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

http://www.youtube.com/user/DoctorNajeeb#p/c/90EE54545509447E/0/KnqIaGbKtAA

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 strandsthe 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 collagenthey 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 adheinplatelet activation the receptor on the platelet surface activated by von willebrand factor gives

signals to the plateletin 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 IXfacotr 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