Hemostasis and its disorders

normal blood clotting and its abnormalities in short
bleeding disorders

1. Pathophysiology BLOOD COAGULATION (Hemostasis) Dr. Dina Hamdy Merzeban Physiology lecturer Fayoum university www.facebook.com/merzeban physiology

2. Hemostasis: Definition: prevention of blood loss after injury

3. Steps of hemostasis: Constriction of the Blood Vesse ls : The constriction of injured blood vessel occurs immediately after injury and may be so marked that the lumen is completely closed. Formation of Temporary Hemostatic Plug: Injury stimulates the platelets to form a mechanical plug to seal the vascular injury. If the cut in the vessel is small, the platelet plug by itself can stop blood loss Completely, but if the cut is large, a blood clot in addition is required to stop bleeding. Blood coagulation: Formation of a blood clot by the intrinsic and to stop the bleeding

4. Constriction of the Blood Vesse ls : The constriction of injured blood vessel occurs immediately after injury and may be so marked that the lumen is completely closed.

5. Formation of Temporary Hemostatic Plug: Injury stimulates the platelets to form a mechanical plug to seal the vascular injury. If the cut in the vessel is small, the platelet plug by itself can stop blood loss Completely, but if the cut is large, a blood clot in addition is required to stop bleeding.

6. Blood coagulation: Formation of a blood clot by the intrinsic and to stop the bleeding

7. Anti- clotting mechanisms

8. Anti- clotting mechanisms   The tendency of blood to clot is balanced in vivo by limiting reactions that tend to prevent clotting inside the blood vessels and to break down any formed clots.

9. General limiting reactions. 1. Smooth vascular endothelium, thus there is no activation of platelets. 2. Presence of heparin, which is a naturally occurring anticoagulant.  

10. B. Specific limiting reactions.   The interaction between thromoboxane A2 and prostacyclin: The interaction between the platelet-aggregating effect of thromboxane A2, and the antiaggregating effect of prostacyclin. This interaction causes a clot to form at the site of injury but keeps the vessel lumen free of clot. Note: aspirin increases prostacyclin  prevent platelet-aggregation , so given to prevent thrombosis.

11. B. Specific limiting reactions. 2. Fibrinolytic System Intact blood vessel walls are provided with a mechanism that inhibit clot formation. Plasminogen receptors are located on the surfaces of many different types of cells e.g. endothelial cells. When plasminogen binds to its receptors, it becomes activated .

12. Fibrinolytic System Plasmin ogen is converted to its active form plasmin, by the action of tissue-plasminogen activator (t-PA). Plasmin (fibrinolysin) is an enzyme that lyses fibrin and fibrinogen

13. It is also activated by urokinase or Streptokinse . Human t-PA is now produced by recombinant DNA techniques for clinical use in myocardial infarction and stroke.

14. In vivo anticoagulants: Point of Comparison   Heparin   Dicumarol Origin: Mast cells and basophils. Plant Mode of action:   blocks the activity of some clotting factors   Inhibits formation of vitamin K dependent clotting factors in the liver Site of action: In vivo & In vitro Only in vivo. Onset: Rapid onset. Slow onset Duration: Short duration Long duration Administration: Intravenous/ intramuscular Orally   Antidote: Protamine sulfate 1% Vitamin K.

15. Abnormalities of Hemostasis: There are three groups of abnormalities that can occur in hemostasis: A . Conditions that cause excessive bleeding B. Conditions that cause excessive intravascular clotting. C. Conditions that cause both excessive bleeding and intravascular clotting.

16. A- Conditions that cause excessive bleeding   1-Thrombocytopenic purpura:   This is due to deficiency of platelets, the symptoms appear when platelet count decreases below 50,000/mm". It is characterized by the presence many subcutaneous hemorrhages called petechiae and prolongation of bleeding time.  

17. A- Conditions that cause excessive bleeding 2-Vitamin K deficiency:  Vitamin K is a fat soluble vitamin synthesized by the intestinal bacterial flora. It is needed for the formation of factors, ll , VIl , IX and X by the liver. Deficiency of this vitamin leads to decrease in the formation of these coagulation factors and thus there is prolongation of coagulation time. Causes: Absence of intestinal bacterial flora which occurs in new born infants Treatment with antibiotics for long periods in adults. Obstruction of biliary ducts which leads to absence of bile needed for absorption of the vitamin.

18. A- Conditions that cause excessive bleeding   3- Hemophilia:   It is a congenital disease characterized by a tendency for severe bleeding after mild trauma. It is a sex linked recessive disease carried by females and manifested almost always in males. It causes prolongation of the whole blood coagulation time.

19. Conditions that cause excessive intravascular clotting (Thromboembolic Conditions):   Causes: Slow blood flow as occurs in leg veins due to long bed rest after operations, or with varicose veins In atherosclerosis due to roughness or vascular endothelium.

20. Conditions with both excessive bleeding and intravascular clotting Disseminated intravascular coagulation(DIC) : It is characterized by wide spread clotting accompanied with bleeding tendency due to consumption of many clotting factors. Causes: Retention of a dead fetus in the uterus for weeks Septicemia

21. Hemostatic Function Tests   1 . Blood count and blood film : The platelet count is reduced in thrombocytopenia. 2. Bleeding time: It is the time needed for bleeding to stop without clotting of the blood. The normal bleeding time is 1-3 minutes and it depends on platelet count and function. It is prolonged in thrombocytopenic purpura. 3 . Tests for blood coagulation:  

22. Hemostatic Function Tests 3 . Tests for blood coagulation: Whole blood coagulation time: It is the time needed for blood to clot. Normally, it is 3-10 minutes at 37 C. It is prolonged in both vitamin K deficiency, hemophilia, and liver diseases. The activated partial thromboplastin time (APTD): Normally it is 30-40 seconds and is prolonged in hemophilia. Prothrombin time: normal value is 15 seconds and is prolonged in vitamin K deficiency.