Lab 1: Blood Composition, Hemostasis, Blood groups, Hemoglobin Flashcards
What is Hemocoagulation?
process by which blood changes from a liquid to a gel, forming a blood clot.
hemostasis: definition
the cessation of blood loss from a damaged vessel, followed by repair.
Overall process of hemostasis
Hemostasis: Vascular contriction
Hemostasis: Formation of platlet plug
- Second step in hemostais
- Importance: Closing minute ruptures in very small blood vessles, may occur thousand of times daily
Mechanism of platelet plug formation
- Platlets begin to swell when they come in contact with a damaged vascular surface (especially with collagen fibers in the vascular wall)
- They assume irregular forms with numerous irradiating pseudopods protruding from their surfaces.
- Their contractile proteins contract and cause the release of granules that contain multiple active factors; they become sticky so that they adhere to collagen in the tissues and to a protein called Von Willebrand factor (vWF) that leaks into the traumatized tissue from the plasma.
- The Platlets secrete (Degranulation- release of granular content)
- ADP
- platelet activating factor (PAF),
- and their enzymes from thromboxane (a vasoconstrictor) TXA2 (stimulates activation of new platelets + increases platelet aggregation)
- Seratonin- attracts more platelets
- Together they act on nearby platelets to activate them as well, and to adhere to the original activated platelets.
- Therefore, at the site of a puncture in blood vessel wall, the damaged vascular wall activates increasing numbers of platelets that attract more and more platelets, forming a platelet plug, blocking blood loss.
- During the subsequent process of blood coagulation, fibrin threads form and attach tightly to the platelets
VWF disease-
PTT higher.why? Go with CF 8 and stable it, not VWF? CF8 will be inhibit by protein C.
PT is normal!
Blood coagulation definition
•Definition: complex cascade of reactions leading to the conversion of soluble fibrinogen into insoluble fibrin
Hemostasis: Blood coagulation (general steps)
What is the first step of blood coagulation?
How is it set in place?
What is the goal?
- Step 1: Initiation of Coagulation- Formation of Prothrombin Activator
- It is set into place by the following:
- (1) trauma to the vascular wall and adjacent tissues;
- (2) trauma to the blood; or
- (3) contact of the blood with damaged endothelial cells or with collagen and other tissue elements outside the blood vessel.
- In each case, this leads to the formation of prothrombin activator, which then causes prothrombin conversion
to thrombin and all the subsequent clotting steps.
The extrinsic pathway: Blood coagulation
Extrinsic pathway: trauma to vascular wall, release of tissue factor/tissue thromboplastin -> cascade
The intristic pathway: Blood coagulation
Intrinsic pathway: trauma begins in blood, collagen presence -> cascade
The common pathway: Blood coagulation
- Factor X and V+ phospholipids+ calcium= prothrombin activator complex
- Prothrombib (factor II) in the presence of Calcium and protease split to form thrombin
- Thrombin acts on fibrinogen (factor I) which is converted into fibrin monomers
- Fibrin momoners are polymerized with calcium unto fibrin fibers (reticulum of clot)
- Fibrin stabalizing facotr (which is activated by thrombin) acts on the fibers bonds to become stronger and causes the formation of multiple cross linkages
- Formation of the secondary plug
Clotting Factors:
Importance of vitamin K in Blood clotting *
Vitamin K: required by the liver for normal activation of prothrombin as well as a few other clotting factors.
In the early stages of polymerization of fibrin monomer molecules are held together with weak noncovalent hydrogen bonding and the newly formed fiber aren’t cross linked = weak fibrin clot
However when fibrin stabilizing factor is present and activated by thrombin acts as a enzyme to cause covalent bonds between the fibrin monomers and cross linkages between fibrin fibers = strong fibrin clot
Clot retraction: fluid is expressed which is called serum as it lacks fibrinogen and other clotting factors that have already been removed à hence is unable to clot. Platelets contribute to clot retraction as they activate thrombosthenin, actin and myosin which cause strong contraction of the platelet spicules attached to the fibrin. Also helps compress the fibrin meshwork into a smaller mass. The process is accelerated and activated by thrombin and calcium ions.
Warrafin- what does it do?
Warfarin- Indirect oral anticoagulated- inhibits the reduction of vitamin k- needed by factors 2,7,9,10, PC and PS
Warfarin is detectable in plasma within one hour and maximum blood levels are reached after about 90 minutes.
Hemostasis: Fibrinolysis
•Organization:
- platelet derived growth factor (PDGF) stimulates fibroblasts and smooth muscle cells to proliferate
- fibroblasts grow over the consolidated platelet plug and initiate the wound healing.
- Fibrinolysis is a secondary, but no less important, event of hemostasis.
- It is necessary to remove the fibrin (hemostatic) plug.
- During fibrinolysis, fibrin is cleaved by plasmin.
- The whole system has four components: plasminogen, plasmin, plasminogen activators, plasminogen inhibitors.
•Dissolution/ Fibrinolysis:
- Healthy endothelium releases tissue plasminogen activator (tPA).
- tPA activates conversion of plasminogen, which is trapped in the clot, to plasmin.
- Plasmin degrades insoluble fibrin to its degradation products.
- When a clot is formed, a large amount of plasminogen is trapped in the clot along with other plasma proteins.
- Activation of plasminogen (profibrinolysin), a globulin that the plasma proteins contain causes it to become a substance called plasmin (fibrolysin).
- The injured tissues and vascular endothelium very slowly release a powerful activator called TPA: tissue plasminogen activator.
- After the clot has stopped the bleeding, t-PA eventually converts plasminogen to plasmin, which in turn removes the remaining unnecessary blood clot.
- Activation of plasminogen (profibrinolysin), a globulin that the plasma proteins contain causes it to become a substance called plasmin (fibrolysin).
- Plasmin is a proteolytic enzyme that digests fibrin fibers and some other protein coagulants such as fibrinogen, factor 5, factor 8, prothrombin, and factor 12.
- Therefore, whenever plasmin is formed it can cause lysis of a clot by destroying many of the clotting factors, thereby sometimes causes even hypocoagulability of the blood.
- In fact, many small blood vessels in which blood flow has been blocked by clots are reopened by this mechanism; thus, the plasmin system remove minute clots from millions of tiny peripheral vessels that eventually would become occluded were there no way to clear them.
Factors that favor thrombosis vs dont favor
Anticoagulants vs Procoagulants
INR- Prothrombin Time
APTT- Activated Partial Thromboplastin Time
