Coagulation
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Questions and Answers

What does formed plasmin degrade fibrinogen or fibrin into?

  • Fibrin degradation products (correct)
  • Thrombin
  • Clotting factors
  • Platelet aggregates

    • What is the reference range for bleeding time using the Ivy method?

  • 1-5 minutes
  • 2-8 minutes
  • 1-7 minutes (correct)
  • 1-6 minutes

    • Which of the following conditions would NOT likely prolong bleeding time?

  • Von Willebrand's disease
  • Thrombasthenia
  • Normal platelet function (correct)
  • Bernard Soulier syndrome

    • What is the primary role of plasminogen activator inhibitor 1 (PAI-1)?

    <p>Inhibits tPA and TcuPA</p> Signup and view all the answers

    Which of the following is a source of false positive in bleeding time assessment?

    <p>Using a BP cuff maintained too high</p> Signup and view all the answers

    What is the normal reference range for the activated coagulation time?

    <p>20 to 35 seconds</p> Signup and view all the answers

    What causes the Bernard-Soulier syndrome?

    <p>Deficiency in platelet receptor IB/IX/V</p> Signup and view all the answers

    What is a potential consequence of insufficient endothelial function?

    <p>Inadequate regulation of hemostasis</p> Signup and view all the answers

    Which method is NOT a platelet function test?

    <p>Lee-White Method</p> Signup and view all the answers

    What induces endothelial cell activation?

    <p>Cytokines</p> Signup and view all the answers

    What does the Ivy Method primarily assess?

    <p>Platelet adhesion</p> Signup and view all the answers

    Which component is critical in thrombus formation?

    <p>Platelet receptors</p> Signup and view all the answers

    What is the primary purpose of the fibrinolytic system in hemostasis?

    <p>Reduce clot size</p> Signup and view all the answers

    Which test is used to evaluate the intrinsic pathway of coagulation?

    <p>Activated Partial Thromboplastin Time (aPTT)</p> Signup and view all the answers

    What can excessive consumption of platelets lead to?

    <p>Decreased platelet count</p> Signup and view all the answers

    What happens to platelets upon activation by prostacyclin?

    <p>They undergo dramatic shape change and release granules.</p> Signup and view all the answers

    What is the role of nitric oxide in the hemostatic process?

    <p>It serves as a product of eNOS.</p> Signup and view all the answers

    What protein is deficient in von Willebrand disease (vWD)?

    <p>von Willebrand factor.</p> Signup and view all the answers

    Which mechanism do heparin-like molecules utilize?

    <p>They bind and activate antithrombin III.</p> Signup and view all the answers

    What is the primary function of thrombomodulin?

    <p>To bind thrombin and modulate coagulation.</p> Signup and view all the answers

    Which coagulation factors are inhibited by the activated protein C/S complex?

    <p>Va and VIIIa.</p> Signup and view all the answers

    How does tissue factor pathway inhibitor function?

    <p>It binds tissue factor and inhibits the complex with factor VIIa.</p> Signup and view all the answers

    What effect does tissue plasminogen activator (tPA) have within the coagulation process?

    <p>It acts as a counterregulatory mechanism promoting fibrinolysis.</p> Signup and view all the answers

    What is the mechanism through which normal endothelium acts as an anticoagulant?

    <p>By preventing exposure of coagulation factors to tissue factor.</p> Signup and view all the answers

    What is required as a cofactor for the activation of protein C?

    <p>Protein S.</p> Signup and view all the answers

    What does plasmin do to blood clots?

    <p>Breaks down the fibrin mesh within the clot</p> Signup and view all the answers

    Which factor does Antithrombin III inhibit?

    <p>Thrombin and other serine proteases</p> Signup and view all the answers

    What activates Protein C and Protein S?

    <p>Binding to vitamin K</p> Signup and view all the answers

    The Tissue Factor Pathway Inhibitor inactivates which type of complexes?

    <p>Tissue factor–factor VIIa complexes</p> Signup and view all the answers

    In which category does the coagulation cascade fall?

    <p>Intrinsic, extrinsic, and common</p> Signup and view all the answers

    What is the role of vitamin K in the coagulation process?

    <p>Acts as a cofactor for protein C and S</p> Signup and view all the answers

    How does the coagulation cascade function in hemostasis?

    <p>By leading to the formation of an insoluble fibrin clot</p> Signup and view all the answers

    What type of proteins are Protein C and Protein S categorized as?

    <p>Vitamin K–dependent proteins</p> Signup and view all the answers

    What is the function of the surface-bound zymogens in the coagulation cascade?

    <p>They are cleaved to form active enzymes</p> Signup and view all the answers

    Which of the following is NOT a characteristic of the coagulation cascade?

    <p>It can occur independently of platelet activation</p> Signup and view all the answers

    What phase of hemostasis is primarily concerned with the formation of a stable fibrin clot?

    <p>Secondary hemostasis</p> Signup and view all the answers

    Which disease is mentioned as an example of a condition related to secondary hemostasis?

    <p>Glanzmann’s thrombasthenia</p> Signup and view all the answers

    What is the purpose of the fibrinolytic system?

    <p>To prevent excessive thrombosis</p> Signup and view all the answers

    What is required for performing platelet function tests?

    <p>Platelet count must be &gt; 75,000</p> Signup and view all the answers

    What role does Thrombin activatable fibrinolysis inhibitor (TAFI) play in fibrinolysis?

    <p>Cleaves C-terminal lysine residues of fibrin</p> Signup and view all the answers

    What is primarily measured during the bleeding time test?

    <p>Time taken for blood vessel constriction and platelet plug formation</p> Signup and view all the answers

    What is a characteristic of α2-antiplasmin compared to plasminogen?

    <p>Its plasma concentration is half that of plasminogen</p> Signup and view all the answers

    Which function is NOT part of secondary hemostasis?

    <p>Formation of a platelet plug</p> Signup and view all the answers

    What occurs during fibrinolysis?

    <p>Fibrin is broken down</p> Signup and view all the answers

    Which of these is a key component involved in the formation of the stable fibrin clot?

    <p>Coagulation factors</p> Signup and view all the answers

    Study Notes

    Fibrinolytic System

    • Fibrinolysis is the breakdown of cross-linked fibrin to prevent excessive thrombosis.
    • Key proteins involved:
      • Plasmin degrades fibrinogen or fibrin
    • Inhibitors of fibrinolysis:
      • Plasminogen activator inhibitor 1 (PAI-1)
      • α2-Antiplasmin (α2-AP)
      • Thrombin activatable fibrinolysis inhibitor (TAFI)

    Platelet Function Tests

    • Bleeding Time
      • Measures time taken for blood vessel constriction and platelet plug formation.
      • Detects defective platelet function.
      • Screening test for acquired and congenital platelet defects.
      • Do not perform if platelet count is < 75,000
      • Reference Range:
        • Ivy: 1-7 minutes
        • Duke: 1-6 minutes
    • Sources of Error:
      • False Positive:
        • BP cuff maintained too high.
        • Incision too deep.
        • Disturbing clot with filter paper (blotting it frequently).
        • Touching incision wound (touch only the tip of the blood during blotting).

    Coagulation Tests

    • Lee-White Method:
      • Used for assessing the ability of whole blood to form a clot.
    • aPTT (Activated Partial Thromboplastin Time):
      • Measures the time it takes for plasma to clot following the addition of a reagent.
      • Includes the intrinsic and common pathways
      • Called "activated" since negatively-charged surface activator (glass or silica) speeds up the rate of reaction.
      • Normal reference range: 20–35 seconds
    • PT (Prothrombin Time):
      • Measures the time taken for plasma to clot after addition of tissue thromboplastin and calcium.
      • Includes the extrinsic and common pathways.
    • INR (International Normalized Ratio):
      • Standardized measure of the extrinsic coagulation pathway.
      • Used to monitor warfarin therapy.
    • TT (Thrombin Time):
      • Measures the time it takes for fibrinogen to clot after the addition of thrombin.
      • Tests the final phase of the coagulation cascade.
    • Test for Fibrinolytic Pathway:
      • Assesses the activity of the fibrinolytic system.
      • Measures plasminogen activator inhibitor-1 (PAI-1) activity.
      • Monitors therapy with fibrinolytic agents.

    Overview of Hemostasis

    • Platelet Activation:
      • Leads to shape change (round discs to flat plates with spiky protrusions).
      • Release of secretory granules.
      • Platelet aggregation occurs.
    • Primary Hemostatic Plug Formation:
      • Forms within minutes.
    • Secondary Hemostasis:
      • Concerned with platelet aggregation and formation of a stable fibrin clot.
      • Involves the interplay of coagulation factors.
    • Glanzmann's Thrombasthenia:
      • A disease involving secondary hemostasis.

    Endothelium

    • Central regulators of hemostasis:
      • Balance between antithrombotic and prothrombotic activities determines thrombus formation or dissolution. -Activated by:
      • Trauma
      • Infectious agents
      • Hemodynamic forces
      • Plasma mediators
      • Cytokines

    Prothrombotic Properties of Endothelium

    • Prostacyclin:
      • Produced by COX-1.
    • Nitric Oxide:
      • Product of eNOS.
    • Adenosine diphosphatase:
      • Degrades ADP.

    Anticoagulant Effects of Endothelium

    • Normal endothelium:
      • Shields coagulation factors from tissue factor in vessel walls..
    • Thrombomodulin and Endothelial Protein C Receptor:
      • Bind to thrombin and protein C, respectively.
      • Thrombin loses its ability to activate coagulation factors and platelets.
      • Thrombin cleaves and activates protein C.
    • Protein C/S complex:
      • Potent inhibitor of coagulation cofactors (Va and VIIIa).
    • Heparin-like molecules:
      • Bind and activate antithrombin III.
      • Inhibits thrombin, factors IXa, Xa, XIa, and XIIa.
    • Tissue Factor Pathway Inhibitor:
      • Binds and inhibits tissue factor/factor VIIa complexes.
      • Requires protein S as a cofactor.

    Fibrinolytic Effects of Endothelium:

    • tPA (tissue plasminogen activator):
      • Counterregulatory mechanism synthesized by endothelium.
      • Converts plasminogen to plasmin, which breaks down the fibrin mesh within the clot.
      • Prevents excessive clot formation and maintains healthy blood flow.

    Exogenous Anticoagulants

    • Antithrombin III:
      • Inhibits the activity of thrombin and other serine proteases (IXa, Xa, XIa, and XIIa).
      • Activated by binding to heparin-like molecules on endothelial cells.
    • Protein C and Protein S:
      • Vitamin K–dependent proteins that act in a complex to inactivate factors Va and VIIIa.
    • Tissue Factor Pathway Inhibitor (TFPI):
      • Produced by endothelium.
      • Inactivates tissue factor–factor VIIa complexes.

    Coagulation Cascade

    • Third arm of homeostatic process:
      • Series of amplifying enzymatic reactions that lead to the deposition of an insoluble fibrin clot.
    • Steps:
      • Each step proteolytically cleaves an inactive proenzyme into an active enzyme, culminating in thrombin formation.
    • Formation of Stable Fibrin Clot:
      • Result of the coagulation cascade.

    Factor Classification

    • Can be:
      • Intrinsic
      • Extrinsic
      • Common
    • Or can be:
      • Surface-bound zymogens
      • Vitamin K-Dependent zymogens
      • Cofactor/Substrates

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