Coagulation System

COAGULATION SYSTEM

Q. 1 Tissue thromboplastin activates:
 A Factor-VII
 B Factor-IV
 C Factor-VI
 D None of the above
Q. 1 Tissue thromboplastin activates:
 A Factor-VII
 B Factor-IV
 C Factor-VI
 D None of the above
Ans. A

Explanation:

Factor VII


Q. 2

All of the following are true about blood coagulation, EXCEPT:

 A

Factor X is part of both intrinsic and extrinsic pathways

 B

Extrinsic pathway is activated by contact with negatively charged surfaces

 C

Intrinsic pathway can be activated in vitro

 D

Calcium is required in several steps of coagulation

Q. 2

All of the following are true about blood coagulation, EXCEPT:

 A

Factor X is part of both intrinsic and extrinsic pathways

 B

Extrinsic pathway is activated by contact with negatively charged surfaces

 C

Intrinsic pathway can be activated in vitro

 D

Calcium is required in several steps of coagulation

Ans. B

Explanation:

Contact with negatively charged surfaces activates the Intrinsic pathway of coagulation and not the Extrinsic pathway.

Intrinsic pathway is also referred to as ‘contact pathway’ and factor XII is also known as contact factor for its role in the initiation of coagulation on contact with negatively charged surfaces.

Extrinsic pathway is activated by tissue factor a cellular lipoprotein exposed at sites of tissue injury

Ref: Robbins pathologic basis of disease 6th edn/page 977.


Q. 3

Which of the following is the earliest event in the clotting cascade?

 A

Binding of platelets to red blood cells

 B

Binding of vitamin K to endothelial cell surfaces

 C

Release of tissue factor by damaged vessels

 D

Secretion of von Willebrand factor by platelets

Q. 3

Which of the following is the earliest event in the clotting cascade?

 A

Binding of platelets to red blood cells

 B

Binding of vitamin K to endothelial cell surfaces

 C

Release of tissue factor by damaged vessels

 D

Secretion of von Willebrand factor by platelets

Ans. C

Explanation:

The clotting cascade consists of a series of ordered enzymatic steps whose end result is the formation of a clot.

There are two limbs of the clotting cascade: the extrinsic pathway and the intrinsic pathway.

The extrinsic pathway relies on the exposure of tissue factor by an injury, which then activates Factor VII, the most abundant of the clotting factors.
 
The intrinsic pathway starts when Factor XII, an inactive serine protease encounters exposed collagen from an injured blood vessel.

Factor XII is transformed into an activated serine protease. Activated Factor XII cleaves inactive Factor XI into activated Factor XI.

This in turn cleaves the inactive form of Factor IX, and the activated Factor IX transforms inactive Factor VII to its active form.

Later events in the actual formation of the clot involve platelets, von Willebrand factor, calcium interacting with endothelial surfaces, and formation of D-dimers
 
Ref: Freedman J.E., Loscalzo J. (2012). Chapter 117. Arterial and Venous Thrombosis. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Q. 4

Endothelial cells synthesize which of the following:

 A

Fibrinogen

 B

Factor-VIII

 C

Factor-X

 D

Factor-XII

Q. 4

Endothelial cells synthesize which of the following:

 A

Fibrinogen

 B

Factor-VIII

 C

Factor-X

 D

Factor-XII

Ans. B

Explanation:

The major site of factor VIII synthesis is in the hepatic endothelial cells. Liver is the major site of fibrinogen and factor X synthesis.

  • Factor VIII circulates in a noncovalent complex with VWF.
  • When associated with VWF the normal half-life of factor VIII is 8 to 12 hours. And the half-life is markedly reduced in the absence of VWF.
  • Factor VIII has six tyrosine residues that are modified by sulfation. Sulfation of these residues is required for optimal activation by thrombin, maximal activity in complex with factor IXa, and maximal affinity of factor VIIIa for VWF.
Ref: Monroe D.M., Hoffman M., Roberts H.R. (2010). Chapter 115. Molecular Biology and Biochemistry of the Coagulation Factors and Pathways of Hemostasis. In J.T. Prchal, K. Kaushansky, M.A. Lichtman, T.J. Kipps, U. Seligsohn (Eds), Williams Hematology, 8e.

Q. 5

Which of the following clotting factor is not involved in intrinsic pathway?

 A

Factor XII

 B

Factor XI

 C

Factor IX

 D

Factor VII

Q. 5

Which of the following clotting factor is not involved in intrinsic pathway?

 A

Factor XII

 B

Factor XI

 C

Factor IX

 D

Factor VII

Ans. D

Explanation:

Intrinsic pathway requires clotting factors VIII, IX, X, XI XII. Factor VII is involved in extrinsic pathway. Other requirements for intrinsic pathway includes proteins such as prekallikrein and high molecular weight kininogen as well as calcium ions and phospholipids secreted from platelets. This pathway is initiated when prekallikrein, high molecular weight kininogen, factor XI and XII are exposed to negatively charged surface. This is called contact phase. Exposure of collagen to a vessel surface is the primary stimulus for the contact phase.

Ref: Medical Biochemistry By Sheriff, Page 405; Textbook of Medical Physiology By Guyton and Hall, 10th Edition, Page 423


Q. 6

Which of the following coagulation factors causes cross linking and stabilization of clot.

 A

Factor XIII

 B

Thrombin

 C

Factor VIII

 D

Factor IX

Q. 6

Which of the following coagulation factors causes cross linking and stabilization of clot.

 A

Factor XIII

 B

Thrombin

 C

Factor VIII

 D

Factor IX

Ans. A

Explanation:

A i.e. Factor XIII

  • Factor XIII (13) also known as fibrin stabilizing factor, when gets activated (by thrombin) cause formation of covalent cross linkages and provide three dimensional strength to fibrin meshwork (stbilization)Q
  • Factor XIII (a) converts a loose mesh of interlacing fibrin strands to a tightly dense aggregate by formation of multiple covalent bonds between fibrin monomers and cross linkages between fibrin fibers. This also requires calcium.

Q. 7

Which of the following is a procoagulation protein ‑

 A

Thrombomodulin

 B

Protein C

 C

Protein S

 D

Thrombin

Q. 7

Which of the following is a procoagulation protein ‑

 A

Thrombomodulin

 B

Protein C

 C

Protein S

 D

Thrombin

Ans. D

Explanation:

Ans. is ‘d’ i.e., Thrombin

Coagulation Cascade

o Coagulation cascade is a series of enzymatic conversions, turning inactive proenzymes into activated enzymes and culminating the formation of thrombin.

o Thrombin then converts the soluble protein fibrinogen precursor into insoluble fibrous protein fibrin. o The blood coagulation pathway are divided into.

1.Extrinsic —>           Activated by tissue factor.

2.Intrinsic —>            Activated by factor XII (Hagmen factor).

o In vivo coagulation is predominantly occurs via extrinsic pathway.

o Clotting is regulated by three types of natural anticoagulants.

  1.  Antithrombin III                           —> Binds to heparin like molecule on endothelial surface and this complex inhibit factor II (thrombin), IX, X, XI, XIL
  2. Protein ‘C’ & ‘S’ —> These are Vit K dependent proteins. Thrombomodulin bind to thrombin and this complex activates protein ‘C’, which then, with the help of protein `S’ as a cofactor, inactivates factor V & VIII.
  3. Tissue factor pathway —>        Secreted by endothelium and inactivates tissue factor VII & factor X. inhibitor ( TFPI)

Q. 8

All of the following are true about blood coagulation, except –

 A

Factor X is part of both intrinsic and extrinsic pathways

 B

Extrinsic pathway is activated by contact with negatively charged surfaces

 C

Intrinsic pathway can be activated in vitro

 D

Calcium is required in several steps of coagulation

Q. 8

All of the following are true about blood coagulation, except –

 A

Factor X is part of both intrinsic and extrinsic pathways

 B

Extrinsic pathway is activated by contact with negatively charged surfaces

 C

Intrinsic pathway can be activated in vitro

 D

Calcium is required in several steps of coagulation

Ans. B

Explanation:

Ans. is ‘b’ i.e., Extrinsic pathway is activated by contact with negatively charged surfaces

Principles pf pharmacology by Golan (Lippincott Williams & Wilkins)

o Contact with negatively charged surfaces activates the Intrinsic pathway of coagulation & not the Extrinsic

pathway, Intrinsic pathway is also referred to as’ contact pathway’ and factor XII is also known as

contact factor for its role in the initiation of coagulation on contact with negatively charged surfaces. Activation of coagulation pathway

o Intrinsic and extrinsic pathways are activated by different mechanisms :‑

1)  Intrinsic pathway

o The intrinsic pathway is largely an ‘in vitro’pathway of coagulation. However, it may be activated ‘in vivo’ also. ‘In vitro’ activation :- Intrinsic pathway may be activated ‘in vitro’ upon interaction of factor XII ( Hageman factor or contact factor) with negatively charged surface such as glass, kaolin, dextran sulphate, ellagic acid, celite, or bismuth subgallate and interaction with hydrophobic surfaces.

ii) ‘In vivo’ activation :- ‘in vivo’ activation occurs as a result of contact activation of factor XII from subendothelial collagen and other components (platelets) following endothelial injury to blood vessels.

o As intrinsic pathway is largely an ‘in vitro’ pathway, it is important for coagulation testing.

2)  Extrinsic pathway

o The extrinsic pathway is largely an ‘in vivo’ pathway and accounts for majority of ‘in vivo’ coagulation. It may also be activated ‘in vitro’ also.

i)           ‘In vivo’ activation :- ‘in vivo’ activation occurs by the expression of tissue factor at the sites of tissue injury.

ii)         In vitro’ activation :- ‘in vitro’ activation occurs by exposure of blood to thromboplastin reagents (tissue factor) derived from tissues.


Q. 9

Fibrin is degraded by-

 A

Plasminogen

 B

Thromboplastin

 C

Plasmin

 D

FD

Q. 9

Fibrin is degraded by-

 A

Plasminogen

 B

Thromboplastin

 C

Plasmin

 D

FD

Ans. C

Explanation:

Ans. is ‘c’ i.e., Plasmin

Fibrinolvtic system

o Coagulation must be balanced with fibrinolysis to limit the hemostatic plug to the site of injury.

o Injured vascular endothelium secret plasminogen activator that converts inactive plasminogen to active plasmin. o Plasmin breaks down fibrin resulting in production of fibrin degradation products.

o Fibrinolytic system is regulated by plasminogen activator inhibitors (PAIs) that are secreted by endothelium.


Q. 10

The following are essential components of the intrinsic coagulation system –

 A

Pre-kallikrein

 B

High molecular weight kininogen

 C

Factor VII

 D

a and b

Q. 10

The following are essential components of the intrinsic coagulation system –

 A

Pre-kallikrein

 B

High molecular weight kininogen

 C

Factor VII

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., Pre-kallikrein; `b’ i.e., High molecular weight kininogen


Q. 11

Major source of Von Willebrand factor (vWF) –

 A

Erythrocytes

 B

Neutrophils

 C

Endothelial cells

 D

Monocytes

Q. 11

Major source of Von Willebrand factor (vWF) –

 A

Erythrocytes

 B

Neutrophils

 C

Endothelial cells

 D

Monocytes

Ans. C

Explanation:

Ans. is `c’ i.e., Endothelial cells

o Circulating factor VIII has two components.

a)       Factor VIIIc (Procoagulant protein)

o This is the smaller component

o-It is synthesized in liver (main source) and kidney.

o It is an intrinsic pathway component required for activation of factor X.

b)       Von willebrand factor (vWF)

o This is the larger component.

o It is produced by endothelial cells (main source) and megakaryocytes.

o It has two major functions ‑

i)    Helps in platelets adhesion by interacting platelet membrane glycoprotein lb-IX.

ii)    Stabilizes factor VIllc.


Q. 12

Vitamin K dependent coagulation factors include:

 A

II and III

 B

IX and X

 C

III and V

 D

VIII and XII

Q. 12

Vitamin K dependent coagulation factors include:

 A

II and III

 B

IX and X

 C

III and V

 D

VIII and XII

Ans. B

Explanation:

Answer is B (IX and X):

Vitamin K dependent coagulation factors include coagulation factor II, VII, IX and X.

Vitamin K dependent Coagulation Factors / Proteins

  • Six proteins involved in clotting require conversion of a number of glutamic acid residues to 7 – carboxyglutamic acid residues before being released into circulation
  • This process of y (gamma) carboxylation occurs in the liver and requires vitamin k and hence these proteins are called vitamin – K dependent
  • These include coagulation factors II, VII, IX and X as well as protein C and protein S.

Vitamin K dependent proteins involved in clotting

  • Coagulation Factor IIQ (Prothrombin)
  • Coagulation Factor VIIQ (Proconvertin)
  • Coagulation Factor IXQ (Christmas factor)
  • Coagulation factor XQ (Stuart Prover Factor)
  • Protein CQ
  • Protein SQ

Q. 13

Converging point of both pathway in coagulation is at:      

 A

Factor VIII

 B

Stuart factor X

 C

Factor IX

 D

Factor VII

Q. 13

Converging point of both pathway in coagulation is at:      

 A

Factor VIII

 B

Stuart factor X

 C

Factor IX

 D

Factor VII

Ans. B

Explanation:

Answer is B (Stuart factor X)

The extrinsic and Intrinsic pathways in coagulation converge at the Stuart factor X.


Q. 14

Extrinsic system (blood coagulation) is triggered by the release of:           

September 2008

 A

Prothrombin

 B

Thromboplastin

 C

Fibrinogen

 D

Thrombin

Q. 14

Extrinsic system (blood coagulation) is triggered by the release of:           

September 2008

 A

Prothrombin

 B

Thromboplastin

 C

Fibrinogen

 D

Thrombin

Ans. B

Explanation:

Ans. B: Thromboplastin

Factor X can be activated by reactions in either of two systems, an intrinsic and an extrinsic system.

The extrinsic system is triggered by the release of tissue thromboplastin, a protein-phospholipid mixture that activates factor VII. The tissue thromboplastin and factor VII activate factors IX and X. In the presence of PL, Ca2+, and factor V, activated factor X catalyzes the conversion of prothrombin to thrombin.

The extrinsic pathway is inhibited by a tissue factor pathway inhibitor that forms a quaternary structure with TPL, factor VIIa, and factor Xa.


Q. 15

Hagemann factor is involved in:

March 2009

 A

Extrinsic pathway

 B

Intrinsic pathway

 C

Fibrinolysis

 D

None

Q. 15

Hagemann factor is involved in:

March 2009

 A

Extrinsic pathway

 B

Intrinsic pathway

 C

Fibrinolysis

 D

None

Ans. B

Explanation:

Ans. B: Intrinsic pathway

Hageman factor is factor XII, also known as glass factor.

The initial reaction in the intrinsic system is conversion of inactive factor XII to active factor XII (XIIa). This activation, which is catalyzed by high-molecular-weight kininogen and kallikrein, can be brought about in vitro by exposing the blood to electronegatively charged wettable surfaces such as glass and collagen fibers. Activation in vivo occurs when blood is exposed to the collagen fibers underlying the endothelium in the blood vessels. Active factor XII then activates factor XI, and active factor XI activates factor IX. Activated factor

IX forms a complex with active factor VIII, which is activated when it is separated from von Willebrand factor. The complex of IXa and VIIIa activate factor X. Phospholipids from aggregated platelets (PL) and Ca2+ are necessary for full activation of factor X.


Q. 16

Extrinsic system of coagulation is activated by

 A

Factor XI

 B

Factor X

 C

Factor XII

 D

Factor III

Q. 16

Extrinsic system of coagulation is activated by

 A

Factor XI

 B

Factor X

 C

Factor XII

 D

Factor III

Ans. D

Explanation:

Ans. is d i.e., Factor III


Q. 17

Factor X is ‑

 A

Hageman factor

 B

Stuart-Prower factor

 C

Christmas factor

 D

Tissue factor

Q. 17

Factor X is ‑

 A

Hageman factor

 B

Stuart-Prower factor

 C

Christmas factor

 D

Tissue factor

Ans. B

Explanation:

Ans. is ‘B’ i.e., Stuart-Prower factor


Q. 18

Pathway activated on contact with glass test tube by itself is termed ‑

 A

Intrinsic pathway

 B

Extrinsic pathway

 C

Both the above

 D

None of the above

Q. 18

Pathway activated on contact with glass test tube by itself is termed ‑

 A

Intrinsic pathway

 B

Extrinsic pathway

 C

Both the above

 D

None of the above

Ans. A

Explanation:

Ans. is ‘a’ i.e., Intrinsic pathway

Contact with negatively charged surfaces activates the Intrinsic pathway of coagulation & not the Extrinsic pathway, Intrinsic pathway is also referred to as’ contact pathway’ and factor XII is also known as contact factor for its role in the initiation of coagulation on contact with negatively charged surfaces.

Activation of coagulation pathway

Intrinsic and extrinsic pathways are activated by different mechanisms :‑

1) Intrinsic pathway

The intrinsic pathway is largely an ‘in vitro’pathway of coagulation. However, it may be activated ‘in vivo’ also.

i)     ‘In vitro’ activation :- Intrinsic pathway may be activated ‘in vitro’ upon interaction of factor XII ( Hageman factor or contact factor) with negatively charged surface such as glass, kaolin, dextran sulphate, ellagic acid, celite, or bismuth subgallate and interaction with hydrophobic surfaces.

ii)     ‘In vivo ‘ activation :- ‘in vivo’ activation occurs as a result of contact activation of factor XII from subendothelial collagen and other components (platelets) following endothelial injury to blood vessels.

As intrinsic pathway is largely an ‘in vitro’ pathway, it is important for coagulation testing.

2) Extrinsic pathway

The extrinsic pathway is largely an ‘in vivo’ pathway and accounts for majority of ‘in vivo’ coagulation. It may also be activated ‘in vitro’ also.

i) ‘In vivo ‘ activation :- `in vivo’ activation occurs by the expression of tissue factor at the sites of tissue injury. In vitro’ activation :- ‘in vitro’ activation occurs by exposure of blood to thromboplastin reagents (tissue factor) derived from tissues.


Q. 19

Preaccelerin is ‑

 A

Eater II

 B

Facter V

 C

Facter VII

 D

Facter X

Q. 19

Preaccelerin is ‑

 A

Eater II

 B

Facter V

 C

Facter VII

 D

Facter X

Ans. C

Explanation:

Ans. is ‘c’ i.e., Facter VII


Q. 20

Loose fibrin accumulated in tight clot in coagulation pathway by factor ‑

 A

X

 B

XI

 C

XII

 D

XIII

Q. 20

Loose fibrin accumulated in tight clot in coagulation pathway by factor ‑

 A

X

 B

XI

 C

XII

 D

XIII

Ans. D

Explanation:

Ans. is ‘d’ i.e., XIII

Loose (soluble) fibrin is converted to insuluble fibrin by thrombin and XIIIa.



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