Ex 4: 3 Apr Coagulation Assessment Spring '25 Flashcards
What is the definition of coagulation?
The process that prevents and stops bleeding, involving the transformation of blood from a liquid to a gel.
What is hemostasis?
Normal hemostasis is a balance between clot generation, thrombus formation, and regulatory mechanisms that inhibit uncontrolled thrombogenesis.
What are the goals of hemostasis?
- Limit blood loss from vascular injury
- Maintain intravascular blood flow
- Promote revascularization after thrombosis
What are the two stages of hemostasis?
- Primary Hemostasis
- Secondary Hemostasis
What occurs during primary hemostasis?
Immediate platelet deposition at the endovascular injury site leads to initial platelet plug formation.
What occurs during secondary hemostasis?
Clotting factors are activated, leading to a stabilized clot formed and secured with crosslinked fibrin.
What role do vascular endothelial cells play in hemostasis?
They have antiplatelet, anticoagulant, and fibrolytic effects to inhibit clot formation.
What are the anti-clotting mechanisms of endothelial cells?
- Negatively charged to repel platelets
- Produce platelet inhibitors such as prostacyclin and nitric oxide
- Excrete adenosine diphosphatase, degrading ADP
- Increase protein C, an anticoagulant
- Produce Tissue Factor Pathway Inhibitor (TFPI)
- Synthesize tissue plasminogen activator (t-PA)
What is the lifespan of platelets?
8-12 days.
What describes the structure of inactive platelets?
They circulate as disc-shaped anuclear cells.
What are the three phases of platelet alteration upon endothelial damage?
- Adhesion
- Activation
- Aggregation
What initiates platelet adhesion?
Exposure to extracellular matrix (ECM) proteins.
What triggers platelet activation?
Interaction with collagen and tissue factor (TF), causing the release of granular contents.
What do alpha granules in platelets contain?
- Fibrinogen
- Factors V & VIII
- von Willebrand factor (vWF)
- Platelet-derived growth factor
- More
What do dense bodies in platelets contain?
- ADP
- ATP
- Calcium
- Serotonin
- Histamine
- Epinephrine
What is the Extrinsic Pathway in hemostasis?
The initiation phase of plasma-mediated hemostasis that begins with endothelial injury, exposing TF to the plasma.
What is the role of the TF/VIIa complex?
It binds to and activates factor X, converting it to Xa, and also activates factor IX in the intrinsic pathway.
What is the intrinsic pathway’s current understanding in hemostasis?
It plays a minor role in initiation and is more of an amplification system for thrombin generation initiated by the extrinsic pathway.
What activates factor XII in the intrinsic pathway?
Contact with a negatively charged surface.
What is the final common pathway in hemostasis?
It begins with factor Xa binding with Va to form the prothrombinase complex, converting prothrombin into thrombin.
What stabilizes the clot during hemostasis?
Fibrin molecules crosslink to form a mesh that stabilizes the clot.
What are the four major coagulation counter-mechanisms?
- Fibrinolysis
- Tissue factor pathway inhibitor (TFPI)
- Protein C system
- Serine Protease Inhibitors (SERPINs)
What is the role of fibrinolysis?
Endovascular tPA and urokinase convert plasminogen to plasmin, which breaks down clots.
What does the Protein C system inhibit?
Factors II, Va, and VIIIa.
What are the common bleeding disorders?
- Von Willebrand’s Disease
- Hemophilia
- Drug-induced bleeding
- Liver disease
- Chronic renal disease
- Disseminated Intravascular Coagulation
- Trauma-induced coagulopathy
What is the most common inherited bleeding disorder?
Von Willebrand’s Disease.
What characterizes Hemophilia A?
Factor 8 (VIII) deficiency, occurring in 1 in 5,000.
What characterizes Hemophilia B?
Factor 9 (IX) deficiency, occurring in 1 in 30,000.
What are the lab findings for Hemophilia?
Normal PT, platelets, bleeding time; prolonged PTT.
What is the primary source of coagulation factors?
The liver.
What is Disseminated Intravascular Coagulation (DIC)?
A pathological hemostatic response causing excessive activation of the extrinsic pathway, leading to multi-organ dysfunction.
What triggers Trauma-Induced Coagulopathy (TIC)?
Acidosis, hypothermia, and/or hemodilution.
What is Thrombophilia?
An inherited or acquired predisposition for thrombotic events.
What is the Factor V Leiden mutation?
A mutation leading to activated protein C resistance, present in 5% of the Caucasian population.
What is Antiphospholipid Syndrome?
An autoimmune disorder characterized by recurrent thrombosis and pregnancy loss.
What does the Prothrombin Time (PT) test assess?
Integrity of the extrinsic and common pathways, reflecting deficiencies in factors I, II, V, VII, and X.
What does the Activated Partial Thromboplastin Time (aPTT) test assess?
Integrity of the intrinsic and common pathways, sensitive to deficiencies in factors VIII and IX.
What is the purpose of the anti-factor Xa activity assay?
Provides a functional assessment of heparin’s anticoagulant effect.
Fill in the blank: The platelet count is a standard _______.
component of coagulation labs.
What does the intrinsic pathway assess?
Integrity of intrinsic and common pathways
Which factors are the intrinsic pathway more sensitive to?
Factor 8 & 9 (VIII, IX)
What is the purpose of the anti-factor Xa activity assay?
Provides functional assessment of heparin’s anticoagulant effect
What is the normal platelet count?
Plt count >100,000 plts/microliter
What does Activated Clotting Time (ACT) measure?
Addresses intrinsic and common pathways, measures responsiveness to heparin
What is the normal range for ACT?
107 +/- 13 seconds
What does Heparin Concentration Measurement determine?
Perioperative heparin concentration
What do viscoelastic coagulation tests measure?
All aspects of clot formation from early fibrin generation to clot retraction & fibrinolysis
Name two types of viscoelastic coagulation tests.
- TEG (Thromboelastogram)
- ROTEM (Rotational Thromboelastometry)
What do antiplatelet agents do?
Inhibit platelet aggregation and/or adhesion
Name the three main classes of antiplatelet agents.
- Cyclooxygenase Inhibitors
- P2Y12 receptor antagonists
- Platelet GIIb/IIIa R antagonists
What do cyclooxygenase inhibitors block?
Cox 1 from forming TxA₂
What is the duration of anti-platelet effects of ASA after discontinuation?
7-10 days
What is the primary anticoagulant that is a vitamin K antagonist?
Warfarin
What is the half-life of Warfarin?
40 hours
What is required for Warfarin to achieve therapeutic INR?
Usually requires heparin until therapeutic effect achieved
What is the reversal agent for Warfarin?
Vitamin K
What does unfractionated heparin do?
Binds to antithrombin, directly inhibits thrombin and Xa
What is the monitoring requirement for unfractionated heparin?
Close monitoring required
What is the half-life of Fondaparinux?
17-21 hours
What are direct thrombin inhibitors?
Bind/block thrombin in both soluble & fibrin-bound states
What is the first Direct Oral Anticoagulant (DOAC)?
Dabigatran (Pradaxa)
What is the purpose of thrombolytics?
Used to dissolve blood clots
Name two categories of thrombolytics.
- Fibrin-Specific
- Non-Fibrin-Specific
What are lysine analogues used for?
Bind & inhibit plasminogen from binding to fibrin
What are two examples of antifibrinolytics?
- Epsilon-amino-caproic acid (EACA)
- Tranexamic Acid (TXA)
What is the standard preoperative guideline for low risk patients taking Warfarin?
Should d/c 5 days prior to surgery & restart 12-24h postop
What is the emergency reversal agent for excessive bleeding due to Warfarin?
Prothrombin Complex Concentrates
True or False: Surgery is contraindicated within 10 days of thrombolytic treatment.
True
What do procoagulants do?
Used to mitigate blood loss
What is the half-life of Bivalirudin?
Shortest HL of direct thrombin inhibitors
What is the antidote for Dabigatran (Pradaxa)?
Idarucizumab
What do DOAC factor Xa inhibitors include?
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
- Edoxaban (Savaysa)
