Blood Thinners: Differences Between Anticoagulants, Thrombolytics, and Antiplatelets
There are a number of drugs that people refer to as blood thinners. Blood thinners actually encompass several classes of drugs, each of which works in a different way and treats different conditions. Most of these drugs do not actually thin the blood. They may work by keeping blood from sticking together, breaking up clotted blood, or changing the way that blood behaves. This article will explain some of the different drug classes that fall under the general heading of "blood thinner." It will also give tips for using some of the different medications.
Please note: This information does not replace a doctor's advice. I am not a doctor. I don't even play one on television.
How does blood clot?
Blood clotting is a complex process that involves four things: platelets, clotting factors, fibrin (a webby, mesh-like substance), and other cells. Platelets and clotting factors float around in your blood all the time.
Blood also contains substances that prevent blood clots. These substances are called anticoagulants. It is the balance of these substances in the blood that allow blood to clot as needed and only when needed.
Clotting factors and anticoagulants are made in the liver. They have the ability to turn on or turn off as needed. When they turn on, the fibrin can activate and turn into a net that covers the place that is torn and bleeding. The fibrin web catches platelets and other blood cells to form a strong patch that can allow the body to stop bleeding and begin to heal. When blood clots are not needed, the body makes anticoagulant to prevent the clots and also creates enzymes to dissolve any unneeded clots.
Each drug class that works on blood clots works on a different part of the clotting sytem. The name blood thinner is not very descript as blood thinning is very different from preventing or treating clots.
Differences between venous and arterial clots
Treating arterial versus venous clots
Anticoagulants: vitamin K antagonists (warfarin), heparin, low molecular weight heparins, heparinoids
Anticoagulants work by interfering with the formation of the fibrin web. They affect the various clotting factors that the liver produces. Venous clots are caused when stationary blood develops unneeded fibrin webs. For this reason, anticoagulants are the best choice for venous clots. Examples of venous clots include a deep vein thrombosis or a pulmonary embolism. This class of drugs is used when these types of clots are showing up. It is also used when an individual has a condition that affects the fibrin and clotting factors. An example is Factor V Leiden.
Vitamin K antagonists: anisindione, Miradon, warfarin, Coumadin, Jantoven, Marevan, Waran, and others
Vitamin K antagonists works by interfering with vitamin K. Vitamin K is used by the liver to create clotting factors and anticoagulants. There are a number of different drugs in this class. Vitamin K antagonists have been around for over 50 years and have had a lot of development. In the United States, warfarin is the mainstay of anticoagulation. It is very rare to see another vitamin K antagonist used in treatment. If a patient is allergic to warfarin, the other antagonists can be considered. This section will focus only on wafarin; however, much of the information here applies to the other vitamin K antagonists as well.
Warfarin impairs the hepatic synthesis of factors II, VII, IX, and X. Because warfarin interferes with both clotting and anticoagulation, patients must use another medication for the first 5 days on warfarin therapy. Heparins and low molecular weight heparins are the drugs currently used to initiate warfarin. These drugs will prevent a blood clot from forming when starting warfarin. If warfarin is not started with an additional anticoagulant, it is likley that the patient will experience blood clots. As warfarin works by interfering with vitamin K, a consistent amount of this vitamin must be consumed every day. Warfarin is monitored by testing that is referred to as an INR test or protime. This test will see how long it takes the blood to clot. Each patient has a target INR. Dose will be adjusted to maintain this target. Common side effects are bleeding, anemia, hair loss, and osteoporosis. Warfarin can not be taken during pregnancy.
- Warfarin is very inexpensive
- Warfarin requires additional medication the first 5 days
- Warfarin must be monitored by regular INR tests
- Warfarin users must consume a consistent amount of vitamin K
- Changes in diet or medication require extra INR testing
- Warfarin can not be used in pregnancy
Low molecular weight heparins: Normiflo (ardeparin), Fragmin (dalteparin), Orgarin (danaparoid), Lovenox (enoxaparin), Innohep (tinzaparin)
Low molecular weight heparins (LMWH) also fall under the anticoagulant category. They inhibit Factors Xa and IIa. Some examples in this class are Normiflo (ardeparin), Fragmin (dalteparin), Orgarin (danaparoid), Lovenox (enoxaparin), and Innohep (tinzaparin). All of these drugs are administered by injection. They can be done at home and can come in vials or pre-filled syringes. Some people may feel squeamish about self-injecting. I know I was worried at first. The needle on my pre-filled Lovenox syringes were very sharp and went in smoothly without effort. LMWH can be used when a patient is starting a warfarin regimen. This will prevent clots during the beginning of warfarin anticoagulation. LMWH also can be used as a stand alone treatment or prevention of blood clots. This drug class has some additional unique uses. It can be used as a prophylactic before a long haul flight or car trip to prevent clots, it can be used during pregnancy to help someone with a clotting condition to carry the baby to term without complications, and it can be used as a bridge therapy so that warfarin is cleared out of the body prior to surgery. One of the best parts of these medications is that the patient does not need blood tests to assess blood levels. The down side is that this class is very new and is high cost.
- Low molecular weight heparins do not need blood monitoring
- Low molecular weight heparins can be used to initiate warfarin
- Low molecular weight heparins are useful in pregnancy
- Low molecular weight heparins can be used at home
- Low molecular weight heparins can be expensive
Tips on giving yourself LMWH
Ice, ice, ice. Low molecular weight heparins cause deep bruises where the shot is given. There are some ways to minimize this side effect. Ice the area for the injection until it is nice and numb. The ice will lessen the pain from the injection and it will also prevent the bruising. After the injection is done, put pressure on the site for at least 10-15 seconds. This will help to stop any subcutaneous bleeding. If the location is sore, ice it for an additional period after the injection. You may consider icing it longer if you have a very sore, large bruise. For more detailed directions, see the link below.
- Tips on giving yourself low molecular weight heparin shots
The main thing I stress is ICE before the shot. You can also ice after, but icing before is really key. It does two things. One, it significantly reduces bruising and you won't find yourself running out of bruise free places to inject in a week...
Direct Thrombin Inhibitors: Pradaxa (dabigatran), hirudin, bivalirudin, lepirudin, desirudin, argatroban
The direct thrombin inhibitor class has some of the newest anticoagulants on the market. They work by binding to the thrombin molecule. Thrombin is a protein that is involved in clotting. It activates many of the clotting factors, including Factor V. There are two ways in which direct thrombin inhibitors act. They can bind to thrombin on the active site (univalent) or on both the active site and exosite 1 (bivalent). Bivalent DTIs may be used in circumstances in which heparin is indicated but not available as an option. They are administered by injection and are not used for long term anitcoagulation. Argatroban is a treatment option when a patient experiences a very rare, life threatening complication of heparin known as heparin-induced thrombocytopenia. Dabigatran (Pradaxa) is the most common of this class. Pradaxa is a recently approved medication and is affective for stroke prophylaxis and atrial fibrillation. The benefit of Pradaxa is that it does not require routine blood monitoring. (Currently, there is no standardized test available to measure the anticoagulant effects of this class of drugs.) The largest problem with this class of drugs is the high risk of bleeding complications.
- Some direct thrombin inhibitors can be used to treat heparin induced thrombocytopenia
- Pradaxa is an oral, prescription blood-thinning medicine used to reduce the risk of stroke and blood clots in people with atrial fibrillation (AFib) not caused by a heart valve problem
- Pradaxa does not require routine monitoring
- There are no blood tests available to monitor the effects of direct thrombin inhibitors
- This class appears to have a higher risks of bleeding complications than warfarin
Factor Xa Inhibitors: Xarelto (rivaroxaban), Eliquis (apixaban)
Xarelto works by inhibiting one of the clotting factors in the blood. It prevents coagulation by working on Factor Xa. By working on Factor Xa thrombin levels are reduced and the probability of clotting is decreased. Xarelto has been found to be especially useful in people who struggle to maintain a consistent INR. Diet has no effect on Xarelto. Xarelto also does not need to have blood tests done to determine its blood levels. Research has shown that standardized dosing works well with this medication. There are currently no "official" methods to reverse Xarelto but doctors have been using methods such as plasma administration to stop the bleeding and induce coagulation.
- No blood work
- Not affected by diet
- No "official" method of reversal
- Has been found to be safer for patients who struggle to maintain INR
Heparinoids are possibly the newest class of anticoagulants. Currently, there is only one drug in this class, Arixtra. Arixtra is a subcutaneous injection that is give once a day. It is usually used short term (only 5-9 days). It is the only anticoagulant that inhibits only factor Xa and does not affect thrombin.
- Arixtra is typically taken once daily
- Arixtra is new and therefore may be expensive
- Arixtra is another anticoagulant option
Heparin is an anticoagulant that works by inhibiting factor Xa and factor IIa, also known as thrombin. It can be used as an injection or an IV. Heparin is an older drug and, much like warfarin, has well known dosing and side effects. Heparin has come under fire in recent years due to recalls. In each of the recalls heparin was recalled due to contamination. Heparin is a natural anticoagulant that is made by the body. Medical heparin comes from the intestinal mucosal tissue of slaughtered pigs and cows. Heparin has a very short half life (about 1 hour) and therefore must be given in frequent doses or on an IV drip. Blood levels of heparin must be watched carefully. As heparin is typically used in hospital settings, the blood testing is not an inconvenience.
- Heparin is typically a hospital based medicine
- Heparin has a short half life (about an hour)
- Heparin is typically given by IV
Platelets are available in blood to plug damage and holes in the circulatory system. Platelets can stick together when there is a wound and when there is inflamation in the arteries (example: atherosclerosis). Arteries are always under pressure as they have muscular walls. This makes them handle blood differently. For this reason, arterial clots are platelet based. Antiplatelets will be prescribed in situations where the arteries may be to blame for a clot or where the arteries may be at risk for clotting. Some examples are:
- TIA (transient ischemic attacks)
- Coronary artery disease
- Heart attack
- Angina (chest pain)
- Peripheral artery disease
- After angioplasty and stent placement
- After heart bypass surgery
- To prevent the formation of blood clots in people with atrial fibrillation
You will note that Factor V Leiden and other clotting disorders are not on this list. Also, pulmonary embolism and deep vein thrombosis (DVT) are absent from this list. This is because antiplatelets are not appropriate therapy for these conditions.
Cyclooxygenase inhibitors: aspirin
Aspirin has become an important medication for many people. Not only does it kill pain, inflamation, and fevers, it also affects platelets. Aspirin blocks the production of thromboxane A-2, a chemical secreted by platelets that helps the platelets to clump. It does this through it COX-1 inhibition. Aspirin is the preferred non-steroidal anti inflammatory drug (NSAID) for blood thinning because the other NSAIDs only change the platelet behavior for a short period of time. Aspirin affects platelets for days rather than mere hours. Aspirin blocks only one of the pathways that work on platelets. For this reason, aspirin is a weak anti-platelet medication. The dose of aspirin that is used depends on the condition that is being treated. 75-150 mg per day is used when aspirin is being used for the long term prevention of strokes and heart attacks. 160-325 ms per days is used for unstable angina and acute heart attacks as the larger dose affects platelets more quickly. Aspirin can cause side effects. The primary side effects are centered around gastrointestinal upset and stomach problems. Sometimes ulcers can occur from aspirin use. Like other blood thinners, patients should watch for problems with bleeding.
- Aspirin is inexpensive
- Aspirin can help with pain as well as blood thinning
- Aspirin should not be used with ulcers
- Although aspirin is over the counter, a doctor should be consulted when using aspirin as a blood thinner
- Aspirin and Heart Disease
Aspirin is used in the prevention of heart attack and stroke due to its ability to act as a blood thinner. This article will explain the risks and use of aspirin for prevention.
- Antiplatelets | Internet Stroke Center
Besides relieving pain, fever and inflammation, aspirin has many other uses. Aspirin is also used as an antiplatelet/platelet aggregation inhibitor (to keep your blood from sticking together).
- Aspirin Therapy and Anti-Platelet Medications - Prevention and Treatment of Heart Attack and Stroke
Read about aspirin therapy to prevent heart attack and stroke. Also learn about other anti-platelet medications such as, thienopyridines, and glycoprotein IIB/IIa inhibitors.
Adenosine diphosphate (ADP) receptor inhibitors: ticlopidine (Ticlid), clopidogrel (Plavix)
This class of antiplatelets contains a very well known medication, Plavix. Plavix is typically taken in one 75 mg dose in the morning. Plavix is used to prevent heart attack and stroke. It may be administered after a heart catheterization if there is concern about plaque breaking loose. Some studies have looked at using Plavix as a migraine preventative. Some studies have reported an increased clotting risk for 90 days after stopping Plavix. For this reason there is some concern about using it for migraine prevention.
- Does not need regular blood testing
- Taken once a day
- May ease migraines
- May cause increased clotting risk for 90 days after stopping the medication
- Very common and popular medication
Ticlid is another medication in this drug class. The dose for Ticlid is typically 250 mg two times a day. Because of possible side effects patients need to have blood work done every 2 weeks for the first 3 months of starting this medication. These blood tests will help to detect potentially fatal white blood cell drops, platelet drops, bleeding or clotting problems, or liver problems.
- Needs blood testing every 2 weeks for the first 3 months
- May cause serious drops in white blood cells or platelets
- Is taken twice daily
Phosphodiesterase inhibitors: cilostazol (Pletal)
Pletal (cilostazol) can not be used in any patient with congestive heart failure. The nice thing about Pletal is that it can be discontinued without the rebound (increase in platelet aggregation) seen in some other antiplatelet medications. Cilostazol widens arteries that supply blood to the legs. Cilostazol also improves circulation by keeping platelets in the blood from sticking together and clotting. This antiplatelet is typically used in intermittent claudication and can increase the distances that patients can walk without pain. Pletal should be taken on an empty stomach. Patients on Pletal should avoid grapefruit as it can cause serious interactions with this medication. Cilostazol should not be used during pregnancy.
- Can be stopped without rebound
- Used in intermittent claudication
- Patients should take it on an empty stomach
- Patients should avoid grapefruit
- Cilostazol should not be used during pregnancy
Glycoprotein IIB/IIIA inhibitors: abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat), defibrotide
This is a collection of medications that are only given in the hospital. They all require IV administration. They are often given with heparin or aspirin before or after a heart procedure to prevent clots. They are also used in heart attack, stroke, and unstable angina. While on these medications patients must have a number of blood tests to ensure that blood chemistry and all blood counts are within safe levels.
- Used in the hospital setting
- Used before or after heart procedures
Adenosine reuptake inhibitors: dipyridamole (Persantine, Aggrenox)
Persantine is dipyridamole by itself. Aggrenox is the combination of aspirin and dirpyridamole. Aspirin and dirpyridamole are more effective when taken together in a pill than they are if taken as separate pills. Dipyridamole prevents platelets, blood cells, and blood vessels from using adenosine. Adenosine is one of the chemicals that the body uses to assist in clot formation. Dipyridamole also causes vasodilation. This opens up the blood vessels so there is more space for the blood to flow freely. Dipyridamole can cause increased headaches when it is first prescribed. In time the headaches tend to lessen. Over the counter treatments can help with the headaches until that side effect lessens. Dipyridamole is considered one of the best treatments to prevent a recurrent stroke in a patient who has already had a stroke.
- May cause increased headaches at treatment onset
- Sometimes combined with aspirin in a single pill
- A strong treatment for preventing recurrent strokes
Thrombolytics are a class of drugs that break up clots that already have formed. This is the only class that is able to dissolved blood clots. Thrombolytics do not prevent clots from occurring. If a person has a stroke and is immediately rushed to the emergency room thrombolytics can be administered to resolve the stroke quickly. Patients who are able to use this treatment frequently have less damage from the stroke. Thrombolytics can also be used when a patient has a pulmonary embolism. The clot busting medication can dissolve the clots in the lungs and allow oxygen to once again reach the blood stream. This is the best course for a highly unstable patient with known pulmonary embolism or recent history of deep vein thrombosis. Work is also being done with deep vein thrombosis itself. Researchers are using small amounts of thrombolytics on DVT clots in order to dissolve the clot before it causes permanent damage to the vein. The problem with thrombolytics is that they have a very high risk of bleeding. They should be used very carefully. With DVT it is necessary to be able to administer this drug just on the clot itself so that the patient is not put at risk of a serious bleeding incident. Care should also be taken when selecting patients with pulmonary embolism or stroke. The cost benefit analysis must be carefully considered.
- Can be used at stroke onset to limit brain damage
- Can be used to open up lungs in unstable pulmonary embolism
- Can be used to prevent damage from deep vein thrombosis
- Must be used with caution to prevent severe and potentially deadly bleeding
- Only used in hospital settings due to risks of bleeding