Hemostasis/Thrombosis I

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Wendy Hampton
7 years ago
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1 HEMOSASIS Primary vs. Secondary vs. ertiary Hemostasis/hrombosis I Normal Hemostasis/hrombosis; Assessment of Clotting System Primary Hemostasis Platelet Plug Formation Dependent on normal platelet number & function Initial Manifestation of Clot Formation Secondary Hemostasis Activation of Clotting Cascade Deposition & Stabilization of Fibrin ertiary Hemostasis Dissolution of Fibrin Clot Dependent on Plasminogen Activation HEMOSASIS & HROMBOSIS HEMOSAIC DISORDERS Suspicions Platelets ets Coagulation Cascade Regulation of Coagulation Spontaneous bleeding Prolonged or excessive bleeding after procedures or trauma Simultaneous bleeding from multiple sites CIRCULAORY SYSEM Low volume, high pressure system Efficient for nutrient delivery to tissues Prone to leakage 2º to endothelial surface damage Small volume loss large decrease in nutrient delivery Minimal extravasation in critical areas irreparable damage/death of organism HEMOSAIC DEFECS Bleeding Platelet Coagulation Problem Disorder Abnormality Petechiae + - Bleeding Sites ime of onset of bleeding Ecchym oses /Hem atom as M ucous M em b rane Immediate Deep issue Delayed + + 1

HEMOSAIC ABNORMALIIES "Screening ests" (History) Dental Extractions

transfusion PLAELES Anucleate cellular fragments; multiple granules,

thrombopoietin Circulate as inactive, non-binding concave discs On

factors Develop ability to bind to each other & subendothelium Resting

2 HEMOSAIC ABNORMALIIES "Screening ests" (History) Dental Extractions Prior Surgery/Biopsy Easy bruising i Heavy menses Deliveries Blood transfusion PLAELES Anucleate cellular fragments; multiple granules, multiple organelles Synthesis controlled by IL-6, IL-3, IL-11, & thrombopoietin Circulate as inactive, non-binding concave discs On stimulation, undergo major shape change Develop receptors for clotting factors Develop ability to bind to each other & subendothelium Resting Platelets PLAELE ACIVAION Platelet Adhesion vwf Initial hrombin Formation R II X -F 2

PLAELE ACIVAION Platelet Activation II X -F Platelet Release xa2,

FORMAION General Features Zymogens converted to enzymes by

phospholipid surface, cofactors hrombin converts fibrinogen to

3 PLAELE ACIVAION Platelet Activation II X -F Platelet Release xa2, ADP, Serotonin, Fibrinogen, hrombospondin II X -F PLAELE PLUG FORMAION General Features Zymogens converted to enzymes by limited proteolysis Complex formation requiring calcium, phospholipid surface, cofactors hrombin converts fibrinogen to fibrin monomer Fibrin monomer crosslinked to fibrin Forms "glue" for platelet plug 3

4 Platelet Release xa2, ADP, Serotonin, Fibrinogen, hrombospondin VIII V IX I II X -F -F VI Va HROMBIN Serine protease Cleaves fibrinogen to fibrin Activates V to Va, VIII to VI Activates platelets-cleaves thrombin receptor Activates XIII to XI In presence of thrombomodulin activates Protein C to APC enase/prothrombinase complex assembly X II VI/I Va/ VI R Va R FIBRIN FORMAION A A B B F XI 4

5 VIAMIN K DEPENDEN CARBOXYLASE Post-translational modification Factors II, VII, IX, X; proteins C & S Converts 1st 7-12 glutamic acids to γ-carboxyglutamic acid Confers calcium binding and lipid binding on these proteins Without vitamin K, secrete desγ-carboxyglutamic acid containing proteins (inactive in coagulation) unt (x 1000) Platelet cou BLEEDING IME vs. PLAELE COUN Minutes γ -CARBOXYGLUAMIC ACID CH 2 CH CH 2 O 2,CO 2 CH 2 NH 3 + CH Vit K Carboxylase NH 3 + CH Glu γ-carboxy Glu PLAELE FUNCION SUDIES Bleeding ime Platelet l Count Platelet Aggregation Studies Clotting ests Recalcification times Blood collected in sodium citrate, a weak calcium chelator Amount designed d to drop calcium concentration to < 1 mm At that level, blood won t clot spontaneously RBC s & platelets centrifuged off, leaving plasma (unclotted liquid portion of blood) 5

6 Prothrombin ime Mixture of: 50% patient s platelet poor plasma 25% Mixture of issue Factor & phospholipid species 25% Calcium chloride (to bring final calcium concentration to c. 3-5 mm) ime to clot formation measured INRINSIC PAHWAY FXII FX FXI HMWK FXIa VIII FIX FI Ca+2 VI VI/I/PL Middle Components Common Pathway V Surface Active Components ap FX F Ca+2 Va Va//PL P FG F EXRINSIC PAHWAY Contact Phase Prothrombin ime (P) F F FVII Prekallikrein Kallikrein Middle Components /F F XII HMWK Common Pathway V Va FX F Ca+2 Va//PL P FG F F XI F X F XIa ap (activated partial thromboplastin time) 50% patient s platelet-poor plasma 25% mixture of phospholipid & surface active agent (Celite, Kaolin) 25% Calcium Chloride to bring calcium concentration to 3-5 mm ime to clot formation measured Intermediate Phase XIa /F/PL F IX VIII VI + F I I/VI/PL F /F F VII/F enase Complex F X F 6

7 Common Pathway I/VI/PL /F/PL F X Ca+2 F X V Va + FX /Va/PL /PL Prothrombinase Complex P Fibrinogen Fibrin monomer CLOING ASSAYS Specific factors/inhibitors Deficiency states of every clotting protein described 50% of any clotting factor will yield normal P and/or ap Mix 1/2 patient plasma with 1/2 factor deficient plasma; then perform P and/or ap Factor deficient plasma with missing factor will prolonged clotting time; all others WNL If more than one clotting assay prolonged, implies inhibitor to clotting protein 7

LABORATORY DIAGNOSIS OF BLEEDING DISORDERS

LABORATORY DIAGNOSIS OF BLEEDING DISORDERS Secondary Hemostasis CIRCULATORY SYSTEM Low volume, high pressure system Efficient for nutrient delivery to tissues Prone to leakage 2º 2 to endothelial surface