Section 5: Coag Cascade Flashcards
Which two concentrations of sodium citrate are used? Which one is more common?
- 3.2% and 3.8%
- 3.2% used most of time
Erythrocetin
Substance with thromboplastic effect (initiates coag cascade)
If have low Hct and more plasma, do you need more or less anticoag?
More
If have high Hct and less plasma, do you need more or less anticoag?
Less
Specimen type in coag vs platelet studies
- Coag studies = PPP
- Platelet studies = PRP
What type of material can activate the coag cascade? What do we use instead?
Glass can activate the coag cascade, so use plastic
Coag sample storage
- Refrigerator temp for 4 hr
- Prothrombin Time (PT) held at RT
- Freeze at <-20C (freeze/thaw fast or ice crystals denature proteins)
What is the Tenase complex in the intrinsic pathway?
- FIXa
- Calcium
- PF3 phospholipid
- FVIII:C
What is the Tenase complex in the extrinsic pathway?
- FVIIa
- Calcium
- TF3
Purpose of Tenase complex
To activate Factor X
Components of the Prothrombinase Complex
- FXa
- FVa
- PF3
- Calcium
What are the Magic Four Factors? Describe them
- FII, VII, IX, and X
- All produced in liver
- All vitamin K dependent
- All depleted by Warfarin therapy
What does Vitamin K do to magic four factors?
Vit K participates in an oxidation reaction that adds a second carboxyl group to make a “complete” factor
How does Warfarin deplete the magic four factors?
Arrests Vit K in storage form and makes it unavailable to make complete factors
The only substance necessary to convert fibrinogen (FIa) to fibrin (FIIa)
Thrombin (FIIa)
Thrombin enhances the activity or modifies _______
Factors V, VIII, XI, and XIII
Describe Factors V and VIII
- Labile factors that are short-lived in stored plasma bc not very stable
- Only factors that are not enzymes
- Referred to as cofactors that only function in complexes
- Inactive forms can participate in cascade
- Targets of Protein C (potent coag inhibitor)
How does Thrombin IIa act upon fibrinogen (I) molecule?
It splits fibrinopeptides A and B tips from the end of the two polypeptide chains, leaving the remainder as fibrin (Ia)
How is Factor XIII activated?
Thrombin + Calcium activate FVIII to stabilize the clot
Where is fibrinogen (FIa) made and what is its function?
- Made in liver
- Cross-links plts in aggregation
- Absorbed in plt alpha granules
Acute phase reactant factor
FIa fibrinogen is APP
High fibrinogen associated with
- Pregnancy/smoking
- MI and stroke
Low and/or dysfunctional FIa associated with
- bleeding
- thrombosis
Describe FII (prothrombin)
- made in liver
- one of magic four
- vit K dependent
FII activated by
Xa, Va, Calcium, PF3
What does FIIa activate?
Activates FV, VIII, XI, XIII, Protein C, and Thrombin Activatable Fibrinolytic Inhibitor (TAFI)
Describe TF3 (aka Factor III)
- Found in all tissues esp. brain, liver, lung, and placenta
- Released from injured tissues
- Cofactor for activation of FVII
- Part of Tenase complex
- No known deficiency of TF3
Factor IV is
Calcium
What must you add to coag screening tests to overcome anticoagulant?
Calcium
Calcium dependent steps in coag cascade
- extrinsic Tenase complex
- intrinsic Tenase complex
- Prothrombinase complex
Factor V attaches to ____ and is inactivated by ____
- Attaches to receptor on activated platelets
- Inactivated by Protein C
Describe Factor VI
It doesn’t exist
What activates FVII?
TFIII and Calcium
Describe Factor VIII
- Coagulant or clottable portion (AHF or VIII:C)
- Made in several tissues but mostly liver
- Heat labile
Factor VIII deficiency causes
Hemophilia A
Factor VIII usually bound to ___
vWF
Unstable if not bound to vWF
FVIII inactivated by
Protein C
Describe vWF
- Made by megakaryocytes and endothelial cells
- ADAMTS13 cleaves vWF into smaller multimers
- Aids plt adhesion to collagen
vWF deficiency causes ___
vWF Disease
What drug stimulates vWF release from ECs?
DDAVP
Factor IX aka
Christmas factor
Factor IX deficiency causes
Hemophilia B
Factor X made where?
Liver
Factor XI made where? Function?
- Made in liver
- Contact factor
- Travels in blood complexed with High Molecular Weight Kininogen (HMWK) to amplify its function
Glass may auto-activate which factor?
FXI
FXI deficiency causes
Hemophilia C
Describe Factor XII (Hagemon Factor)
- Made in liver
- Contact factor that is activated by contact with subendothelial tissue
- FXIIa activates FXI with cofactor HMWK
What is the only factor deficiency that does NOT cause bleeding?
Factor XII deficiency
How is prekallikrein converted to Kallikrein?
XIIa activates Prekallikrein
Role of Kallikrein + XIIa
To make more XII
Kallikrein role
- Activates kinin and fibrinolytic pathways
- Kinins act as vasodilators and smooth muscle relaxants to reestablish blood flow
Consequences of Factor XII deficiency
- Alternate activation of IX by VIIa/TF3/Calcium
- Thrombosis due to lack of fibrinolytic pathway activation (no clot breakdown)
Describe where Factor XIII is made and its function
- Made in liver
- Functions to form covalent bonds btwn D domains in polymerized fibrin
Which factor is not tested for in coag screening tests? What to do instead?
- Factor XIII not tested
- Urea clot lysis detects deficiency
Describe where Prekallikrein is made and its function
- Made in liver
- Functions as contact factor
- Activated by XIIa
- Attached to HMWK
Cofactor for PK activation
HMWK
Kallikrein activate what?
- More XII
- Plasminogen to plasmin
- Hydrolyzes bradykinins from HMWK to initiate kinin system
Describe PK deficiency
- does NOT cause bleeding
- usually asymptomatic but may see abnormal clotting due to lack of fibrinolytic pathway activation
Describe where HMWK (Fitzgerald factor) is made and its function
- Made in liver
- Contact factor that complexes with XI and PK
- Cofactor with XIIa to activate XI
- Substrate for Kallikrein in kinin production
HMWK deficiency consequences
- does NOT cause bleeding
- usually asymptomatic but may see abnormal clotting due to lack of fibrinolytic pathway activation
Bradykinins
- Not really part of cascade, it just gets made
- Functions to increase vascular permeability, contract smooth muscle, dilate small blood vessels, induce pain/inflammation, and release prostaglandins from tissues
