Blood Clotting…and Not Clotting

    Over a gallon of blood circles your body every 45 seconds, under pressure, in a network of arteries, veins and capillaries.  Any leaks in the system must be plugged and repaired. Some ruptures are emergencies requiring outside help, but most are fixed handily by a well calibrated system of physical and chemical reactions in your body.  You watch this process every time you cut yourself shaving or slicing tomatoes, but it also happens microscopically, all over your body, when blood vessels are damaged internally by trauma or infection or chronic degenerative changes in the walls of arteries.  

How clotting happens 

Hemostasis, the first step in controlling bleeding, involves mechanical measures like pressure, cautery or stitches to stop blood flow from damaged blood vessels. Hemostasis alone is ineffective and must to be accompanied by blood clotting, a process triggered by blood platelets, which are tiny little disc shaped cell fragments that accumulate at the site of blood vessel injury. About a trillion platelets circulate in the blood, speeding by over 10,000 square feet endothelial cells that line the inside walls of blood vessels. When damage exposes collagen and other proteins in the endothelial cells and surrounding tissues, platelets gather to plug the defect, while secreting chemicals that draw white blood cells to the scene. An orderly sequence of chemical reactions, known as the clotting cascade, then produces in a stringy mass of sticky protein called fibrin, which fills the gaps between the platelets. Over the next few days to weeks, as healing proceeds, the clot gradually dissolves and disappears in a process called lysis. Your scab falls off to reveal new skin underneath.

Balance between clotting and not clotting

Blood also must not clot to carry out its normal function of transporting oxygen and carbon dioxide and nutrients and waste. If blood clots occur inside blood vessels, they block blood flow and cause damage in surrounding tissues. Health problems like strokes and heart attacks, and clots in the heart, lungs and leg veins occur because local conditions like inflammation and slow blood flow trigger the clotting process. For example, when atrial fibrillation causes failure of atrial pumping, blood pools in the recesses of the upper chambers of the heart and clots may form.  Slow and turbulent blood flow in arteries narrowed by inflamed cholesterol plaques sets off the clotting process. Immobilization, bed rest or even prolonged sitting can promote clot formation in the leg veins.

Manipulation of the clotting system

Health problems like these, as well as the need to hasten clotting in some medical situations, drive attempts to manipulate the clotting system. Infusions of platelets and other blood products correct bleeding in the operating room and in medical conditions that lead to poor clotting, but, more commonly, medical problems require suppressing the blood clotting response. Most people are familiar with anti-clotting drugs, called “anticoagulants,” that interfere with one or more of the chemical processes in the clotting cascade. They are used for common heart problems like atrial fibrillation, leg vein clots and after heart valve replacements to prevent the foreign valve materials from triggering clotting. Most people are also familiar with “antiplatelet” drugs like aspirin used to help prevent heart attacks and strokes by interfering with the ability of platelets to start the clotting process. 

Pharmacological aid in breaking down clots 

A third type of intervention employing “thrombolytic” drugs aims to dissolve clots that have already formed.Thrombolytic drugs are used in hospitals, in the acute setting of clots that have caused heart attacks and strokes. When injected into arteries, they dissolve clot and restore blood flow though the problem area of the blood vessel that triggered the clotting process, or through an artery in the brain that has been suddenly blocked by a clot that traveled there from the heart.

Blood “thinners”

 Anticoagulant drugs are often incorrectly called blood thinners, but they do not change the thickness of blood. They block reactions in the clotting cascade. Heparin, when injected intravenously, causes the most direct and immediate interference, so doctors opt for this choice (or other similar drugs if a patient is allergic to heparin) when stopping clot formation is urgent. The insertion of an artificial heart valve, which will trigger clot formation on its surface, the presence of leg clots which may break off and travel to the lungs, or the onset of atrial fibrillation call for prompt blocking of clot formation, while the transition is made to oral anticoagulant drugs.

Oral anticoagulant drugs take a few days to slow the speed of blood clotting.  Of the oral drugs available for blocking clotting, coumadin is the oldest and most frequently used because its anticoagulant effects can be stopped quickly, if necessary. The ability to reverse anti-clotting effects is important if the anticoagulated patient develops a bleeding problem or is at risk of falling or other injury. Coumadin’s effects are reversed by intravenous injection of Vitamin K. People taking coumadin must have their blood checked regularly to monitor the rate at which the blood clots, and adjust doses accordingly. Other newer oral anticoagulants are popular because they do not require testing, but are more expensive and their effects cannot be reversed as quickly.  Intramuscular drugs are available for home use, usually when anticoagulation is a temporary treatment.

Drugs that make platelets less sticky

Antiplatelet drugs like aspirin and persantin are often prescribed to prevent clot formation in the coronary arteries, though the evidence about their benefits is mixed.  Far more common, however, is the unsuspected antiplatelet effect encountered by people using many over the counter products, particularly non-steroidal anti-inflammatory drugs (NSAIDS) used for pain, and some supplements like fish oil. Aspirin and NSAIDS are implicated in stomach bleeding episodes and in heavy menstrual bleeding.

 In addition to its role in repairing leaks and keeping blood running freely through the vast network of blood vessels in the body, the complex chemistry of the blood clotting system is revealing itself to be intricately involved in other aspects healing and in immune-mediated inflammatory states (such as COVID-19). The attempt to immunize against the SARS-COV2 virus has also focused attention on blood clotting, with the antigen chosen to stimulate antibody formation triggering serious adverse events involving both clotting and bleeding, as well as unsuspected clot formation in very small blood vessels. Knowledge is accumulating rapidly and, as it does, expect to see blood platelets revealed as much more than pieces of cells used to plug holes and the clotting system more closely related to the inflammatory system.  

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