This is the power point that explains about the blood and blood cells. Power point describes about the mechanism of coagulation and defense cells of our circulatory system.

1. PLATELETS AND HEMOSTASIS
Dr. Renu Yadav
Physiology

2. Formation of platelets
Normal platelet count= 150,000–400,000/µL

4. PLATELETS
• Megakaryocytes form platelets by pinching of
bits of cytoplasm and extruding them on
circulation
• Smallest formed elements of blood.
• Anuclear fragments of megakaryocytes
• Developmemt of platelets –Thrombopoiesis
• Half-life- 8-12 days
• Destroyed by reticuloendothelial systems and
(spleen)

5. Structure of platelets
1. Cell membrane-
– Glycoprotein- prevents adherence to normal endothelium
– Phospholipids- Activates multiple stages in blood coaagulation
2. Cytoplasm- contains
I. Contractile proteins
• actin, myosin & thrombosthenin
II. Golgi apparatus & endoplasmic reticulum synthesize
• new enzymes & store Ca2+)
III. Mitochondira
• (forms ATP & ADP)
IV. Enzyme system
• synthesize prostaglandins
V. Fibrin stabilizing factor
• helps in coagulation
VI. Growth factor
• vascular endothelial cells, vascular smooth muscle cells, and fibroblasts ----
cellular growth ---repair damaged vascular walls

6. Functions of Platelets
• They secrete procoagulants, or clotting factors, which promote
blood clotting.
• They secrete vasoconstrictors, which cause vascular spasms in
broken vessels.
• They form temporary platelet plugs to stop bleeding.
• They dissolve blood clots that have outlasted their usefulness.
They phagocytize and destroy bacteria.
• They secrete chemicals that attract neutrophils and monocytes to
sites of inflammation.
• They secrete growth factors that stimulate mitosis in fibroblasts
and smooth muscle and help to maintain the linings of blood
vessels.

7. Blood vessel lumen

8. STEPS IN HEMOSTASIS
• Injury to wall of blood vessels
1. vascular constriction,
2. formation of a platelet plug (Temporary hemostatic
plug formation)
3. blood coagulation-- formation of a blood clot
4. Clot retraction
5. eventual growth of fibrous tissue into the blood clot to
close the hole in the vessel permanently by definitive
plug formation and dissolution of clot

9. Mechanisms of hemostasis
exposed

10. STEPS IN HEMOSTASIS

11. STEPS IN HEMOSTASIS……
1. Vasoconstriction is due to
a) Local myogenic response-
• Platelets release the vasoconstrictors
• serotonin and thromboxane A2;
• the clotting protein thrombin stimulates endothelial cells to secrete the
highly potent vasoconstrictor endothelin-1.
2. Platelet plug formation occurs at the site of damage in capillaries,
arterioles, and venules.
Plug formation is called primary hemostasis
3. Clot formation occurs in which a fibrin mesh forms together
• with platelets and other trapped blood cells.
• Clot formation is called secondary hemostasis, and is closely coordinated
with primary hemostasis

12. STEPS IN HEMOSTASIS
Temporary Hemostatic plug formation

13. Formation of temporary platelet plug
 Injury to vessels disrupt endothelium exposes
collagen
 Platelets adhere to collagen via von Willebrand factor
 Binding produces platelets activation & trigger
platelets to release contents of their granules
 Release ADP+ ADP receptors on platelets membrane
further accumulation of more platelets (Platelets
aggregation)
 Thromboxane A2 , platelet-activating factor (PAF)-
stimulates platelets aggregation
 Vicious cycle of activation- forms loose platelet plug-
called primary or temporary hemostatic platelet plug

14. Platelet disorders
• platelet disorder versus bleeding due to a plasma coagulation
defect (coagulopathy).
• Bleeding that results from defective platelet function typically
occurs superficially in sites such as the skin (e.g., petechiae and
ecchymosis) and mucous membranes.
• In contrast, patients who bleed secondary to clotting factor
dysfunction will suffer “deep” bleeds, such as in the deep
subcutaneous tissues or muscles causing a hematoma, or in the
joints causing hemarthrosis.

16. Vitamin K in blood coagulation
• Factor II, VII, IX and X are vit K dependent
clotting factors.

17. Hemostasis…
Definitive hemostatic plug (Definitive clot)-
•loose aggregation of platelets in temporary plug is bound
together & converted into definitive clot by fibrin
•conversion of soluble fibrinogen into insoluble fibrin.
Blood coagulation- 3 essential steps
A. Formation of prothrombin activator (PTA)- complex of
Xa, Va, phospholipids & Ca2+; both by intrinsic & extrinsic
pathway
B. Conversion of prothrombin to thrombin
C. Conversion of fibrinogen to fibrin fibers

18. Hemostasis contd….

19. Blood trauma or contact
with collagen
VIII a

20. PROTHROMBIN ACTIVATOR
Rate-limiting factor in
causing blood coagulation
Blood trauma or contact
with collagen
Tissue trauma

21. Extrinsic pathway
Tissue thromboplastin (TPL)
Tissue pathway inhibitor
(TPI)
PL
Ca
TPL
Ca++
(III)

24. Interaction Between the Extrinsic
and Intrinsic Pathways
• The extrinsic pathway
– can be explosive; once initiated,
– With severe tissue trauma, clotting can
– occur in as little as 15 seconds.
• The intrinsic pathway
– is much slower to proceed,
– usually requiring 1 to 6 minutes
– cause clotting.
BUT
sustained hemostasis requires activity of intrinsic
pathway

25. Hemostasis contd….
(1)
(2)
(3)
(1)
(2)
(3)

26. Hemostasis contd….
• Blood clot- meshwork of fibrin fibers + entrapped
blood cells, platelets & plasma; adsorb thrombin

27. Anticlotting mechanism
1. Endothelium of blood vessels (prevents
extension of clots)
2. Antithrombin action of fibrin and
Antithrombin III .
3. Heparin sulphate-antithrombin III system

28. Anticoagulating process
• Tissue factor pathway inhibitor (TFPI) is anchored to the
endothelial cell membrane and blocks the action of activated
factor VII in the extrinsic pathway.
• Antithrombin III inhibits coagulation by binding to activated factor
X and thrombin; the binding of antithrombin III is augmented by
heparan sulfate molecules on the surface of endothelial cells.
• Thrombomodulin inhibits coagulation by binding to thrombin.
• Proteins C and S act together to inactivate activated factors V and
VIII, which are cofactors in the clotting cascades.

29. ANTICLOTTING MECHANISM
1. Endothelium of blood vessels (prevents
extension of clots)
a) Smoothness of endothelial cell surface
b) Glycocalyx on the endothelium which repels
clotting factor and platelets
c) Produce thrombomodulin (thrombin binding
protein) on their surfaces.
d) Secretes tissue-plasminogen activator (t-PA)
e) Synthesize and release PGI2 and nitric oxide
f) Secrete tissue factor pathway inhibitor
g) Dynamics of blood flow

30. Lysis of Blood Clot
Action of Plasminogen activator
• Plasminogen in plasma protein-
lysis of fibrin
• Also digests other protein
coagulant—factor V , Factor
VIII, prothrombin and factor XII

31. Anticlotting mechanism
(thrombomodulin,and plasminogen in endothelial cell)
Basic fibrinolytic system
Thrombin indirectly inhibits blood coagulation
Thrombin,
T-PA
U-PA
+

32. ANTICLOTTING MECHANISM contd…..
2. Antithrombin action of fibrin
~ 85-90% of thrombin formed- adsorbed in fibrin fibers-
prevents spread of thrombin
3 Heparin sulphate-antithrombin III system
• Heparin sulphate- heparin like substance – coats vascular
endothelium
• When it binds with antithrombin III
– anticoagulant effect ---- removes thrombin 100 –
1000 times more
– also removes activated factor XII, XI, X & IX

33. Clotting time increase
1. ITP
2. Thrombasthenia
Bleeding time increase
deficiency of factor II, VII, IX and X are vit K dependent clotting factors.
Hemophilia= Hemophilia A- factor VIII deficiency (85%)
Hemophilia B- factor IX deficiency (15%)
Thrombocytopenia
Von wilebrand’s disesae – deficiency of Von wilebrand’s factor

34. Lab test
• Bleeding time (BT)
• Clotting time (CT)
• Prothrombin time (PT)
• Partial thromboplastin time (PTT)
• Activated Partial thromboplastin time (APTT
• Thrombin time (TT)

35. Blood coagulation tests
VII, X along
with V and, II
(XII,XI,IX,X and VIII)
Thrombin,
Fibrinogen, Fibrin
PT
APTT
TT

36. Blood coagulation tests
• Bleeding time (BT)
– 1 t0 5 mins (depends on methods)
• Clotting time (CT)
– 5 -12 mins
• Prothrombin time (PT)- II, V , VII and X
– 12 – 16 secs
• Partial thromboplastin time (PTT)-
30-40 secs
• Activated Partial timethromboplastin (APTT
– 35-40 secs
• Thrombin time-
– 15- 20 secs
Intrinsic pathway
(XII,XI,IX,X and VIII

37. THANKYOU