Blood clots...?

Question

What causes blood clots?

Answer 1

Multiple school of thought are there, it is platelets aggregation, fat, triglycerides, and cholestrol. They all combine to form this action.

Answer 2

Coagulation (or the forming of solid clots from liquid blood) is a complex interaction that is made up of two major components

1. Pro-thrombotic (or clot forming) factors - Clotting is, in general a good thing. You want to be able to clot in order to prevent hemorrhage, or massive bleeding, from minor cuts, bruises, and abrasions that occur every day. Your ability to form blood clots is mediated by two major components of your blood - your platelets and your clotting factors.

A. Platelets - these are non-nucleated cells that contain granules. Platelets are essential to the formation of clot and form what is known as a "platelet plug" when they encounter a hole in the endothelium (the single cell thick lining of our blood vessels). There are proteins on the surface of cells that are underneath the endothelial layer that activate platelets by binding to a surface protein on the platelet called von Williebrand's factor. A series of reactions causes a meshwork of platelets to form around the exposed and damaged blood vessel. This meshwork acts as a lattice for the 2nd component of your blood to form a firmer clot. The forming of the platelet plug is termed "primary" hemostasis.

B. Coagulation factors - there are two pathways that contribute to the formation of fibrin clots. These are long and complex pathways that involve clotting factors that are numbered in reverse order from 1-13 (or maybe even more, I can't remember). The degranulated platelets cause an increase in the activation of the higher number of the clotting factors (for instance factor 12 is the first factor activated in the intrinsic pathway while factor 7 is the first factor activated in the extrinsic pathway), which in turn activate lower numbers of clotting factors until factor 2 is activated. Factor two is called fibrinogen in its unactivated form and fibrin in its activated form. When fibrin gets made it is cross linked by activated factor 13, and it inserts into the interstices of the platelet plug. Fibrin clots are generally called "red thrombi", due to their color while platelet clots are generally called "white thrombi". The addition of fibrin to the clot is termed "secondary" hemostasis.

2. Once clotting starts the body must have a way to stop it. Otherwise a little cut would cause all the blood in your body to clot (not a good thing) instead of just clotting over where you cut yourself. There are a number of anti-thrombotic molecules that are floating around in your blood. These get activated when they encounter clot by some of the same activated factors that are causing you to clot - this sounds confusing, the same thing causing two separate and differing outcomes - but it's all about the balance between clotting and lysis. Some of these molecules include
A. Protein C and Protein S - Genetic changes that cause a deficiency of Protein C are one of the more common causes of hereditary predisposition to excessive clotting.
B. Antithrombin III - the drug Heparin (recently in the news as the drug given in a high dose by accident to Dennis Quaid's twins) works by increasing the activity of this endogenous molecule.
C. Plasminogen and it's activated form Plasmin - This molecule is what the body uses to dissolve clots that have already formed. Drugs such as tPA (tissue plasminogen activator) are sometimes given by doctors to turn on the Plasmin in your body if you have a clot in one of the blood vessels to your brain and body.

So blood clots are caused by the activation of your pro-throbotic factors (such as platelets and clotting factors) in response to endothelial injury. There is a classic triad (or three things) that doctors learn is the cause of pathologic (or maladaptive) clotting known as Virchow's Triad. Usually some of these are present in a person who gets a pathologic blood clot such as a Deep Vein Thrombosis (blood clot in the legs)

Virchow's Triad
1. Endothelial Injury - damage to a blood vessel is the most common cause of clot. But blood vessels can be damaged in other ways besides cutting yourself. Smoking damages all the blood vessels in your body diffusely, thus causing a person to be more likely to clot, for example.

2. Stasis - When blood is not flowing it is more likely to clot. Thus people who are not moving for a long time, such as people bedbound after breaking a leg or people on long trans atlantic flights, are more likely to have blood clots.

3. Hypercoagulation - This is a wastebasket of things that make you more prone to clotting. People who are pregnant are hypercoaguable, people with certain types of cancer (like pancreatic cancer) are more likely to clot, and people with a genetic defect of an anti-clotting molecule are more likely to clot.

So overall you can see it's complex. But blood clotting is a normal process that can, given the right set of circumstances (such as Virchow's Triad) happen when it's not supposed to. These clots can get stuck in your lungs, brain, heart or extremities and cause a lack of blood flow to those areas, causing pain and possibly death. Let me know if you need any further explination or help understanding anything.