Blood Coagulation Flashcards
Steps of hemostasis
- Initiation
- Localization
- Propagation/amplification
- Termination
- Elimination
Vessel wall - endothelial cells and subendothelial components
Initiation
Platelets- circulating cellular elements
Localization
Plasma coagulation proteins (factors)
Propagation/Amplification
Plasma coagulation protein inhibitors
Termination
Fibrinolytic system
Elimination
Clinical test to to assess the functionality of intrinsic pathway, Used to test for common congenital hemophilias (deficiencies in IX, VIII, or XI) and to monitor heparin treatment
activated partial thromboplastin time (APTT)
Normal time range for APTT test
30-50 seconds
Prolongations in the aPTT are observed in deficiencies of factors…
XI, IX, VIII, X, and V, prothrombin, or fibrinogen
In APTT test ____ and ____ are added to the test plasma sample
Kaolin and cephalin
Refers to tissue factor, which is expressed on subendothelial cells
Extrinsic pathway
Clinical test to assess the functionality of the extrinsic pathway.
Prothrombin time (PT) Used to test for the rare congenital deficiencies: More often it is used to diagnose acquired bleeding disorders resulting from vitamin K deficiency, oral anticoagulants (e.g. warfarin), and liver disease
Added to test plasma sample in PT test
Lipidated tissue factor
Normal range for PT test
10-15 seconds (shorter pathway)
Prolongations in the PT are observed in deficiencies of
factors VII, X, V, prothrombin, or fibrinogen.
Deficiencies in all of the factors, except factor , lead to a bleeding tendency in the affected individual
XII
Activated factor enzymes are designated with an
“a” e.g. factor Xa
sequence of zymogen to enzyme conversions, with each enzyme activating the next zymogen in the sequence
waterfall or cascade
Roles of thrombin
- Cleaves Fibrinogen
- Activates Platelets
- Activates procofactors (FV and FVIII)
- Activates zymogens (FVII, FXI and FXIII)
Common constituents of coagulation complexes
- Vitamin K-dependent (VKD) zymogen
- Ca2+
- Protein cofactor(s):
- Protein C: Protein S- inhibits FVa and FVIIIa Specific inhibitor for Protein C (Protein C inhibitor; PCI)
- Protein Z + Ca2+ Protein Z-dependent protease inhibitor inhibits FXa
- Appropriate membrane surface -
- activated platelets (VIIIa/IXa complex, Va/Xa complex) -subendothelial cells, typically fibroblasts (TF/VIIa complex)
Group of related, fat soluble compounds, which differ in the number of side-chain isoprenoid units
VITAMIN K
The reduced form of vitamin K2 (vitamin KH2) is required for
the post-translational, gamma-carboxylation of several proteins involved in blood clotting
Gla-Containing Proteins
- Prothrombin
- Factor VII
- Factor IX
- Factor X
- Protein C
Haplotype A represents individuals at risk for __________and haplotype B represents individuals at risk for
excessive anticoagulation with standard warfarin dosing, subtherapeutic anticoagulation from standard warfarin dosing
Deficiency of _______ is rare because of its wide distribution in nature, and its production by intestinal bacteria
Vitamin K
Vitamin K deficiency found in individuals with ______ and ______. It is associated with _________
liver disease and fat malabsorption.; bleeding disorders
This group is at risk for Vitamin K deficiency
Newborn infants (especially preemies) Placenta is insufficient in the transfer of maternal vitamin K
Heparin fragments _____ enhance ____ inhibition of _____ and ____
(18 & 5); AT3; thrombin and FXa
Hemophilias A and B are cause by deficiencies in factors _____ or _____, respectively
VIII or IX Affect 1 in 10,000 males
Hemophilia is inherited as a
recessive X-linked trait (Mom would be an unaffected carrier)
Hemophilia is treated by
- administration of factor VIII or factor IX concentrates
- Recombinant factor VIII or IX proteins
- Gene therapy trials
Hemophilias A and B are cause by deficiencies in factor, _____ or _____respesctively
VIII or IX
Genetic defects of bleeding disorders/hemmorrhages are
- platelet abnormalities
- blood vessel wall abnormalities
- clotting factor deficiencies (hemophilias)
- excess clot breakdown (fibrinolysis)
Acquired defects of bleeding disorders/hemmorrhages are
- liver disease (site of clotting factor synthesis)
- vitamin K deficiency
- autoimmune disease (platelet destruction)
- trauma
Bleeding disorders can span the spectrum from _______vessels to _______…
weeping blood; full-fledged…internal and external hemorrhage
Hemorrhage is treated by
factor replacement
Thrombosis can be manifested as _________ It is the major cause of _______and ______.
a transient, short-term or episodic event in individuals with chronic or recurring clotting.; both stroke and heart attacks.
The genetic defects of thrombosis
clotting factor INHIBITOR deficiencies decreased fibrinolysis
Acquired defects of thrombosis:
Atherosclerosis Lupus anticoagulants
Blood coagulation factors and diseases:
- Increased expression of Antithrombin II, TPA, PAI –
- High plasma Fibrinogen levels–
- Genetic variants in FII–
- Inflammatory Markers and FI, FVIII–
- Endothelial Tissue Factor upregulation –
- Associated with Atrial Fibrillation, Strokes
- Thromboembolism
- Associated with severity of colorectal cancer
- Associated with increased risk of HCC (Patients with HCV)
- Associated with chronic renal diseases
- Associated with increased risk of heart failure
Pharmacologic Approaches to Prevent Thrombosis
Antiplatelet agents - block activation, aggregation or intraplatelet agonist synthesis
Effective anticoagulant therapy includes both antiplatelet and antithrombin agents
NECESSITY FOR BLOOD CLOTTING
- PREVENT EXCESSIVE
BLOOD
LOSS FROM THE BODY
- PREVENTS BLOOD
PRESSURE FROM FALLING
TO A LOW LEVEL AS
PRESSURE IS NEEDED
- SEALS A WOUND
- PREVENTS THE ENTRY OF
MICROORGANISMS AND
FOREIGN PARTICLES
INTO THE BODY THROUGH
THE WOUND
