plasma coag system

Where is Fibrinogen found?

1. Plasma

2. Alpha granules

How is each domain of the Fibrinogen monomer connected?

3 pairs of non-identical polypeptide chains

How is each Fibrinogen monomer connected?

Disulfide bonds

Where does a platelet bind to the Fibrinogen molecule?

C-terminal on the D domain

What does Thrombin (F2a) do, and what allows this to happen?

1. Cleaves fibrinopeptides into a fibrin monomer

2. Results in a change in the net charge and spontaneous polymerization

How does FXIIIa cross link the fibrin monomer into a polymer?

By establishing covalent bonds

What domain on the polymer changes and how?

The E domain changes from a negative to a positive.

What are the two functions of Fibrinogen, and which form performs what function?

1. Polymeric form forms Fibrin

2. Monomers form links platelets.

Which factors are not synthesized in the liver?

1. TF (F3)

2. FVIII

3. Ca2+ (FIV)

What does Vitamin K do to synthesize certain factors? How does Warfarin work?

1. Adds an extra carboxyl group

2. Results in inactive, “acarboxy” forms of coag proteins

What factors are in the Contact Factor group?

1. FXI

2. FXII

3. Prekallikrein (PK)

4. High molecular weight Kininogen

What is the Contact factor group important for, and which factor is the exception?

1. In vitro clotting

2. FXI

What does a high concentration of thrombin do?

Inactivates factors

What does a deficiency of protein c and s lead to?

Thrombosis

What does Plasmin do?

Convert Fibrin into Fibrin Degradation Products (FDPs)

What is the primary Plasminogen activator? What is it made by?

1. tPA (Tissue Plasminogen activator)

2. Vascular endothelial cells

What do clot-busting drugs consist of?

1. TPA

2. Streptokinase

3. Urokinase

What are three drawbacks of clot-busting drugs?

1. Expensive

2. Acts on all plasminogen and cause bleeding

3. Antigenic

What does Plasminogen Activator Inhibitor act on?

tPA and uPA

What clears FDPs, and what effect can they have in higher concentrations?

1. Liver

2. Anticoagulant effect

What type of assay is both FDP and D-dimer assays?

Immunoassays

What is a normal level of FDP? FDP and D-dimer assays are important for detecting which conditions?

1. Low levels

2. DIC, PE, DVT

What are five reasons for prolonged clotting time?

1. Factor deficiency

2. Factor is made but defective

3. Inhibitor (Ab) to factor

4. Non-specific inhibitor (APS)

5. Patient on anticoagulant

What pre-analytical error can cause prolonged PT results?

Over-dilution

What HCT% is normal for proper dilution?

22-55%

What is the temperature requirements for PT/APTT tests? How long can you store a PT and APTT test?

1. < 24 degrees Celsius

2. PT: < 24 hours

3. APTT: < 4 hours

What is the storage requirement if the patient is on heparin for APTT tests?

< 1 hour

When do you start and stop the timer in a PT test?

1. Start: After addition of Reagent Thromboplastin

2. Stop: Fibrin formation

What is the reference interval for PT?

10-13 seconds

What is the INR equation and what is it used for?

1. (PT sec/mean normal PT)^ISI

2. Warfarin therapy eval

What are the two reagents in APTT?

1. Activated Partial Thromboplastin

2. CaCl

What activates Thromboplastin?

Kaolin

What is the APTT test used for, and what is the reference interval

1. Heparin therapy

2. 25-40 secs