What causes blood to clot? And what prevents blood from clotting?
The Yin and the Yang of the blood clotting system: We need blood to clot at points of injury, to plug up the hole and prevent us from bleeding uncontrollably. And we need the clot to be localized to the point of injury and not propagate through our blood vessels, bringing circulation to a halt, like a bad traffic jam. These two systems are in fine balance, keeping each other in control.
There are several components of the clotting system:
-Clotting proteins are mainly produced in the liver; some are produced in the lining of the blood vessels. These circulate in an inactivated state. An injury activates the ones first in line, which then serially activate the ones further down the line, much like a line of dominos. At the end of the cascade, proteins are activated, which form an activated fibrin mesh at the bleeding point. This in turn traps circulating platelets, which form a plug. These activate other platelets and the cells lining the blood vessels, starting the healing process at the point of injury.
This is not a linear process, but has many feedback loops, which make the process well controlled and efficient.
Then how does the clot not spread to the entire circulatory system?
The liver also produces anti- clotting and clot dissolving proteins. These get to work and start limiting the clot to injured blood vessel.
This system is upset under many circumstances.
Uncontrolled bleeding can be a result of
- Liver disease, which decreases the production of clotting proteins.
- Medicines that decrease the production of clotting proteins.
- Low platelet counts from bone marrow disease or chemotherapy don’t form the plug efficiently.
- Medicines interfere with platelet function, making them less sticky. These medicines are useful in prevention of heart attacks or strokes, e.g. Aspirin. Other drugs decrease platelet production due to their effect on the bone marrow.
- Inherited deficiencies of clotting proteins like Hemophilia A and B, which result in inadequate production of Factors 8 or 9.
Unwanted clotting can be a result of
- Deficiency of clot dissolving proteins, either inherited or caused by liver disease.
- Poor circulation or sedentary lifestyle, causing blood to pool.
- Dehydration and long periods of immobility e.g. long car or plane rides or postoperative recovery periods.
- Inflammatory illnesses can cause the lining of the small blood vessels to trigger activation of the clotting cascade.
- Autoimmune diseases produce antibodies that contribute to unwanted clotting.
- Some cancers cause a higher risk of clots. When a clot occurs in the absence of other risk factors, it may be the first presentation of a hidden malignancy. A search for an underlying cancer is important.
Because of such variable reasons, the treatment needs to be tailored to the cause, and the situation. Management of an acute bleed or clot requires urgent attention.
An acute bleed may require replacement of the clotting factors intravenously, e.g. in hemophilia, or platelets, if there numbers are seriously low. Prevention requires recognition of risk factors and avoidance of triggers.
An acute clot requires prompt administration of blood thinning injections, as well as pills that decrease clot formation for the long term. Thus far, the oral pill used has been a medicine called Warfarin aka Coumadin. This works by decreasing the production of clotting factors in the liver, and has to be closely monitored with regular blood tests. The dose has to be adjusted according to the INR, which measures the level of blood thinning. Newer medicines have come on the market that act further downstream in the clotting process, and do not need constant monitoring of the INR. They do not appear to have greater bleeding rates than Warfarin, but we also do not have an easy antidote to them, if bleeding should occur, whereas Warfarin related over-anticoagulation could be reversed with Vitamin K injections.
We cannot yet change the inheritance of factor deficiencies, or the presence of inflammatory disorders, but we can control for other variables that contribute to bleeding or clotting, and take preventive measures when indicated.