Doria and Saxena

Question 1

Thrombophilia

Answer 1

Inappropriate activation of hemostatic system with excessive thrombus formation. Most common cause of death is the U.S. Abnormalities can be acquired or hereditary. Complications secondary to ischemia or necrosis of distal organs.

Question 2

Define thrombus

Answer 2

Intravascular mass of platelets, fibrin and entrapped cells and is attached to a vessel and can grow or be dislodged at distant sites as an embolus.

Question 3

Define Hemostasis

Answer 3

Carefully balanced process task maintenance of fluid blood flow to ultimately keep internal body environment constant. Process of clot formation and lysis and vessel repair and involves series of complex and regulated events.

Question 4

Coagulation

Answer 4

Concerned with the formation of insoluble fibrin clot from proteins present in the blood that are in an inactive state (zymogen)

Question 5

Coagulation deficiencies

Answer 5

Slow rate of coagulation, prolonged clot formation, bleeding tendencies

Question 6

3 majors facets that act simultaneously in hemostasis

Answer 6

Vasculature: contracture and dilation - diminish or increase flow, localize the reaction.
Platelets: form aggregate plugs and aid in secondary coagulation.
Coagulation factors: support the unstable platelet plug with fibrin formation and late breakdown.

Question 7

Where are coagulation factors produced

Answer 7

Mostly in the liver, 8 (vWF) in megakaryocytes and endothelial cells of the liver, 8 (C) in macrophages and 13 in megakaryocytes.

Question 8

Nomenclature of factors

Answer 8

Factor I Fibrinogen​

Factor II Prothrombin​

Factor III Tissue thromboplastin (tissue factor)​

Factor IV Calcium​

Factor V Labile factor (proaccelerin)​

Factor VI Not assigned (was activated Factor V)​

Factor VII Stable factor (serum prothrombin conversion accelerator or SPCA)​

Factor VIII Antihemophilic factor, von Willebrand factor​

Factor IX Christmas factor (plasma thromboplastin component or PTC)​

Factor X Stuart Prower factor​

Factor XI Plasma thromboplastic antecedent (PTA)​

Factor XII Hageman factor (contact factor)​

Factor XIII Fibrin stabilizing factor (FSP)​

Fitzgerald factor HMWK (high molecular weight kininogen)​

Fletcher factor Prekallikrien

Question 9

Factor 1 ( fibrinogen)

Answer 9

chromosome 4, produced in liver, normal level is 250 mg, substrate, in all pathways.

Question 10

Factor 2 (prothrombin)

Answer 10

chromosome 11, produced in liver, vitamin K dependent, serine protease, thrombin precursor, in all pathways.

Question 11

Factor 3 ( tissue thromboplastin)

Answer 11

Chromosome 1, transmembrane glycoprotein found in most nonvascular cells, not in plasma, cofactor of factor 7 in the extrinsic and common pathway.

Question 12

Factor 4 ( calcium)

Answer 12

required in many coag reactions

Question 13

Factor 5 ( proaccelerin)

Answer 13

Labile factor, chromosome 1, produced in liver, cofactor in prothrombinase complex in all pathways.

Question 14

Factor 7 ( proconvertin, stable)

Answer 14

chromosome 1, produced in liver, vitamin k dependent, serine protease, component of extrinsic Xase complex in extrinsic only.

Question 15

Factor 8 ( antihemophilic factor, von Willebrand factor)

Answer 15

chromosome X, produced in the megakaryocytes, cofactor in intrinsic xase complex in intrinsic only.

Question 16

Factor 9 ( plasma thromboplastin component, Christmas factor)

Answer 16

Chromosome X, produced in the liver, vitamin K dependent, cofactor in intrinsic Xase complex, intrinsic only.

Question 17

factor 10 ( Stuart Prower factor)

Answer 17

Chromosome 13, produced in liver, vitamin k dependent, serine protease, component of prothrombinase complex, in all pathways.

Question 18

Factor 11 ( plasma thromboplastin antecedent)

Answer 18

chromosome 4, produced in liver, most bound to HK in circulation, serine protease, contact factor, intrinsic only

Question 19

Factor 12 ( Hageman factor)

Answer 19

Chromosome 5, produced in liver, serine protease, contact factor, intrinsic only.

Question 20

Factor 13 ( fibrin stabilizing factor)

Answer 20

Chromosome 6 and 1, produced in liver or megakaryocytes, transglutamase in all pathways.

Question 21

Fitzgerald Factor

Answer 21

HK, High molecular weight kininogen, Williams factor. Chromosome 3, produced in liver, contact factor, complex with prekallekrein and FXI, in intrinsic.

Question 22

Fletcher factor ( Prekallekrein)

Answer 22

chromosome 4, bound to HK in circulation, serine protease, complex with PK, in intrinsic

Question 23

Co - factors

Answer 23

Factors 5, 8, HK. no enzymatic activity and enhances reactivity of associated protease. substrate is fibrinogen, enzymes are activated by conformational change or proteolytic cleavage of zymogen peptide bonds.

Question 24

Prothrombin group

Answer 24

factors 2, 7, 9 AND 10, requires calcium and vitamin K, attaches -COOH group to glutamic acid, deficient proteins PIVKA. Vitamin K deficiency in parenteral feeding, neonate, liver disease, gut surgery, antibiotic therapy.

Question 25

Fibrinogen group

Answer 25

Factors 1, 5, 8, and 13. Consumed during clotting, absent from serum, responds to thrombin. Acute phase proteins

Question 26

Contact group

Answer 26

Factors 11, 12, PK, HK. Involved in initial activation and requires negatively charged surface. Stable and found in serum. No bleeding associated with deficiency except for factor 11.

Question 27

How is intrinsic pathway activated

Answer 27

Factor 12 is activated by autoactivation, by a foreign substance or other charge dependent, glass, acid, cellite, plasmin, kallikrein. Factor 12a and HK activates prekallikrein to kallikrein to produce more factor 12. Complex with factors 9a, 8a, platelet factor 3 and calcium activates the common pathway.

Question 28

Extrinsic Pathway

Answer 28

Factor 3 is a cell membrane protein found almost subendothelial cells and when exposed to injury, factor 3 is exposed and binds factor 7 and factor 7a and with calcium activate factor 7. The activated Factor 7 complex can activate the common pathway via Factor 10 and the intrinsic pathway via Factor 9.

Question 29

Common Pathway

Answer 29

Factor 1 0activated by extrisnic and intrinsic pathways, factor 5 activated by thrombin. Complex with 10a, 5a, factor 3, and calcium activates factor 2 to thrombin. Thrombin acts on fibrinogen to produce fibrin. Factor 13a acts on fibrin clot.

Question 30

Fibrinogen

Answer 30

Most abundant factor in serum and responsible for ESR. Thrombin cleaves portions of alpha and beta chains at the arginine-glycine bonds of the E nodule and converts it to a net positive charge.

Question 31

What converts fibrinogen to fibrin

Answer 31

Thrombin. Thrombin also degrades factor 5 and 8. Aggregate platelets and initiates thrombolysis, and involved in inflammation.

Question 32

Fibrinolysis

Answer 32

Main function is the removal of excessive fibrin from the circulation in a controlled manner and prevent expansion of coag, and allow progression of vascular and tissue repair and restoration of function. Activated in response to initiation of coag. Key enzyme is plasmin, which degrades fibrin.

Question 33

Plasmin

Answer 33

Degrades fibrin, fibrinogen, 5 and 8. Enhance 11 and 11a, enhance prekallekrein to kallekrein. Cleave C3 to fragments.

Question 34

Liver clearance

Answer 34

Major site of factor production and primary site for removal of activated factors with their inhibitors and degradation products. LDL receptor related protein found on hepatocytes and live macrophages and degrades activated factors.

Question 35

Antithrombin

Answer 35

Most important anti - coagulant and all degrades serine proteases, especially thrombin and also plasmin. HSP localizes reaction