HEMATOLOGY 2 - PAGE 23 TO 48 (IN HOUSE REVIEW)

Factor III and Factor IV

Coagulation factors are produced primarily in the liver excep these two factors.

Factor VIII

This specific factor is produced in a number of tissues however, the major production site is the liver.

Megakaryocytes and Endothelial cells

vWF portion of VIII: vWF is made by these two type of cell.

Factor VII

6 hours

Factor ___ has the shortest half-life for about ____ hours

1. Liver dysfunction

2. Factor VII

3. Prothrombin Time

4. Extrinsic pathway

With acute (1) ______________, levels of (2) factor ______ are reduced early. (3) _____ is a very good test to assess liver function in the acute setting because this factor is needed for (4) __________ pathway.

1. Factor VIII deficiency

2. Factor IX deficiency

3. X-linked recessive

All deficiency of coagulation factors are transmitted as autosomal recessive with the exception of (1) Factor ______ deficiency and (2) Factor ______ deficiency, which are transmitted as (3) ________ recessive.

Fibrinogen or Factor 1

Factor with this description:

● Mol. Weight (Daltons): 340,000

● Half-life (hours): 100 to 150

● Mean plasma concentration: 200 to 400 mg/dL

Fibrinogen

This is the most concentrated of all the plasma procoagulants.

100 mg/dL or 80-100 mg/dL

Fibrinogen level is below ____ mg/dL or ___—___ mg/dL. PT and aPTT will be prolonged.

Liver

Fibrinogen is synthesized in this specific organ.

Prothrombin or Factor II

Factor with this description:

● Mol. Weight (Daltons): 71, 600

● Half-life (hours): 60

● Mean plasma concentration: 10 mg/dL

Tissue Factor /Tissue Thromboplastin /Thrombokinase or Factor III

Factor with this description:

● Mol. Weight (Daltons): 44,000

● Half-life (hours): insoluble

● Mean plasma concentration: None

Calcium Ions or Factor IV

Factor with this description:

● Mol. Weight (Daltons): 40

● Half-life (hours): N/A

● Mean plasma concentration: 8 to 10 mg/dL

Proaccelerin/ Labile Factor/ Thrombogen or Factor V

Factor with this description:

● Mol. Weight (Daltons): 330,000

● Half-life (hours): 24

● Mean plasma concentration: 1 mg/dL

Factor V Leiden

This mutant factor is not inactivated by protein C-protein S complex leading to excessive clot formation.

Proconvertin/ Stable Factor or Factor VII

Factor with this description:

● Mol. Weight (Daltons): 50,000

● Half-life (hours): 6

● Mean plasma concentration: 0.05 mg/dL

Factor VII

Vitamin K-dependent factor that is synthesized in the liver. This binds to tissue factor.

Antihemophilic Factor A (AHF-A)/ Antihemophilic globulin (AHG) or Factor VIII

Factor with this description:

● Mol. Weight (Daltons): 330,000

● Half-life (hours): 12

● Mean plasma concentration: 0.01 mg/dL

1. Plasma

2. vWF

3. Thrombin

Free factor VIII is unstable in ________ (it circulates bound to ____). During coagulation, _______ cleaves factor VIII from vWF and activates it.

1. Hemophilia A (Classic Hemophilia)

2. X-linked recessive

3. Prolonged aPTT

4. Normal PT

Deficiency in factor VIII causes _________, an _______ recessive bleeding disorder characterized by ________ aPTT with ______ PT.

Factor VIII, Factor VIIIC, Factor VIII:C

Factor VIII complex is symbolized as follow based on this characteristics:

• refers to procoagulant portion

• measured by standard Factor VIII assays and APTT

• markedly decreased in Hemophilia A

Factor VIII: Ag

Factor VIII complex is symbolized as follow based on this characteristics:

• refers to the antigenic properties

• measured by immunoassays

Factor VIIIR:RCo

Factor VIII complex is symbolized as follow based on this characteristics:

• refers to the portion responsible for platelet aggregation in the presence of ristocetin

• termed as ristocetin cofactor

Factor VIII:vWF

Factor VIII complex is symbolized as follow based on this characteristics:

• also termed the von Willebrand factor

• required for normal platelet adhesion

vWF:Ag

Factor VIII complex is symbolized as follow based on this characteristics:

• antigenic portion of the von Willebrand factor

• was previously termed Factor VIII related antigen (VIIIR:Ag)

• measured by immunoassays

von Willebrand Factor

Factor with this description:

● Mol. Weight (Daltons): 600,000 to 20,000,000

● Half-life (hours): 24

● Mean plasma concentration: 1 mg/dL

Platelet and Collagen

VWF has receptor sites for BOTH ______ and _______.

GP Ib/IX/V

This glycoprotein is the primary platelet surface receptor for VWF

Factor VIII

VWF carries and stabilized _______ in circulation, protecting it from proteolytic degradation; deficiency leads to decrease of this factor.

Christmas Factor/ Antihemophilic Factor B (AHF-B)/ Plasma Thromboplastin Component (PTC) or Factor IX

Factor with this description:

● Mol. Weight (Daltons): 57,000

● Half-life (hours): 24

● Mean plasma concentration: 0.3 mg/dL

1. Hemophilia B

2. Christmas Disease

3. X-linked recessive

4. Prolonged aPTT

5. Normal PT

Factor IX Deficiency causes _________ (_______ disease), __________ recessive bleeding disorder characterized by _______ aPTT with _______ PT

Stuart-Prower Factor or Factor X

Factor with this description:

● Mol. Weight (Daltons): 58,800

● Half-life (hours): 48 to 52

● Mean plasma concentration: 1 mg/dL

Antihemophilic Factor C (AHF-C)/ Plasma Thromboplastin Antecedent (PTA) or Factor IX

Factor with this description:

● Mol. Weight (Daltons): 143,000

● Half-life (hours): 48 to 84

● Mean plasma concentration: 0.5 mg/dL

1. Hemophilia C

2. Rosenthal syndrome

3. Autosomal Recessive

4. Ashkenazi Jews

5. Trauma or Surgery

Factor IX Deficiency causes _________ (_________ syndrome); inherited in an ____________ pattern (most common in _______________ populations); bleeding typically occurs after ______ or ______ rather than spontaneously.

Hageman Factor/ Glass Factor/ Contact Factor or Factor XII

Factor with this description:

● Weight (Daltons): 85,000

● Half-life (hours): 35

● Mean plasma concentration: 35 to 50 μg/mL

Factor XII

This factor deficiency prolongs APTT but does not cause any clinical bleeding.

Fibrin Stabilizing Factor/ Fibrinase/ Laki-Lorand Factor or Factor XIII

Factor with this description:

● Mol. Weight (Daltons): 320,000

● Half-life (hours): 150

● Mean plasma concentration: 2 mg/dL

1. Factor XIII

2. Thrombin

3. Calcium

A transglutaminase zymogen that is activated by ________ and _______; it cross-links fibrin monomers by forming covalent bonds between glutamine and lysine residues, creating a mechanically stable and fibrinolysis-resistant clot

Prekallikrein (aka: Fletcher Factor)

Factor with this description:

● Mol. Weight (Daltons): 85,000

● Half-life (hours): 35

● Mean plasma concentration: 35 to 50 μg/mL

High-molecular-weight Kininogen/Reid Factor/ Williams Factor/ Fitzgerald Factor/ Flaujeac Factor (HMWK)

● Mol. Weight (Daltons): 120,000

● Half-life (hours): 156

● Mean plasma concentration: 5 mg/dL

Phosphatidylserine

Platelet phospholipids (NOT in the list), particularly _________, are considered coagulation factors also. They were once called collectively as platelet factor 3 (PF-3)

o Prothrombin (II)

o VII

o IX

o X

o XI

o XII

o Prekallikrein

o XIII

Eight coagulation factors are enzymes that circulate in an inactive form called zymogens. These are:

o Tissue factor (III)

o Factor V

o Factor VIII

o HMWK

The coagulation factors that function as cofactors are:

XII, XI, IX, and VIII

(12, 11, 9, and 8)

INTRINSIC COAGULATION PATHWAY FACTORS (4)

III and VII

(3 and 7)

EXTRINSIC COAGULATION PATHWAY FACTORS (2)

X, V, II, and I

(10, 5, 2, and 1)

COMMON COAGULATION PATHWAY FACTORS (4)

I, V, VIII, XIII

(1, 5, 8, and 13)

4 factors called the fibrinogen group.

Fibrinogen Group:

I, V, VIII, XIII

(1, 5, 8, and 13)

According to the properties of these 4 factors are:

• Thrombin sensitive group

• Absent in serum

• Calcium independent

Fibrinogen Group:

I, V, VIII, and XIII

These specific factor groups (4) are increased in these categories:

1. Pregnancy

2. Inflammation

3. Stress

4. Oral contraceptives

II, VII, IX, and X

(2, 7, 9, and 10)

4 factors called the prothrombin group.

PROTHROMBIN GROUP

II, VII, IX, and X

(2, 7, 9, and 10)

According to the properties of these 4 factors are:

1. Present in aged serum (except ______)

2. Vitamin K-dependent

3. Calcium dependent

1. Barium Sulfate

2. Aluminum Hydroxide

Prothrombin group is absorbed from plasma using this two chemicals.

Contact group

XII, XI, PK, HMWK

This is also known as the contact group consists of 4 factors.

Contact Group

According to the properties of these 4 factors are:

• Vitamin K-independent

• Calcium-independent

PIVKA (Protein Induced by Vitamin K absence)

Term for abnormal (inactive) forms of vitamin K–dependent factors (II, VII, IX, X) produced when vitamin K is deficient or warfarin is present

Factor I, V, VIII, and XIII

(1, 5, 8, and 13)

Thrombin activates these 4 factors.

1. 9a

2. PF-3

3. Calcium (Factor IV)

4. 8a

Tenase complex includes these 4 factors and substances.

1. 10a

2. PF-3

3. Calcium

4. 5a

Prothrombinase complex includes these 4 factors and substances.

Calcium (Factor IV)

This factor is involved in all phases of coagulation except in the contact phase.

5M Urea

Stabilized fibrin clot is not soluble to 5M _____.

35 to 45 seconds

Reference range for APTT/aPTT

PT/APTT

An example of a clot-based coagulation screening test (2).

1. 15 minutes

2. 2500 X g

3. <15,000

PT and APTT is prepared by specimen centrifugation for ___ minutes at ________ X g; plasma platelet count should be _______.

COMMON COAGULATION FACTORS: X, V, II, and I

INTRINSIC COAGULATION FACTORS: XII, XI, IX, and VIII

aPTT is a screening test for these factors.

aPTT

This test monitors the unfractionated heparin therapy.

10 - 13 seconds

Reference range for Protime (PT)

EXTRINSIC COAGULATION PATHWAY: VII

COMMON COAGULATION PATHWAY: X, V, II, and I

PT is a screening test for these factors.

1. Protime

2. Warfarin or Coumadin

3. International Normalized Ratio

This test monitors the oral anticoagulant _______ therapy via _______

International Normalized Ratio

This is a standardized way of reporting PT. It is merely a mathematical calculation (corrects for the variability in PT results caused by variable sensitivities of the thromboplastin agents used by laboratories).

INR = [Patient’s PT / Mean Normal PT] ISI

INR formula?

1. 2.0 to 3.0

2. 2.5 to 3.5

Target INR range of _.0 to _.0 is recommended for most indications. The physician adjusts the Coumadin dosage to achieve the desired INR. (if the patients has a mechanical heart valve it is adjusted to?

1. Longer

2. Shorter

Theoretically, the more sensitive the thromboplastin reagent, the (1) ________ the resulting PT; the less sensitive the reagent, the (2) ________ the resulting PT.

Coumarin Drugs

Therapeutic anticoagulant that is vitamin K antagonist and used orally.

1. Dicumarol

2. Phenprocoumon

3. Acenocumarol

4. Warfarin

4 examples of coumarin drugs.

Warfarin

This is the most commonly used coumarin drug.

1. Factor II, VII, IX, X (Vit K dependent)

2. Protein C and S

3. International Normalized Ratio (INR)

Warfarin antagonized these factor and proteins ___ and ___. This also follows the _____ for monitoring.

Vitamin K

FFP - Fresh Frozen Plasma

PCC - Prothrombin Complex Concentrate

rVIIa

For reversal of Warfarin these 4 substances must be used.

1. Unfractionated Heparin

2. Intravenously

This is routinely used in cardiac surgery. This therapy requires monitoring with Partial Thromboplastin Time or activated clotting time assay. It is administered ________

1. Heparin

2. Thrombin

3. Factor Xa

This substance has no anticoagulant activity of its own. This acts as an anticoagulant by accelerating the binding of antithrombin to target enzymes. E.g., _______ and factor ______

1. Protamine Sulfate

2. Salmon Sperm

For neutralizing UFH this chemical is used it is a protein extracted from this specific animal.

1. Activated Coagulation Time (ACT)

2. High

Another example of a clot-based coagulation screening test. A point of care assay that is used in clinics, at the inpatient’s bedside in the cardiac catheterizations laboratory, or in the surgical suite, and it is specifically useful at the _____ UFH dosages.

1. Low-Molecular-Weight Heparin (LMWH)

2. antithrombin III

3. Activated Factor X

4. Subcutaneous

This is produced by the controlled fragmentation of heparin; it reacts with the regulatory protein ____________ to inhibit activated factor _________ but not thrombin (factor IIa); and it is administered by ___________ injection.

BBL Fibrometer

Mechanical / Electromechanical that uses electromechanical clot detection system that measures a change in conductivity between two metal electrodes in plasma.

Diagnostica Stago Analyzers

Mechanical / Electromechanical that uses an electromagnetic field detects the oscillation of a steel ball within the plasma-reagent solution. Viscosity starts to increase as fibrin strands form, slowing the movement. When the oscillation decreases to a predefined rate, the timer stops, indicating the clotting time of the plasma.

Photo-Optical (Turbidometric)

Coagulometers that use this principle detect a change in plasma optical density during clotting.

Nephelometric

A modification of photo-optical end-point detection. Here, 90-degree or forward-angle light scatter, rather than OD, is measured.

Chromogenic (Amidolytic)

It uses a synthetic oligopeptide substrate conjugated to a chromophore (usually para-nitroaniline, pNA) to measure specific coagulation factor activity based on the factor's enzymatic (protease) properties; it is useful for evaluating specimens from patients with circulating inhibitors or on anticoagulant therapy because inhibitors do not interfere with this method.

1. Fresh Plasma

2. Prolonged

Substitution test that contains all coagulation factors at normal levels; used as a universal correction reagent to demonstrate that a ________ PT or APTT is due to a factor deficiency rather than an inhibitor.

1. Aged Plasma

2. 37°C

3. Factor V and Factor VIII

Substitution Test that is ________ that has been incubated at ___°C for 2–3 days; it is deficient in the labile factors Factor ____ and Factor ____.

1. Aged Serum

2. Factor VII, XI, X, XI, and XII

Substitution Test that is a _______ that has been allowed to age; it is deficient in fibrinogen, Factor V, Factor VIII, and Factor II (prothrombin) because these are consumed during clotting, but it contains Factors ____, ____, ____, ____, and ____.

1. Adsorbed Plasma

2. Barium Sulfate

3. Aluminum Hydroxide

4. Factor V, VIII, XI, XII and XIII

Substitution Test that a plasma treated with _________ (BaSO₄) or __________ (Al(OH)₃); this adsorption removes the vitamin K-dependent factors (Factor II, VII, IX, and X), but it retains ________ and Factors ____, _____, _____, _____, and ______.