MMSC423 Exam 1 (copy)

Factor I

Factor I

Fibrinogen

Factor II

Prothrombin

Factor III

Tissue Factor

Factor IV

Ionic Calcium

Factor V

Labile factor

Factor VII

Stable factor proconvertin

Factor VIII

Antihemophilic factor

Factor IX

Christmas factor

Factor X

Stuart-Prower

Factor XI

Plasma thromboplastin

Factor XII

Hageman factor

Factor XIII

Fibrin-stabilizing factor

What factors are serine protease?

Factor II, VII, IX, X, XI, XII, Prekallikrein

What factors are cofactors

Factor III, V, VIII, HMWK

What factors are transglutaminase

XIII

What factors are in the Extrinsic pathway complex

Ca, VIIa, TF

What factors are in the Intrinsic pathway complex

Ca, PF, VIIIa

What factors are in the prothrombin complex

Ca, PF, Xa, Va

Hematology

study of blood cells (RBCs, WBCs, platelets) and the blood forming tissues in both the healthy and pathological states

Buffy coat

the white layer of WBCs and platelets that accumulate at the middle of separated non-clotted blood

Hemostasis

arrest of bleeding by spontaneous formation of hemostatic platelet plug; cellular, chemical, and fluid elements of blood in constant exchange to maintain the balance between supply and demand

Major elements of plasma

Water, Proteins, Antibodies, Lipids, CHO, electrolytes, clotting factors, enzymes, vitamins, and hormones

Serum vs Plasma

Serum is fluid obtained when coagulated blood has been centrifuged whereas plasma is obtained when its anticoagulated blood

Serum vs Plasma (in relation to Fibrinogen)

Serum does NOT contain Fibrinogen (a clotting factor) and plasma DOES (because no clot has formed)

How are platelets produced?

Endometriosis (maturation of cells in megakaryocytic lineage) occurs in the megakaryocytic lineage to produce platelets

1. Released from MK-III

What is the life-span of platelets?

7-10 days (very short)

What does the platelet ultrastructure including?

Peripheral zone, So gel zone, Membrane zone, and organelle zone

Discuss the constituents/functions of the peripheral zone

1. Glycoproteins: binding of different coag factors to platelet

2. Open canalicular system: allows substances contained in alpha and dense granules to be released and enable aggregation

3. Glycocalyx: contains blood group antigens and HLA Ags

Discuss the constituents/functions of the so gel zone

1. Microtubules: actin and myosin microtubules that maintain structure and shape of platelet

2. Actin

3. Microfilaments, contractile proteins

Discuss the constituents/functions of the membrane zone

1. Dense tubular system: stores calcium, thromboxane A2 and phospholipase C

Discuss the constituents/functions of the organelle zone

1. Alpha granules

2. Dense granules

3. Glycogen

4. Mitochondria

5. Golgi apparatus

Discuss adhesion vs aggregation

Adhesion: when platelets bind to elements of the vasculature when there is a breach

Aggregation: when irreversibly bind to one another

Discuss the variables in adhesion

1. vWF and collagen bind to their receptors on platelets to stop them from exiting (imagine using gorilla glue to stop a leak)

2. Fibrinogen with Ca binds to receptor and activates

Discuss the variables in Aggregation

1. Thromboxane A2 and ADP are released from DTS to aggregate

2. Fibrinogen with help of Ca facilitates

Discuss the process of platelet plug formation

1. There is a breech

2. vWF is released bc it binds to collagen and platelets have the receptor for vWF

3. Platelets bind via a bridge (GP-Ib) to the receptor and change in shape to increase surface area

4. Fibrinogen receptors are then released due to platelet activation (GPIIb/IIIa)

5. Alpha and dense granules are released

   1. Alpha: releases more vWF and PDGF to help wound healing

   2. Dense: ADP is released and Thromboxane which binds to their receptors and caused more platelets to be activated

6. Circulating fibrinogen from liver binds to new fibrinogen receptors and now platelets can heal to one another (now we have a plug aka aggregation)

Cyclooxygenase

enzyme that transforms arachidonic acid to prostaglandin endoperoxides; aspirin INHIBITS

Thromboxane A2

the converted version of PG endoperoxides that causes further aggregation

(can not be created without cyclooxygenase because this transforms arachidonic acid to PG endoperoxides)

Coagulation cascade model pathways

Intrinsic, extrinsic, and common

Intrinsic system

1. Collagen is released

2. XIIa is produced

3. XIIa combines with HMWK cofactor to turn PK into K

4. Xlla combines with HMWK cofactor to activate XIa

5. XIa with Ca activates IXa

6. Ixa w/ cofactor VIIIa & Ca & PF  create intrinsic tenase complex

7. Complex activates Xa

Extrinsic system

1. Injury occurs

2. III is released

3. VIIa produced

4. Combines with TF

5. Vlla & TF combine with Ca to form extrinsic tenase complex

6. Complex activates X to Xa

Common pathway

1. Xa combines with Ca, PF, and factor Va to form prothrombinase complex

2. Complex activates II

3. IIa activates I (which is unstable bc its soluble)

4. IIa activates XIII

5. XIIIa combines with Ca and stabilizes soluble Ia

6. End with stable fibrin clot (insoluble fibrin polymer)

Cofactor

A clotting factor that acts to enhance the activation of another clotting factor

What coagulation factors function as cofactors

TF, VIII, V, and HWMK

Site of synthesis, requirement of K and function of Factor 1

found in alpha granules of platelets, polymerizes and forms fibrin, can act as acute phase reactant

Site of synthesis, requirement of K and function of Factor 2

Synthesized in liver, vitamin K dependent, acts as serine protease to cleave factor I to Ia and factor XIII to XIIIa

Site of synthesis, requirement of K and function of Factor 3

present throughout body, function is cofactor to VII

Site of synthesis, requirement of K and function of Factor 4

required for aggregation of platelets, function is as mineral allosteric activator of other factors

Site of synthesis, requirement of K and function of Factor 5

in alpha granules, function cofactor to X, serine protease involved in prothrombinase complex

Site of synthesis, requirement of K and function of Factor 7

serine protease that is used to make extrinsic tenase complex, vitamin K dependent, produced by liver

Site of synthesis, requirement of K and function of Factor 8

cofactor to factor IX, part of intrinsic tenase complex, synthesized in liver and endothelial cells

Site of synthesis, requirement of K and function of Factor 9

serine protease that is part of the intrinsic tenase complex, vitamin K dependent, synthesized in liver

Site of synthesis, requirement of K and function of Factor 10

serine protease that forms the prothrombinase complex in common pathway, vitamin K dependent, produced in liver

Site of synthesis, requirement of K and function of Factor 11

serine protease that converts factor IX to IXa, produced in liver but can be found in platelets

Site of synthesis, requirement of K and function of Factor 12

serine protease that functions to cleave PK to K and factor XI to XIa, produced in liver

Site of synthesis, requirement of K and function of Factor 13

transglutaminase (only one) that stabilizes soluble fibrin monomer with covalent bonds to insoluble fibrin polymer

What factors of vitamin K-dependent

Factor II, VII, IX, and X

Discuss role of vWF in relation to VIII

vWF and VIII circulate together as a complex in the plasma

vWF is the protective carrier for VIII (protects from degrading)

List the functions of thrombin, antithrombin, TFPI, and activated Protein C: THROMBIN

thrombin: activate V, VIII, XI, XIII; aggregate platelets, activate protein C

Function of antithrombin

a substance in the blood that limits the blood’s ability to clot (coagulation) and the primary inhibitor of thrombin

Function of TFPI

inhibit FXa, inhibit VIIa and TF

Function of protein C

inactivate Va and VIIIa to slow down coagulation

Explain the structure of fibrinogen assessing how it’s function is related to its structure

3 pairs of polypeptide chains: alpha, beta, and gamma held together by disulfide bonds

these bonds allow for a stable fibrin clot (because they are covalent)

Summarize the functionality of the vitamin K dependent factors

these factors bind VK epoxide to obtain a Ca binding region

VK epoxide is carboxylated VK hydroxyquinone with a negative charge (due to 2 carboxyl groups) that allows Ca to bind

Compare and contrast the different naturally occurring inhibitors of coagulation in relationship to their function (called anticoagulants): NITRIC OXIDE

inhibits platelet adhesion and aggregation

Hep sulfate

enhances the actions of antithrombin

TFPI

inhibits factors Xa, VIIa, and TF to slow down coagulation system

Thrombomodulin

activates protein C

EPCR

increase protein C activation rate

Compare and contrast the intrinsic pathway, common pathway, and the extrinsic pathway of coagulation in the Cascade Model of Coagulation and list factors involved in the tenase complex and prothrombinase complex

has factor HMWK, XIa, XIIa, K, and IXa, VIIIa while extrinsic pathway with TF, VIIa

both contact Ca

extrinsic pathway complex: TF, VIIA, Ca

intrinsic pathway complex: IXa, VIIa, Ca, PF

Describe the three phases of Cell-based model of coagulation and factors involved: INITIATION

VII in blood is activated by TF which forms extrinsic tenase complex and leads to activation of IX and X, leading to thrombin, leading to platelet activation via PAR1 and PAR2

Amplification

platelets are activated, vWF is released, and V, VIII, XI are activated on platelet surface

Propogation

Xa is produced and IXa-VIIIa complex and prothrombinase complex leading to massive amounts of thrombin; platelets are linked by fibrinogen through receptors GPIIb/IIIa

Discuss the process of fibrinolysis including the role of tissue plasminogen activator (TPA), plasminogen and plasmin; state regulators of fibrinolysis

the breakdown of fibrin by plasmin

regulators: plasminogen activator inhibitor-1 and TAFI (both inhibit)

TPA converts plasminogen to plasmin

Compare and contrast coagulation factors in the prothrombin group, contact group, and fibrinogen group delineating factors in each group as well as factors contained in serum, plasma, and absorbed plasma: PROTHROMBIN GROUP

II, VII, IX, and X

not present in adsorbed plasma and all except II are in serum

Fibrinogen group

I, V, VIII, XIII

all present in adsorbed plasma but not in serum

Contact group

XI, XII, PK, HMWK

present in both absorbed plasma and serum