Lecture 18: Hemostasis 2 and 3 Flashcards
What is the start of the platelet plug phase?
Platelets attach to the exposed collagen in the underlying basement membrane of injured endothelial lining of surface blood cells
Do platelets normally adhere to endothelial surface of blood cells?
Nope
What is the first sign of platelet activation during the platelet plug formation?
Change of shape and extension of many projections which extend to adjacent platelets
During activation, platelets synthesize and release:
- ADP
- Thromboxane A2
- Serotonin
- Ca
- Platelet-Derived Growth Factor (PDGF)
What is the primary stimulus for platelet aggregation, shape changes, and platelet secretion?
ADP
ADP is released by….
and causes…..
in platelet plug formation
Released by activated platelets and by endothelial cells at the injury site.
Causes surface of nearby circulating platelets to become sticky, so that they adhere to the first layer of aggregated platelets
Thromboxane A2 is released by ____ _____ and has two major effects:
Activated platelets
- Stimulates platelet aggregation and release of ADP individual platelets
- Stimulates smooth muscle contractions in vessel walls, enhancing vascular spasms
Serotonin (platelet plug formation)
Assists thromboxane A2 in stimulating local vasoconstriction
Ca (platelet plug formation)
Required for platelet aggregation and by several steps in the clotting process
Platelet derived growth factor (PDGF) (platelet plug formation)
A peptide that promotes vessel repair by stimulating the division of endothelial cells, smooth muscle cells and fibroblasts
Positive feedback loop that produces and reinforces the platelet plug
Platelet phase proceeds rapidly due to each arriving platelet releasing ADP, thromboxane A2, and Ca which stimulates further aggregation
What factor limits the growth of the platelet plug
prostacyclin
Vascular and platelet phases occur
a few seconds after injury
Coagulation phase occurs
about 30 seconds or more after blood vessel damage has occurred
(Clotting/coagulation phase) Clotting leads to the conversion of
circulating fibrinogen into fibrin, catalyzed by the enzyme thrombin, at the site of the vessel injury
As fibrin network grows,
it covers surface of platelet plug, traps additional platelets in a fibrous tangle, and forms a blood clot that seals off the damaged part of the vessel
Normal coagulation cannot occur unless plasma contains
the necessary clotting factors (Ca and 11 different proteins called procoagulants)
Another name for procoagulants
proenzymes
Procoagulants can be converted to
active enzymes which direct essential actions in clotting response
Clotting factors are identified by
roman numerals
All but three (III, IV, and VIII) are synthesized and released by
the liver and are always present in circulation
Activated platelets release five procoagulants during the platelet phase:
Factors III, IV, V, VIII, and XIII
The activation of one enzymes during the coagulation phase creates
an enzyme that activates a second proenzyme, and so on in a chain reaction or cascade
The clotting cascade may be triggered by:
- Intrinsic pathway
2. Extrinsic pathway
What two things affect every aspect of the clotting process
Ca
Vitamin K
Both intrinsic and extrinsic pathways of coagulation require the presence of
Ca
Vitamin K must be present in adequate amounts for the liver to synthesize what four clotting factors?
- Factor II - prothrombin - common pathway
- Factor VII - proconvertin - extrinsic pathway
- Factor IX - Christmas factor - intrinsic pathway
- Factor X - Stuart-prower factor, thrombokinase - extrinsic and intrinsic pathways
Vitamin K is ___ soluble and is absorbed with
fat
dietary lipids
How is vitamin K obtained
from the diet
is also manufactured by bacteria within the large intestine
What leads to vitamin K deficiency and what are the consequences of it?
- Inadequate diet, disorder that affects fat digestion/absorption (like problems with bile production)
- Eventually will cause the breakdown of the clotting process due to a lack of procoagulants
What happens in clot retraction?
- Fibrin network appears and platelets/rbcs stick to the fibrin strands
- Platelets contract
- Fluid (serum) is squeezed from clot
Clot retraction is also called
syneresis
Serum
Plasma, minus the fibrinogen and other clotting precursors that were removed during clotting process
Two reasons why clot retraction is important
- Pulls torn edges of the vessel closer together, which reduces the residual bleeding and stabilizing the injury site
- Reduces the size of the damaged area, making it easier for the fibroblasts, smooth muscle cells and endothelial cells to complete repairs
Fibrinolysis
clot removal
Plasminogen activators
- Tissue plasminogen activator (t-PA)
- Streptokinase
- Urokinase
4 anticoagulants that circulate in the blood to help prevent clotting during normal conditions
- Antithrombin III
- Heparin
- Prostacyclin
- Tissue Plasminogen Activator (tPA)
Antithrombin III
Inhibits several different procoagulants, including thrombin
Heparin
- Released by basophil, mast cells, and endothelial cells.
- Accelerates activation of antithrombin II
Prostacyclin
- Released healthy endothelial cells.
- Inhibits platelet aggregation and opposes the stimulatory action of ADP
Tissue plasminogen activator
- Secreted by endothelial cells
- Converts plasminogen to plasmin which enzymatically degrades fibrin (clots)
5 important drugs that are anticoagulants
- Heparin - stimulates antithrombin III
- Warfarin - depress synthesis of several clotting factors (II, VII, IX, and X) by blocking the use of Vitamin K by the liver
- tPA - stimulates plasmin formation
- Streptokinase - forms an active complex with plasminogen, which then converts uncomplexed plasminogen to plasmin
- Urokinase - directly degrades fibrin
To prevent blood clotting, samples may be treated with:
- EDTA
2. CPD
Ethylenediaminetetroacetic acid (EDTA)
Removes Ca from plasma thus preventing coagulation
Citratephosphate dextrose
- Removes Ca from plasma, preventing coagulation
- Used in blood banks
