Overview of Anticoagulation
Hemostasis is the body’s way of forming clots to stop bleeding. It consists of four steps. The first step occurs when a blood vessel is damaged by something like an injury, diabetes, high blood pressure, or smoking. This damage causes a protein called the Von Willibrand factor (VWF) to be released. This protein helps tiny particles in the blood called platelets stick to the site of the damage.
The second step is the formation of the clot itself. A series of reactions take place that convert inactive proteins in the blood into active ones. These active proteins help to increase the size of the clot. One protein called factor 3, which is usually kept hidden inside our blood vessels, gets exposed when a blood vessel is damaged, setting off a chain reaction.
Another protein, factor 11, when activated also helps in the clot formation by leading to the activation of other factors. Certain factors then work together to convert a protein called prothrombin into thrombin. Thrombin helps convert fibrinogen in the blood to fibrin which forms a stable clot.
The third step is to stop the formation of the clot and control its size to prevent it from causing problems like inflammation and tissue damage that can lead to conditions like deep vein thrombosis. The process also ensures that the blood remains fluid enough to flow through the body.
The final step is the dissolution of the clot after the wound is healed. This step ensures the removal of the clot and allows tissue to return to normal.
Sometimes doctors give medicines, called anticoagulants or blood thinners, that interfere with different steps of the clotting process. They work by blocking specific clotting factors, preventing the formation of a firm clot.
Taking these medicines during pregnancy is important, as pregnancy increases the risk of dangerous clots forming in the veins. This risk rate further increases after birth and can stay high for up to twelve weeks. It is especially high for women who already have a higher risk of blood clots.
Anatomy and Physiology of Anticoagulation
Anticoagulants are medications that help reduce the formation of blood clots, necessary for some medical conditions. They work by impacting different stages of the blood’s clotting process. Some of these medications work directly by stopping specific proteins that cause clotting, while others work indirectly by either attaching to a protein called antithrombin or blocking vitamins critical for the production of clotting factors in the liver.
There are several types of anticoagulants:
Unfractionated Heparin (UFH): This group of drugs, including heparin, works by forming complexes with a protein known as antithrombin 3 to neutralize certain proteins involved in blood clotting. These drugs act quickly and are relatively short-lived in the body. Doctors monitor the effectiveness of UFH with some tests, like the activated partial thromboplastin time (aPTT), which measures how long it takes the blood to clot.
Low Molecular Weight Heparin (LMWH): Medications like enoxaparin and dalteparin belong to this category. These drugs stay active in the body longer than UFH. While these can also be monitored using anti-factor 10a activity, routine monitoring isn’t typically required, except in specific cases like pregnancy or kidney disease.
Vitamin K Dependent Antagonists (VKA): A common example is Warfarin. These work by blocking a critical step in the use of vitamin K, a nutrient necessary for making several proteins involved in the clotting process. Warfarin’s effectiveness can be influenced by diet, medications, and some genetic variants. It requires consistent monitoring with a test called the international normalized ratio (INR), which measures clotting time.
Direct Thrombin Inhibitors: Known drugs such as Bivalirudin, and Dabigatran, stop the formation of a protein called thrombin that plays a fundamental role in blood clotting.
Direct Factor 10a Inhibitors: These, like Rivaroxaban, Apixaban, work by directly attaching to a protein called Factor Xa, stopping it from triggering a crucial step in the clotting process. They are typically taken orally.
The terms Direct Oral Anticoagulants (DOACs), New Oral Anticoagulants (NOACs), or Target-Specific Oral Anticoagulants (TSOACs) refer to oral medicines that specifically inhibit proteins involved in the clotting process. According to global guidelines, the preferred term is DOACs. These drugs have shown similar impact as traditional anticoagulants, with some research suggesting a lower risk of bleeding. They are also easier to dose and are less affected by diet and other medications.
Why do People Need Anticoagulation
If you’re having heart-related issues or facing a major surgery, your doctor might recommend a type of medicine called an anticoagulant. These medicines are often referred to as “blood thinners,” but they don’t actually make your blood thinner. Instead, they help prevent blood clots from forming in your blood vessels, which lowers your risk of certain problems, like heart attacks and strokes. Deciding which anticoagulant to use is not a one-size-fits-all decision. Your doctor will take into account your personal preferences, how likely you are to get blood clots, and other health problems you have.
Anticoagulants are used in a few different situations. This includes people who have atrial fibrillation (an irregular heart rhythm), venous thromboembolism (blood clots in the veins), and those who’ve had a heart valve replacement. Sometimes, blood clots in the veins can be the first sign of a different health problem.
In the case of a heart attack, anticoagulants like heparin are usually given right away. They can lower the risk of more blood clots forming if they’re used for at least 48 hours. If you had a procedure to open up blocked heart arteries, heparin is also used. If you’re not having this procedure, you could be given a different type of anticoagulant.
If you have a blood clot in the chamber on the left side of your heart, research shows that starting anticoagulation early can stop the clot from moving to other parts of your body. Usually, the anticoagulation is given for three to four months because that’s when the risk of the clot moving is the highest. Another disease that can result in a blood clot in the heart is called ventricular aneurysm, which is a bulge in the wall of your heart’s major pumping chamber that can occur after a heart attack. Anticoagulation can help prevent blood clots especially for those with irregular heart rhythms.
In people with artificial heart valves, anticoagulation is needed. Usually, a type of anticoagulant that depends on vitamin K is used. If you can’t take this type of medicine for some reason, you could be given heparin instead.
Anticoagulants are also an important part of treating blood clots in the veins, including ones in the deep veins of the legs or ones in the lungs. The length of time you would need to take these medicines depends on what caused the clot in the first place and other health problems you might have. Sometimes, anticoagulants are used as a preventative measure in certain situations, such as being in the hospital, recovering from surgery, or having cancer.
For cancer patients, the chance of having a blood clot can be higher due to certain factors released by cancer cells. Research shows that a specific type of heparin, called low-molecular-weight heparin, might be better than other types of anticoagulant for cancer patients.
There can also be a condition where heparin itself causes the body to make antibodies that can lead to blood clots. It’s called heparin-induced thrombocytopenia. Even though having less platelets usually increases the risk of bleeding, in this case, it causes a higher risk of blood clots. Therefore, some other non-heparin anticoagulants are recommended.
Finally, anticoagulants might also be needed during pregnancy for treating blood clots in the veins, heart valve problems, and certain complications due to an immune reaction to normal body substances. Warfarin, a kind of anticoagulant, is very effective at preventing blood clots in pregnant women with artificial heart valves. However, it can cause birth defects if used in the first three months, so heparin is usually preferred during this period.
When a Person Should Avoid Anticoagulation
Sometimes, doctors advise against the use of anticoagulants – medicine that prevents blood from clotting too quickly – in certain patients who have specific medical conditions. These situations are absolutely contraindicated, meaning the medicine should not be used at all. This happens in the following conditions:
* If a person is currently bleeding.
* If a person has a problem with their blood clotting, a condition known as coagulopathy.
* If a person has recently undergone major surgeries.
* If a person is experiencing acute intracranial hemorrhage, which is a sudden bleeding inside the skull.
* If a person has gone through a significant injury, called major trauma.
In some cases, doctors might consider using anticoagulants even if a person has certain medical conditions. However, the use of these medicines will require a lot of careful thought and monitoring. This is generally seen in the following conditions:
* If a person had bleeding in the stomach or intestines, called a gastrointestinal bleed.
* If a person has had minor surgeries.
* If a person has a tear or a bulge in the wall of the main artery leading away from the heart, called aortic dissection or aneurysm.
Lastly, doctors should be extra careful when prescribing these medicines to the following groups of patients:
* Elderly people.
* Pregnant women.
Equipment used for Anticoagulation
When you’re on medication that prevents your blood from clotting, called anticoagulants, it might be necessary to regularly check the level of these drugs in your blood. These checks are especially important in certain situations, including if you are bleeding or at risk for blood clots, undergoing planned surgical procedures, dealing with an overdose, managing multiple health conditions that require this medicine, about to have surgery, or have liver disease.
Generally, you don’t need regular checks if you’re on a specific type of these medications called direct oral anticoagulants (DOACs), unless you’re at high risk of bleeding especially when your brain is concerned. Then, special tests called anti-10a or anti-2a activity assays are recommended because they give precise information about the risk.
If a doctor suspects that you might have bleeding problems, they would do several tests. Some tests can be done right at your bedside, such as measuring how quickly your blood clots. These tests include prothrombin time (PT) and activated partial thromboplastin time (aPTT), which are measures of how long it takes for your blood to clot, fibrinogen assay which checks for a protein that helps in clotting, and a whole blood platelet function test which assesses how well your blood platelets are working.
Other important tests include:
- CBC: A complete blood count that looks at different parts of your blood, including checking the number and appearance of your platelets, which are cells that help control bleeding.
- Bleeding Time: A rarely used test that shows how fast bleeding can stop. It helps diagnose problems with platelets and blood vessel contraction, conditions like Von Willibrand disorder and thrombocytopenia, which affect blood clotting.
- Clotting Time: It measures the time it takes for your blood to clot in a lab setting. This step considers the standard time to be between 8 to 15 minutes. However, not all researchers agree on using this test as a base screening tool.
Prothrombin Time (PT)/INR is a crucial test used to check how quickly your blood clots. If these times are longer than normal, it could mean that you have a clotting factor deficiency or something is inhibiting the clotting factor. An antiphospholipid antibody condition can sometimes result in delayed clotting times. Normal PT levels usually range from 11 to 13 seconds, but may vary depending on the lab doing the test.
Activated Partial Thromboplastin Time (aPTT) assesses different clotting pathways in your body. Typical values range from 25 to 35 seconds, again depending on the lab. Thrombin Time looks at the final step in the clotting process. Abnormal times could be due to anticoagulants like heparin, dabigatran, argatroban, and any fibrinogen abnormalities, a protein that’s key to the clotting process.
Some tests are specific to individual clotting factors in the blood. For example, the Clot Solubility test is used to check for a deficiency of factor 13. This factor is vital as it crosslinks the fibrin clot after its formation. Fibrin D-dimer, a substance released when a blood clot dissolves, is checked to see if there are any blood clotting issues.
Possible Complications of Anticoagulation
People who are on anticoagulation therapy, which is a type of treatment to prevent blood clots, may have an increased risk of bleeding. There are several factors that can increase this risk, some of which are related to the person, while others are linked to the anticoagulation medicine used.
Some anticoagulants like warfarin can present a higher chance of notable bleeding than other ones known as direct oral anticoagulants. This risk also depends on the dose of the anticoagulant and the use of other medicines such as antiplatelet agents, which also increase the chance of bleeding.
The individual’s chances of bleeding may be influenced by their age, race (with a higher risk for Black/Brown populations), underlying health issues, if they’ve recently had surgery, or if they have a medical condition that affects blood clotting.
If someone needs to urgently reverse the effects of anticoagulation due to a serious bleeding situation, there are steps to take. Firstly, we stop the medicine. We can then use various methods such as activated charcoal within two hours of the last anticoagulant dose, hemodialysis (a treatment that filters waste and water from your blood), red blood cell or platelet transfusion to treat anemia or a low platelet count respectively, or surgery in some cases. There are also specific reversal agents that can be used depending on the type of anticoagulant, for instance, Protamine sulfate for heparin and Idarucizumab or Andexanet alfa for Direct Oral Anticoagulants.
These methods work to counteract the anticoagulant’s effects, which can be quite helpful in emergencies where the patient is experiencing life-threatening bleeding.
What Else Should I Know About Anticoagulation?
Managing blood-thinning medication during and after surgery can be challenging for doctors. They need to balance the risk of blood clots, bleeding, and the timing of these medications for patients who are having planned procedures. A strategy called “bridging anticoagulation” is sometimes used. This involves using a specific kind of medicine called low molecular weight heparin in situations where there’s a high risk of blood clots forming. However, if a patient’s risk is low, bridging is not necessary. In cases where the risk is significant, bridging is required. Recommendations from notable healthcare authorities such as the American College of Cardiology, American Heart Association, and Heart Rhythm Society are also considered.
When starting blood-thinning treatment with a drug called warfarin, certain guidelines are followed. For example, if a patient has a form of heart rhythm disorder called nonvalvular atrial fibrillation without complications, no bridging with a heparin product is necessary. Bridging isn’t recommended for those at low or medium risk of developing a blood clot. However, for patients with a mechanical heart valve, recent blood clot in the veins or active blood clot in the arteries, bridging with heparin is necessary during the initiation of treatment. This is also the case for patients who had a coronary stent placement within the past 12 weeks.
The effectiveness of direct oral anticoagulants (a type of blood-thinning medication) can be observed about two to three hours after starting treatment, so heparin bridging can be stopped. For Vitamin K antagonists (another type of blood thinner), the heparin bridging might last four to five days until the Vitamin K antagonists start to work effectively.
