MOD 5 Flashcards
Name 3 reasons why we have pro-thrombotic factors
- stops the skin from bleeding
- healing bone fractures
- prevents fatal hemorrhages
Why are pregnant women at risk for fatal hemorrhages
A blood clot can occur when the placenta detaches during childbirth, can have a thromboembolism which can travel to the lungs
Name 3 things anti-thrombotic factors can prevent
- heart attack
- stroke
- PE
Contrast primary hemostasis vs secondary hemostasis
Primary: platelet plug
Secondary: stabilization of plug with fibrin –> coagulation
Name 4 core components of hemostasis
- vessel walls (vascular endothelial cells)
- platelets
- coagulation
- fibrinolytic system
- -> defects in any of these can lead to too little or too much clotting
Name 3 events following an arterial injury
- Vascular spasm - vasoconstriction limits blood flow to the area
- Platelet plug
- Coagulation
Name 3 steps aiding the formation of a platelet plug
- Endothelial cells secrete von Willebrand factor
- Platelets secrete chemicals and other PDGF to attract other platelets to the area
- Platelet plug held together by insoluble fibrin
Name…
a) 2 things endothelial cells secrete normally to prevent clotting
b) 2 things endothelial cells secrete normally to prevent a platelet plug
a) heparin-like molecule and thrombomodulin
b) prostacyclin and NO
The lifespan of platelets?
7-10 days
The point where intrinsic and extrinsic pathway converge
Factor 10
What is the main regulatory step of the coagulation system and why?
Thrombin Activation as a small amount can amplify a big response…
One molecule of factor 10 could catalyze 1000 molecules of thrombin, 1 ml of blood has enough thrombin to convert all the fibrinogen in the body to fibrin
Name 3 things that assist in turning off the coagulation system
- Antithrombin 3 - serine protease cleaving 10a and thrombin
- Protein C - Vit K dependent zymogen, requires thrombin to bind to thrombomodulin (endothelial receptor) to become a serine protease that can cleave 5a and 8a
Name 3 anticoagulant DRUGS
- Warfarin
- Heparin
- Direct oral anticoagulants
Name 4 reasons why warfarin isn’t the best choice of blood thinner
- Narrow therapeutic window
- Drug diet interactions
- Difficulty to determine the dose - need to administer frequent INR testing and observation
- Not immediate; as a Vit.K antagonist it can only terminate the synthesis of more factors 2,7,9,10, not destroy the ones currently in the body - may need to give heparin for an immediate solution and warfarin will kick in later
Let’s talk heparin,
A) name two types of heparin
B) What is its effect?
C) Is heparin naturally occurring, man-made or both?
A) i. Long chain unfractionated heparin, IV injected - need to keep measuring APTT and adjusting dose to get the right amount
ii. Low molecular weight heparin (LWM) short chain, given according to weight, easier to administer
B) Assists antithrombin III in breaking down the clot
C) Both! It can also be secreted by MAST cells and basophils
Why are cirrhotic people more likely to bleed?
Cirrhotic people have liver damage, therefore the liver cannot process Vit K, therefore the factors 2,7,9,10 aren’t being produced and coagulation issues will arise - patient more likely to bleed
What largely synthesizes alpha 2 macroglobulin and what 3 cells locally secrete it?
The liver, and macrophages, fibroblasts and adrenocortical cells
How would you know if a disorder of coagulation/hemostasis was acquired or inherited?
Inherited diseases present as single gene defects in an otherwise well patient
Acquired diseases present commonly as issues with multiple parts of the coagulation process in patients already systemically ill
What is iatrogenic enhancement?
Enhancement of a process with man administered drugs
What is factor V Leiden
Protein C deficiency, not directly affecting clotting but slows down the process
Name 3 factors affecting (stimulating or inhibiting) the conversion of plasminogen to plasmin, and whether it inhibits or stimulates it
a) alpha 2 macroglobulin antiplasmin (-)
b) Tissue plasminogen factor (+)
c) TPF drugs; can be naturally made: urokinase and T-PA
and man-made: streptokinase
How does factor 8 contribute to a positive feedback cycle?
factor 8 assists factor 9 in cleaving 10-10a, 10a activates antihemophilic factor which encourages more clotting and more factor 8!
What is a common consequence of a bleeding disorder
Hemarthrosis - bleeding into the joint spaces
Treatment for Hemophilia
Recombinant factor 8
