Secondary Hemostasis Flashcards
Secondary Hemostasis timing and factors
-occurring at same time as primary hemostasis
-uses coagulation factors and cofactors called serine proteases that are either circulating or released from platelets
Goal of hemostasis
-create an insoluble, fibrin clot that stabilizes and replaces the platelet plug
Anti-coagulation role in secondary hemostasis
-keep the fibrin clot concise and in the area of endothelial injury without excessive formation
-also resorbs the fibrin clot as the endothelium regrows/repairs
Secondary hemostatic disorder
-delayed hemorrhage (several hours or longer)
Coagulation factors
-Fibrinogen (Factor I)- concentrate on surface to give structure for fibrin
-Tissue Factor (TF; Factor III)- triggers secondary hemostasis
-Ca2+ (Factor IV)
-Prothrombin (Factor II) – modulates procoagulation
-Factors VII, IX, X,XI XII
Coagulation cofactors
**from platelets, assist other factors
-Factor V
-Factor VIII
Intrinsic pathway
-includes everything except TF and VIIa
Extrinsic pathway
-includes common pathway and TF and VIIa
-begins when TF (released from damages tissues) and VIIa combine
Common pathway
-Factor X and its following factors
-Prothrombin becomes thrombin which recruits fibrinogen to make fibrin
>also activates many different areas
Prolonged PTT vs.normal PT
-Normal PT indicates that common pathway is not an issue
-narrows it down to intrinsic pathway
Three stages of secondary hemostasis
**all stages are overlapping, not sequential
1.Initiation
2. Amplification
3. Propagation
Initiation of secondary hemostasis
-mainly extrinsic pathway
-start of thrombin production
Amplification of secondary hemostasis
-increasing levels of thrombin production
Propagation of secondary hemostasis
-mainly intrinsic pathway
-maximized thrombin production
Pathway Steps
-TF released and attaches to cell surface
-TF combines to VII which forms the tenase complex?
-Activates factor X
-Factor X combines with Factor V
-Results in activation of Prothrombin (Factor II) to Thrombin (factor IIa)
>leads to activation of fibrinogen (factor I) to fibrin (factor Ia)
>also leads to intrinsic pathway activation
Prothrombinase complex
-Includes Xa and Va which results in prothrombin to thrombin activation
Factor XII
-physically cleaved by collagen fibres
-activates Factor XI and intrinsic pathway
Factor II vs. Factor XII activation of intrinsic
-factor II is better at activating the intrinsic pathway than Factor XII
Making factors sticky
1.Platelets have Ca 2+ on surface
2.Factors II, IX, VII, X (1972) gain negative charge
3.Postive and negative charges attract= sticky
Gamma-glutamyl carboxylase
-adds negative charges to help factors II, VII, IX, and X stick to the positively charged platelets
Why are platelets positively charged?
-because they are covered in Ca2+
Factor XIII
-helps to crosslink fibrin strands into rafts
-activated by factor IIa (thrombin)
Inhibitors of coagulation
-factors that prevent clotting
Antithrombin
-inactivates thrombin
-can be measured in the plasma
What enhances antithrombin?
-enhanced by heparan sulfate (produced by endothelial cells and injections of heparin)
Nephrotic syndrome
-antithrombin loss
-results in hypercoagulation; inappropriate thrombus formation and death
Thrombomodulin
-binds thrombin and inhibits its function
-activates protein C and cofactor protein S which inactivates cofactors Va and VIIIa
Tissue factor pathway inhibitor
-inhibits tissue factor
-how endothelial cells and platelets release factors that work to finely tune a precise clot only in the area of damaged endothelium
Fibrinolysis
-Tissue plasminogen activator (tPA) is released from damaged endothelial cells and converts circulating plasminogen to plasmin
>Plasmin has high affinity for fibrin and cleaves it into fibrin degradation products which can me measured
Clinical manifestations of defects in secondary hemostasis
1.Ecchymoses
2. Internal and external hemorrhage
Tests for secondary hemostasis disorders
-PT and PTT tests
-FDP measurement- assesses degree of fibrinolysis (how much coagulation is occurring?)
-Antithrombin measurement- excessive loss leading to hypercoagulation
Hemophilia A
-deficiency of factor VIII
-detected in PTT
Hemophilia B
-deficiency in factor IX
-detected in PTT
Vitamin K antagonist toxin
-detects via prolongation in both PT and PTT
Hepatic failure
-insufficient coagulation factor synthesis
-can result in prolongation in both PT and PTT
DIC
-consumptive coagulopathy
-a number of potential causes
-results in both hypocoagulation and hypercoagulation, thrombocytopenia, induced thrombopathia, erythrocyte fragmentation
