Hemostasis And Coagulation Flashcards by Tumisang Bale

Q

3 aspects of hemostasis

A

Endothelium
Platelets and plasma factors

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Q

3 types of plasma factors

A

Coagulation, anticoagulation, fibrinolytic factors

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Q

Function of regulatory factors

A

Limit accumulation of platelets and fibrin

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Q

Primary hemostasis

A

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

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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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Q

Definition of secondary hemo
Aim

A

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

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Q

Func of endothelial cells

A

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

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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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Q

Endo cell
Anticoagulation

A

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

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Q

Anticoag and antiinflam

A

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

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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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Q

Endo Prothrombotic and procoagulative

A

Thromboxane A2 and Vw factor

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Q

Describe VW factor
Storage
Liver source
Rceptor

A

In weible pallade bodies
In platelet alpha granules

gpIb-IX-V

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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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Q

Normal platelet count

Regulator

Type of granules

A

150-400x10⁹/L
Thrombopoietin

Alpha and dense granules, release mediators

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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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Q

What activates fibrin

A

Prothrombinase complex, have procoagulation activity

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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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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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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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Q

Func of fibrinogen platelet binding

A

Formation of crosslinks between platelets….their aggregation

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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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Q

P. Inhibitors

A

ADPase, produce AMP
NO, Prostacycline

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Q

Synthesis of TXA2

A

From arachodonic acid, by COX during p.activation

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What forms thrombinase complex Tenase complex Primary complex of contact system

F Xa,Va, release fibrin at site of primary hemo VIII,IX HMWK, PREKALLIKREN factor XII, collagen

Cellular injury stimulus

Tissue factor, works on factor VII first TFPI inhibits.

Combination of phospholipids and tissue factor Platelet tissue factor gene Factor III role

Thromboplastin F3 gene, in subendo and leukocytes Initiate thrombin formation from zymogen prothrombin

Contact activation pathway Importance

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

Deficiency that do not cause bleeding in contact acti pathway

FXII, HMWK, prekallikrein

Secondary hemo inhibitors

Protein C and help from S= VIIIa and Va Antithrombin= thrombin FXa TFPI = F VIIa

Amplification of secondary system

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

Cofactor that binds VWF

Factor VIII

Describe F XIIIa

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

Describe F XIIIa

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

That drives the coagulation pathway

Tissue factor

Two phase of secondary hemo

Initiation by TF Amplification by thrombin

Plasma coagulation factors in extrinsic p. Injured cells In intrinsic, injured platelets

F III VII IV and Ca IXa and VIIIa phospholipids, ca

What indueces formation of fibrin polymer

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

Fibrinolysis produces

Fibrin fragments, same as coagulation Plasmjnogen to Plasmin to fibrin

List the Coagulation inhibitors

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

MOA of heparin

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

MOA of thrombin

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

MOA of thrombin

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

MOA of thrombin

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

MOA of thrombin

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

MOA of thrombin

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

MOA of thrombin

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

MOA of thrombin

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

MOA of thrombin

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

What deactivates antithrombin III

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

Relationship between bile salts and bitamin k Pancreas

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

Anti aggregants Anti coagulants Thrombolytics

Antiplatelet/antiaggregants agents

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)

Role of phosphodiesterase intracellular

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

Role of beraprost, epoprostenol, iloprost, Cilostazol, dipyridamole

Role of direct thrombin inhibitors

Indirect thrombin inhibitors Unfractioned heparin Pharmacokinetics Inhibitors

Anti Xa/ anti IIa Ratio is 1 Half life of 1hr Antidote, protamine sulphate Platelet factor 4 is a Natural inhibitor

Low molecular weight heparin, indirect

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

Indirect Synthetic pentasaccharides

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

Hirudins Type of inhibitor Activity

Prophylaxis and therapy of VTE Direct inhibitors Selective Anti IIa Lepirudin aPTT mode of therapy

Factors for gamma carboxylation modification

Vit k dependent II, VII, IX, X PRO C and S

Describe Vit k dependent carboxylation Aim

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

Warfarin Moa Half life Antidote

Vit k antagonist 40h Vitamin k

Pt aPTT

1. Monitor warfarin

Vit k dependent factors deficiency Consequence

Protein C and F. VII, shortest half life Cause warfarin induced skin necrosis

Describe thrombolytic therapy

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

Describe TT therapy

Hemorrhagic diathesis Thrombophilias

1. Vasculopathies Thrombocytopenia Coagulopathy 2. White and red thrombus Occlution of microcirculation, APS, HITT, MPN