Glossary of Coag intro

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What are 3 structural levels of the vasculature?
1. EC lining
2. Subendothelium
3. Vasoconstriction
What does the EC lining release that affects coag?
1. Prostacyclin
2. Tissue fluid
3. ADP
What is prostacyclin?
What is Thromboxane?
-PGI2/Prostacyclin inhibits plt aggregation, dilates.
-TxA2 is a potent aggregator
where does PGI2 come from?
where does TxA2 come from?
PGI2 - EC cells
TxA2 - vasoconstriction
How do ADP and ADPase affect coag?
ADP --> procoagulant
ADPase --> anticoagulant
How do these alter coag?
-Plasminogen activators
-Tissue Thromboplastin
Plasmin activ = anti
Thromboplast = procoagulant
How do ThromboMODULIN and ThromboPLASTIN compare?
Thrombomodulin inhibits coagulation.
Thromboplastin supports coagulation.
What is the importance of the KININ system in coag?
Bradykinin is most important;
-Pain mediator
-Activated by Thrombin (FxII)
What are the serine protease inhibitors?
-Natural anticoagulants
List the 4 serpins
2. a2-antitrypsin
3. a2-macroglobulin
4. HC-II (heparin cofactor)
What are 3 possible factors that make the vasculature resist coagulation?
1. Heparan Sulfate
2. PGI2 (prostacyclin)
3. Smooth surface/neg charge
What 5 factors are released from injured vessel lining?
1. Tissue Thromboplastin
2. Plasminogen Activator tpA
3. ADP
4. ADPase
5. vWF
What do platelets release in their release reactions?
1. ADP
2. Serotonin
3. Thromboxane
What 3 things are on the SURFACE of platelets?
1. PGI2
2. Neg charge
3. Heparan sulfate
What activates:
-Intrinsic pathway factors?
-Extrinsic pathway factors?
Intrinsic: exposed collagen
Extrinsic: tissue thromboplastin
So tissue thromboplastin is another name for:
Tissue factor
What's the diff between serum and plasma?
Plasma: has coag factors
Serum: doesn't
What factors are COFACTORS?
V, VIII-C (8a), HMWK, Protein S, PF-3
What factor is a transamidase?
Factor XIII
What are the 4 serpins?
What are the 3 natural anticoagulants?
1. Thrombomodulin
2. Protein c
3. Protein S
What are the 3 groups that factors are classified into?
1. Vit K dependent
2. Consumable
3. Signalling/kinin/Contact
What are the Vit K factors?
2,7,9,10, Proteins C/S
What are the Consumables?
1, 5, 8, 13
What are the signalling, contact factors?
11, 12, Prekallikrein, HMWK.
Where are they produced?
-VitK dependent factors
-Consumable fators
-Contact factors
Vit K = liver
Consumable = liver EXCEPT Fx8
Contact = liver
Where is Factor 8 produced?
Endothelial cells
Where are they found?
-VitK dependent factors
-Consumable fators
-Contact factors
Vit K: serum
Consumables: ONLY plasma
Contact fxs: serum AND plasma
Where is Thrombin mostly seen?
What factors are assoc w/ it?
-Not appreciably in serum, consumed in clotting.
-Thrombomodulin (activ ProtC)
What is Factor VII also called?
Stable factor - in vitro; ironically has the shortest half-life in the body.
What does Factor 7a do?
Complexes with Tissue factor (thromboplastin) and activats factor X
What CAN Fx 7 activate?
What activates fx 7?
12, 10, 9, or itself (7)
What helps Fx 9a activate Fx 10?
8a and PF3
What is deficiency of Fx 9 called?
Hemophilia B
What helps Fx 10 to activate prothrombin?
Fx V and PF3
What is the PURPOSE OF protein C/thrombomodulin complex?
To keep the coagulation LOCAL
What activates Protein C?
Thrombomodulin/Thrombin complex
Other than inactivating Factors V and VIII, what does APC do?
Stimulates tPA release to break clots.
Why are the consumables called that?
They are eaten up when a clot forms.
What factors are found in platelet granules?
1, 2, and 13.
What's a unique characteristic of the consumables?
APR - increase in pregnancy, inflammation, oral contraceptive use
What are the consumables again?
1 (fibrinogen) 5 8 13
What is the structure of fibrinogen?
2 alpha chains
2 gamma chains
2 beta chains
What does fibrinogen do and how?
Helps platelet aggregation b/c its in platelet granules and on their surfaces.
what is FIBRINOGEN a substrate for?
1. Thrombin -> activates it
2. Plasmin -> destroys it!
What is yielded from:
-Plasmin chomping
-Thrombin chomping
Thrombin = fibrnopeptides a/b

Plasmin = d and e fragments
Whats factor 5 known as, why?
Labile factor -> storing destroys it.
What does Factor 5 do?
Cofactor for Xa/Ca to activate prothrombin.
What accompanies Fx VIII?
Von willebrand factor - linked covalently.
What is the inheritance of:
8C = sexlinked recessive
vWF = autosomal dominant
How is 8C activity measured?
How is vWF measured?
-immunologic methods
Where are 8C and vWF produced?
Endothelial cells
How is vWF deficiency SCREENED for? (3 methods)
1. Platelet function studies
2. History
3. Immunologic/electrophorese
How is VIII:C activity measured?
With an 8C assay
Which can females have; Hemophilia A or von Willebrand's syndrome?
vWF -> not sex linked.
what is vWF important for?
Platelet adhesion
What is the role of factor 13?
A transamidase - stabilizes fibrin clots.
How is Factor 13 activity detected?
UREA test
What symptom associated with Fx 13 defic?
Umbilical cord oozing.
Which kinin-contact group member is important for activating fibrinolysis?
Factor 12 --> Hageman
What's another name for factor 12?
Hagemann factor, or GLASS CONTACT FACTOR
What does Factor 12 deficiency usually cause?
Thrombosis, even though no history of bleeding.
What activates Fx 12?
Making contact with a negatively charged membrane - phospholipid, glass, etc.
What kinin is activated by Fx 12 fragments?
BRADYKININ - potent vasodilator, factor controlling bp
What can Fx 12/12a do?
-Activate plasminogen
-Activate prekallikrein
-Activate XI
What is the ONLY FACTOR of the contact group that causes a bleeding problem if deficient?
Factor 11!!!! XI
What does HMWK form?
What is unique about PK?
Prekallikrein; deficiency prolongs PTT, and won't immediately correct without 1-hr incubation.
What are the miscellaneous factors?
3 - tissue thromboplastin (tissue factor)
4 -> calcium!
What is the role of tissue thromboplastin?
Cofactor of Fx VII; to activate factor 10.
What is activated to what in the coag cascade?
Zymogen activated to serine protease
What are the serine proteases?
9-12, 7, 2, Kallikrein, Plasmin, and Protein C
What are the cofactors?
5, 8, Ca, PF3, HMWK
Protein S
What's neither a serine protease or a cofactor?
What is it then?
Factor 13; a transamidase.
How is the intrinsic cascade started?
-Activators activate F12
-or its bypassed-
-11 activated by collagen
What does F12 activate?
Fx 11, PK, and plasminogen.
What happens in the middle phase of the intrinsic cascade?
11a activates 9 -> 9a, then with VIIIa/PF3/Ca activates 10. Then it activates Thrombin.
How does Thrombin affect the middle phase after it is activated?
Accelerates the steps before it to enhance the cascade.
What are the 3 parts of the terminal phase of the caog cascade?
1. Proteolytic - fibrinogen
2. Polymerization - of fragmn
3. STabilization - via 13
What 2 things can interfere with the terminal phase?
1. Dysfibrinogenemia
2. Paracoagulation
What is paracoagulation?
When fibrogen is split into FSPs; these inhibit polymerization.
What activates Plasminogen?
What dampens down the coagulation cascade? (2)
1. Protein C eventulaly destroys V and VIII
2. IIa is consumed by thrombomodulin.
What are the 7 inhibitors of the coag cascade?
1. Protein C/S
3. antiplasmin
4. a2-macroglobulin
5. a2-antitrypsin
6. HC-II
7. Bloodflow (shear force)
What is the principle of the PROTIME?
-addition of calcium
-addition of tissue factor
-Initiates CONTACT cascade (extrinsic)
what is the ratio of reagent to test plasma?
What factrs does the protime measure?
2, 5, 7, 10
Also TF/Ca/Fibrinogen
What is the tissue factor again?
What causes abnormal PT results?
-Liver disease
-Factor deficiency
-Coumadin therapy
For the PT INR:
-What is the normal range?
-What is the therapeutic?
Normal = 0.8 - 1.5
Therapeutic = 2-3
What are the reagents in the PTT?
-Patient plasmin
what is the source of heparin?
-Mast cells
-GI mucosa
what is the therapeutic range for heparin?
2-2.5 x the basiline PTT
What are 3 indications for heparin/
1. Pre-Sx prophylactic
2. Pulmonary embolism
3. DIC
What are 3 contraindications for heparin?
1. Liver disease
2. HIT
3. ATIII deficiency
What are sources of error in the coag tests?
-Inappr. anticoagulant
-clotted specimens
-gross lipemia
-gross hemolysis
-contaminated specimens from IV line
-Older than 2hr specimens
What commonly causes abnormal
PT: Coumadin, Fx VII, Liver, Vit K defic

PTT: Heparin, Fx VIII, IX, severe liver disease

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