N-acetylcysteine and clotting have an interconnected link that can explain much about what treatment options are required in specific cases.

Acetylcysteine, commonly known as N-acetyl cysteine (NAC), is the supplemental form of the amino acid cysteine. It has been claimed that taking NAC supplements protects against health concerns such as diabetes, liver diseases, alcohol and substance disorders, psychiatric disorders, and some cancers.

Understanding N-Acetyl Cysteine 

Cysteine is a precursor to the antioxidant glutathione. In the human body, this is synthesized by the liver. Cysteine is an amino acid, one of the building blocks for protein. The unique feature of NAC is that it can reduce disulfide bonds, due to cysteine. As a result, NAC is an antioxidant that decreases platelet aggregation and reactive oxygen species.

NAC plays a pivotal role by binding two other amino acids, glutamine and glycine, to make glutathione. Glutathione is an antioxidant that has protective properties against various diseases and disorders. “Glutathione is known to play essential roles in regulating cellular activities, neutralizing free radicals, besides providing immune-protective properties. Acetylcysteine uses also include being used as a medication to treat acetaminophen (paracetamol) overdose, contrast nephropathy prophylaxis, and the like. NAC is also been used as a mucolytic agent in chronic bronchopulmonary disorders (like pneumonia, bronchitis) and cystic fibrosis to loosen mucus formation,” says Plaboni Sen, Research Scholar, Department of BSBE, IIT Guwahati.

Clinical Trials 

NAC, on account of its antioxidant, mucolytic, and anti-inflammatory properties, has been known to prevent thrombosis. Prof. Siddhartha S. Ghosh, Department of BSBE, IIT Guwahati notes:

It is currently being investigated as a therapeutic drug against thrombotic thrombocytopenic purpura (NCT01808521), which shows significant action of the drug leading to reduced thrombosis and reduced serum inflammatory cytokines. Moreover, NAC reduces the chances of heart disease by reducing oxidative damage to tissues in the heart. Research evidence suggests that NAC increases nitric oxide production, which helps veins dilate, thereby improving blood flow. This in turn expedites blood transit back to the heart, hence lowering the risk of heart attacks.

NAC should be used carefully by physicians in the context of oxidative injury with heightened thrombosis, as it is usually used in combination with other antiplatelet agents and needs the acetylcysteine dosage to be monitored. The side effect of NAC is that it may cause bleeding in poorly chosen patients, like one with a subclinical bleeding disorder in conjunction with other antiplatelet agents.

Anticoagulant Properties

NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. Therefore, acetylcysteine dosage administration should be regulated under close supervision. However, many other medications have been known to inhibit the formation of blood clots.

These include anticoagulants (for example, heparin or warfarin) that slow down the body’s ability to form clots; and antiplatelet drugs (for example, aspirin) that prevent platelets from clumping together to form a clot. Blood clots can reach organs like the lungs, heart, and brain. It can also disrupt the flow of blood causing issues like heart attack and stroke.

Platelet Activation

Dr. Govind Eriat, Consultant, Hematology and Bone Marrow Transplant, BGS Gleneagles Global Hospital explains:

NAC will destroy disulfide bonds, which are present in clots and mucus plugs. NAC has mucolytic and anticoagulant activity that breaks clots by destroying the sulfur bonds between large VVF (Vesicovaginal fistula) multimers, which hold an arterial clot together and with platelets. NAC’s common uses are in countering aspirin poisoning and breaking down mucus plugs in the chest by oral tablets or inhalation. We also routinely use NAC as a renal and hepatic protective agent prior to long surgeries and contrast administration for CCT, MRI, and Angiogram in critically ill patients. This is used intravenously in cardiac surgery to augment the activity of antiplatelet agents intraoperatively in certain centers for aortic surgeries.

N-Acetyl Cysteine attenuates systemic platelet activation. This is studied and published as a research article by Wang in the Redox Biology journal. Dr. Karthiyayini Mahadevan, Head of Wellness and Wellbeing at Columbia Pacific Communities says, “One of the important factors for a blood clot formation is the platelet aggregation over which the blood clot formation happens. This is facilitated by a clotting factor called the Von Willebrand Factor multimer. The N Acetyl Cysteine can reduce the intrachain disulfide bonds in large proteins like the Von Willebrand factor (VWF) Multimer.” This has been postulated in a study that NAC might cleave the VWF multimers. This proteolysis of VWF is a reason why NAC has been tried in acute stroke, acute coronary syndrome or ischemia in any area.

Bleeding Disorders And NAC

NAC is known to slow the process of blood clotting. Thereby it increases the risk of bruising and bleeding in patients suffering from bleeding disorders such as Hemophilia, the Von Willebrand disease.

“Therefore, the administration of NAC in people suffering from such bleeding disorders should avoid its consumption. NAC has been proven safe for adults when provided as a prescription medication. However, its overdose may cause nausea, vomiting, diarrhea, and constipation. Upon inhalation, it also causes mouth swelling, runny nose, drowsiness, and coughing. Besides, adverse symptoms after the administration of inhaled NAC include bacterial pneumonia, sore throat, and drug-induced pneumonia,” says Sen and Ghosh.

Judicious Usage

Clotting is a protective mechanism to prevent bleeding. The clotting happens with a well-balanced stream of clotting and thrombolytic agents that are produced within the body. “There are many blood thinners that play a vital role in preventing blood clots. There are anticoagulants, which prevent blood clots. Naturally, the liver synthesizes certain proteins which play a major role in checking bleeding and clotting by secreting various proteins which include clotting factors and NAC. So, if the liver is taken care of, then it would set a balance in the coagulation pathway,” says Mahadevan.

NAC is a precursor to glutathione, an antioxidant, that helps in taking care of processes involving oxidative stress. By providing a protein as an antioxidant, NAC helps in checking accelerated aging. The role of NAC in giving positive outcomes in key health issues is something that needs more attention as it can assist in better recovery rates in chronic respiratory conditions, fertility, and brain health, among others.

Bindu Gopal Rao is a freelance writer and photographer based in Bengaluru, India. She write across a variety of topics and documents her work on BinduGopalRao and on Instagram @bindugopalrao

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