Platelet Physiology and Hemostasis

Platelet Physiology and Hemostasis

1. Hemostasis

Hemostasis is a complex process that helps the body stop bleeding when a blood vessel is injured. It involves two stages:

• Primary Hemostasis: This is the rapid stage and involves vasoconstriction and platelet plug formation.

• Secondary Hemostasis: This stage is longer and involves the formation of a blood clot.

2. Platelets

• Platelets are non-nucleated cells, measuring 2-4 µm in size, with a count of about 1300-400,000 platelets/mL of blood.

• Platelets have a lifespan of about 7-10 days.

• Platelets are negatively charged due to the phospholipids in their membranes.

• Platelet cytoplasm contains granules, ADP, and thromboxane A2.

• Platelets are produced from large, multinucleated cells in the bone marrow.

• The platelet membrane has three layers and many deep invaginations, increasing the surface area and making platelets porous.

• About 2/3 of platelets circulate in the blood, while the remaining 1/3 reside in the spleen.

3. The Role of Platelets in Primary Hemostasis:

• Platelets play a critical role in primary hemostasis and platelet plug formation.

• Normally, platelets circulate freely in the blood.

• When a blood vessel is injured, collagen is exposed, and platelets adhere to the collagen via von Willebrand factor.

• This adhesion activates platelets, causing them to swell, change shape, and release granules from their cytoplasm, including ADP and thromboxane A2.

• The release of these substances enhances platelet aggregation, leading to platelet plug formation. Platelets also present fibrinogen receptors, facilitating fibrinogen binding to this structure.

• Von Willebrand factor is a protein produced by the vascular endothelium.

4. Vasoconstriction:

• When a blood vessel is injured, the self-hemostatic mechanism is activated.

• Primary hemostasis begins with vasoconstriction of the blood vessel, which is strong and prolonged in large arteries and veins.

• The mechanism of vasoconstriction involves neural reflexes from the blood vessels or surrounding tissues, leading to smooth muscle contraction at the site. Additionally, the appearance of electrical potential at the injury site also causes vasoconstriction.

• Local vasoconstriction lasts for about 20-30 minutes, during which time platelets adhere to each other.

• The greater the number of blood vessels injured, the greater the vasoconstriction.

5. Blood Coagulation:

• Blood coagulation is the phenomenon of blood changing from a liquid state to a gel, manifested by the formation of a blood clot.

• Secondary hemostasis, or coagulation, is the process of forming a blood clot. The blood clot consists of fibrin fibers encasing the platelet plug and blood cells within it.

6. Coagulation Factors:

• Factor I (Fibrinogen): Synthesized in the liver; decreased in liver diseases, affecting coagulation.

• Factor II (Prothrombin): Unstable protein, separated into thrombin. Continuously produced by the liver.

• Factor III (Tissue Thromboplastin): Antibacterial.

• Factor IV (Ca): Not produced by the liver.

• Factor V (Proaccelerin, accelerin):

• Factor VII (Proconvertin, convertin):

• Factor VIII (Antihemophilic Factor A): Related to Hemophilia A.

• Factor IX (Antihemophilic Factor B):

• Factor X (Stuart):

• Factor XI (PTA):

• Factor XII (Hageman):

• Factor XIII (FSF): Stabilizes fibrin fibers.

7. Production of Coagulation Factors:

• Most coagulation factors are produced in the liver, except for factor IV (Calcium).

• Factors II, VII, IX, and X are produced in the presence of vitamin K.

8. Stages of the Coagulation Process:

• Stage 1: Formation of prothrombinase complex.

• Stage 2: Formation of thrombin.

• Stage 3: Formation of fibrin.

9. Nature of Blood Coagulation:

• Blood coagulation requires the participation of fibrin (fibrinogen), thrombin (converts fibrinogen to fibrin), and thrombinase (X) (converts prothrombin to thrombin).

• Thrombinase has two activation pathways: the intrinsic pathway and the extrinsic pathway.

10. The Intrinsic Pathway:

• The intrinsic pathway is activated when collagen fibers from the damaged endothelial cell layer are exposed.

• Reaction chain: XII -> XI -> IX -> VIII -> X.

11. The Extrinsic Pathway:

• The extrinsic pathway is initiated by factor III (tissue thromboplastin) + VII.

• Reaction chain: VII + III -> X.

12. Specific Stages of the Two Pathways:

• Intrinsic Pathway: XII -> XI -> IX -> VIII + V -> X -> thrombin -> fibrin -> XIII -> poly fibrin.

• Extrinsic Pathway: VII + III + V -> X -> thrombin -> fibrin -> XIII -> poly fibrin.

13. Evaluation of the Two Coagulation Pathways:

• The intrinsic pathway is evaluated using the partial thromboplastin time (PTT).

• The extrinsic pathway is evaluated using the prothrombin time (PT).

14. Post-Coagulation Stage:

• Clot Retraction: Pulls the edges of the wound together, preventing bleeding and promoting wound healing. This is accomplished by retractozyme.

• Clot Lysis: Occurs after 24-48 hours, preventing thrombus formation and restoring blood flow.

• Clot lysis is carried out by fibrin + plasmin.

15. Coagulation Regulation:

• Regulated by anticoagulants.

• Anticoagulants include: Antithrombin, Heparin, Antithromboplastin.

16. Anticoagulants:

• Antithrombin: Present in the blood, inhibits thrombin, preventing the conversion of fibrinogen to fibrin.

• Heparin: Produced by mast cells and basophils, inhibits thrombinase formation and promotes the interaction of thrombin with antithrombin, inactivating thrombin.

• The anticoagulant effect of Heparin lasts for 3-4 hours before being destroyed by heparrinase in the blood.

17. Extracorporeal Anticoagulation:

• Sodium Citrate: Combines with Ca, forming an inseparable complex, removing Calcium.

• Sodium Oxalate: Removes Calcium.

• High-Concentration Salts.

• Dicumarol: Competes with vitamin K, inhibiting the synthesis of factors II, V, VII, IX, and X. Acts slowly and for a long time, effective in the human circulatory system.

• Effect of Dicumarol: After 12 hours, coagulation activity decreases by 50%; after 24 hours, decreases by 20%; after 3 days of discontinuing treatment, coagulation activity returns to normal.

18. Some Methods for Treating Coagulation Disorders:

• Using coagulation factors:

• Vitamin K: Treats hemophilia.

• Fresh frozen plasma: Contains many coagulation factors, treats acute bleeding.

• Using fresh tissue slices: In surgery, used for hemostasis in craniotomy, tooth extraction, as it contains tissue thromboplastin, activating factor VII and providing factor III.

• Gammacaproic acid: Counteracts fibrinolytic factors.

19. Hemostatic Disorders in Clinical Practice:

• Decreased prothrombin complex: Due to vitamin K deficiency (liver disease, liver inability to secrete bile into the gastrointestinal tract -> lack of bile, decreased vitamin K absorption).

• Hemophilia:

• A: Deficiency of factor VIII.

• B: Deficiency of factor IX.

• C: Deficiency of factor XI, not sex-linked.

• Thrombocytopenia: Unlike hemophilia, bleeding due to thrombocytopenia often originates from small veins and capillaries, leading to petechiae all over the body. Hemophilia involves bleeding from larger blood vessels.

• Thrombosis:

• Blood clot forming in place: Thrombus.

• Moving blood clot: Emboli.

• Emboli in the left ventricle: Arteries of the brain, kidneys.

• Emboli originating from the right ventricle: Lungs.

• DIC (Disseminated Intravascular Coagulation): The presence of dead or damaged tissue releases thromboplastin, leading to the formation of numerous small blood clots, consuming excessive coagulation factors, resulting in bleeding.

20. Platelet Physiology:

• Approximately 75,000 new platelets are produced daily.

• Complete renewal occurs within 4 days.

• The spleen is the platelet reservoir. When there is bleeding, burns, or sympathetic stimulation, the spleen releases platelets into the blood.

21. Tests to Evaluate the Primary Hemostasis Stage:

• Bleeding time (BT)

• Platelet count

• Tourniquet test

• Clot retraction

22. Fibrin Formation:

• Fibrinogen (thrombin, Ca) -> Fibrin S (XIII) -> Fibrin I.

23. Pathological Blood Coagulation:

• When the blood vessel is damaged, the presence of a blood clot is physiological.

• The presence of a blood clot without any injury is pathological and includes:

• Blood stasis.

• Blood vessel inflammation (due to bacteria, allergies, toxins).

• Arteriosclerosis (high blood lipid accumulation).

• Endothelial damage.

24. Coagulation Time:

• Intrinsic coagulation time: APTT = TCK (from 25-33 seconds).

• Extrinsic coagulation time: PT or TQ (from 12-15 seconds).

25. Activity of the Two Coagulation Pathways:

• When a blood vessel is injured, both coagulation pathways are activated simultaneously.

• Tissue thromboplastin: Extrinsic pathway.

• XII + collagen: Intrinsic pathway.

• The activation of the extrinsic pathway also activates the intrinsic pathway.

• In a test tube, blood only uses the intrinsic pathway, while in the body when a finger is cut, hemostasis occurs faster (due to the participation of both pathways).

26. Characteristics of the Two Pathways:

• Extrinsic pathway: Has an explosive nature, the speed is limited only by the amount of thromboplastin, XII, VII, and V.

• Intrinsic pathway: With severe tissue injury, extrinsic coagulation takes 15 seconds, while the intrinsic pathway takes 1-6 minutes.

Note:

• This text was rewritten based on the provided information and supplemented with relevant details to ensure clarity and coherence.

• Some medical terms have been clarified.

• Please read the text carefully to understand platelet physiology and the process of hemostasis.

Hopefully, this text is helpful!