In the intrinsic pathway blood must come in contact with _________ and in the extrinsic pathway blood must come in contact with _________-
Charged particles; tissue factor
Coagulation Factors
Synonyms for I, II, III, IV, V, VI, VII, VIII, IX, X, XI, XII, and XIII
Bleeding disorders
Genetic defects:
platelet abnormalities
blood vessel wall abnormalities
clotting factor deficiencies (_________)
excess clot breakdown (____________)
Acquired defects:
liver disease
vitamin______deficiency
autoimmune disease (_______destruction)
trauma
Hemophilias
fibrinolysis
K
Platelet
Transglutamidase is activated by ____________.
Thrombin
The Vitamin K Cycle
Intrinsic pathway by numbers
XII–> XI–> XIa–>IX–>IXa–>X–>Xa–> II–>IIa
In platelets, the expression of this membrane surface is ___________
Activation- dependent
Hemophilias A and B
Hemophilia A is caused by a deficiencies in factor________and Hemophilia B is cause by deficiency in factor ________.
Affect ~1 in 10,000 males
Inherited as a _________X-linked trait
VIII;IX
Recessive
PROCESSES INVOLVED IN BLOOD CLOTTING
- Injury causing rupture of blood vessels
- Platelets clump at wound
- THROMBOKINASE is released
- Thrombokinase converts prothrombin to thrombin
- Thrombin converts fibrogen to fibrin
- A meshwork of threads form over the wound
- Trap erythrocytes & platelets
- Blood clot forms, scab falls off, and new skin formed
Thrombin
Cleaves ____________
Activates _________
Activates procofactors:_______ and _________
Activates zymogens: ________, ________, and __________
Fibrinogen
Platelets
V and VIII
VII, XI and XIII
5 Steps of Hemostasis
1) . INITIATION
2) . LOCALIZATION
3) . PROPAGATION/AMPLIFICATION
4) . TERMINATION
5) . ELIMINATION
Heparin binds to _________ to inhibit blood coagulation
Antithrombin
Thrombosis Embolism
Causes:
- A local blood clot is formed on the damaged rough inner wall of the _________
- ___________ of the artery
- __________trapped and blocks blood flow
Artery
Blockage
Embolus
Thrombin Time (TT)
In this test, __________ is added to ________
The normal range is __________ seconds (varies slightly depending on the laboratory)
Prolongations in the TT are observed in ____________ deficiency or ___________ deficiency resulting from consumption of fibrinogen in _______________, or may occur following treatment with fibrinolytic drugs
Thrombin; plasma
10-15
congenital fibrinogen; acquired fibrinogen
DIC (disseminated intravascular coagulation)
Common constituents of coagulation complexes
Vitamin K-dependent (VKD) zymogen
Ca2+
Protein cofactor
- activated platelets (VIIIa/IXa complex, Va/Xa complex)
- subendothelial cells, typically fibroblasts (TF/VIIa complex)
How are bleeding disorders treated?
Factor replacement
____________ is the major cause of both stroke and heart attacks.
Thrombosis
Cofactors used in conversion of prothrombin to thrombin
Ca 2+ and vitamin K
Blood Coagulation
Deficiencies in all of the factors, except factor _____, lead to a bleeding tendency in the affected individual
Described as a ‘waterfall’ or ‘cascade’ sequence of _______ to ________ conversions, with each enzyme activating the next zymogen in the seqeunce
XII
Zymogen; enzyme
Intrinsic Pathway of Blood Coagulation
No factors _________ to the blood are involved
Clinical test to assess the functionality of this pathway is the ____________
________ and ______ are added to the test plasma sample
The normal range is ________seconds
Prolongations in the aPTT are observed in deficiencies of factors ________________
Used to test for common _______________ (deficiencies in IX, VIII, or XI) and to monitor _______treatment
activated partial thromboplastin time (APTT)
Kaolin; Kaolin
30-50
XI, IX, VIII, X, and V, prothrombin, or fibrinogen.
Congenital hemophilia; heparin
Two possible extrinsic pathways by numbers
VIIa–>IX–>IXa–>X–>Xa–> II–>IIa
VIIa–>X–>Xa–> II–>IIa
Thrombosis
Genetic defects:
clotting factor __________ deficiencies
decreased ___________
Acquired defects:
_____________
_____________
Inhibitor
Fibrinolysis
Lupus anticoagulants
Atherosclerosis
Haemophilia
Causes:
- Lack of ________ for production of clotting factor ________
- An impaired __________ mechanism
Treatment:________
Gene; VII
Clotting
Generic engineering of factor VII
VITAMIN K
Group of related, _______soluble compounds, which differ in the number of side-chain _________units
_______ derived (vitamin K1) and synthesized by _________bacteria (vitamin K2)
The ________form of vitamin K2 (vitamin KH2) is required for the post-translational, gamma-__________ of several proteins involved in ________
Fat; isoprenoid
Plant; Intestinal
Reduced; Carboxylation
Blood Clotting
Heart Attack
Causes:
- The _________is partially blocked.
- Blockage cuts off ________ supply
- Extensive heart_________ damage
Coronary artery
Oxygen
Muscle
Haplotype A represents individuals at risk for ___________anticoagulation with standard __________dosing, and haplotype B represents individuals at risk for __________ anticoagulation from standard ____________dosing.
Excessive; warfarin; subtherapeutic; warfarin
Site of clotting factor synthesis
Vitamin K
Extrinsic Pathway of Blood Coagulation
Extrinsic refers to _________ factor, which is expressed on ________ cells
Clinical test to assess the functionality of this pathway is the __________ time
__________tissue factor is added to test plasma sample
The normal range is __________ seconds
Prolongations in the _______ are observed in deficiencies of factors VII, X, V, prothrombin, or fibrinogen.
Used to test for the rare congenital deficiencies in these factors: More often it is used to diagnose acquired ______ disorders resulting from__________deficiency, oral _________, and________ disease
Tissue; subendothelial
Prothrombin
Lipidated
10-15
Protothrombin time (PT)
Bleeding; Vitamin K; anticoagulants; liver
Vitamin K deficiency
Deficiency of vitamin K is rare because of its wide distribution in nature, and its production by __________ bacteria
Found in individuals with ________disease and__________malabsorption - it is associated with _______- disorders
Newborn infants (especially preemies) are also at risk
- ________is insufficient in the transfer of maternal vitamin K
- Concentration of circulating vitamin K drops immediately after_______, and it recovers upon absorption of_________.
Intestinal
Liver; Fat; Bleeding
Placenta
Birth; food