Term
| What causes transient arteriolar vasoconstriction? |
|
Definition
1) reflex neurogenic
2) endothelin (secreted by endothelial cells) |
|
|
Term
|
Definition
| platelets - adhesion, activation, aggregation |
|
|
Term
|
Definition
| addition of coagulation cascade activation via tissue factor & platelet phospholipids => thrombin & fibrin |
|
|
Term
| What are the 4 normal antithrombotic mediators? |
|
Definition
1) plasma membrane
2) antiplatelet
3) anticoagulant
4) fibrinolytic t-PA (tissue-type plasminogen activator) |
|
|
Term
Function
plasma membrane as a antithrombotic mediator |
|
Definition
|
|
Term
| What are the 3 antiplatelet antithrombotic mediators? |
|
Definition
| 1) prostacyclin (PGI2)
2) NO
3) ADPase |
|
|
Term
| What are the 3 anticoagulant antithrombotic mediators? |
|
Definition
1) heparin-like molecules
2) thrombomodulin
3) TFPI (tissue factor pathway inhibitor) |
|
|
Term
Function
heparin-like molecules |
|
Definition
| bind & amplify action of antithrombin III => inhibition of thrombin & other activated coagulation factors |
|
|
Term
|
Definition
| binds thrombin => activation of protein C & protein S => degradation of Va & VIIIa |
|
|
Term
|
Definition
| inhibits tissue factor-mediated coagulation (Xa & VIIa complex) |
|
|
Term
| What are the 3 prothrombotic mediators in an endothelial injury or activation? |
|
Definition
1) proplatelet
2) procoagulant
3) anti-fibrinolytic |
|
|
Term
What is the proplatelet mediator?
How does it work? |
|
Definition
| von Willebrand factor (vWF) => mediation of platelet adhesion to the ECM |
|
|
Term
What is the procoagulant?
How does it work? |
|
Definition
| tissue factor => activation of extrinsic pathway of the coagulation cascade |
|
|
Term
| What is the anti-fibrinolytic? |
|
Definition
| PAIs (plasminogen activator inhibitors) |
|
|
Term
| What does the primary hemostatic plug consist of? |
|
Definition
|
|
Term
| What allows for platelet adhesion? |
|
Definition
| platelet GpIb - vWF - ECM |
|
|
Term
| How do α granules encourage platelet secretion/activation? |
|
Definition
| => multiple proteins inc. vWF, V, VII, fibrinogen, fibronectin, & platelet factor 4 |
|
|
Term
| How do δ granules (dense bodies) encourage platelet secretion/activation? |
|
Definition
| => substrates s.a. Ca2+ & ADP (for coagulation cascade & platelet activation/aggregation respectively) |
|
|
Term
| What are translocated to platelet surfaces for the coagulation cascade? |
|
Definition
|
|
Term
| What is synthesized by arachidonic acid to encourage platelet secretion/activation? |
|
Definition
|
|
Term
| What 4 things enhance platelet aggregation? |
|
Definition
| 1) ADP
2) TxA2
3) thrombin
4) fibrinogen |
|
|
Term
| What does fibrinogen bind to enhance platelet aggregation? |
|
Definition
| GpIIb-IIIa receptors (exposed during platelet activation) |
|
|
Term
| What 3 endothelial factors inhibit platelet aggregation? |
|
Definition
| 1) prostacyclin (PGI2)
2) NO
3) ADPase |
|
|
Term
|
Definition
| amplifying series of circulating, inactive proenzymes which are subsequently cleaved to form activated enzymes at sites of endothelial injury. |
|
|
Term
| *What are the 5 components of reaction complexes in the coagulation cascade? |
|
Definition
| 1) inactive coagulation factor (substrate)
2) previously activated coagulation factor in cascade
3) Ca2+
4) phospholipid surface (provided by platlets)
5) cofactor |
|
|
Term
| What is formed by the common pathway connecting extrinsic & intrinsic pathway of the coagulation cascade? |
|
Definition
|
|
Term
Function
Thrombin (IIa) in the coagulation cascade |
|
Definition
1) proteolytically cleaves soluble fibrinogen => insoluble fibrin (Ia)
2) activates XIII => XIIIa & other coagulation factors |
|
|
Term
| What does thrombin do to platelets? |
|
Definition
| enhances platelet activation & aggregation |
|
|
Term
Function
Thrombin (IIa) on endothelial cells |
|
Definition
1) stimulates leukocyte adhesion
2) modulates procoagulant & anticoagulant functions |
|
|
Term
| What are the 4 anticoagulants? |
|
Definition
1) antithrombin III
2) protein C
3) protein S
4) TFPI |
|
|
Term
|
Definition
| inhibits thrombin & other activated coagulation factors |
|
|
Term
| What markedly enhances AT III function? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What activates proteins C & S? |
|
Definition
| activated by thrombomodulin-thrombin complex |
|
|
Term
|
Definition
| inhibits tissue factor-mediated coagulation |
|
|
Term
| What is the enzyme of the fibrolytic system? |
|
Definition
|
|
Term
|
Definition
| degrades fibrin => fibrin split products |
|
|
Term
| What is plasmin generated from? |
|
Definition
|
|
Term
| How is plasmin generated from plasminogen? |
|
Definition
1) *t-PA
2) u-PA (urokinase-like plasminogen activator)
3) streptokinase |
|
|
Term
| *What produces t-PA (tissue-type plasminogen activator) |
|
Definition
|
|
Term
| *When is t-PA most effective? |
|
Definition
|
|
Term
| What counteracts the activity of plasmin? |
|
Definition
| inhibitors of plasmin & plasminogen activators |
|
|
Term
| In blood collection, what is whole blood? |
|
Definition
|
|
Term
| What blood collection tube is used in whole blood collection? |
|
Definition
|
|
Term
| Why would whole blood blood need to be collected? |
|
Definition
|
|
Term
|
Definition
| liquid component of blood (virtually cell-free supernatant of anticoagulated blood obtained after centrifugation) |
|
|
Term
| What blood collection tube is used for plasma collection? |
|
Definition
| light blue top with sodium citrate |
|
|
Term
| Why would plasma need to be collected? |
|
Definition
|
|
Term
|
Definition
| liquid (extracellular) portion of blood after coagulation is complete (plasma without clotting factor) |
|
|
Term
| What blood collection tube is used for serum? |
|
Definition
| red top w/ no additive (or one with clot activators) |
|
|
Term
| Why would serum need tobe collected? |
|
Definition
| routine chemistry & serology |
|
|
Term
| What are the 3 ways to evaluate platelets? |
|
Definition
1) platelet count
2) examination of peripheral blood smear ± bone marrow
3) platelet function assays |
|
|
Term
| What is examination of the peripheral blood smear ± bone marrow looking for with platelets? |
|
Definition
| evidence of abnormalities in destruction/production |
|
|
Term
Function
platelet function assays |
|
Definition
1) test for abnormalities in platlet adhesion & aggregation (primary hemostasis
2) differentiate b/w platelet abnormalities due to aspirin or other causes |
|
|
Term
| What have platelet function assays replaced? |
|
Definition
|
|
Term
*def
intrinsic & extrinsic pathways of blood coagulation |
|
Definition
| interconnected, self-amplifying pathways by which activation of the coagulation cascade can be initiated |
|
|
Term
| *Is the intrinsic or extrinsic pathway of blood coagulation more important in vivo? |
|
Definition
|
|
Term
| *What do both the intrinsic & extrinsic pathways of blood coagulation lead to? |
|
Definition
| common pathway of the coagulation cascade & activation of fibrinolytic system |
|
|
Term
Which of the intrinsic and extrinsic pathways of blood coagulation is the contact activation pathway?
tissue factor pathway? |
|
Definition
I: contact activation
E: tissue factor |
|
|
Term
| What is required for the intrinsic (contact activation) pathway? |
|
Definition
| substances found within the vasculature |
|
|
Term
| What is required for the extrinsic (tissue factor) pathway? |
|
Definition
| tissue factor (which is extrinsic to the vasculature) for initiation |
|
|
Term
Blood Coagulation Pathways
[image] |
|
Definition
1) intrinsic pathway
2) extrinsic pathway
3) final common pathway |
|
|
Term
|
Definition
| measurement of the integrit of the extrinsic & common pathways of coagulation (VII, X, V, II, & I) |
|
|
Term
| What are the factors contributing to the time it takes for a fibrin clot to form in a PT test? |
|
Definition
| 1) citrated, platelet poor plasma
2) tissue factor
3) phospholipid (sub for platelet membrane)
4) excess Ca2+ (toreverse effects or citrate) |
|
|
Term
| What are the 3 frequent causes of PT prolongation? |
|
Definition
1) deficiency of Vit K
2) decreased synthesis of coagulation factors
3) increased consumption of coagulation factors |
|
|
Term
| Why would Vit K deficiency lead to PT prolongation? |
|
Definition
| it's a cofactor for the γ-carboxylation of glutamate in synthesis of factors II, VII, IX, & X (& other proteins) |
|
|
Term
| Who are at risk for Vit K deficiency? |
|
Definition
1) infants
2) use of coumarin-derived anticoagulants (s.a. warfarin)
3) fat malabsorption |
|
|
Term
def
international normalized ration (INR) |
|
Definition
| calculation used to standardize the PT b/w various laboratories |
|
|
Term
def
aPTT (activated partial thrombin time) |
|
Definition
| measurement of the integrity of the intrinsic & common pathways of coagulation (XII, XI, IX, VIII, X, V, II, I) |
|
|
Term
| What are the factors contributing to the time it takes for a fibrin clot to form in an aPTT test? |
|
Definition
| 1) citrated, platelet-poor plasma
2) particulate contact activator
3) phospholipid (sub for platelet membrane)
4) excess Ca2+ (to reverse effects of citrate) |
|
|
Term
| What are the 6 frequent causes of aPTT prolongation? |
|
Definition
1) hereditary deficiency of any of the clotting factors (except VII & XIII)
2) acquired inhibitors to the above coagulation factors
3) antiphospholipid (anticardiolipin) Ab
4) heparin therapy (or contamination)
5) liver disease and/or Vit K deficiency
6) increased consumption of coagulation factors |
|
|
Term
What is deficient in hemophilia A?
hemophilia B? |
|
Definition
|
|
Term
| What factor is most likely to acquire an inhibitor to cause prolonged aPTT? |
|
Definition
|
|
Term
| What does thrombin activate in the intrinsic pathway? |
|
Definition
|
|
Term
| What does thrombin activate in the extrinsic pathway? |
|
Definition
|
|
Term
| What does thrombin act on in the combined pathway? |
|
Definition
|
|
Term
Which test is used to monitor heparin therapy?
coumadin therapy? |
|
Definition
heparin: aPTT
coumadin: PT |
|
|
Term
| What are the factors contributing to the time it takes for a fibrin clot to form in a TT (thrombin time) test |
|
Definition
1) citrated, platelet-poor plasma
2) thrombin |
|
|
Term
| What are the 2 frequent causes of prolongation of thrombin time? |
|
Definition
1) deficiencies/defects in fibrinogen (inherited or acquired)
2) inhibitors of thrombin |
|
|
Term
Function
fibrinogen assays |
|
Definition
| determine qualitative & functional abnormalities of fibrinogen |
|
|
Term
| What are the 3 causes of thrombosis? |
|
Definition
1) *endothelial injury or dysfunction
2) abnormal blood flow (stasis & turbulence)
3) hypercoagulability |
|
|
Term
| How does abnormal blood flow (stasis & turbulence) cause thrombosis? |
|
Definition
| => disruption of laminar flow => endothelial injury/dysfunction, platelet adhesion, & accumulation of activated coagulation |
|
|
Term
| *What causes a venous thrombi? |
|
Definition
|
|
Term
| What are the 2 types of hypercoagulability? |
|
Definition
1) primary (hereditary)
2) secondary (acquired) |
|
|
Term
| What are the 4 causes of primary hypercoagulability? |
|
Definition
1) factor V (Leiden) mutation
2) prothrombin mutation
3) increased homocysteine (inherited enzyme abnormalities)
4) anticoagulant deficiencies (AT II, proteins C & S) |
|
|
Term
| Why does factor V mutation cause hypercoagulability? |
|
Definition
| it's unable to be lysed by protein C |
|
|
Term
Sx
anticoagulant deficiencies |
|
Definition
| recurrent venous thrombi & pumlonary thromboemboli in young adulthood |
|
|
Term
| What are the 5 causes of secondary hyercoagulability? |
|
Definition
1) malignant neoplasms
2) oral contraceptive use/pregnancy
3) smoking
4) heparin-induced thrombocytopenia syndrome type 2 (HIT)
4) antiphospholipid (anticardiolipin) Ab syndrome (kupus anticoagulant syndrome) |
|
|
Term
| What do malignant neoplasms lead to cause hypercoagulability? |
|
Definition
| procoagulants (i.e. Trousseau syndrome) |
|
|
Term
|
Definition
| migratory thrombophelbitis |
|
|
Term
| Why do pregnancy/oral contraceptives cause hypercoagulability? |
|
Definition
|
|
Term
|
Definition
| serious limb & life threatening complication of heparin therapy occuring 5-10 days post exposure |
|
|
Term
| How does HIT syndrome cause hypercoagulability? |
|
Definition
| Ab complexes form b/w heparin & platelet factor IV => activation platelets by complexes binding their Fc receptors => amplification of the process, as well as endothelial cells => increased risk of thrombosis involving large blood vessels & decreased platelet count (due to condumption & increased splenic clearance) |
|
|
Term
| What is the pathogenesis of antiphospholipid (anticardiolipin) Ab syndrome? |
|
Definition
| Ab formed against phospholipids of certain plasma protein epitopes exposed by phospholipid binding (some coagulation factors & anticoagulants) |
|
|
Term
Effect
antiphospholipid (anticardiolipin) Ab syndrome in vitro |
|
Definition
|
|
Term
Effect
antiphospholipid (anticardiolipin) Ab syndrome in vivo |
|
Definition
|
|
Term
| What are the 2 classifications of antiphospholipid (anticardiolipin) Ab syndrome? |
|
Definition
1) primary (de novo)
2) secondary (in associated with an autoimmune diease i.e. SLE) |
|
|
Term
Sx
antiphospholipid (anticardiolipin) Ab syndrome |
|
Definition
recurrent thromboembolic episodes
pregnancy complication
thrombocytopenia |
|
|
Term
| How does a medical examiner tell the difference b/w a thrombi & a postmortem clot? |
|
Definition
post mortem clot:
1) gelatinous
2) not attached to the vascular wall
3) evidence of blood settling - dark red layer at bottom, yellow "chicken fat" layer at top
thrombi:
1) firm
2) attached to vascular wall
3) evidence of blood flow - alternating layers of platelets/fibrin (pale pink) with RBCs (dark red) |
|
|
Term
| Are thrombi more conspicuous in arterial or venous circulation? |
|
Definition
|
|
Term
| What are the 2 subtypes of thrombi? |
|
Definition
1) mural thrombi
2) vegetations |
|
|
Term
|
Definition
| thrombi adherent to the walls of large chambers |
|
|
Term
|
Definition
| thrombi formed on the heart valves |
|
|
Term
| Where are the common arterial sites of thrombi? |
|
Definition
| coronary, cerebral, & femoral arteries |
|
|
Term
| *What are the common sites for venous thrombi? |
|
Definition
| deep leg & pelvic veins (phlebothrombosis) |
|
|
Term
| What are the 4 possible outcomes of a thrombus? |
|
Definition
1) dissolution (resolution)
2) propagation
3) embolization
4) organization |
|
|
Term
def
dissolution of a thrombus |
|
Definition
| complete degradation by the fibrinolytic system |
|
|
Term
def
propagation of a thrombus |
|
Definition
| enlargement of the thrombus |
|
|
Term
def
emboliation of a thrombus |
|
Definition
| detatchment or fragmentation & travel to a distant site |
|
|
Term
def
organization of a thrombus |
|
Definition
| inflammation & repair process where inflammation occurs then ingrowth of granulation tissue => focal thickening of the vascular intima & recanalization |
|
|
Term
|
Definition
| capillaries of the granulation tissue anastamose & reestablish blood flow thru the thrombus |
|
|
Term
| What are the 2 consequences of a thrombus? |
|
Definition
1) Vascular obstruction
2) embolism |
|
|
Term
| What does a venous thrombus vascular obstruction cause? |
|
Definition
|
|
Term
| What does a venous thrombus arterial obstruction cause? |
|
Definition
| infarction (ischemic necrosis) |
|
|
Term
| Where does a venous thrombus embolism go? |
|
Definition
| lungs (esp. from deep leg veins) |
|
|
Term
| Where does an arterial thrombus embolism go? |
|
Definition
| kidneys, spleen, brain, extremities |
|
|
Term
| What causes disseminated intravascular coagulation (DIC)? |
|
Definition
| massive systemic activation of coagulation => multiple widespread microthrombi => consumption of platelets & coagulation factors, plus activation of fibrinolysis => hemorrhagic diathesis |
|
|
Term
| What are the frequent lab findings in a DIC? |
|
Definition
decreased platelet count
prolinged PT & aPTT
increased fibrin degradation products |
|
|
