Hemostasis, surgical bleeding, and transfusion Flashcards
T/F: The synthesis of prostacyclin (PGI2) and nitric oxide (NO) is largely responsible for the antiplatelet properties of the intact endothelium.
True; Both of these substances inhibit platelet aggregation, and NO also inhibits platelet adhesion. The vasodilation induced by NO also helps to prevent clot formation by promoting low-turbulence blood flow.
T/F: The vasoconstriction induced by NO helps to prevent clot formation by promoting low-turbulence blood flow.
False; NO induces vasodilation, which does reduce turbulence.
T/F: Platelet aggregation and adhesion are up-regulated by enzymes on the endothelial surface that degrade adenosine diphosphate (ADP).
False: Platelet aggregation and adhesion are prevented by enzymes on the endothelial surface that degrade adenosine diphosphate (ADP).
T/F: The electropositive charges on endothelium and platelets physically prevent adhesion.
False; The electronegative charges on endothelium and platelets physically prevent adhesion.
T/F: Endogenous heparin-like substances are present on the endothelial surface, contributing substantially to anticoagulation.
True
_______________ act as cofactors for antithrombin, which inactivates thrombin and coagulation factors ___, ____, _____, and ____.
Glycosaminoglycans; VIIa, IXa, Xa, and XIa.
T/F: When vessel injury occurs, endothelial cells can express tissue factor (TF) and downregulate expression of thrombomodulin, becoming procoagulant.
True
T/F: Activated endothelial cells release von Willebrand factor (vWF) from the Weibel-Palade bodies, promoting platelet adhesion.
True
Platelets contain _______ _________, ____________ and lysosomes, which store the majority of platelet proteins needed for the initiation of coagulation.
dense granules; α-granules; lysosomes
The ____________ are the largest and most prevalent storage granules, comprising the majority of the storage capacity of platelets.
α-granules
____________ contain a number of proteins involved in platelet aggregation and cohesion, including fibrinogen, factor V (FV), factor VIII (FVIII), fibronectin, vWF, platelet-derived growth factor (PDGF), and platelet factor 4.
α-granules
What is “stored” in dense granules?
Dense granules store calcium, ADP, adenosine triphosphate (ATP), and serotonin.
What is the strongest stimulant for the release of the contents of the dense granules?
Thrombin
T/F: Platelet lysosomes contain predominantly acid hydrolases, responsible for degradation of unwanted cellular debris after complete activation of fibrin formation.
True
T/F: Platelet adhesion is mediated by expression of P-selectin on the activated endothelium and by the platelet receptor GPIbα, which attaches to vWF.
True
T/F: Thrombin, collagen, ADP, and thromboxane A2 promote platelet activation.
True
After the platelet plug bridges the gap between endothelial cells, ___________, produced by neighboring healthy endothelial cells, prevents unwanted expansion of platelet aggregates by decreasing further ADP release.
prostacyclin (PGI2)
The __________ pathway, or “contact activation” pathway, is initiated by the activation of factor ______ and subsequently factor ___ through the exposure of blood to a negatively charged surface.
intrinsic; factor XII (FXII); XI
T/F: Contact proteins such as high-molecular-weight kininogen (HMWK) and prekallikrein interact with FVII to accelerate its activation.
False; Contact proteins such as high-molecular-weight kininogen (HMWK) and prekallikrein interact with FXII to acclerate its activation. The activation of factor VII is by TF present in fibroblasts or other tissue factor–bearing cells.
What catalyzes the activation of factor IX by factor XIa?
calcium
What catalyzes the binding of factor IXa to procoagulant VIIIa?
calcium
What steps in the coagulation cascade are facilitated by calcium?
(intrinsic)
The activation of factor IX by factor XIa.
The binding of factor IXa to procoagulant VIIIa.
(common)
The convertion of prothrombin (factor II) to thrombin (IIa) by factor X.
The stabilization of the fibrin clot by cross-linking strands of fibrin monomer by factor XIIIa .
The ________ pathway is initiated by the activation of factor VII by TF present in fibroblasts or other tissue factor–bearing cells.
extrinsic
Which of the following is not one of the three overlapping phases of the cell-based model of coagulation?
- amplification
- fibrinolysis
- initiation
- propagation
fibrinolysis
T/F: Simultaneous activation of the fibrinolytic system with activation of coagulation is responsible for prevention of excessive fibrin deposition and restoration of nutrient blood flow to affected tissues.
True
Fibrinolysis, in conjunction with _____________ released by surrounding healthy endothelial cells, inhibits unwanted expansion of the fibrin clot.
prostacyclin (PGI2)
___________, an inactive zymogen produced primarily in the kidney and liver, is the principal component of the fibrinolytic system.
Plasminogen
How is plasminogen converted to plasmin?
Plasminogen activators such as tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) convert plasminogen to plasmin.
The activation of the intrinsic pathway also activates plasminogen conversion to plasmin, through the action of kallikrein.
What is the role of plasmin in the fibrinolytic system?
Plasmin degrades fibrinogen and fibrin into soluble fibrin(ogen) degradation products (FDPs).
Plasmin also inactivates other members of the coagulation cascade, such as factors Va and VIIIa, and actively degrades prekallikrein and HMWK. Through these mechanisms, plasmin not only degrades fibrin(ogen) but also downregulates coagulation.
What are the products of fibrin(ogen) degradation?
The products of fibrinogen or fibrin degradation are the FDPs designated fragment X, fragment Y, and fragments D and E.
Plasmin degradation of cross-linked fibrin results in the D-dimer fibrin degradation product.
What does an increase in D-dimers indicate?
increased fibrin production (and degradation) or liver dysfunction (these fragments are removed by mononuclear phagocytes in the liver).
What are the principal inhibitors of coagulation (proteins that enzymatically bind with coagulation factors to form inactive complexes)?
The principal inhibitors of coagulation are antithrombin, heparin, protein C, protein S, and tissue factor pathway inhibitor (TFPI).
Where are platelets formed?
megakaryocytes in bone marrow and in the lungs.
This serine protease inhibitor is responsible for modulation of clot formation and is responsible for 70% to 80% of thrombin inhibition
in the coagulation system.
Antithrombin (AT); AT is a glycoprotein produced in the liver and in endothelial cells that binds aggressively to thrombin.
T/F: A stable thrombin-antithrombin (TAT) complex is removed by the reticuloendothelial system.
True
T/F: The cofactor heparin alters the arginine site of AT and dramatically increases its ability to interact with thrombin.
True; Heparin is a highly sulfated glycosaminoglycan, ranging in molecular weight from 3 to 30 kDa. It is produced primarily in mast cells located in the lung, liver, kidney, heart, and gastrointestinal tract. Heparin causes a conformational change in AT, which increases the activity of AT 1000-fold.
Where is heparin produced in the body?
It is produced primarily in mast cells located in the lung, liver, kidney, heart, and gastrointestinal tract.
Heparin releases ____ _____ ________ _________ from endothelial cells, thereby liberating one of the most effective inhibitors of the factor VIIa-TF complex.
tissue factor pathway inhibitor (TFPI)
T/F: Protein C is a vitamin C–dependent zymogen with primary inhibitory action on factors Va and VIIIa.
False; Protein C is a vitamin K–dependent zymogen with primary inhibitory action on factors Va and VIIIa.
Protein C is activated by __________________ complexes. This reaction is potentiated by the endothelial protein C receptor, which is located mainly in ______ vessels.
thrombomodulin-thrombin; large
When activated protein C is released into circulation, it associates with protein S and is able to inactivate which factors?
factors Va and VIIa.
T/F: Activated protein C is also profibrinolytic, since it inhibits plasminogen activator inhibitor-1 (PAI-1) and indirectly inhibits thrombin-activatable fibrinolysis inhibitor (TAFI) as a result of thrombin inhibition.
True
Tissue factor pathway inhibitor (TFPI) is a group of lipoprotein-bound proteins produced primarily by ________ and _____________ cells.
platelets; endothelial
T/F: In the presence of calcium, tissue factor pathway inhibitor (TFPI) inhibits factor VIIa-TF activation of factor X, thereby
dramatically decreasing the primary cellular initiator of coagulation.
True
What is the importance of calcium in the thrombomodulin–protein C–protein S pathway during the inhibition of coagulation?
In the presence of calcium, tissue factor pathway inhibitor (TFPI) inhibits factor VIIa-TF activation of factor X, thereby
dramatically decreasing the primary cellular initiator of coagulation.