HEMOSTASiS
HEMOSTASIS

 DEFINITION
- Heme = blood
- stasis = to halt

 It is the process of forming clots in the wall of
damaged bl...
Stages of Hemostasis
Vascular Constriction
Formation of Platelet Plug

Formation of blood clot

Fibrinolysis
Events in Hemostasis
 Vascular Constriction
- local myogenic spasm
- local autacoid factors from traumatized
tissues and ...
STAGES OF
PRIMARY HEMOSTASIS
 Platelet Adhesion
 Platelet Activation
 Platelet Aggregation
plATElET AdHESiOn
plATElET AcTivATiOn :
plATElET rElEASE AcTiOn
plATElET

AggrEgATiOn
SEcOndAry HEMOSTASiS
 “Cascade of reactions” by
Macfarlane, R.G.,1967
It

states that ‘inactive’ enzymes are
activated, a...
Clotting Factors
Factor I

Fibrinogen

Factor II

Prothrombin

Factor III

Thromboplastin

Factor IV

Calcium

Factor V

L...
PROPERTIES OF MOIETIES
INVOLVED IN BLOOD COAGULATION
 Contact system
- F-XII, Prekallikrein, F-XI
 Vit-K dependent coagu...
ENZYME CASCADE SEQUENCE

STAGE 1: FORMATION OF PROTHROMBIN
ACTIVATOR
STAGE 2: CONVERSION OF PROTHROMBIN INTO
THROMBIN
STAG...
Intrinsic Pathway
Conversion of Prothrombin to Thrombin &
Fibrin Polymerization
Extrinsic Pathway
WHY BLOOD DOES NOT CLOT IN
CIRCULATION ?
 Endothelial surface factor
-smoothness
-layer of glycocalyx
-Negatively charged...
FIBINOLYSIS
METHOD OF STUDY
 HEMOSTATIC FUNCTION TESTS
-Bleeding time
-Clotting time
-Prothrombin time
-Partial prothrombin time
-Thr...
BLEEDING TIME (B.T)
 Definition ;
- time interval between the skin puncture
and spontaneous , unassisted stoppage
of blee...
CLOTTING TIME ( C.T )
 Definition ;
- time interval between entry of blood into glass
capillary tube, or a syringe, and f...
PROTHROMBIN TIME (P.T)
 Normal P.T ; 15 – 20 sec.
 Clinical Significance ; bleeding tendency
occurs below 20% (Normal pl...
DISORDERS OF COAGULATION
 Defective blood clotting
- deficiency of clotting factors (I, II, V,
VIII, IX, X)
- deficiency ...
DEFICIENCY OF FACTORS
Hemophilia – A
(Classical Hemophilia)
 Factor VIII deficiency
Hemophilia – B
( Christmas disease)
 Factor – IX deficiency
Hemophilia - C
 Factor – XI
(Plasma thromboplastin anticedent)
deficiency.
Hemophilia - D

 Factor – XII
( Hageman factor) deficiency

28
Hemophilia
 Factor – VIII deficiency
 Inheritance – Sex linked,
-X-chromosome, females are carrier
 Diagnosis - CT incr...
Purpura
 Purple coloured petechial hemorrhages
and bruises in the skin.
 Characterized by spontaneous
hemorrhages beneat...
Diagnosis
 CT – N
 BT – increased
 Capillary endothelium resistance –
decreased
 Skin Microscopy
- Primary Purpura
-Sk...
Forms/Classification
 1. Thrombocytopenic Purpura

-Low platelet count
Clinically - Mild Purpura - > 50,000/µL
- Moderate...
Name the conditions where bleeding time
is prolonged and clotting time is normal ?
 1. Low platelet count
 2.Functional ...
Name the conditions where clotting time is
prolonged and bleeding time is normal ?
 1. Hereditary coagulation disorders
i...
ANTICOAGULANTS
 Natural Anticoagulants


Heparin
 Antithrombin or Heparin co-factors
 Protein C







Heparin

Potent Anticoagulant
First isolated from liver
Polysaccharide, MW- 15000-18000
Facilitates action of...
Synthetic Anticoagulant
 Vitamin K Antagonist

i.

Coumarin derivatives – Dicumarol

ii. Warfarin
iii. Phenindione
iv. Ni...
Hemostasis
Hemostasis
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Hemostasis

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Hemostasis

  1. 1. HEMOSTASiS
  2. 2. HEMOSTASIS  DEFINITION - Heme = blood - stasis = to halt  It is the process of forming clots in the wall of damaged blood vessels & preventing blood loss while maintaining blood in a fluid state with in the vascular system.  Spontaneous arrest physiological process. of bleeding by
  3. 3. Stages of Hemostasis Vascular Constriction Formation of Platelet Plug Formation of blood clot Fibrinolysis
  4. 4. Events in Hemostasis  Vascular Constriction - local myogenic spasm - local autacoid factors from traumatized tissues and platelets - nervous reflex  Formation of platelet Plug - primary hemostasis
  5. 5. STAGES OF PRIMARY HEMOSTASIS  Platelet Adhesion  Platelet Activation  Platelet Aggregation
  6. 6. plATElET AdHESiOn
  7. 7. plATElET AcTivATiOn : plATElET rElEASE AcTiOn
  8. 8. plATElET AggrEgATiOn
  9. 9. SEcOndAry HEMOSTASiS  “Cascade of reactions” by Macfarlane, R.G.,1967 It states that ‘inactive’ enzymes are activated, and the ‘activated’ enzymes in turn activates other inactive enzymes until final step is reached.
  10. 10. Clotting Factors Factor I Fibrinogen Factor II Prothrombin Factor III Thromboplastin Factor IV Calcium Factor V Labile factor, or proaccelerin Factor VI Non – existent Factor VII Stable factor or proconvertin Factor VIII Antihaemophilic Factor IX Christmas factor or Antihaemophilic factor B Factor X Stuart – Prower factor Factor XI Plasma thromboplastin antecedent or Antihaemophilic factor C Factor XII Hageman factor or Contact factor Factor XIII Fibrin stabilizing factor or Laki – Lorand factor factor / globulin A
  11. 11. PROPERTIES OF MOIETIES INVOLVED IN BLOOD COAGULATION  Contact system - F-XII, Prekallikrein, F-XI  Vit-K dependent coagulation proenzymes -F- II, VII, IX, X  Cofactors -HMW Kininogen ,F-V, F-VIII, Protein-S, Tissue factor, Platelet lipid  Factor of fibrin deposition -Fibinogen,F-XIII  Inhibitors -Protein-C, Antithrombin-III,Extrinsic Pathway Inhibitor
  12. 12. ENZYME CASCADE SEQUENCE STAGE 1: FORMATION OF PROTHROMBIN ACTIVATOR STAGE 2: CONVERSION OF PROTHROMBIN INTO THROMBIN STAGE3: CONVERSION OF FIBRINOGEN INTO FIBRIN
  13. 13. Intrinsic Pathway
  14. 14. Conversion of Prothrombin to Thrombin & Fibrin Polymerization
  15. 15. Extrinsic Pathway
  16. 16. WHY BLOOD DOES NOT CLOT IN CIRCULATION ?  Endothelial surface factor -smoothness -layer of glycocalyx -Negatively charged  Velocity of circulation  Natural anticoagulants  Activation of Fibrinolytic system  Liver removes activated clotting factors
  17. 17. FIBINOLYSIS
  18. 18. METHOD OF STUDY  HEMOSTATIC FUNCTION TESTS -Bleeding time -Clotting time -Prothrombin time -Partial prothrombin time -Thrombin time
  19. 19. BLEEDING TIME (B.T)  Definition ; - time interval between the skin puncture and spontaneous , unassisted stoppage of bleeding.  Method ; “Duke’s method”  Other methods ; “ivy” Bleeding time  Normal bleeding time ; 1 – 5 min. 20
  20. 20. CLOTTING TIME ( C.T )  Definition ; - time interval between entry of blood into glass capillary tube, or a syringe, and formation of fibrin threads.  Method ; Wright’s capillary glass tube  Other Methods ; Duke’s Drop method, Lee and White test-tube method  Normal Clotting Time ; 3 – 6 min.
  21. 21. PROTHROMBIN TIME (P.T)  Normal P.T ; 15 – 20 sec.  Clinical Significance ; bleeding tendency occurs below 20% (Normal plasma prothrombin = 30- 40 mg/dl)  Low prothrombin suggest Vit. K def. and liver and biliary diseases.  Prolonged suggests deficiency of factor II, V, VII, and X. 22
  22. 22. DISORDERS OF COAGULATION  Defective blood clotting - deficiency of clotting factors (I, II, V, VIII, IX, X) - deficiency of Vit- K -von Willebrand disease - anticoagulant overdose  Defective capillary contractility - Purpura  Thrombosis
  23. 23. DEFICIENCY OF FACTORS
  24. 24. Hemophilia – A (Classical Hemophilia)  Factor VIII deficiency
  25. 25. Hemophilia – B ( Christmas disease)  Factor – IX deficiency
  26. 26. Hemophilia - C  Factor – XI (Plasma thromboplastin anticedent) deficiency.
  27. 27. Hemophilia - D  Factor – XII ( Hageman factor) deficiency 28
  28. 28. Hemophilia  Factor – VIII deficiency  Inheritance – Sex linked, -X-chromosome, females are carrier  Diagnosis - CT increased, BT- normal  Treatment - Fresh blood transfusion - Injecting factor – VIII and IX - Injecting thrombin or thromboplastin
  29. 29. Purpura  Purple coloured petechial hemorrhages and bruises in the skin.  Characterized by spontaneous hemorrhages beneath the skin, mucous membrane and internal organ.  Capillary abnormality  Types - Primary (Idiopathic) –congenital or heriditary , seen in children - Secondary (Symptomatic) - allergies, infections, drugs, cancer
  30. 30. Diagnosis  CT – N  BT – increased  Capillary endothelium resistance – decreased  Skin Microscopy - Primary Purpura -Skin capillaries irregular and distorted - Secondary Purpura – Capillries normal, presence toxic agents, capillaries do not contract effictively
  31. 31. Forms/Classification  1. Thrombocytopenic Purpura -Low platelet count Clinically - Mild Purpura - > 50,000/µL - Moderate Purpura - > 10,000 /µL - Fulminant Purpura -> 1000 /µL     2. Athrombocytopenic Purpura 3. Thromboasthenic Purpura 4. Haemorrhagic Purpura Treatment - Injection of ACTH - Splenectomy
  32. 32. Name the conditions where bleeding time is prolonged and clotting time is normal ?  1. Low platelet count  2.Functional platelet defect ; i.Drugs : aspirin, large dose of penicilin ii.von Willebrand disease iii.others : uremia, cirrohosis, leukemia  3. Vessel wall defects ; i. Prolonged corticosteroid trt. ii. Allergic purpura iii. Infections : typhus, bacterial endocarditis iv. Deficiency of Vit – C v. Connective tissue diseases
  33. 33. Name the conditions where clotting time is prolonged and bleeding time is normal ?  1. Hereditary coagulation disorders i. Hemophilias ii. von Willebrand disease iii. Afibrinogenemia or dysfibrinogenemia  2. Acquired Coagulation disorders i. Vit – K def. ii. Liver disease iii. Intravascular clotting iv. Anticoagulant therapy  3. Newborns
  34. 34. ANTICOAGULANTS  Natural Anticoagulants  Heparin  Antithrombin or Heparin co-factors  Protein C
  35. 35.       Heparin Potent Anticoagulant First isolated from liver Polysaccharide, MW- 15000-18000 Facilitates action of antithrombin-III Inhibits active form of IX, X, XI, and XII Origin - granules of basophils - mast cells contains IgE (Reagin), heparin, histamine, aid in defecnc mechanism  Destruction – Heparinase in liver  Uses - maintains fluidity of blood, - prevention of post-operative intravascular coagulation
  36. 36. Synthetic Anticoagulant  Vitamin K Antagonist i. Coumarin derivatives – Dicumarol ii. Warfarin iii. Phenindione iv. Nicoumalone  Removing Ca2+ from blood - Sodium citrate, sodium oxalate, sod. Edeate (EDTA)  Snake Venom - fibrinogenopenia  Cold - 5-100C
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