Blood clotting is a crucial bodily function that prevents excessive bleeding from injuries. However, in some cases, excessive clotting can lead to life-threatening conditions such as stroke, deep vein thrombosis (DVT), and pulmonary embolism (PE). Anticoagulants, commonly known as blood thinners, help prevent harmful blood clots. Understanding their types, uses, risks, and proper management is essential for individuals prescribed these medications.
Types of Anticoagulants
Anticoagulants are broadly classified into two major types based on their origin and chemical nature:
Natural Anticoagulants
Heparin
Heparin is one of the most well-known natural anticoagulants. It is produced by basophils (white blood cells) and saliva. Heparin’s primary action is to inhibit thrombin, an enzyme that plays a crucial role in converting fibrinogen to fibrin, the protein that forms blood clots. By inhibiting thrombin, heparin prevents the formation of blood clots. The concentration of heparin is 0.1-0.2 mg/ml.
Hirudin
Hirudin is another natural anticoagulant derived from the saliva of leeches. Similar to heparin, it works by directly inhibiting thrombin, making it effective in preventing clot formation.
Artificial Anticoagulants
Artificial anticoagulants are synthetic substances chemically engineered for medical and laboratory use. They are typically used to prevent blood clotting in patients at risk of clot-related diseases, such as deep vein thrombosis, heart attack, or stroke.
EDTA (Ethylene Diamine Tetra Acetic Acid)
EDTA is one of the most commonly used anticoagulants in hematology. It works by binding to calcium ions in the blood, preventing them from participating in clotting processes. The absence of calcium disrupts the coagulation cascade, ensuring the blood remains fluid.
Oxalate
Oxalate is another artificial anticoagulant that prevents coagulation by chelating calcium. When calcium ions bind with oxalate, they form insoluble calcium oxalate, which cannot participate in clotting. Oxalates are typically used in blood collection tubes for chemical analysis and hematological tests.
Citrate
Citrate works similarly to EDTA by binding to calcium ions. However, unlike EDTA, citrate forms a soluble complex with calcium, which makes it useful for coagulation studies. Citrate is widely used in blood donation, erythrocyte sedimentation rate (ESR) tests, and other laboratory procedures that require anticoagulation.
Fluoride Oxalate
Fluoride oxalate is a mixture of sodium fluoride and potassium oxalate. Fluoride acts as an antiglycolytic agent, inhibiting glycolysis (the breakdown of glucose) in red blood cells. This helps preserve blood glucose levels during laboratory testing, making fluoride oxalate an ideal choice for glucose estimation.
Classification of Anticoagulants
Anticoagulants can also be classified based on the form in which they are used:
Dry Anticoagulants
Dry anticoagulants are typically powders mixed with blood before testing. Examples include EDTA, oxalate, and fluoride.
Wet Anticoagulants
Wet anticoagulants are solutions that are used directly with blood. Examples include ACD (Acid Citrate Dextrose) solution and sodium citrate.
The Action of Heparin
Heparin’s action primarily inhibits thrombin, an enzyme crucial for blood clotting. By binding to antithrombin III, heparin enhances antithrombin activity, inhibiting thrombin and preventing fibrinogen from being converted into fibrin. This action ensures that blood remains liquid and does not form clots unnecessarily.
Heparin is typically present in the body in very low concentrations, around 0.1-0.2 mg/ml. In addition to preventing clotting, heparin is widely used in clinical and laboratory settings for various tests.
Uses of Heparin
Heparin is used in various medical and laboratory procedures due to its ability to prevent blood clotting. Some common uses include:
- Osmotic Fragility Test – This test helps to determine the fragility of red blood cells.
- Blood Gas Analysis – Heparin is often used in blood gas analysis to prevent coagulation.
- Karyotyping – Heparin prepares for karyotyping (chromosome analysis).
- Electrolyte Estimation – Heparin helps maintain electrolyte stability in blood samples.
- G6PD and PK Deficiency Testing – Heparin tests for glucose-6-phosphate dehydrogenase and pyruvate kinase deficiencies.
Why Heparin is Not Always Used
While heparin is highly effective in preventing blood clotting, it does have limitations. Heparin is expensive compared to other anticoagulants, and it can cause issues such as platelet clumping and leukocyte aggregation. These factors make it unsuitable for automated cell counters. Furthermore, heparin has a limited duration of action and can lead to bluish discoloration in blood samples, making smear preparation less satisfactory.
EDTA: Ethylene Diamine Tetra Acetic Acid
EDTA is widely used in hematology. It prevents blood clotting by binding to calcium ions in the blood. Calcium is essential for activating several clotting factors, so EDTA effectively halts the clotting process by binding to calcium.
Types of EDTA
- Disodium EDTA – Also known as Versene, disodium EDTA is commonly used in laboratory tests.
- Dipotassium EDTA – Known as Sesquestrene, this form of EDTA is used in clinical analysis.
- Trisodium EDTA – The most widely used form of EDTA in laboratory settings.
- Tripotassium EDTA – Often used in specific medical tests.
Why EDTA is the Anticoagulant of Choice for Hematology
EDTA is particularly beneficial for hematology because it preserves cell morphology up to 2-3 hours after blood collection. Additionally, EDTA prevents the clumping of platelets, which is essential for accurate platelet counts.
Disadvantages of EDTA
- Expense – EDTA is more expensive than other commonly used anticoagulants.
- Not Suitable for Coagulation Studies – EDTA is ineffective for studies requiring clotting, such as prothrombin time or activated partial thromboplastin time.
- Excess EDTA – Excess EDTA can cause platelet disintegration and affect test results.
Oxalate: Mechanism and Types
Oxalate works by chelating calcium ions in the blood, forming insoluble calcium oxalate precipitates. This process prevents calcium from being available for the coagulation cascade, thus inhibiting blood clotting.
Types of Oxalate
- Potassium Oxyalate—This is used for chemical analysis but shrinks red blood cells, making it unsuitable for certain tests such as peripheral smears or ESR.
- Ammonium Oxalate – Causes swelling of red blood cells and is also unsuitable for peripheral smears or ESR.
- Double Oxalate – A balanced mixture of potassium and ammonium oxalate that can be used for tests like hemoglobin estimation, RBC count, and ESR. It balances the swelling effect of ammonium oxalate and the shrinkage effect of potassium oxalate. It is in the ratio of 3:2. This is also known as the Wintrobes mixture, which is balanced oxalate or Hellers and Pauls mixture.
Citrate: Mechanism and Uses
Citrate works by binding with calcium to form calcium citrate, which prevents coagulation. Unlike EDTA, citrate forms a soluble complex, making it useful for various laboratory procedures. It is used as a wet anticoagulant. It is not used for cell counting or Hb estimation as it causes blood dilution. The most commonly used is trisodium citrate.
Acid Citrate Dextrose is an anticoagulant used in blood banks. Citrate Phosphate and dextrose Adenine have replaced it.
Common Uses of Citrate
ESR (Erythrocyte Sedimentation Rate)
3.8% Sodium citrate is used for Erythrocyte Sedimentation Rate (ESR) by the Westergrans method. Sodium citrate is mixed with blood in a ratio of 1:4 (0.4 ml of sodium citrate and 1.6 ml of blood)
Coagulation Studies
3.2% Sodium Citrate is used in coagulation studies, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT). The ratio of anticoagulant to blood is 1:9.
Oxalate-Fluoride Mixture
Sodium fluoride, when combined with potassium oxalate, acts as an antiglycolytic agent by inhibiting glycolysis. This combination is ideal for glucose estimation, as it prevents the breakdown of glucose during blood sample storage.
FAQs
1. What are anticoagulants used for?
Anticoagulants prevent blood clots, reducing the risk of stroke, DVT, and PE.
2. How do anticoagulants prevent blood clots?
They inhibit clotting factors or prevent platelet aggregation, ensuring smooth blood flow.
3. What foods should I avoid while taking anticoagulants?
Foods rich in vitamin K (e.g., spinach, kale) can affect warfarin’s effectiveness.
4. How do I manage excessive bleeding on anticoagulants?
Seek medical help immediately. Apply pressure to bleeding wounds and inform healthcare providers of anticoagulant use.
5. Do all anticoagulants require regular blood tests?
Warfarin requires frequent INR testing, while DOACs need periodic kidney and liver function monitoring.
6. What is the primary function of an anticoagulant?
Anticoagulants prevent blood from clotting, ensuring the blood remains fluid and can flow freely through the blood vessels.
7. Why is EDTA preferred in hematology?
EDTA preserves cell morphology and prevents platelet clumping, making it ideal for hematological analysis, including platelet counting.
8. Can Heparin be used for all blood tests?
Heparin is not suitable for all blood tests. It is avoided in tests like automated cell counters due to platelet clumping and background discoloration.
9. What is the effect of citrate on blood tests?
Citrate binds to calcium ions, preventing clotting. It is commonly used in coagulation studies and ESR tests.
10. Why should oxalate not be used for peripheral smear preparation?
Oxalate causes RBC shrinkage (potassium oxalate) or swelling (ammonium oxalate), distorting blood cell morphology and making it unsuitable for peripheral smear preparation.
Anticoagulants are essential tools in both medical and laboratory settings. From natural anticoagulants like heparin and hirudin to synthetic options such as EDTA, oxalate, and citrate, each anticoagulant serves a specific purpose based on its unique mechanism of action. Understanding anticoagulants’ different types, uses, and limitations ensures that they are applied effectively for accurate diagnosis and treatment in clinical practices.
