Coagulation Pathway

Category: Education

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Slide 2: 

Vessel injury vasocontriction Reduced Blood flow Collogen exposure Platelet Release reaction Primary Haemostatic plug Platelet fusion STABLE HAEMOSTATIC PLUG Factor XII Thrombin fibrin Tissue Thromboplastin Blood Coagulation

Normal haemostasis involvesinteraction of : : 

Normal haemostasis involvesinteraction of : Blood vessels Platelet Coagulation factors

Initial arrest of haemorrhage : 

Initial arrest of haemorrhage Vasoconstriction & elastic recoil of severed blood vessel Formation of platelet plug

Coagulation Pathway : 

Coagulation Pathway Activation of blood clotting factors Fluid blood ? insoluble fibrin clot

Coagulation Cascade : 

Coagulation Cascade • Factors Circulate In Inactive Form – Proenzyme – Procoagulant • Enzymatic Cleavage To Active Form • Remaining Portion Becomes Active Cleavage Enzyme – Serine Protease • “Activated Clotting Factor” – “VIIa” – Cleaves Next Procoagulant Factor

Blood vessel injury : 

Blood vessel injury Platelet adhere to exposed subendothelial tissue - subendothelial microfibrils binds to vWH which binds to pH membrane Ib complex - spherical shape with pseudopods ? Interaction between pHs

Platelet activation : 

Platelet activation Glycoprotein 11b/111a binding pH aggregation Binding with vWF Promoting adhesion

Platelet release reaction : 

Platelet release reaction Collagen exposure Thrombin ADP - lysosomal enzyme Serotonin - b thromboblobulin Fibrinogen - heparin neutralising factor (PF4) Secretion of plt. granules:-

Cell membrane : 

Cell membrane Release thromboxane A2 Potentiate pH aggregation vasoconstriction

ADP : 

ADP Cause platelet to swell Adhesion Result on more release reaction Further plt. aggregation

Platelet Procoagulant activity : 

Platelet Procoagulant activity Exposed membrane phospholipid (PF3) X Xa Prothrombin Thrombin IXa, VIIIa Xa Va Ca++

Blood Coagulation : 

Blood Coagulation Biological amplification system (lmol X la ? 2x108 mol of fibrin) Circulating precursor Proteolysis Activation Fibrinogen ? fibrin (form stable clot with platelets)

Tissue Factor - TF : 

Tissue Factor - TF not expressed normally disruption of endothelium ? TF expression ? formation of FVII/TF complex ? activation of FVII ? FVIIa/TF

FVlla/TF complex : 

FVlla/TF complex Activate FX & FIX Xa, lla, FVlla, FIXa ? activate FVII (positive feedback)

FVlla, TF FXa : 

FVlla, TF FXa Binds with TFPl ? quarternary complex ? Inhibits further generation of Xa, IXa

More Xa in formed : 

More Xa in formed X Xa - FVIII FVIIIa - FIX FIXa FIXa, FVIIIa Thrombin XIa

Thrombin : 

Thrombin Activate FVII, FV FXI Platelet FXIII

Old Coagulation Pathway : 

Old Coagulation Pathway Extrinsic & intrinsic pathway Able to test the ‘2 pathways’ Able to understand coagulation Fail to represent the true picture

Inaccuracy of the old Pathway : 

Inaccuracy of the old Pathway No clinical problem with deficiency of FXII, prekallikrein or HMWR ( APTT) FXI deficiency – don’t always present with bleeding FVII deficiency ? bleeding (even tho entrisnic pathway is intact) FVII activate FIX, FX TF is a natural constituent of many nonvascular cells Identification of TFPI

Coagulation Cascade Newer Thoughts : 

Coagulation Cascade Newer Thoughts Surface Antigens • Play Role In Activation • Localize Coagulation • Some Factors Need Two Activators • Second “Co-Factor” • Create “Reaction Complex” • Require Phospholipid Surface

Coagulation Cascade Testing : 

Coagulation Cascade Testing Intrinsic and Extrinsic Pathways - Presence of Platelet Phospholipid Needed to Test Intrinsic Pathway Partial Thromboplastin Time Platelet Phospholipid Substitute - Chloroform Extract from Rabbit Brain –Thromboplastin - Reflects Clotting Ability of Intrinsic andCommon Pathway

Intrinsic Pathway Test - PTT : 

Intrinsic Pathway Test - PTT Modified By “Surface Activating Factors – XII & XI “Activated Partial Thromboplastin Time” – Maximum Activation of Contact Factors • XII, XI, Prekallilrein, & High Molecular Weight Kinogen – More Consistent , Reproducible • Eliminates Lengthy Contact Activation Phase • Normals – PTT: 40 – 100 secs (> 120 Abnormal) – aPTT: 25–35 secs

Extrinsic Pathway Test : 

Extrinsic Pathway Test Prothrombin Time– Activity of Factor VII Intrinsic Pathway Factors X, V, II, & I– Addition of Tissue Thromboplastin and Ca+ Time to Clot Formation

Slide 36: 

PREPARED BY PN. BOOB PA INIT 36 ............. sekian ..................

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