Normal hemostasis.pptx

hemostasis.

1. Dr sandeep singh Haemostasis

2. Haemostasis Process of formation of hemosatic plug to halt bleeding & restore normal blood flow. Hemostasis is a precisely orchestrated process involving platelets, clotting factors, and endothelium that occurs at the site of vascular injury and culminates in the formation of a blood clot, which serves to prevent or limit the extent of bleeding.

3. Component of Hemostatic System Vessel wall-Endothelial cells & subendothelial extracellular matrix i.e. collagen Platelets Coagulation system -coagulation factors & coagulation inhibitors Fibrinolytic system

4. Sequence of events at site of vascular injury during hemostatsis

5. Clot stabilization and resorption . Polymerized fibrin and platelet aggregates undergo contraction to form a solid, permanent plug that prevents further hemorrhage. At this stage, counterregulatory mechanisms are set into motion that limit clotting to the site of injury and eventually lead to clot resorption and tissue repair.

6. Role of platelet in hemostasis Forming the primary plug that initially seals vascular defects and by providing a surface that binds and concentrates activated coagulation factors.

7. Platelet adhesion { Subendothelium —VWF— GPIb receptor on platelet} Shape change ( from round disc to flat plate with multiple spiky protrusion) Release reaction from alpha ( Fibrinogen, Factor V, Fibronectin , Platelet factor 4, PDGF, TGF-beta) & dense granules (ADP, ATP, Calcium ions, Serotonin, epinphrine ) Platelet aggregation {through platelet GPIIb-IIIa receptor binding to fibrinogen & form primary haemostatic plug } Platelets

8. Coagulation cascade series of amplifying enzymatic reactions that lead to the deposition of an insoluble fibrin clot – secondary hemostatic plug

9. Common Pathway

10. Fibrinolytic system Plasminogen PAI-1 tPA α 2 antiplasmin Plasmin Fibrin FDP (D dimer )

11. Coagulation normally is restricted to sites of vascular injury by: Coagulation factors present in inactivated forms require enzymatic activation Circulating inhibitors of coagulation factors, such as antithrombin III, whose activity is augmented by heparin-like molecules expressed on endothelial cells Expression of thrombomodulin on normal endothelial cells, which binds thrombin and converts it to an anticoagulant Activation of fibrinolytic pathways (e.g., by association of t-PA with fibrin

12. Role of endothelium Has both prothrombotic and antithrombotic properties. Antithrombotic properties are divided into : Platelet inhibitory effect : intact endothelium act as a barrier prevents binding of platelet with vWF & collagen. Release PGI2 & NO Anticoagulant effects: exert via expression of various molecules like thrombomodulin , heparin like molecule, TFPI Fibrinolytic effect-

13. Basic function of HAEMOSTATIC system The haemostatic mechanisms have 2 primary functions : 1 . To promote local haemostasis at the site of injured blood vessel . 2 . To ensure that the circulating blood remains in fluid state while in the vascular bed i.e. to prevent the occurrence of generalised thrombosis.

14. Why Bleeding disorders? Failure of normal haemostatic mechanism. Injury to vascular endothelium Platelets defects Coagulation defects Fibrinolytic system defects Combination of all these

15. What are Bleeding disorders Group of disorders of diverse aetiology , characterised by abnormal tendency to bleed either spontaneously or after slight trauma.

16. Accordingly, there are specific tests for assessing each of these components: A. Blood vessel wall : Tests for disordered vascular haemostasis B. Platelets : Tests for platelets and their functions C. Plasma coagulation factors : Tests for blood coagulation D . Fibrinolytic system : Tests or fibrinolysis E. Inhibitors : Tests for coagulation inhibitors

17. Basic approach of bleeding disorder Comprehensive clinical examination Screening tests Specific tests then Patient’s clinical history Family history Details of site of bleeding Frequency of bleeding Character of haemostatic defect

18. History s/o bleeding disorder : Spontaneous bleeding. Bleeding from more than one site Recurrent episodes of bleeding . Severe bleeding from trivial trauma. Excessive bleeding following Sx procedures like tooth extraction & tonsillectomy. Spontaneous haemarthrosis or deep hematoma formation. Recurrent epistaxis without seasonal variation Menorrhagia H/O taking drugs & nutritional supplements like aspirin, garlic, ginger exacerbate bleeding.

19. INHERITED DISORDERS ACQUIRED DISORDERS Early age of presentation Family history positive More severe Bleeding is the dominant feature Single factor defect Later age of presentation Family history usually negative Less severe Clinical picture is dominated by the underlying disorder e.g.DIC Multiple hemostatic defect

20. Findings Disorders of Platelet/1° hemostatic defect Disorders of Coagulation/2° hemosatic defect Petechiae Superficial ecchymosis Deep dissecting hematomas Haemarthrosis Bleeding from the superficial cuts & scratches. Positive family history Bleeding from mucous membrane Characteristic Characteristic, usually small & multiple Rare Rare Persistent often profuse Rare Prominent Rare Common, usually large & solitary Characteristic Characteristic Minimal Common May occur

21. Petechiae ( 1 – 2 mm ) Purpura (≥ 3 mm) Ecchymosis (> 1 – 2 cms ) Petechiae : Tiny pin point ecchymoses Purpura : Small reddish-purple discoloration on the skin that do not blanch on applying external presssure over them. Ecchymosis : reddish or bluish discoloration on the skin due to extravasation of the blood due to ruptured blood vessels. These patches are larger than pupura and do not blanch on applying external presssure over them

22. Screening Test for Primary Haemostasis Hb,PCV -asses blood loss Hess test Bleeding time –platelet & vascular defects Platelet count -Quantitation of platelets PBS - 1) Quantitative & morphological abnormalities of platelets 2)detection of underlying hematological disorder PFA-100 system-platelet function

23. Screening Test For Secondary Haemostasis CT- coagulation phase PT-Extrinsic & common pathway APTT-Intrinsic & common pathway TT-Fibrinogen function

24. E. INVESTIGATION OF COAGULATION INHIBITORS Important inhibitors are as under : 1. Antithrombin III : This binds to thrombin and forms thrombin-antithrombin complex which does not permit coagulation . 2. Protein C and S Activated protein C : acts as anticoagulant by cleaving and inactivating activated factor V and VIII. This reaction is further augmented by a cofactor, protein S. Deficiency of protein C and S, or failure of action of activated protein C on activated factor V due to mutation of the target site on factor V (Leiden factor) leads to hypercoagulability .