hemostasis for medical students iii (03!04!2015)

Hemostasis3/9/2015

Shu-Ling Liang Ph.D.*

Platelets IPlatelets lack nuclei and are 2-4 m in diameter and aggregate at the sites of vascular injury.Production is regulated by CSF and thrombopoietin and are formed by pinching off bits of cytoplasm of megakaryocytes in the bone marrow.Following extruded from the bone marrow, 60%- 75% of the platelets are in the circulating blood, and the remainder are mostly in the spleen.Splenectomy causes an increase in the platelet count (thrombocytosis).

Shu-Ling Liang**

Shu-Ling Liang


Platelets IIMembranes of platelets contain receptors for collagen, ADP, von Willebrand factor and fibrinogen, thrombopoietin.Cytoplasm of platelets contains actin, myosin, glycogen and lysosomes.Two types of granules in cytoplasm of platelets :

(1) dense granules, which secret serotonin, ADP, and other adenine nucleotide in response to platelet activation. (2)-granules, which contained clotting factors and platelet-derived growth factor (PDGF), the latter stimulates wound healing and is a potent mitogen for vascular smooth muscle.The amount of thrombopoietin in circulation bonds to the platelets serves as a sensor to control platelet production.

Shu-Ling Liang**

Shu-Ling Liang


Platelets associated disordersThrombocytopenic purpura: decrease in platelet count , deficient in clot retraction and a poor constriction of ruptured vessels. Clinical symptoms includes easy bruisability and multiple subcutaneous hemorrhages.Thrombasthenic purpura: purpuric bleeding in patients with normal platelet counts, but abnormal platelet function.

Shu-Ling Liang**

Shu-Ling Liang


Plasma and plasma proteins The normal plasma volume is about 5% of body weight.Plasma proteins consist of albumin, globulin and fibrinogen, which help maintain the oncotic pressure (osmotic force is about 25 mm Hg across the capillary wall) and severs as buffer of the blood (at pH 7.4, they are in the anionic form).Certain plasma proteins function in transportation and binding the hormone to prevent them from being filtered via glomeruli, e.g. Thyroxine-binding globulin.Certain plasma proteins are involved in blood clotting, e.g. Fibrinogen.

Shu-Ling Liang**

Shu-Ling Liang


HypoproteinemiaCauses: prolonged starvation, malabsorption syndrome due to intestinal disease, liver diseases and nephrosis.Edema tends to develop due to the decrease in the plasma oncotic pressure.

Shu-Ling Liang**

Shu-Ling Liang


Shu-Ling Liang**

Shu-Ling Liang


Plasma vs. Serum*Serum: with the fibrinogen and clotting factors II, V and VIII removed from plasma and a higher serotonin level.Shu-Ling Liang**

Shu-Ling Liang


Hemostasis: the stoppage of bleedingFormation of a platelet plug.Blood coagulation: Clot formation, a process that transformation of blood into a solid gel called a clot and consisting of a protein polymer know as fibrin.Blood coagulation occurs locally around the original platelet plug and is the dominant hemostatic defense.The function of blood coagulation is to support and reinforce the platelet plug and to solidify blood that remains in the wound channel.

**Shu-Ling Liang

Shu-Ling Liang

vWFvWF: von Willebrand factorADPSerotonin*Fibrinogen form the bridges between aggregating platelets.*The contraction of platelets via actin and myosin cause compression and strengthening of the platelet plug.Role of platelets in formation of a platelet plug*

PGI2 and NO prevent the spread of platelet aggregation from a damaged site**Shu-Ling Liang

Shu-Ling Liang

Cyclooxygenase Pathways for eicosanoid synthesisAspirin**Shu-Ling Liang

Shu-Ling Liang

Platelet aggregation*Shu-Ling Liang*

Shu-Ling Liang

Simplified diagram of the clotting pathway123Activation of platelets causes platelets to display specific plasma membrane receptors and platelet factor (PF), a particular phospholipids, which function as a cofactor in the steps mediated by the bound clotting factors.

4. activate platelets**Shu-Ling Liang

Shu-Ling Liang

Clotting cascade consist of two pathwaysThe intrinsic pathway: everything necessary for it is in the blood.The extrinsic pathway: a cellular element outside the blood is needed.

*Shu-Ling Liang*

Shu-Ling Liang

Intrinsic & Extrinsic clotting pathways merge and generate of thrombin(not a plasma protein)**Shu-Ling Liang

Shu-Ling Liang

**Shu-Ling Liang

Shu-Ling Liang

Intrinsic and extrinsic clotting pathways merge and generate of thrombin(glass vs. silicone tube)(cofactor)(cofactor)(not a plasma protein)+*The roles calcium plays in clotting are not shown**Shu-Ling Liang

Shu-Ling Liang

Fibrin is the essential component of the clot **Shu-Ling Liang

Shu-Ling Liang

Roles of the liver in clotting(e.g. prothrombin)**Shu-Ling Liang

Shu-Ling Liang

Factors limit clot formationTissue factor pathway inhibitor (TFPI), secreted by endothelial cells. Protein C: trigger by thrombin binds to its receptor, thrombomodulin, on endothelial cells.Antithrombin III

activated by bind to heparin, present on thesurface of endothelial cell. **Shu-Ling Liang

Shu-Ling Liang

Clotting and anticlotting actions of thrombin**Shu-Ling Liang

Shu-Ling Liang

Basic fibrinolytic system*Endothelial cells secret tissue plasminogen activator (t-PA).**Shu-Ling Liang

Shu-Ling Liang

**Shu-Ling Liang(TFPI)

Shu-Ling Liang

Anti-clotting drugs on preventing and treating of blood vessel clottingAspirin: it inhibits cyclooxygenase, therefore, reduces thromboxane A2 production from platelets.Fibrinogen blockers: block the binding of fibrinogen to platelets.Oral anticoagulants: drugs that interfere with the action of vitamin K.Heparin: an endothelial cell cofactor for anti-thrombin III, it also inhibits platelet function.Plasminogen activators: dissolves a clot after it is formed, e.g. recombinant t-PA and Desmodus rotundus Salivary Plasminogen Activator (DSPA).Leeche saliva: anesthetic, vasodilator and anticoagulant.

**Shu-Ling Liang

Shu-Ling Liang

Shu-Ling Liang Ph.D.

Shu-Ling Liang Ph.D.*Shu-Ling Liang Ph.D.























hemostasis for medical students iii (03!04!2015)

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