Welcome to Scribd, the world's digital library. Read, publish, and share books and documents. See more
Download
Standard view
Full view
of .
Look up keyword
Like this
3Activity
0 of .
Results for:
No results containing your search query
P. 1
Chok Biochem 3rd Shift Reviewer Blood Coagulation

Chok Biochem 3rd Shift Reviewer Blood Coagulation

Ratings:

4.0

(1)
|Views: 15 |Likes:
Published by api-3742802

More info:

Published by: api-3742802 on Oct 15, 2008
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as DOC, PDF, TXT or read online from Scribd
See more
See less

03/18/2014

pdf

text

original

BLOOD COAGULATION
Hemostasis \u2013 cessation of bleeding from a cut or severed vessel
Thrombosis \u2013 endothelial damage or removal
Four Phases
\u2022
Local vasoconstriction - \u2193 blood flow distal to injury
\u2022
Platelet plug formation \u2013 thrombin activation\ue000 platelet adhiesion to exposed collagen\ue000 release of activated
platelet substances = \u2191 vasoconstriction and adherence\ue000 platelet shape change, aggregation
\u2022
Hemostatic clot (thrombus) formation \u2013 via bifurcated cascade of proteolytic proteins
\u2022
Fibrinolysis \u2013 dissolution of fibrin clot
Blood Coagulation Factors
Facto
r
Name
Pathway
Function
I
Fibrinogen
Both
Becomes fibrin by removal of 2A and 2B peptides
II
Prothrombin
Both
Becomes thrombin with Xa
III
Tissue Factor
Extrinsic
Activates X with VIIa
IV
Calcium
Both
Enzyme activator
V
Proaccelerin
Both
Catalyzes thrombin formation by Xa
VII
Proconvertni
Extrinsic
X\ue000 Xa
VIII
Antihemophilic
Intrinsic
X\ue000 Xa with IXa, hemophilia A
IX
Christmas Factor
Intrinsic
Gla-containing, X\ue000 Xa, hemophilia B
X
Stuart Factor
Both
Prothrombin\ue000 Thrombin
XI
Plasma Thromboplastin
Antecedent
Intrinsic
IX\ue000 IXa with Ca
XII
Hageman factor
Intrinsic
Prekallikrein\ue000 kallikrein, XI\ue000 XIa
XII
Fibrin stabilizing factor
Crosslinks precipitated fibrin monomers
Coagulation Pathways
Pathway
Substrate
Product
Enzyme
Notes
Intrinsic Contact
Phase
Prekallikrein
Kallikrein
Damagesurface
XII
XIIa
Kallikrein, HMK
XI
XIa
XIIa, HMK, Ca
Intrinsic Tenase
Complex
IX
IXa
XIa, Ca, PI
VIII
VIIIa
Thrombin
X
Xa
VIIIa, Ca, PI
2-6 mins, components intrinsic
to blood
Extrinsic
VII
VIIa
Trauma, Ca, PI
X
Xa
Tissue factor, VIIa, Ca, PI
within 15 sec
Final Common
Prothrombi
n
Thrombin
Xa, Ca, PI, Va
Fibrinogen
Fibrin
Thrombin
Soft clot
Fibrin
Crosslinked clot
XIIIa
Hard clot
VItK dependent clotting factors
\u2022
Modification of II, VII, IX, X\ue000 \u03b3 carboxyglutamate (Gla)
\u2022
Dihydroquinone (reduced) + O2\ue000 Epox ide (oxidized) = proton abstractor = Gla residues
\u2022
Epoxide + VitK reductases + dithiol cofactors\ue000 D i h yd r o q u i n o n e active
\u2022
Gla residues much stronger Ca chelators\ue000 Ca bridges between II, VI, IX, X and membrane
Final Common Pathway Factors
\u2022
Prothrombin \u2013 single chain glycoprotein from liver, active \u03b1 molecule @ N terminal, propeptide with 3 domains: Gla, Kringle 1,
Kringle 2
o
Conversion \u2013 prothrombinase complex (platelet anionic phospholipids, prothrombin, Va, Ca, Xa); cleave Arg-Thr bond =
release propeptide
\u2022
Thrombin \u2013 A & B chains with disulfide bonds, serine protease, release fibrinopeptides, converts XIII\ue000 XIIIa
\u2022
Fibrinogen \u2013 soluble, 3 pairs of non-identical, but homologous chains (A\u03b1, B\u03b2, \u03b3\u03b3) with disulfide bonds; central \u03b1\u03b2\u03b3, terminal \u03b2\u03b3 C-
terminals; highly anionic fibrinopeptides (-8 central, -4 peripheral)
o
Conversion \u2013 A&B cleavage by thrombin\ue000 +5/-4 charge = non-covalent aggregation; with FSF-XIIIa = covalent isopeptide
bonds
Fibrinolysis
\u2022
Demolishing of fibrin, elimination of blood clots for wound repair, activated by fibrin
\u2022
Fibrin activates plasminogen activators\ue000 plasmin (Arg-Val cleaving)\ue000 cleave 3x stranded coiled segments @ covalent
crosslinkages
\u2022
Plasmin active only with fibrin, inactivated by \u03b12 antiplasmin
\u2022
Activated by urokinase (kidneys), streptokinase (streptococci with ASA), tissue plasminogen activator (vascular endothelium during
injury or stress)
Anticoagulants
\u2022
Calcium ion chelators \u2013 fluoride, oxalate, citrate
\u2022
Antithrombin coagulants (in vivo)
o
Antithrombin III \u2013 inhibits all active proteases except VIIa, 75% antithrombin activity
o
\u03b12 macroglobulin \u2013 20-25% antithrombin activity

You're Reading a Free Preview

Download
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->