Flashcards in MHD: Normal Hemostasis Deck (52):
What is the major event of normal hemostasis?
The formation of a hemostatic plug when blood vessels are ruptured or injured
What is abnormal hemostasis?
Pathological activation of clotting factors leading to formation of a clot when there are no ruptured vessels.
Hemostasis depends on interactions between what 3 entities?
Blood vessel wall
Coagulation and fibrinolytic systems
What is the first step of primary hemostasis?
Vasoconstriction occurs reflexively in order to try to minimize blood loss
What is the vasoconstrictive agent involved with the first step of primary hemostasis?
Endothelin, released by the endothelial cells near the site of injury
After vasoconstriction, what are the next steps of primary hemostasis?
Platelet adherence to newly exposed collagen
Activation: degranulation release of ADP, TXA2, 5HT
Aggregation: degranulation recruits additional platelets to form hemostatic plug
What are the two types of platelet granules?
Light granules (Alpha): contain proteins including PF4, PDGF
Dense granules (Beta): contain ADP, Ca2+, histamine, 5HT, and Epi
What is the general function of primary hemostasis? What about secondary hemostasis?
Primary Places Plug
What factor is released to initiate secondary hemostasis?
Tissue factor released from the endothelial cells at the site of injury
What two events occur simultaneously during secondary hemostasis?
Release of tissue factor
Coagulation proteins form complexes on platelet surface
What is the product of the coagulation cascade?
Thrombin is formed, which then converts fibrinogen to fibrin
What process forms the stabilized permanent hemostatic plug?
Cross linking of fibrin forms a stable platelet t-thrombin plug
Describe the cells contained in the permanent hemostatic plug.
RBCs and WBCs become trapped in the plug in addition to the platelets that make up the majority of the plug
What two outcomes of hemostasis are controlled by the endothelium?
Normally, endothelium has an antithrombotic effect
If there is injury to the endothelium, then there is a prothrombotic effect
Describe the antiplatelet effect of the endothelium
Prevents contact between collagen and platelets/coagulation proteins
Secretion of prostacyclin and nitric oxide
Describe the anticoagulant effect of the endothelium
Endothelial membranes express antithrombin (heparin cofactor) and thrombomodulin.
Thrombomodulin combines with thrombin to activate protein C
Protein S (cofactor for C) is also secreted
Describe the fibrinolytic effect of the endothelium
The endothelial cells secrete plasminogen activators (t-PA) which converts plasminogen to plasmin, thus promoting fibrinolysis
What factors of the clotting pathway are degraded by activated protein C?
Va and VIIIa
Describe the prothrombotic effect of the endothelium
Following injury, endothelia secrete von Willebrand factor (VWF), which allows platelets to attach to newly exposed collagen
What 3 molecules are released by endothelia for during the prothrombotic response to injury?
What is the definition of a platelet?
Discoid, anuclear cells that play a major role in hemostasis
Describe the composition of the plasma membrane of platelets
Contains many glycoprotein receptors
What are the three reactions that platelets undergo after exposure to subendothelial proteins?
Describe the process of platelet adhesion
GPIb on platelet membrane connects to collagen via VWF
Describe the process of platelet activation
GPIIb/IIIa receptor activation leads to release of granular content including ADP, Ca2+, and TXA2
The phospholipid complex (exposed negatively charged phospholipids on platelet surface) leads to activation of the intrinsic pathway
Describe the process of platelet aggregation
ADP and TXA2 are released from platelets to recruit, activate and aggregate platelets
5HT and TXA2 vasoconstrict
Thrombin formed via intrinsic pathway
What factor is thrombin in the coagulation cascade?
converts fibrinogen to fibrin
What enzyme stabilizes the fibrin clot?
Transamidase (Factor XIIIa) and TAFIa stabilize the fibrin clot
What are the three components of the clotting cascade?
What is the common factor activated by both the intrinsic and extrinsic pathway of the clotting cascade?
Factor X is activated to Xa by both pathways
List the order of factors activated during the intrinsic pathway?
XII (Hageman factor) --> XIIa
XI ---> XIa (activated by thrombin)
IX --> IX a (activated by XIa)
VIII --> VIIIa (activated by thrombin)
VIIIa then activates X to Xa
What factors are involved with the extrinsic pathway?
VII gets activated to VIIa by Tissue factor
VIIa then activates X to Xa
What factors are involved with the common pathway?
5, 2, 1
Thrombin activate V to Va
Va and Xa activate II (Prothrombin) to IIa (Thrombin)
IIa converts fibrinogen (I) to fibrin (Ia)
What lab test measures intrinsic pathway factors?
APTT (XII, XI, IX, VIII)
What lab test measures extrinsic pathway factors
Which pathway does heparin act on ?
Which pathway does warfarin act on ?
What type of enzyme are almost all clotting factor proteins?
Serine proteases (All except XIIIa, which is a transamidase)
Which factors are members of the fibrinogen group?
I, V, VIII, XIII
"5+8 x 1 = 13"
Which factors are members of the prothrombin group?
II, VII, IX, X
What structural similarity exists between the members of the prothrombin group?
II, VII, IX, X all contain gamma carboxy glutamic acid for binding of calcium
Which factors are members of the contact group?
Also: Prekallikrein (Fletcher factor), and HMW Kininogen (Fitzgerald factor)
What are the two major inhibitors of the coagulation system?
Antithrombin III (AT)
Tissue factor pathway inhibitor (TFPI)
What drug is associated with ATIII function?
ATIII mediates the anticoagulant action of heparin
Heparin-ATIII inactivates thrombin and other factors
What is the function of the fibrinolytic system?
These enzymes are responsible for breaking down clots
What is the main fibrinolytic enzyme?
Plasmin: breaks fibrin into fibrin split products
What are the main inhibitors of the fibrinolytic system?
Plasminogen activator inhibitor (PAI)
Thrombin activatable fibrinolytic inhibitor (TAFI)
What substances activate plasminogen to plasmin?
Tissue plasminogen activator (tPA)
Pathologic transition of the state of blood from fluidity to non-fluidity
What is the difference between a thrombus and an embolus?
Thrombi are stationary. They can progress and break into mobile pieces throughout the circulation which are called Emboli.
What are the factors leading to thrombosis?
Virchow's triad: endothelial injury, abnormal blood flow, hypercoagulability