1. Hemostasis and blood coagulation Dr.sahar j kadhum

2. Hemostasis means prevention of blood loss.
This achieved by several mechanisms including
Vascular spasm
Formation of platelets plug
Formation of blood clot (blood coagulation)
Growth of fibrous tissue into the blood clot
To close the whole vessel permanently

4. Vascular spasm
The most immediate protection against blood loss is vascular spasm(constriction of broken vessel).
The trigger for vascular spasm
1-stimulation of pain receptors ,cause vessel to constrict.
2-traumatic wall of vessels contract due nervous reflexes and local myogenic spasm, and local factors from tissue and blood platelets

5. Formation of platelets plug
Platelets are not cells .
but small fragments of megakaryocyte cytoplasm .(other name to it thrombocytes)
Platelets are small round ,or oval discs 2-4um in diameter.
its formed in bone marrow from megakaryocytes which is extremely large cell of hematopoietic series that fragmented into platelets.

7. The normal concentration of platelets in blood is 150,000-300,000/uL.
Platelets not have nucleus and not reproduce.
Half life 8-10 days.

8. In their cytoplasm there are active factors
1-they have growth factors that stimulate mitosis in fibroblast and smooth muscle and help to repair damaged vascular wall.
2-they have actin, myosin &(thrombosthenin) that cause contraction of platelets(clot retraction).

9. 3-prostaglandin local hormone that cause local vascular and tissue reaction. 4-ADP,adenosine diphosphate ,ATP adenosine triphosphate. 5-contain large quantities of Ca- ion 6-contain fibrin stabilizing factorXIII

10. They form temporary platelets plugs to stop bleedings.
They dissolve blood clots that have out lasted their usefulness.
The cell membrane of the platelets also important ,on its surface is a coat of glycoproteins that causes it to avoid adherence to normal endothelium and yet to adhere to injured areas of vessel wall .
also platelets membrane contain phospholipid that activate blood clotting process(platelets factor3-PF3).

11. Mechanism of the platelets plug
platelets come in contact with a damaged vascular surface like collagen fibers in vascular wall or damaged endothelial cells.
The platelets swell ,and become irregular and sticky ,and stick to collagen fibers in the injured tissue and also to protein called von willebrand factor.

12. And secrete large quantities of ADP and enzymes Thromboxane A2 in turn action on nearby platelets and stimulate them to form platelets plug.

13. -Formation of blood clot
The blood clot developed in15-20 seconds if vascular injury severe and 1-2 minutes if trauma is minor.

14. Mechanism of blood coagulation
The clotting takes in 3 steps
1-formation of prothrombin activator ,which is complex of activated substances occur in response to rupture or damage of blood vessels.
2-prothrombin activator catalyze the conversion of prothrombin to thrombin.
3-the thrombin act as enzyme convert fibrinogen to fibrin fibers ,fibrin enmesh platelets ,blood cells and plasma to form the clot.

19. in The extrinsic mechanism ,damage of blood vessels release tissue factor called thromboplastin (factor III).
Factor III with calcium Ca ,activate factor VII, to active factor VII.
Active factor VII activate factor X.

20. The intrinsic mechanism.
Trauma to blood or exposure of blood to collagen,will
1-activate factorXII
2-and release of platelets phospholipid(platelets factor3,PF3) .
Active factorXII will activate factor XI to active factorXI
in (presence of high molecular weight kininogen).
active factor XI will activate factors IX,
in that order ,each serving as enzyme that catalyzes the next step.

21. And finally
1-active factor IX,
2-platelets thromboplastin factor(PF3),
3-active factorVIII,
4-Ca
Will activate factor X to active factor X

22. Once factor X is activated ,the remaining events are identical in the intrinsic and extrinsic mechanism.
Factor X ,combine with V ,Ca ,platelets thromboplastin factor PF3,to produce enzyme (prothrombin activator)

23. The most important difference between extrinsic and intrinsic pathway is the extrinsic can have explosive nature ,once initiated .its speed of occurrence is limited by amount of tissue factor released from traumatized tissues or by quantities of factor X,VII,V in the blood.
with severe trauma ,clotting can occur in 15 second, while intrinsic usually 1-6 minutes to cause clotting

24. Prothrombin activator act on prothrombin (factor II),converting it to thrombin.
Thrombin(factor II) convert fibrinogen to fibrin.
Fibrin monomer forms loose mesh at first. ,thrombin also activate factor XIII to active XIII which, causes the formation the fibrin polymer, dense aggregation of fibers that forms the structural basis of the clot .

25. Prevention of clotting in normal vascular system
The intravascular anticoagulants
1-endothelial surface factor
A-the smoothness of endothelium ,which prevent contact activation of the intrinsic clotting system.
B-layer of glycocalyx ,a mucopolysaccharides adsorbed to the inner surface of the endothelium ,which repels the clotting factor and platelets .

26. c- A protein bound with endothelial membrane ,thrombin which bind thrombomodulin ,this thrombomodelin –thrombin complex not only slows the clotting process ,but also activates a plasma protein ,protein C ,that acts as an anticoagulant by inactivating activated factors V ,and VIII.

27. 2- antithrombin factor
The most important anticoagulant in the blood itself that remove thrombin from blood the most powerful.
1-the fibrin fibers that themselves are formed during the process of clotting
2-an alpha globulin called antithrombin III or anti thrombin-heparin co factor ,about %

28. Of thrombin formed adsorbed to the fibrin fibers as they develop
Of thrombin formed adsorbed to the fibrin fibers as they develop. The thrombin that does not adsorb to fibrin fibers ,soon combines with antithrombin III ,which block the effect of the thrombin on the fibrinogen and inactivates it within minutes
3- heparin is a conjugated polysaccharides ,formed by the basophilic mast cells located

29. In the pericapillary connective tissue throughout the body .
It prevents blood coagulation by combining with antithrombin –heparin co factor which makes this factor combine with thrombin .
The antithrombin heparin complex remove several other activated coagulation factors in addition to thrombin from circulating blood. The other include factors XII,XI IX,X

30. prevention of blood coagulation outside the body.
1- heparin ,it prevent the blood coagulation when added to sample of blood outside the body
2-(calcium deionizing agent) used for preventing coagulation is
sodium ,ammonium ,or potassium citrate. The citrate ion combines with calcium in the blood to cause an un ionized ,Ca compound

31. 1-un ionized Ca compound
2- lack of Ca
will prevents coagulation in the blood.
3-collecting of blood in siliconized containers, will not clot for 1 hour or more because it prevents contact activation of platelets and factor XII ,which are effects that initiate the intrinsic clotting mechanism.

32. 4-coumarin derivate(warfarin) these are used internally to prolong the coagulation time from the normal rang of about 2-3 minutes to 10 minutes .
vitamin K is essential for the formation of prothrombin by the liver ,these substances when given they interfere with action of vit K and this cause a decrease in the formation of prothrombin by the liver and this causes prolongation of coagulation time, and this prevents the occur of blood clots

33. BLOOD DISEASE
1-decreased (prothrombin factorII ,factor VII IX and X ) caused by vitamin K deficiency.
2-Hepatitis ,cirrhosis (replacement of liver cells by fibrous tissue), acute yellow atrophy and
3- the presence of a stone in the common bile duct (in which bile does not reach the duodenum )and this effect on the absorption of vit K .

34. All these factors cause a severe tendency to bleed .
These liver disease often cause decreased production of prothrombin and the other factor both because of poor vitamin K absorption and because of the diseased liver cells.

35. Hemophilia It is hereditary disease associated with bleeding tendency,
It affects the male only ,the female is not affected by the disease ,because at least one of her two X chromosomes is deficient ,she will be a hemophilia carrier.
3 types
1-hemophiliaA,factor-VIII deficiency

36. Thrombocytopenia 2-hemophilia B deficiency of factor IX
3-hemophilia C deficiency of factor XI
Treatment by giving deficient factor
Thrombocytopenia
Due to low platelets causes by drugs ,chemicals ,or unknown cause called idiopathic thrombocytopenia ,bleeding occur when platelets decreased to 50,000/ul if decreased to 10…/ul the bleeding is lethal