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Som 205 > Hemostasis And Coagulation > Flashcards

Hemostasis And Coagulation Flashcards

1
Q

3 aspects of hemostasis

A

Endothelium
Platelets and plasma factors

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2
Q

3 types of plasma factors

A

Coagulation, anticoagulation, fibrinolytic factors

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3
Q

Function of regulatory factors

A

Limit accumulation of platelets and fibrin

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4
Q

Primary hemostasis

A

Generate platelet
Platelets and vessel wall
Adhesion, activation and aggegation of platelets
Vasocontriction

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5
Q

Secondary hemostasis
Action, components, function

A

Proteolytic cleavage of plasma coagulation factors
Transform blood to thrombus, has fibrin
Dominant hemo defense, on top of platelet plug to reinforce

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6
Q

Definition of secondary hemo
Aim

A

Cascade reaction of plasma coagullation factors
Generate fibrin net and hemo plug

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7
Q

Func of endothelial cells

A

Maintain fluidity of blood, secrete anticoagulatio factors NO, prostaglandin, endothelin
Antiplatelet and anticoagulants

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8
Q

Endo cells
1)Antiplatelet

A

1) prostacycline PGI2, NO, perivascular relaxation of sm muscle

CD 39 and 73( ATP,ADP to AMP ) called immunologic switches. ATP driven proinfla immune to antiinfla state mediated by adenosine.

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9
Q

Endo cell
Anticoagulation

A

EPCR, TM, Protein S, TFPI, GAG, AT-III, tPA, plasminogen receptor

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10
Q

Anticoag and antiinflam

A

Protein S, prostacycline, Tissue factor pathway inhibitor( -ve fXa, fVII), tPA, AT-III

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11
Q

Found on lumen:
1.AT-III cofactors

2.Thrombin cofactor

Endothelial protein C receptor

ADPase and plasminogen receptor

A

1.Glycosaminoglycans and heparan sulphates, natural ones
Inhibit F. IIa,Xa

2.Thrombomodulin, positive protein C

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12
Q

Endo Prothrombotic and procoagulative

A

Thromboxane A2 and Vw factor

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13
Q

Describe VW factor
Storage
Liver source
Rceptor

A

In weible pallade bodies
In platelet alpha granules

gpIb-IX-V

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14
Q

What causes major thrombotic func

A

Endo dysfunction brought by toxic injury( lipopolysaccharide of gram -ve bac) and hypoxia(sepsis,shock,infla,trauma)

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15
Q

Normal platelet count

Regulator

Type of granules

A

150-400x10⁹/L
Thrombopoietin

Alpha and dense granules, release mediators

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16
Q

List glycoprotein receptors on platelets

A

VW f= gp lb-IX-V
collagen= gp Ia-IIa, gpVI, gpIV
Fibrinogen=gp IIb-IIIa

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17
Q

What activates fibrin

A

Prothrombinase complex, have procoagulation activity

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18
Q

Activated ( bind collagen )Platelets release

A

Platelet factor 4 from a.granules, inc coagulation, heparin like effects

serotonin
ADP and thromboxane A2
Beta thrombomodulin

Morphological surface change

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19
Q

Func of beta thrombomodulin

A

Strong fibroblast and weak neutrophil chemoattractant
Stimulate glucose meta
Megakaryocyte maturation
Plasminogen activator in human fibroblast

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19
Q

Func of beta thrombomodulin

A

Strong fibroblast and weak neutrophil chemoattractant
Stimulate glucose meta
Megakaryocyte maturation
Plasminogen activator in human fibroblast

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20
Q

Func of fibrinogen platelet binding

A

Formation of crosslinks between platelets….their aggregation

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21
Q

Platelet activators

A

subendothelial Collagen, bind receptors
ADP, serotonin bind P2Y1, P2Y12
Thromboxane A2, acti platelet produce for amplification
Thrombin, bind protease activated receptor
Adrenaline

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22
Q

P. Inhibitors

A

ADPase, produce AMP
NO, Prostacycline

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23
Q

Synthesis of TXA2

A

From arachodonic acid, by COX during p.activation

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24
Q

What forms thrombinase complex

Tenase complex

Primary complex of contact system

A

F Xa,Va, release fibrin at site of primary hemo

VIII,IX

HMWK, PREKALLIKREN factor XII, collagen

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25
Q

Cellular injury stimulus

A

Tissue factor, works on factor VII first
TFPI inhibits.

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26
Q

Combination of phospholipids and tissue factor

Platelet tissue factor gene

Factor III role

A

Thromboplastin

F3 gene, in subendo and leukocytes

Initiate thrombin formation from zymogen prothrombin

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27
Q

Contact activation pathway

Importance

A

Formation of primary complex on collagen
Kininogen(HMWK), prekallikrein,F XII
convertion of last 2 into active form
FXI convertion
F IX activation
Tenase complex formation
Acitvation of FX

Involved in inflammation and innate immunity. Bradykinins, kallidin( cleaved kallikrein by HMWK

28
Q

Deficiency that do not cause bleeding in contact acti pathway

A

FXII, HMWK, prekallikrein

29
Q

Secondary hemo inhibitors

A

Protein C and help from S= VIIIa and Va

Antithrombin= thrombin FXa
TFPI = F VIIa

30
Q

Amplification of secondary system

A

When thrombin is activated, acts on XI, VIII, V activations

31
Q

Cofactor that binds VWF

A

Factor VIII

32
Q

Describe F XIIIa

A

Transglutaminase
Catalyze formation of covalent bonds btwn lysine and glutamine residues in fibrin, form stabilized cross linked fibrin clot

33
Q

Describe F XIIIa

A

Transglutaminase
Catalyze formation of covalent bonds btwn lysine and glutamine residues in fibrin

34
Q

That drives the coagulation pathway

A

Tissue factor

35
Q

Two phase of secondary hemo

A

Initiation by TF
Amplification by thrombin

36
Q

Plasma coagulation factors in extrinsic p.
Injured cells

In intrinsic, injured platelets

A

F III
VII
IV and Ca

IXa and VIIIa phospholipids, ca

37
Q

What indueces formation of fibrin polymer

A

Active thrombin by prothrombinase complex
Activated fibrinogen on prothro complex
Thrombin and Ca, XIIa final step.

38
Q

Fibrinolysis produces

A

Fibrin fragments, same as coagulation
Plasmjnogen to Plasmin to fibrin

39
Q

List the Coagulation inhibitors

A

Antithrombin III
TFPI, bind Xa, Then this inhibits TF:VIIa complex
PRO C and S

40
Q

MOA of heparin

A

Bind antithrombin III, inc flexibility of reactive site loop…..inacti thrombinand Xa,

41
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked f

42
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked fibrin monomers

43
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked fibrin monomers

44
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked f

44
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked fibrin monomers

45
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked fibrin monomers

46
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked fibrin monomers

46
Q

MOA of thrombin

A

Cleave fibrinopeptide, in central region of fibrinogen, convert to covalently linked fibrin monomers

47
Q

What deactivates antithrombin III

A

Serine protease bind and block acitve site ahile heparin co factor dissociates

48
Q

Relationship between bile salts and bitamin k
Pancreas

A

Are fat soluble, require bile salts to make mixed micelles, form chylomicrons, go into lacteals, and portal circulation to liver

Have vitamin binding protein, need proteolytic action of pancreatic enzy to be free

49
Q

Anti aggregants

Anti coagulants

Thrombolytics

A
50
Q

Antiplatelet/antiaggregants agents

A

ACETYLSALICYCLIC ACID..Aspirin, aspegic,godasal = COX inhibitors , decrease TXA2

Phosphodiesterase inhi….dipyridamole, aggrenox
ADP receptor inhi, clopidogrel(plavix) ,ticlopidine( ticlid)

Gp IIb-IIIa inhi….tirofiban, heptapeptide eptifibatid, abciximab(prevent clumping)

51
Q

Role of phosphodiesterase intracellular

A

Regulate cGMP and cAMP by converting them to AMP, prevents stimulation of gpIIB-IIIa

52
Q

Role of beraprost, epoprostenol, iloprost,

Cilostazol, dipyridamole

A
53
Q

Role of direct thrombin inhibitors

A
54
Q

Indirect thrombin inhibitors
Unfractioned heparin

Pharmacokinetics

Inhibitors

A

Anti Xa/ anti IIa Ratio is 1
Half life of 1hr

Antidote, protamine sulphate

Platelet factor 4 is a Natural inhibitor

55
Q

Low molecular weight heparin, indirect

A

Ratio 2.4
5hr half life

Enoxaparine, dalte,nadroparine

more than 18 saccharides to inhi FIIa

P.sulohate on only Anti IIa activity, small anti xa can not bind

56
Q

Indirect
Synthetic pentasaccharides

A

When there is heparin contraindication
17hr h.life

Selective antiXa activity
5 saccharide units needed for Xa and At III
IIa more than 18

fondapariux and no antidote. No HITT

57
Q

Hirudins

Type of inhibitor

Activity

A

Prophylaxis and therapy of VTE

Direct inhibitors

Selective Anti IIa

Lepirudin

aPTT mode of therapy

58
Q

Factors for gamma carboxylation modification

A

Vit k dependent

II, VII, IX, X PRO C and S

59
Q

Describe Vit k dependent carboxylation

Aim

A

Hydroquinone to vit k epoxide,
Vit k epoxide reductase to quinone,
Vit k reductase( from quinone) back to cycle

Produce non functional coagu factors, called pro indu by by vit k absence

E.g gamma carboxyglutamate by vit k oxidation

60
Q

Warfarin

Moa

Half life

Antidote

A

Vit k antagonist

40h

Vitamin k

61
Q

Pt

aPTT

A
  1. Monitor warfarin
62
Q

Vit k dependent factors deficiency

Consequence

A

Protein C and F. VII, shortest half life

Cause warfarin induced skin necrosis

63
Q

Describe thrombolytic therapy

A

Dissolution of arterial clot
Recanalization of occluded artery
Prevent ischemia

Indirect: streptokinase;in some streptococci, complexes plasminogen , acyivates other plasminogens

Direct rt-plasminigen activator; alteplase, cleaves plasminogen to plasmin

64
Q

Describe TT therapy

A
65
Q

Hemorrhagic diathesis

Thrombophilias

A
  1. Vasculopathies
    Thrombocytopenia

Coagulopathy

  1. White and red thrombus
    Occlution of microcirculation, APS, HITT, MPN

Som 205 (3 decks)

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