Hemostasis and Coagulation cascade Flashcards
How to monitor warfarin?
PT/INR (International normalized ratio)
Vit K antagonist?
Warfarin
Most coagulation factors are serine proteases except?
Factors V and VIII which are glycoproteins
What primarily inactivates factors Va and VIIIa
Activated protein C
How is protein C activated and how does it work?
Protein C is activated by thrombomodulin found on endothelial cells.
It binds thrombin and the thrombomodulin:thrombin complex activates protein C. With protein S as co-factor, APC inactivates Va and VIIIa
Nitric oxide and Prostacyclin?
Released by endothelial cells that make up the inner surface of blood vessels, in the absence of injury.
NO - dilate blood vessels
Prostacyclin- Bind to receptors located on platelets to ultimately prevent platelet activation and aggregation.
Action reversed when blood vessel is damaged.
von wilderbrand factor?
When blood vessel is damaged, vwf helps platelets adhere to exposed collagen, causing the platelets to activate and change shape
Initiation (Primary hemostasis)
endothelial injury results in transient vasoconstriction.
→ exposure of subendothelial collagen
→ vWF, which is stored in Weibel-Palade bodies of endothelial cells and α-granules of platelets, binds the exposed collagen
Example of direct thrombin inhibitor
Dabigatran
Direct factor Xa inhibitor examples
Rivaroxaban, Apixaban, Edoxaban
Disadvantages of warfarin
Slow onset, Needs to be monitored, many drug and food interactions
Activated partial thromboplastin time (aPTT)
measures the time it takes plasma to clot when exposed to substances that activate the contact factors, which assesses the intrinsic and common pathways of coagulation. Normal range is approximately 25 to 35 seconds.
Contact factors?
Contact factors include prekallikrein and high molecular weight kininogen (HMWK)
What does thrombin time assess?
The thrombin time (TT) assesses the final step in the common pathway (fibrinogen to fibrin), the conversion of fibrinogen to fibrin, following the addition of exogenous thrombin.
Factor XIII?
Crosslinks fibrin. This function is not tested by the PT, aPTT, or TT.
PT test?
The prothrombin time (PT) measures the time it takes plasma to clot when exposed to tissue factor, which assesses the extrinsic and common pathways of coagulation.
The PT test is performed by recalcifying citrated patient plasma in the presence of tissue factor and phospholipid and determining the time it takes to form a fibrin clot. The formation of a fibrin clot is detected by visual, optical, or electromechanical methods.
The result is measured in seconds and reported along with a control value and/or an INR. the normal range is approximately 11 to 13 seconds.
Heparin typically prolongs PT. True/False
False.
Heparin typically prolongs the aPTT alone (because PT reagents contain heparin-binding agents (eg, heparinase, polybrene) that block heparin effect), but at high levels heparin can prolong both tests.
Heparins (unfractionated or low molecular weight) and fondaparinux should in theory prolong the PT because they inhibit thrombin and/or factor Xa.
Warfarin typically prolongs the PT alone. True/False
True!
Warfarin typically prolongs the PT alone, but at high levels warfarin can prolong both tests.
Causes of prolonged PT
Inherited:
Factor VII deficiency
Acquired: Mild vitamin K deficiency Liver disease Warfarin* DIC
Causes of prolonged aPTT
Inherited:
Deficiency of factor VIII, IX, or XI
Deficiency of factor XII, prekallikrein, or HMW kininogen (not associated with a bleeding diathesis)
von Willebrand disease (variable)
Acquired:
Heparin, dabigatran, argatroban, direct factor Xa inhibitors (variable)*
Acquired inhibitor of factor VIII, IX, XI, or XII
Acquired von Willebrand syndrome
Lupus anticoagulant (more likely to be associated with thrombosis than bleeding)
Causes of prolonged PT and aPTT
Inherited:
Deficiency of prothrombin, fibrinogen, factor V, or factor X
Combined factor deficiencies
Acquired:
Liver disease
DIC
Severe vitamin K deficiency
Anticoagulants (supratherapeutic doses of many anticoagulants, combined heparin and warfarin, direct thrombin inhibitors, anticoagulant rodenticide poisoning)*
Acquired inhibitor of prothrombin, fibrinogen, factor V, or factor X
Amyloidosis-associated factor X deficiency
Factor II?
Thrombin
What initiates the extrinsic pathway? How?
clotting is initiated when blood is exposed to tissue factor (like when injury occurs)
Tissue Factor (thromboplastin) forms a complex with factor VIIa
How is the intrinsic pathway activated?
by exposure of Factor XII (Hageman factor) to
1) subendothelial collagen or
2) HMWK (high molecular weight kininogen)
to produce Factor XIIa
What does factor XIIa do?
1) activates factor XI –> XIa
2) activates plasminogen –> plasmin
3) activates kininogen system –> kallikrein and bradykinin
What does factor IXa do?
forms a complex with Factor VIII, Tissue Factor (III), calcium to activate factor X –> Xa in the final common pathway
So what two ways can factor X get activated?
via Tissue Factor:Factor VIIa and calcium in the extrinsic path
via IXa:Ca, VIIIa, and Tissue Factor in the intrinsic pathway
What does Factor Xa do?
with the help of Factor Va and Ca, coverts prothrombin –> thrombin (IIa)
What does thrombin do?
1) fibrinogen –> fibrin
2) XIII –> XIIIa
3) activates VIII–> VIIIa in the intrinsic pathway
XIIIa?
converts soluble fibrin monomers into insoluble fibrin by enhancing the cross-linking to strengthen the fibrin clot
