HEMOSTASIS

1. HEMOSTASIS By Prof\ Sameh Shamaa Prof Of medical Oncology and Internal medicine Mansoura Faculty Of Medicine HEMOSTASIS

2. HEMOSTASIS Def:- stoppage of bleeding from the blood vessels Mechanisms • v.c of blood vessels • platelet plug formation • Blood coagulation (fibrinogen fibrin) • Clot retraction • fibrinolysis to dissolve the clot HEMOSTASIS

3. PRIMARY HEMOSTASIS includes the processes that result in the formation of the platelet plug. Necessary factors-: -The blood vessels : the vessel walls esp. the subendothelial layer. - The platelets - 2 plasma glycoproteins: - fibrinogen -Willebrand factor ,which also presents inside the platelets

4. Mechanisms: 1-v.c of the bl. vessel. 2- Platelets adhesion to subendothelial layer, ( Willebrand factor is necessary for this stage) adhesion of platelets-3- platelets secretion: their activation and secretion of ADP,adrenaline, noradrenaline –> aggregation & activation of other platelets. 4- Aggregation of platelets. 5- Formation of capillary plug. HEMOSTASIS

5. Exploration of the 1ry homeostasis • Important points in the history of any bleeding patients : HEMOSTASIS

6. Family history • Duration (recent onset or since childhood) • Duration of the bleeding episode. • Circumstance of bleeding (spontaneous, after trauma, or surgery) HEMOSTASIS

7. Type and character of bleeding: - • Purpuric spots (capillary or platelets defect not characteristic of hemophilia) • Hematoma, hemarthrosis or large ecchymoses at the site of trauma : suggests hemophilia (coagulation defect) • Sudden severe bleeding from multiple sites after prolonged surgery or during obstetric procedures suggests acquired fibrinogen defect HEMOSTASIS

8. 2) Investigations : HEMOSTASIS

9. Capillary resistance test of Hess • Platelets count • Bleeding time time needed for the platelet plug formation If . N. ------ Normal 1ry homeostasis . ↑ ------ platelet or vascular defect. HEMOSTASIS

10. Capillary resistance test of Hess: sphygmomanometer cuff above the cubital fossa and raise the pressure to 100 mm Hg (or midway between systolic & diastolic if systolic pressure <100) for 5 - 7' minutes- deflation  '3 minutes later  count the number of petichea in area of 3 cm diameter, 1 cm below the cubital fossa  Normally up 10 if more than 20, means platelets or capillary wall defect HEMOSTASIS

11. Other tests only done if there is a prolonged bleeding time with normal platelet count • Measurement of capillary resistance • Measurement of Willebrand factor • Platelets function tests (Adhesiveness, Aggregation) • other tests for platelets (clot retraction, ↓ prothrombin consumption). HEMOSTASIS

12. Coagulation of Blood Def :- represent the conversion of fibrinogen (soluble protein) to fibrin (insoluble) meshwork which occludes the point or vessel rupture. HEMOSTASIS

13. First Step :Activation of factor X BY One of 2 systems: I-urgent system II-delayed system (Extrinsic system.) (Intrinsic system.) HEMOSTASIS

14. systems of coagulation I-urgent system. II-delayed system Extrinsic system. Intrinsic system. 12-20'' (seconds) 4-8' (minutes) In vivo only. In vivo & in vitro Due to tissue damage. due to contact with foreign surface ↓ ↓ Tissue factor activation of contact system ↓ ↓ X < ------------------------------------IX a < ---------------- IX ↓ Xa ↓ 2- prothrombin thrombin 3-fibrinogen Fibrin HEMOSTASIS

15. EXTRINSIC SYSTEM FACTORS NICESSORY ARE: Factor X Tissue factor and Factor VII Tissue F. VIIa VII Xa X Blood vessel HEMOSTASIS

16. INTRINSIC SYSTEM Necessary factors: - XII (Hageman factor) - Contact system XI Kallikrene kininogene - F. IX - F. VIII - F. X - Ca. ++ - phospholipids of the platelet’s membrane HEMOSTASIS

17. Contact System: Foreign surface |--------------------------------------------------| Kalierne XII kininogene Fragmentation XIIa XI XIa Rest of intrinsic pathway IX HEMOSTASIS

18. Rest of intrinsic pathway IX Platelets Ca ++ IXa X VIIIa VIII Xa II IIa HEMOSTASIS

19. Second Step: of Coagulation Thrombin Formation: (IIa) Factors needed: - prothrombin (II) Ca++ platelets - Xa IIVCa++ - V (acceleririe) Xa - phospholipids - Ca + + IIa HEMOSTASIS

20. 3rd Step :Fibrin Formation Fibrin Formation:- ------------------------ IIa XIII XIIIa (Fibrinogen) -------------------- Ia (Soluble fibrin) Insoluble Fibrin HEMOSTASIS

21. Physiological anticoagulants • 1- Serine protease inhibitors :inhibit the coagulation cascade. • 2-Neutralizers of activated coagulation factors (components of protein C system) HEMOSTASIS

22. 1-Serine protease inhibitors: • 1-Antithrombin (III). • 2-Heparin and heparin like substance. • 3-Alpha 1 antitypsin. • 4-Alpha 2 macroglobulin HEMOSTASIS

23. 2-Neutralizers of activated coagulation factors:(components of protein C system) • 1-Protein C: synthesized in the liver, vit. K dependant, activated by thrombin. • 2-Thrombomodulin. • 3-Protein S and C4b-binding protein. HEMOSTASIS

24. Fibrinolysis is the process wherein a fibrinclot, the product of coagulation, is broken down.Its main enzymeplasmin cuts the fibrin mesh at various places, leading to the production of circulating fragments that are cleared by other proteases or by the kidney and liver HEMOSTASIS

25. HEMOSTASIS

26. Measurement When plasmin breaks down fibrin, a number of soluble parts are produced. These are called fibrin degradation products (FDPs). FDPs compete with thrombin, and so slow down the conversion of fibrinogen to fibrin (and thus slows down clot formation).

27. Exploration of the coagulation • whole blood clotting time Normally 4-10 minutes Generally ---> N. in platelets defects. ↑ = coagulation defect But not very sensitive: - only +ve when blood coagulation is very defective HEMOSTA fibrinolysis (Hyperfibrinolysis), SIS HEMOSTASIS

28. (2) One stage prothrombin time: general exploration or the extrinsic pathway (Quick time) N : 16-18 sec. • addition of tissue thromboplastin + • ca++ to decalcified plasma ---> measure the time till coagulation occur. • Affected by factors VII,X, V, II & fiboinogen (only severe defect) HEMOSTASIS

29. (3) partial thromboplastin time (PTT) or CKT(cephaline koalin time) General exploration of the intrinsic pathway clotting time of recalcified plasma in the presence of phospholipid (cephaline), while koalin powder for activation of Hageman factor'. Affected by factors XII, XI, IX, VIII, X, II HEMOSTASIS

30. Thrombin time detect the defects in the conversion of fibrinogen ---> fibrin Measured by addition of thrombin to citrated patients plasma If polonged • Abnormalities of fibornogen (hypo or hyper or dysfibrinogenemia) • Heparin • Presence of some abnormal proteinswhich inhibits the polymerisation of monomers of fibrin. (e.g myeloma protein HEMOSTASIS

31. (5)Deficiency of F XIII (fibrin stabilizing factor ) detected by noting the solubility of fibrin in 5M urea or 1% monochloroacetic acid (can't dissolve fibrin in the presence of factor XIII).In congenital defect of f. XIII ---> dissolution of the clot in <10. (6) Assay for each cogulation factor is available HEMOSTASIS

32. (7) Detection of coagulation inhibitors: 1-Inhibitors for a specific factor (especially F. VIII) usually ---> severe hemorrhage 2- Inhibitors against platelets or tissue phospholipids ---> prolongation of tests of coagulation (Quick or CKT) e.g L.E but usually no hemorrhagic manifestations 3- if there is ↑of Quick test or CKT or thrombine:- 50% of normal plasma + 50% of patient plasma (incubation at 370c for I hour) repeat the test If become normal ---> factor defect if no correction ---> presence of inhibitors. HEMOSTASIS

33. PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE B.T Platelets count Quick test CKT Thrombin time Dosage of fibrinogen HEMOSTASIS

34. PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE I- B.T↑, platelets ↓( ↓80.000; mm3) Thrombocytopenia 2- B.T↑, platelets normal Qualitative platelets abnormalities Willebrand disease congenital or acquired platelet factor tests dosage of factor VIII HEMOSTASIS

35. PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE 3- ↑Quick + ↑CKT Other tests are N Acquired defect of several defect of factor common for factors (II, VII, X,V) 2 pathways ex. X or V or II 4- Quick N., ↑ CKT: either: I- Hemophilia Aor B. 2- Rarely ---> defect of one factor of the contact system (XII, or XI or others) HEMOSTASIS

36. PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE 5- Quick ↑, CKT N isolated defect of factor VII in 3, 4..5 dosage of the factors with suspected deficiency, also search for inhibitors. Ex: - ↑ Quick, normal dosage of factors---> hyperfibriongenemia which inhibit the test - ↑Quick +↑CKT + no F. defect --->? Inhibitors, e.g. antiphospholipides. HEMOSTASIS

37. PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE 6-↑T.T either: * heparine in the blood or in the tube. Here T.T can be corrected by adding either a- toluidine blue b-Reptilase time (incomplete thrombin not sensitive to heparin and not inhibited by antithrombin III). * If (a-b also defective) ---> troubles of fibrin polymerisation :either due to abnormal fibrin (dysfibrinogenimia) or inhibition e.g by ---> myeloma protein or F.D.P. HEMOSTASIS

38. PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE 7- ↓fibrinogen * congenital afibrinogenimia or hypofibrinogenimia • Acquired hypofibrinogenimia e.g.liver cirrhosis. • consumption of fibrinogen: e.g.D.I.V.C, fibrinolysis HEMOSTASIS

39. PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE 8-All tests ate Normal: * Capillary fragility (usually only ecchymoses ) ---> measurement of cap.fragility. * deficient factor XIII * no hemostatic troubles. HEMOSTASIS

40. Thank You HEMOSTASIS