HEMA 2: MIDTERMS PART 1

hemostasis

prevents blood loss after vessel injury

Plasma proteins, Cellular elements

key components of the hemostatic system (2)

Coagulation

 process whereby, on vessel injury, plasma proteins, tissue factors, and calcium interact on the surface of platelets to form fibrin clot

plasma

procoagulants are found and transported by

Factor III and IV

Nearly all are glycoproteins synthesized in the liver except

Fibrinogen

 is the substrate for the enzymatic action of thrombin, the primary enzyme of the coagulation system

Thrombin

converts fibrinogen to fibrin

1935

Fibrinogen and Prothrombin (Factor II) were identified

1945-1950

Factors V and VII were identified

1950s

Factors IX and X were identified

International Committee for the Standardization of the Nomenclature of the Blood Clotting Factors

In 1958, the ___ officially named the plasma procoagulants and cofactors using Roman numerals in the order of their initial description or discovery.

platelet factor 3

Platelet phospholipids were once collectively called

High molecular weight kininogen

belongs to the kinin systems

Prekallikrein

belongs to kallikrein system

Substrate, Zymogen/ enzyme precursor, Ionized calcium, Cofactor

Coagulation factors

Fibrinogen

only substrate in the cascade that does not become an activated enzyme

Zymogen/ enzyme precursor

They have no biologic activity until converted by enzymes to active forms

Factor II, VII, IX, X, XI, XII, PK, XIII

Examples of Zymogen/ Precursor (8)

Cofactors

• Are non-enzymatic proteins

• component that aids in the activation of zymogen to active enzyme

• Each binds its particular serine protease

Factor III, V, VIII, HMWK

examples of cofactors (4)

Protein S

cofactor of ACP

Cofactor

creates more potent reaction

serine proteases, transglutaminase/ tansamidase

When zymogens (inactive form) are converted into enzymes (active form) they become  either

serine proteases

proteolytic enzymes of trypsin family that activates other specific factors in the coagulation sequence

serine protease

use serine as the active site and acts on its substrate by hydrolyzing peptide bond, digesting the primary backbone & producing small polypeptide fragments.

1. Thrombin

2. VIIa

3. IXa

4. Xa

5. Xia

6. XIIa

7. Kallikrein

example of serine proteases (7)

Transglutaminase/ transamidase

Catalyzes the transfer of amino acid in gamma chains of fibrin polymer

transglutaminase/ transamidase

Cross-links fibrin polymer, thus, providing physical strength to fibrin clot

Factor XIIIa

example of transglutaminase

Fibrinogen

Factor I

Prothrombin

Factor II

Tissue Thromboplastin

Factor III

Calcium

Factor IV

Proaccelerin

Factor V

Proconvertin

Factor VII

Anti-hemophilic Factor A

Factor VIII

Plasma thromboplastin component

Factor IX

Stuart-Prower Factor

Factor X

Plasma thromboplastin antecedent

Factor XI

Hageman

Factor XII

Fibrin Stabilizing Factor

Factor XIII

341,000

MW of Factor I

200-400 mg/dl

Normal value in plasma of Factor I

3-4 days

Half life of Factor I

Thrombomodulin, Protein S, Protein Z

Part of control system (3)

63,000

a2 globulin with MW

Factor II

Converted to thrombin when exposed to Va, Xa, PF3 and Ca++

Va, Xa, PF3 and Ca++

Factor II is converted to thrombin when exposed to (4)

Pro-portion, Thrombin portion

2 portion of Factor II

60 hours

half life of factor II

Pro-portion (fragment 1.2)

responsible for the binding the prothrombin molecule

tissue factor and phospholipids

factor III is a mixture of

Factor III

 a lipoprotein found in tissues, membranes of fibroblasts, smooth muscle cells, and monocytes during inflammation and sepsis.

Factor III

Acts as a cofactor in activating extrinsic pathway

brain and lungs

factor III is exceptionally high concentrations are found in the

Factor IV

Required in the several steps in coagulation pathway. Very important in every step of the cascades

Factor V

a cofactor that speeds the transformation of prothrombin to thrombin

Factor V

It is the most unstable factor and deteriorates rapidly at room temperature

12-14 hours

half life of Factor V

300,000

A globulin with MW (Factor V)

Factor X

Factor VII activated by tissue thromboplastin, After activation, it activates Factor

60,000

B globulin with MW (Factor VII)

4-6 hours

Half life of Factor VII

Factor VII

used to delineate/differentiate factor VII (increase PT alone) and liver disease (increase all factors)

>1,000,000

A glycoprotein with MW (Factor VIII)

VIII:C, VIII:vWF

two functional subunits of Factor VIII

Factor VIII:C

is the active and small portion of the molecule and can be measured by the clotting assays.

Kupfer cells of the liver

Factor VIII:C production site is in

Factor VIII:vWF

is the total factor VIII molecule consisting of a low molecular weight unit (VIII) and a high molecular weight unit (vWF)

Factor VIII:vWF

It increases the half life of factor VIII

Factor VIIIR:Ag

is the antigenic portion of the molecule capable of stimulating antibody production and measured by immunoassay (FVIII)

Factor VIIIR:RCo

• demonstrates ristocetin cofactor activity

• important in platelet aggregation

A cofactor

• Active in Intrinsic pathway

• Necessary for formation of plasma thromboplastin

A cofactor

Deteriorates rapidly in stored plasma (even in refrigerated temperature)

12 hours

Half life of A cofactor

Hemophiliac A

Factor VIII deficiency

VWF

• Acts as a carrier for the coagulant portion of the Factor VIII complex; constitutes greater that 90% of this complex

VWF

Synthesized in the endothelium and megakaryocytes and present in the α granules of the platelets

Factor IX

• Absent in adsorbed plasma

• Active in intrinsic system

• Necessary to form plasma thromboplastin

24 hours

Half life of Factor IX

62,000

glycoprotein MW of Factor IX

Factor II, VII, IX, X

Vitamin K dependent (4)

Factor X

• Absent in adsorbed plasma

• Active in intrinsic and extrinsic system

• Activated form acts with Va, Ca++ and PF3 to form active thromboplastin

40 hours

Half life of X

Factor XI

One of the contact factors of the intrinsic system

HMWK, Factor XII

For the activation of Factor XI, ___ is needed as a cofactor with XII

45 hours

Half life of Factor XI

Factor XII

Activated by negatively charged substances such as exposed collagen. In vitro, it is activated by glass

Activate XI, Converts prekallikrein to kallikrein, Activates plasminogen in the fibrinolytic system

XIIa has several functions (which are aided by cofactor HMWK): (3)

deficiency of Factor XII

is the ONLY factor defciency that causes no coagulation problems

FACTOR XIII (FIBRIN STABILIZING FACTOR)

transglutaminase/transamidase that is responsible of catalyzing the formation of fibrin polymer

FACTOR XIII (FIBRIN STABILIZING FACTOR)

Necessary to form a stable clot (causes cross-linking of fibrin monomers)

3-5 days

half life of Factor XIII

HIGH MOLECULAR WEIGHT KININOGEN (HMWK)

Glycoprotein, produced in the liver

High Molecular Weight Kininogen

Part of the contact group of factors and involved in the feedback loop at the beginning of the intrinsic pathway

6.5 days

Half life of HMWK

Prekallikrein

γ globulin, produced in the liver

Prekallikrein

Part of the contact group of factors and involved in the feedback loop at the beginning of the intrinsic pathway

When converted to kallikrein by Factor XII it then loops back and accelerates the activation of larger amounts of Factor XII, Converts HMWK to kinins, Activates plasminogen, Activates the complement system, Acts as a chemotactic factor to attract macrophages

PK is converted to kallikrein and has several functions: