Block 2b Hemostasis Flashcards
What are the 4 steps of hemostasis?
1) vascular constriction 2) platelet plug formation 3) clot formation 4) fibrous tissue repair
What are the 3 mechanisms for vascular constriction in hemostasis?
1) myogenic response of vascular smooth muscle 2) local vasoconstrictors 3) CNS ischemic response
What substances are local vasoconstrictors?
prostaglandins & thromboxane A2
What is the myogenic response in vascular constriction?
damage to vasculature –> contraction & spasm
What is the half-life of a platelet?
8-12 days
Where are platelets cleared?
in spleen by macrophages
What are the dimensions of a platelet?
1-4 um discs
What substances can platelets secrete?
prostanoids & growth factors
Where are platelets produced, and what cellular elements do they have?
produced in spleen – no nucleus, but they do have ER & Golgi
What is the result of low platelet counts?
thousands of small hemorrhages in small vessels
Where is prothombin produced?
in liver with required Vit. K
What is the rate-limiting step in clot formation?
PT –> thrombin activation
How is prothombin activator formed?
by endothelium after vessel rupture
What are the requirements for PT activation?
PT activator & sufficient Ca++
What is the concentration of PT?
15 mg/dL (abundant & unstable –> thrombin)
How is a weak clot formed?
spontaneous polymerization of fibrin monomers
How is a strong clot formed?
thrombin activates transglutaminase (13a) to cause amid polymerization of fibrinogen monomers
What are the terminal sequences of fibrin monomers?
Gly-His-Arg or Gly-Pro-Arg
What does thrombin do?
causes proteolysis of fibrinogen –> fibrin monomers
How are platelets activated?
collagen
What substances do platelet granules release?
ADP & TXA2
How is a loose plug formed?
more and more platelets are activated to bind sticky granules
How are strong/solid plugs formed?
fibrin binds loose plug
How does serum differ from plasma?
serums lacks clotting factors
What substances catalyze clot contraction?
increased thrombin, increases Ca++
How are clots lysed?
plasminogen –> plasmin (activated by tPA, which is released by tissues)
What triggers the extrinsic clotting pathway?
tissue trauma (outside the vessel)
What triggers the intrinsic clotting pathway?
blood trauma or contact with collagen
What is the result of the intrinsic clotting pathway?
clotting factor cascade
What is theresult of the extrinsic clotting pathway?
formation of tissue thromboplastin
What pressure range favors clot formation?
< 60 mmHg
What factors prevent clots?
1) constant flow 2) endothelium 3) anticoagulants
What factors of the endothelium help prevent clotting?
1) smooth glycocalyx coating 2) thrombomodulin
How does thrombomodulin prevent clotting?
binds & inhibits thrombin; activates plasma protein C (another thrombin inhibitor)
What are the physiologic anticoagulants?
1) fibrin adsorbs & inhibits thrombin for the major effect 2) antithrombin III inhibits thrombin 3) heparin binds & increases antithrombin III activity
Where are heparin concentrations increased?
mast cells & basophils (lung beds & pericapillary tissues)
What issues can cause excessive bleeding?
1) low [clotting factors] 2) Vit. K deficiency 3) hemophilia (clotting factor deficiency) 4) thrombocytopenia
What are the most common clotting factor deficiencies?
Factor 8 most common, 15% Factor 9
How is hemophilia inherited?
X-linked
Where are clotting factors synthesized?
liver
What diseases can cause low clotting factor levels?
hepatitis, cirrhosis
How are DVTs treated?
anticoagulants, vena cava filter, tPA thrombolysis
What is a normal INR?
0.9 - 1.3
What is the goal INR during anticoagulant therapy?
3-Feb
What is normal PT time?
12 seconds
How is clotting time measured
1) drawn blood is oxalated to inhibit PT 2) excess Ca & tissue factor added 3) PT time measured
What is the half-life of heparin?
1.5 - 4 hours
Describe the structure of heparin?
heterogenous polysaccharide of various molecular weights (LMWH is commonly used)
How do coumarins work?
decrease PT & decrease factor 2/7/9/10 synthesis in liver
What is the onset of coumarins?
8-12 hours
What is the increase in clotting time when heparin is used?
6 mins to >30 minutes
Describe the INR equation?
fraction of normal PT raised to tissue factor sensitivity
What is the effect of factor 10a?
forms PT activator
How are platelets necessary for clot retraction?
links fibrin via actin-myosin skeleton to cause contraction & serum expression