1. Dr. Shaikh Mujeeb Ahmed Assistant Professor AlMaarefa College
HEMOSTASIS
HMIM BLOCK 224
Dr. Shaikh Mujeeb Ahmed
Assistant Professor
AlMaarefa College

2. Objectives
Define hemostasis and explain the mechanisms that help to achieve it.
Review the major steps in coagulation.
Explain how to prevent coagulation.

3. Hemostasis Hemostasis refers to the stoppage of bleeding
Actions that limit or prevent blood loss include:
Blood vessel spasm
Platelet plug formation
Blood coagulation

5. Platelets Formed in bone marrow, 150-400,000 /µl
Sequestered in spleen (30%)
2-4 m in diameter, life span 8-12 days, no nucleus
Active cytoplasm
actin + myosin
enzyme synthesis + storage of calcium
synthesis of prostaglandins
dense granules containing ADP, serotonin and ATP
a-granules (fibrinogen, PDGF, vWF, fibronectin)
fibrin stabilizing factor

6. Platelets Membrane Receptors: thrombin, ADP, epi, serotonin
Adhesion proteins: vWF, fibronectin, collagen, fibrinogen
coat of glycoproteins adhesion to injured areas
phospholipids activation of intrinsic pathway
adenylate cyclase cAMP activate other platelets

7. Blood Vessel Spasm Blood vessel spasm
Triggered by pain receptors, platelet release, or serotonin
Smooth muscle in blood vessel contracts

8. Platelet Plug Formation

9. Stages of platelet plug formation
Platelet adhesion
von Willebrand factor (vWF)
Platelet activation
Ca++ release
Pseudopodia
Granule discharge
Integrin on surface
Thromboxane formation (TXA2)
Platelet aggregation

10. Blood Coagulation Blood coagulation
Triggered by cellular damage and blood contact with foreign surfaces
A blood clot forms
This is a:
Hemostatic mechanism
Causes the formation of a blot clot via a series of reactions which activates the next in a cascade
Occurs extrinsically or intrinsically

11. CLOTTING FACTORS

12. Clotting Cascade
Series of steps involving 12 plasma clotting factors that lead to final conversion of fibrinogen into a stabilized fibrin mesh
May be triggered by
Intrinsic pathway
Involves seven separate steps
Set off when factor XII (Hageman factor) is activated by coming into contact with exposed collagen in injured vessel or foreign surface such as glass test tube

13. Intrinsic Pathway
Figure 36-4; Guyton & Hall

14. Clotting Cascade Extrinsic pathway Requires only 4 steps
Requires contact with tissue factors external to the blood
Tissue thromboplastic released from traumatized tissue directly activates factor X

15. Extrinsic Pathway
Figure 36-3; Guyton & Hall

16. Clot Pathways

17. Clot under microscope

18. Fate of Blood Clots
After a blood clot forms it retracts and pulls the edges of a broken blood vessel together while squeezing the fluid serum from the clot
Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls
Plasmin digests the blood clots
A thrombus is an abnormal blood clot
An embolus is a blood clot moving through the blood vessels

19. Prevention of Coagulation
The smooth lining of blood vessels discourages the accumulation of platelets and clotting factors
As a clot forms fibrin absorbs thrombin and prevents the clotting reaction from spreading
Anti-thrombin inactivates additional thrombin by binding to it and blocking its action on fibrinogen
Some cells such as basophils and mast cells secrete heparin (an anticoagulant)

21. Clinical Application

22. Abnormal Blood Clotting
Thrombus
Abnormal intravasculaar clot attached to a vessel wall
Emboli
Freely floating clots
Factors that can cause thromboembolism
Roughened vessel surfaces associated with atherosclerosis
Imbalances in the clotting-anticlotting systems
Slow-moving blood
Occasionally triggered by release of tissue thromboplastin into blood from large amounts of traumatized tissue
Hemophilia
Excessive bleeding caused by deficiency of one of the factors in the clotting cascade

23. Coagulation Defects I. Vitamin C deficiency
lack of stable collagen (elderly, alcoholics)
II. Hepatic failure
almost all clotting factors are made in the liver
III. Vitamin K deficiency
required for II (prothrombin), VII, IX, and X
fat malabsorption due to lack of bile secretion
IV. Hemophilia
Factor VIII (hemophilia A 1/10,000),
Factor IX (hemophilia B 1/100,000)
chromosome X

24. Coagulation Defects Coagulation Defects
V. Thrombocytopenia
bleeding small capillaries and blood vessels mucosal, skin
low number of platelets
ITP- autoimmune (common)

25. Hemophilia
Hemophilia A is classic hemophilia (a disease referring to the inability to clot blood).
It is an X-linked disorder resulting from a deficiency in factor VIII,
Individuals with deficiencies in factor VIII suffer
Joint and muscle hemorrhage,
Easy bruising and
Prolonged bleeding from wounds.
Treatment of hemophilia A is accomplished by infusion of factor VIII concentrates prepared from either human plasma or by recombinant DNA technology.

26. Male suffer from disease.
HEMOPHILIA
It’s a X linked disease
Females are carriers
Male suffer from disease.

27. Hemophilia B
Hemophilia B results from deficiencies in factor IX.

28. Antihemostatic Drugs Heparin Potentiates antithrombin III.
Antithrombin III inactivates various coagulation factors including thrombin
Used in prevention of Deep vein thrombosis (DVT) & Pulmonary embolism (PE)
During heart surgery & hemodialysis

29. Antihemostatic Drugs
Aspirin is an important inhibitor of platelet activation. By virtue of inhibiting the activity of cyclooxygenase (COX), aspirin reduces the production of TXA2 by platelets. Aspirin also reduces endothelial cell production of prostacyclin (PGI2), an inhibitor of platelet aggregation and a vasodilator. 

30. Antihemostatic Drugs
The drug clopidogrel: Plavix is an irreversible inhibitor of the ADP receptor on platelet membranes. When ADP binds to platelets they are activated and aggregate leading to amplification of the coagulation response, thus Plavix interferes with this process. 

31. Antihemostatic Drugs
The plasminogen activators also are useful for controlling coagulation.
tPA is highly selective for the degradation of fibrin in clots.
Used particular during the short period following myocardial infarct.
Streptokinase (an enzyme from the Streptococcibacterium) is another plasminogen activator

32. TESTS PLATELET DISORDER COAGULATION DISORDERS Bleeding time – 2-6 min.
Increased in thrombocytopenia
COAGULATION DISORDERS
Clotting time – 5-11 min.
Increased in hemophilia
Partial thromboplastin time (PTT)
For intrinsic & common pathway
Normally less than 45 sec.
Prothrombin time (PT)
For extrinsic & common pathway

33. SUMMARY