Flashcards in Lecture 5: Blood Clotting Deck (89)
What gives rise to platelets?
___ are needed for blood clotting
How do megakaryocytes give rise to platelets?
Edges of megakaryocyte break off to form platelets (cell fragments)
giant cells with many copies of DNA in the nucleus
Half life of platelets?
____ increases platelet numbers by...
stimulating production of platelets
How is blood clotting regulated? (3 phases)
1. vascular phase
2. platelet phase
3. coagulation phase
Exposed collagen & tissue factors cause vasoconstriction of the damaged blood vessel. Vasoconstriction minimizes blood loss.
Vascular phase controlled by...
nervous system & muscles (neurogenic & myogenic control)
Vasoconstriction in vascular phase prolonged by...
3. Thromoboxane A2
1. Collagen exposed to blood stream; bind platelets passing by in the blood
2. Factors released from trapped platelets attract more platelets
3. Platelets aggregate to form plug
What makes von Willebrand factor?
What does von Willebrand factor bind to?
What are the factors released from platelets?
PAF (platelet activating factor)
When are factors released from platelets?
during platelet phase
What does serotonin and thromboxane cause?
What do activated platelets look like?
spiky outer surface
Purpose of activating platelets?
they can adhere to each other better
What do inactivated platelets look like?
disk-like cell fragments
What prevents platelet adhesion/activation during normal situations?
What releases NO and prostacyclin
Prostacyclin is made up of...
Prostaglandin I2, PGI2
Why is aspirin given after mild heart attacks?
Precursor for thromboxane is arachidonic acid.
Enzyme cyclooxygenase cleaves ADA -> PGH2 -> thromboxane.
Aspirin stops CO activity, so thromboxane can't be made.
Since thromboxane is used to vasoconstrict & aggregate platelets, these don't happen as easily.
Function of von Willebrand factor?
- link platelet with collagen
- draw platelet into exposed collagen area
- keep VII in circulation longer
What happens during vascular phase?
What happens during platelet phase?
Platelets are actively trying to stop bleeding (loose platelet plug)
What happens during coagulation phase?
- Proper blood clot forms via coagulation cascade
- Fibrinogen -> fibrin
Long strand of fibre that reinforces loose platelet plug
One piece of fibrinogen
Inactive form of fibrin
What do all the factors released from platelets cause?
What are the effects of thromboxane?
Cyclooxygenase catalyses what reaction?
arachidonic acid -> PGH2
What can PGH2 become?
Why is prostacyclin activity not affected when aspirin is taken?
Endothelial cells can still make more CO
What is the sturdiest form of fibrin?
What enzyme cleaves fibrinogen to fibrin?
is fibrin soluble / insoluble?
How does fibrin become cross-linked?
Factor XIII & Ca++ catalysed
Summary of coagulation cascade
1. Contact activation pathway
2. Tissue factor pathway
3. Common pathway
1->3 or 2->3
Contact activation pathway
tissue factor pathway
trigger for intrinsic pathway
collagen in bld vessels exposed due to injury
What is the function of ADP?
Attract more platelets to damaged area
Trigger for extrinsic pathway
Damaged tissue exposes thromboplastin
What does factor XI and factor VII activate?
Factor X (common pathway)
What activates prothrombin activator?
Purpose of prothrombin activator?
prothrombin -> thrombin
What activates factor XIII?
What is the beginning of the common pathway?
active factor X
Where are many plasma factors used for blood clotting made?
Cascade of intrinsic pathway
1. Exposed collagen activates factor XII
2. Factor XII & Ca++ activate Factor XI
3. Factor XI & Ca++ activate factor IX
4. Factor IX, factor VIII, Ca++, PL activate factor X
what regulates levels of factor VIII?
von Willebrand factor (keeps VIII around for longer)
Vit K needed for the synthesis of...
What drugs blocks the action of vit K?
Coumadin / Warfarin
-> less blood clotting
What vitamin helps blood clotting?
Cascade of extrinsic pathway
1. Factor III from thromboplastin activate Factor VII
2. VII + III activate IX
3. III and VII // Ca++ // PL -> activates X
X activates VII
vWf disease (symptoms)
problem with quality or quantity of vWf
problem with blood clotting
Which areas are most affected by the lack of vWf?
areas w/ small number of capillaries (skin, GI, uterus)
treatment for vWf disease?
protein that releases vasopressin to endothelial cells: stimulate release of vWf
Hemophilia A need to be injected with...
Hemophilia B due to deficiency in...
Symptoms of hemophilia
internal and external bleeding that doesn't stop easily
which pathway is still active in those with haemophilia?
Extrinsic, but not enough to have normal blood clotting efficiency
Purpose of plasmin
fibrin -> fibrin fragments (easy to break up and remove)
Which enzymes are responsible for the formation of plasminogen -> plasmin?
What enzymes are used for fibrinolysis (anticoagulants)?
5. Protein C
tPA released by...
damaged endothelium (released very slowly)
precursor of plasmin
Thrombin has positive feedback on...
1. VII activation
2. VIII activation
3. IX activation
4. XI activation
5. V activation
What activates protein C?
thrombin -> (catalysed by protein S)
function of protein C?
1. stop activation of VIII
2. stop activation of V
function of TFPI?
stop VII activation
function of antithrombin?
1. stop IX activation
2. stop X activation
3. stop XI activation
4. stop XII activation
5. stop thrombin
tissue factor pathway inhibitor
Where is plasminogen / plasmin released from?
Where is tPA released from?
Where is TFPI released from?
Where is antithrombin released from?
Where is protein c released from?
tPA is activated by...
TFPI is activated by...
Antithrombin is activated by...
Blood vessel in brain bursts, and blood leaks into brain
Blood clot gets stuck in artery going into brain
blood clot attached to vessel wall (less O gets to tissues)
Floating blood clot
tissue plasminogen activator
What is a treatment for stroke?
tPA given within 3-4 after a stroke
this breaks down the blood clot