivated?
activated is all crunched up and stringy so it can latch onto endothelium and to each other
inactivated looks like potato chips
Describe the steps in primary hemostasis
5
- platelet adhesion
- shape change of platelet
- platelets release granules (ADP anf TXA2) in order to
- recruit more platelets
- aggregation or hemostatic plug
What does clopidogrel inhibit?
ADP
What does aspirin inhibit?
TXA2
Primary hemostasis/platelet plug formation is defective when what happens?
3
Low platelets
Decreased vWF
Medications that inhibit platelets
What medications inhibit the platelet plug formation?
And how do they do this?
2
Aspirin (inhibits prostaglandin synthesis including thromboxane A2)
Clopidrogel (inhibits the ADP pathway)
What does VWF do?
2
- acts as a glue and binds platelets to the endothelium/collagen.
- It also prolongs the life of factor 8 (usually only lasts for a few seconds and with vwf it can last for a few min)
What is secondary hemostasis?
coagulation
How is the clotting pathway activated?
2
- a defect in the vessel endothelium or
2. disruption in the vessel wall.
What is the intrinsic pathway activated by?
2
- Exposed collagen in the vessel. 2. This sets forth the catalyst to activate factor XII (Hageman factor)
What is hagemen factor?
factor 7
What are the important factors of the intrinsic pathway?
5
Hageman factor, factors VIII, IX, XI and calcium
What are important factors in the extrinsic pathway?
3
Tissue factor III, VII and calcium
What is tissue factor activated by?
3
inflammatory cytokines, cell injury and vessel injury (bleeding into the tissue)
Common pathway starts and ends with what?
Describe how it gets from start to finish
7
Starts with 10 and ends with fibrin (10-prothrombin-thrombin-fibrinogen- fibrin- fibrin strands-corsslinked fibrin strands)
How fast is clot formation completed?
3-6 minutes
What is clot retraction?
when the platelets contract and draw the edges of the blood vessel closer together
Why is fibrinolysis necessary and how long does it take to happen?
- necessary to remove clots as the blood vessel heals
2. Within 2 days of clot formation and continues until clot is fully dissolved
What is the formaiton of plasmin dependant on?
3
- activation of plasminogen by tPA, XIIa and thrombin.
What would be some things that activate plasminogen?
4
vasoactive drugs,
venous occlusion ,
increased body temp,
exercise
What does plasmin do?
digests the fibrin in the clot and breaks it up
What regulatory mechanisms are in place to limit clot growth?
2
- Removal of clotting factors (dilutional)
- Inhibition of activated clotting factors
- antithrombinIII
- protein C
- protein S
What does antothrombin III inhibit?
2
Inactivates thrombin and X
What does protein C inactivate?
Inactivates V and VIII
What does protein S activate?
Accelerates the action of Protein C
How does heparin work?
Heparin is produced from where?3
binds to AT (antithrombin II) causing a conformation change activating it. This then inactivates factor 10a and thrombin
mast cells, basophils, and surface of endothelium
Why does liver damage affect hemostasis?
most of the clotting factors are synthesized in the liver
What vitamin is required for synthesis of 4 clotting factors and what are these factors?
- vitamin K
2. 2, 7, 9, 10
What is the role of calcium in the clotting cascade?
Calcium helps to activate multiple clotting factors throughout the entire coagulation cascade.
