Platelets and coagulation system ( exerpt from Dr. Najeeb lecture on youtube

Coagulation- process by which soluble fibrinogen is converted into insoluble fibrin Fibrinogen is produced by liver Mechanisms in which blood are kept in liquid form: 1. Endothelial cells produced: NO, PGI2(prostacyclines2= form of prostaglandin), ADP diphosphatases: these are antiplatelet agents that don’t allow platelets to stick on the healthy endothelial cells and keep platelets inactivated . they are also vasodilators which relaxes smooth muscles of endothelium Platelets are membrane bound cytoplasm containing cellls without any nucleus, if activated, undergo reaction that makes up plug. Platelet size Size is 2-3 microns, (RBC is 7-8 microns). Life span is 8-10 days Thrombocytopenia= low number of platelets 2. Healthy endothelial cells expressed heparin sulfate on their surface ( hep. Sulfate is a molecule on which a special type of molecule can seat) - Antithrombin 3 (AT3 made by the liver)when attached onto the heparin sulfate , AT3 become active,once become active: Cut down throbin molecules , inactivate factor IX and X

3. Another molecule expressed on the surface on the endothelial cells called thrombo modulent( modulate the function of thrombin- these bind with throbin and bounded throbin activates protein C , protein C digest factor V and VII

4. Endothelial cells also produce tissue plasminogen activator ,when fibrin is present in the endothelial system Convert other protein from the liver called plasminogen into plasmin. Plasmin takes the fibrin strandsthe fibrin will breakdwown into fibrin degradation products

When healthy endothelial cells are injured: 3 steps to stop the bleeding 1. Vascular constriction – early response to injury - Nerve endings around the injured endothelium release vasoconstrictors ( called neurogenic reflex vasoconstriction) 2. Smooth muscels contraction ( reflex myogenic constriction) 3. When endothelial cells are injured, produced vasoconstrictors called endothelin  acts on the smooth muscles and constricts them (endothelial derived endothelin mechanism) Note: when endothelial cells are lost during injury , they lost the antiplatet and anticoagulatant properties which keep the blood in liquid form(discussed above) - Injured cells start producing chemical substances  stick on the exposed underline collagenthey have special hooks that hook up passing platelets these chemical molecules also produces sticking glue that sticks platelets over that area.( these chemical molecules are called von willebrand factor)

Note: platelets have surface glycoprotein receptors (GP1 b)where von willebrand factor attached The process where platelets stick on the exposed collagen surface of endothelium is called platelet adhein.

After platelet adheinplatelet activation  the receptor on the platelet surface activated by von willebrand factor gives signals to the plateletin the platelet, phospholipidase enzymes are activated  convert phospho lipids into arachidonic acid (AA) with the action of cyclooxygenase or COX enzyme these AA are broken down into thromboxin A2 (TXA2) TXA2 are vasoconstrictor and platelet aggregator) Note: aspirin makes platelet inactivated by blocking the COX enzyme Activated platelets starts releasing granules

What are these granules:alpha and delta granules( delta granules look like a SAC= contain Serotonin,ADP and Calcium)

S= serotonin= vasoconstrictor A= Adenosine Phosphate= platelet activating substance =activates other more platelets The drug ticlopidine works on ADP and make platelets less sticky therefore less thrombotic event C= Calcium Factor xII activates Factor XI Factor XI activates factor IXfacotr IX activates factor X Calcium held an activating factor to another activating factor inorder to activate Note: activating factors are also dependent on Vit K. to be active Alpha granules contain some coagulating factors fibrinogen,platelet derived growth factor -platelet derived factor attracts fibroblast to the area of injury , these fibroblast make more collagen to seal the injury

Platlet adhein= the first layer of platelet cells that are attached to the surface of exposed collagen of the injured endothelium. When von willebrand activates these platelets , it releases its granules (release reaction) to attract more platelets to the site , this is now called platelet aggregation that makes up the platelet plug ( primary hemostatic plug). Surfaces of the platelet plug start expressing platelet factors and start the coagulation process. This is the deposition of fibrins across and around the plug to make it stronger and tighter, now called secondary hemostatic plug. How is fibrinogen converted to fibrin? If u take a few ml of blood and put it on a very clean glass tube, it coagulates, why? 1. Intrinsic pathway- the process of coagulation without addition of external factors to the blood. It is the intrinsic property of the blood that initiates the coagulation. If you add citrate to the blood in the tube , citrate are negatively charge and neutralize the calcium,it can block the intrinsic property of the blood 2. Extrinsic pathway- tissue juice or tissue factor are produce by the injured cells, these factors activates extrinsic pathway. During t he activation of intrinsic pathways , when factor IX is already activated, in the presence of phospholipid, Calcium and factor VIII, factor X will be activated once factor X is activated, it acts on prothrombin in the presence of phospholipid, calcium and factor V to be converted to thrombin these thrombin breakdown fibrinogen into fibrin monomers that are deposited around the aggregated platelet. Meanwhile, thrombin also activates another substance called thrombin stabilizing factor or Factor XIII which stabilize the fibrin monomers by cross linking them -

In the extrinsic pathway, some of the tissue factors released by the injured cell activates Factor VII which can also activate Factor 1X and X

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