Hemostasis & Coag Flashcards
Hemostasis
general
Innate, stepwise processes within the body that occurs following vessel injury → clot formation and cessation of bleeding
hemostasis
steps
Primary and secondary
Primary hemostasis
Platelet adhesion, activation, and aggregation to the damaged vascular endothelium, forming a plug (weak) that stops the bleeding temporarily
Secondary hemostasis
Activation of the coagulation cascade resulting in the formation of a more stable plug (strong fibrin clot)
Vasoconstriction
general
The blood vessel transiently constricts tolimit blood flow to the area
Vessel wall injury and constriction:
1. Site of injury
2. Constriction caused by endothelin release
3. Exposed collagen fibers
what drives vasoconstriction
What drives vasoconstriction?
* Neural stimulation reflex:innate contraction of the vascularsmooth muscles upon injury
* Endothelin:a vasoconstrictorsecreted from the damaged endothelial cells
* Thromboxane A2: a vasoconstrictor released fromactivated platelets
Primary Hemostasis
Following an endothelialcell injury, the following processes occur with theplateletsto form a temporary platelet plug:
Adhesion
Activation
Aggregation
Secretion
Primary Hemostasis
Platelet Adhesion
Platelets adhere to the site of injury with exposure to subendothelial components
What drives adhesion?
Platelet Gplb receptors tightly bind von Willebrand factor (vWF) which is released from injured endothelial cells
Other adhesion interactions with collagen, glycoprotein receptors, and tyrosine kinase receptors leading to adherent “activated” platelets
primary hemostasis
von Willebrand factor
glycoprotein that serves as the initial stationary foundation for clot formation
primary hemostasis
platelet activation
Activatedplateletsenhance further platelet adhesion and aggregation, and stimulatesecretion
Primary Hemostasis - Platelet Activation
Platelet activators
potent and weak
Potent platelet activators:
Thrombin: produced in the coagulation cascade
Collagen: interacts withplatelets at the site of injury
Weaker platelet activators:
ADP: acts in an autocrine fashion → released byplateletsto help activate otherplatelets
Epinephrine
Primary Hemostasis - Platelet Activation
Activatedplatelets will..
Undergo shape change to become an elongated pseudopod → new shape is extremely adherent
Activate theirGpIIb/IIIareceptors
Release their granules (alpha and dense)
Primary Hemostasis -
Platelet Aggregation
GpIIb/IIIareceptorspresent on the activated plateletsbegin binding to fibrinogen
Fibrinogen
Symmetricalmolecule
Canbind2plateletssimultaneously forming bridges betweenplatelets → platelet aggregation and formation of aprimary hemostatic plug
Primary Hemostasis - Platelet Secretion
Activated platelets release their granules (alpha and dense)
Primary Hemostasis - Platelet Secretion
Functions of secreted substances from granules of platelets
Recruit and activate additionalplatelets
Stimulate expression of GpIIb/IIIa onplatelets→ enhancedaggregation
Promotevasoconstriction
Stimulate the process of vascular repair via fibroblast/smooth muscle cellrecruitment
Contribute to initiation of thecoagulation cascade
Secondary Hemostasis – Coagulation Cascade
general
Series of reactions that ultimately generates a strong, cross-linkedfibrinclot
A number ofcoagulation factors undergo sequential activation by 1 of the 2 pathways
Secondary Hemostasis – Coagulation Cascade
Extrinsic pathway
Extrinsic pathway: primarily responsible forinitiationof the cascade; activated by tissue factor (factor 3) released by injured endothelial cells
ends with factor 10.
Secondary Hemostasis – Coagulation Cascade
intrinsic
Intrinsic pathway: primarily involved inamplificationof the cascade; activated by negatively charged collagen in the subendothelial matrix
starts with 12 ends with 10
Secondary Hemostasis – Coagulation Cascade
Common pathway:
Common pathway:
The extrinsic and intrinsic pathways join together to form the final common pathway when factor X is activated
Formation of thefibrinclot occurs at the end of the common pathway
starts with 10
ends with factor 13 which is fibrin clot
where do the Factors come from?
The liver is responsible for the formation of most factors (hepatocytes)
Factors XIII, XII, XI, X, IX, VII, V, II, and I
Exceptions:
Factor III and VIII originate from endothelial cells
Factor IV (calcium ion) is freely available in plasma
there is no factor 6
as zymogens
inactive form of factors for coagulation
Become activated → act as a catalyst to cleave the next zymogen
Zymogen to enzyme activation was denoted with the letter a – Example: XII → XIIa
which factors belong to which pathways
Pathway Factors
Extrinsic pathway: III and VII
Intrinsic pathway: XII, XI, IX, and VIII
Common pathway: X, V, II, I, and XIII
vitamin K
general
Lipid cofactor that is required for normal blood clotting
Primarily synthesized in the colon as a byproduct of bacteria
Activated by epoxide reductase in theliver
Vitamin K-dependent factors:
Factors II, VII, IX, X
Undergo carboxylation to become functional
Inhibition of Coagulation
general
The body produces several substances that inhibit platelet binding,aggregation, andsecretion = natural anticoagulants
natural anticoagulants
Tissue factor pathway inhibitor (TFPI)
Inhibits the activation of factor X
Located primarily on the surface of microvascular endothelial cells
natural anticoagulants
Antithrombin III
Natural circulating anticoagulant produced by theliver
Inhibits activated forms of factors II, IX, and X
natural anticoagulants
ProteinsC and Protein S
C:
Vitamin K-dependent factors produced by theliver
Protein C cleaves and inactivates factors V and VIII
S:
Vitamin K-dependent factors produced by theliver
Augments the activity of protein C
Fibrinolytic Phase
The fibrinolytic system functions to remove the clot after the vasculature is repaired
Prevents excessive fibrin deposition
This process is accomplished primarily by plasmin
Fibrinolytic Phase
Plasmin
Plasmin
Cleaves fibrin fibers (fibrinolysis) to form fibrin-degradation products
Cleaves other clotting factors (V, VIII, IX and X)
Plasminogen is activated →converted to plasmin by:
Tissue plasminogen activator (tPA)
Urine plasminogen activator (uPA)aka urokinase
Both are secreted by endothelial cells
Coagulation Studies
general
Group of hematologic studies that reflect the function of blood vessels,platelets, and coagulation factors
Uses of coagulation studies
Evaluation of abnormal bleeding orthrombosis
Pre-operative testing
Management ofanticoagulationtherapy
Assist inresuscitationmanagement during massive transfusions
Prothrombin Time (PT)
Time taken for theplasma to clot when exposed totissue factor
Measures function of the extrinsic and common pathways
Normal range: ~11–13 seconds
prothrombin time
elevated in:
Warfarintherapy
Vitamin K deficiency
Deficiency of factors II, V, VII, and X
Liverdisease
Disseminated intravascular coagulation(DIC)
prothrombin time (PT)
International Normalized Ratio (INR)
International Normalized Ratio (INR)
A ratio comparing the patient’s PT to a reference PT
Measures function of theextrinsicandcommonpathways
Normal range: approximately 0.8–1.1
Activated Partial Thromboplastin Time (aPTT)
Time taken for theplasmato clot when exposed to a negatively charged substance (which activates the intrinsic pathway)
Measures function of both the intrinsic and common pathways
Normal range: ~25–40 sec
Activated Partial Thromboplastin Time (aPTT)
elevated in
Elevated in:
Heparin therapy
Hemophilia(abnormal factor VIII or IX)
von Willebrand disease(vWD)
Liverdisease
Disseminated intravascular coagulation(DIC)
Bleeding time (BT)
Measures the time for bleeding to stop after a lancet incision
Indirect measure of platelet function
Normal range: 2–7 minutes
prolonged in:
Thrombocytopenia
Disseminated intravascular coagulation(DIC)
von Willebrand disease(vWD)
Renal failure
NSAIDand/oraspirinuse
Laboratory Evaluation of Coagulation
Fibrinogen
Precursor tofibrin
Abnormally low levels can increase bleeding risk
Bleeding tends to occur when levels < 100 mg/dL
Normal range: 200–400 mg/dL
Laboratory Evaluation of Coagulation
D-dimer
Primary fibrin-degradation product
Released upon cleavage of cross-linkedfibrinby plasmin
Indicates recent or ongoing coagulation and fibrinolysis
Normal range: < 500 ng/mL
Elevated in:
DVT/PE
Stroke
Disseminated intravascular coagulation(DIC)
Covid-19 infection
