Hemostasis Physiology Flashcards
What are the platelet precursors and how do they develop into platelets?
megakaryocytes
fragment into a lot smaller platelets
Can platelets produce ATP?
Yes, have mitochondria
What is the purpose of platelets’ growth factor?
induces fibroblast activity after clot formation to cause connective tissue formation and closing of the vessel defect
What are the contractile proteins of platelets?
myosin
actin
thrombosthenin
How do platelets prevent binding to healthy endothelial cells?
surface is coated by glycoproteins - repulse adherence to normal endothelium - causes only adherence to injured endothelial cells
What is the half life of platelets and how are they eliminated?
about 10 days
dogs: 5-7 days
destroyed by macrophages
Describe the formation of a platelet plug
tissue injury - exposed collagen and vWF - platelets bind to this and become activated
* form pseudopods
* swell and become sticky
* release granules –> attract more platelets
* release TXA2, ADP, PAF –> attract more platelets
enough to stop bleeding of tiny inuries - otherwise fibrin required
What platelet receptors bind vWF?
Gp1b
What are the 2 possible fates of a blood clot?
- dissolution
- connective tissue integration via fibroblasts
What are the 2 stages of fibrin monomer binding?
- early stages - fibrin monomers held together by weak noncovalent hydrogen bonding - no cross-linking - weak clot and can be broken apart easily
- within next few minutes - fibrin stabilizing factor (XIII, activated by thrombin) - forms covalent bonds ebtween fibrin monomers - strong meshwork
Explain the steps of clot retraction
within few min of clot formation - contraction, expression of serum withn 20-60 min
platelets activate thrombosthenin, actin, myosin - cause strong contractions
Describe the steps of the extrinsic pathway
TF exposure - activates and binds to circulating FVII –> activates FX —> binds with FV to form prothrombin activator complex with Ca2+ and phospholipids
How is FV activated?
Initially inactive as part of the prothrombin activator complex
once small amounts of thrombin activated –> will activate FVa which accelerates the prothrombin activation
Describe the Intrinsic pathway
exposure to collagen or blood trauma => FXII activation and phospholipid release from platelets
=> FXIIa activated FXI, this step requires kallikrein and is accelerated by prekallikrein
=> FXIa activates FIX
=> FXIa + VIIIa + phospholipids + platelet factor 3 => activate FX
=> FXa + FV => prothrombin activator
What factor do platelet phospholipids contain?
Platelet factor 3
How do the speeds of the extrinsic versus intrinsic pathway compare?
Extrinsic pathway is very fast, can happen within seconds
Intrinsic pathways takes minutes to cause clotting
What are characteristics of the endothelium that help keep clotting at bay
- smooth surface - prevents contact activation
- glycocalyx - repels clotting factors and platelets
- thrombomodulin on the endothelial surface - binds thrombin and also activates APC
- endothelial cells produce NO and PGI2 –> vasodilation and platelet inhibition
What are the 2 ways thrombin is removed from the blood to prevent excessive clotting?
- 85-90% of activated thrombin is absorbed by the fibrin fibers of the clot
- bindings with antithrombin III
what factors does the heparin-antithrombin complex bind and inhibit?
II
IX
XII
What cells produce heparin and in what organs are they most abundent?
basophils
mast cells
within the tissues surrounding capillaries of the lungs and liver
Describe the role of vitamin K for clotting factors
within the liver => cofactor of carboxylase =>
- gamma-carboxylation of glutamic acid of clotting facotrs => adds carboxyl group to glutamic acid residues on II, VII, IX, X, PC, PS => facilitates addition of extra negative charge on glutamic acid
- allows these factors to bind Ca++ which enables them to bind Phosphatidylserine of the phospholipid layer
in the process Vitamin K becomes oxidized - inactive
recycled by Vitamin K epoxide reductase complex 1 (VKORC1)
How is vitamin K produced and what is needed for its absorption?
intestinal bacteria produce Vitamin K
fat absorption - e.g., lack of bile can prevent fat absorption and therefore reduce vitamin K absorption
Describe how Prothrombin testing works
blood drawn - citrated or oxalated (i.e., binds Ca+)
for test - large amount Ca+ added + TF (usually grown from placentas)
=> activates extrinsic pathway => time to clotting measured
What can be used to standardize PT measurements between laboratories and machines?
International normalized ratio (INR)
tissue factor batches come with an international sensitivity index (ISI) - i.e., indicates activity of the TF produced
INR = (PT patient/PT control) ^ISI
