Blood thinning (anticoagulant)
Blood clots are involved in many diseases of the cardiovascular system. Anticoagulant drugs are said to reduce the risk of blood clots developingOur content is pharmaceutically and medically tested
What does anticoagulant mean?
- In Germany, around one million people take long-term anticoagulant medication.
- Our blood clotting is a complex interplay between the formation and re-dissolution of blood clots. On the one hand, this constant interlocking ensures rapid hemostasis.
- On the other hand, it ensures that the blood remains fluid and the vessels pass through. The hemostasis with the inclusion of coagulation is called hemostasis.
- When coagulant factors predominate, there is an imbalance. Then a blood clot (thrombus) that closes the blood vessels may form.
- Anticoagulant therapy can prevent this risk and possible feared consequences such as heart attack, stroke or pulmonary embolism.
Blood clots: unpredictable course
A blood clot (blood clot, thrombus) can either lead to a vascular occlusion at the place where it originated. This is then a thrombosis. If the thrombus is carried along with the bloodstream and later gets stuck in the vascular system, it is called an embolism, for example a pulmonary embolism.
When is permanent blood thinning necessary?
Anticoagulant treatment is an important part of therapy for various cardiovascular diseases. The duration depends on the individual characteristics of the clinical picture and on continuing risk factors.
After repeated thromboses and embolisms, experts often recommend long-term treatment with anticoagulants.
- The most common cause is persistent atrial fibrillation. Without blood thinning, this cardiac arrhythmia is often associated with a considerable risk of stroke and requires long-term therapy.
- Even after mechanical heart valves have been inserted, inhibiting blood clotting is important throughout your life.
- After a thrombosis or pulmonary embolism, blood thinning for three to six months is usually sufficient. Sometimes it is necessary for years or for life to prevent further clots from forming.
When injured, clotted blood forms a scab
© W & B / Bernhard Huber
What happens during normal blood clotting?
Blood coagulation takes place on several levels at the same time. An injury to the vessel wall initially leads to a narrowing of the vessels at the injured site. Under the influence of a certain factor from the blood and the vessel wall (von Willebrand factor), platelets (thrombocytes) floating in the blood clump together.
The clumped blood platelets give off substances that promote the accumulation (aggregation) of further blood platelets. A "temporary" clot, a so-called platelet thrombus (white thrombus), develops.
At the same time, substances from the injured vascular wall ("outer path"), mostly from the endothelium (see picture below: This is how a vascular occlusion occurs) and, in parallel, from certain blood cells ("inner path") activate the plasmatic blood coagulation.
This actual blood coagulation takes place in several stages, one speaks of a coagulation cascade. The impetus is primarily provided by a so-called tissue factor.
This substance activates a coagulation factor. The activated factor activates the next factor and so on. At the end of the coagulation cascade, the action of the active factor thrombin (factor IIa) results in the formation of fibrin, which corresponds to a clot. Fibrin forms networks and acts like an adhesive.
In several steps, the first (white) platelet thrombus finally develops into a stable blood coagulation thrombus. This fibrin clot also contains other blood components such as red blood cells (hence also called red thrombus).
In the course of the wound healing - and so that the affected vessel remains open - the plug must of course be dissolved again. This is ensured by another system in the blood which, together with the coagulation, forms a finely tuned, constantly active balance: fibrinolysis. An important substance in it that dissolves the thrombus is plasmin. There are also other substances that "control" individual coagulation factors in order to avoid excessive coagulation.
Typical blood thinning drugs and their areas of application
- Drugs used to inhibit platelet aggregation
Active ingredients that reduce the clumping of blood platelets are called platelet aggregation inhibitors. Its main area of application is the prevention of blood clots in the area of the arteries.
This treatment is appropriate for people with known arteriosclerosis, i.e. calcification of the arteries. The coronary arteries, the cerebral vessels, the abdominal and / or leg vessels are often affected.
In atherosclerosis, blood clots can form on torn plaques
© W & B / Astrid Zacharias
The most common active ingredient for arterial disease is acetylsalicylic acid (ASA). The remedy is mainly known from headache treatment. To effectively inhibit the clumping of blood platelets, however, significantly lower amounts of active ingredient (75 to 100 milligrams) are generally required than for pain treatment (ASA pain tablets, for example, contain 500 milligrams).
Other frequently used substances to reduce the sticking together of blood platelets are active ingredients such as clopidogrel, prasugrel and ticagrelor. They are mainly used for treatment after a heart attack and / or after the introduction of stents into the coronary arteries, cerebral vessels or leg vessels together with ASA.
The choice of the active ingredient and the duration of the treatment are determined by the doctor in each individual case. When two of the substances are administered at the same time, this is called double (dual) platelet inhibition.
This is done for a couple of weeks or months. In the long term, one drug is generally sufficient, usually ASA or clopidogrel.
- Plasma coagulation inhibitors
For a long time, heparin and so-called vitamin K counterparts (phenprocoumon, warfarin) were the only substances (anticoagulants) that were available to inhibit plasmatic coagulation. In recent years, the new oral active ingredients dabigatran, rivaroxaban, apixaban and edoxaban (oral means: to be taken by mouth) have been developed.
For information in advance: There are a total of 13 coagulation factors. They were numbered with Roman numerals according to the order in which they were discovered. Factors II, VII, IX and X are formed in the liver depending on vitamin K.
These four vitamin K-dependent factors are blocked by the drugs phenprocoumon and warfarin, which inhibits blood clotting.
Heparins (so-called high and low molecular weight heparins) and the new oral blood coagulation inhibitors mainly block a single coagulation factor: factor Xa (the "a" in turn stands for the active form of a coagulation factor; see section above: "What happens during normal blood coagulation ? ") or thrombin (factor IIa).
Trained patients can also use heparin syringes themselves
© W & B / Frank Boxler
Heparin: Usually as an injection under the skin
The main area of application for heparins is the prevention of thromboses (thrombosis prophylaxis), for example after operations, injuries and when bedridden due to serious illnesses. They are also used in therapy after venous thrombosis or pulmonary embolism.
The active ingredient heparin has been used for a long time to prevent and treat thromboses and embolisms. In recent decades, so-called low molecular weight heparins have increasingly played a role in these areas of application. Well-known active ingredients are enoxaparin, certoparin, tinzaparin, dalteparin, nadroparin and reviparin.
They inhibit blood coagulation by mainly acting as an opponent of the activated coagulation factor X (i.e. factor Xa) (see above).
The low molecular weight heparins have advantages over conventional heparin for many areas of application. These include improved effectiveness, simplified use and fewer bleeding complications. Therefore, they have largely replaced the original heparin (for simplicity we will generally call it heparin).
Heparins take effect shortly after they have been injected into the fatty tissue under the skin ("abdominal injections", subcutaneous). A syringe is required once a day to prevent thrombosis and once or twice a day to treat thrombosis. The dose per syringe is adjusted according to medical requirements. It is of course lower in thrombosis prevention than in thrombosis treatment.
There are also occasions when doctors can administer heparin into a vein, for example in the case of acute cardiovascular diseases in which blocked vessels are reopened (heart attack, stroke, threatened tissue destruction of a limb).
Fondaparinux is another active ingredient for the prevention and treatment of thromboses and embolisms. Like heparin, the drug inhibits factor Xa, but is produced using genetic engineering. It is injected under the skin once a day.
For permanent blood thinning or long-term treatment, however, anticoagulants are necessary, which the person concerned can take in the form of tablets. These are the vitamin K opponents (coumarins such as the substances phenprocoumon and warfarin mentioned above) and the new (direct) oral anticoagulants. These are called NOAKs or DOAKs for short. For some people who need permanent blood thinning, the latter in particular can make everyday life easier.
Vitamin K antagonists (phenprocoumon, warfarin)
The vitamin K inhibitor warfarin and phenprocoumon, which is mainly used in Germany, are probably the best-known active ingredients for thinning the blood. These so-called coumarins have been an established anticoagulant in medicine since the 1940s.
In a dose-dependent manner, they suppress the formation of the vitamin K-dependent coagulation factors II, VII, IX and X in the liver (see above: "Inhibitors of plasma blood coagulation").
They are approved for all of the above-mentioned areas of application (see section: "When is permanent blood thinning necessary?" Above). Please note the following:
- The anticoagulant effect of phenprocoumon and warfarin does not set in until some time after the start of treatment, when the existing coagulation factors have been used up or reduced and the liver is then less replenished. During this time, adequate protection against thrombosis must be ensured through the short-term simultaneous administration of heparin or fondaparinux. It also takes several days after discontinuing phenprocoumon until the coagulation factors are reproduced in their normal levels again.
- The supply of vitamin K can accelerate the normalization of the coagulation function, and the supply of PPSB (i.e. the four vitamin K-dependent coagulation factors as an infusion) can immediately remove the anticoagulant.
- The doctor must check the effect of phenprocoumon and warfarin at regular intervals by measuring the so-called INR (prothrombin time), a blood value. Under certain conditions, those affected can also measure the coagulation value themselves and adjust the dose accordingly after training.
- Foods containing vitamin K in particular can have an influence on the effects of phenprocoumon and warfarin. Patients should be supplied with vitamin K-rich (green) vegetables and herbs such as broccoli, watercress, fennel, green and Brussels sprouts, spinach, peas, watercress and chives, evenly distributed over the week.
- A variety of other drugs can also increase or decrease the effects.
If atrial fibrillation is detected in the ECG, action is required due to the increased risk of clot formation
© W & B / Jörg Neisel
New oral (direct) anticoagulants
For a few years now, new anticoagulants in tablet form, i.e. oral active ingredients, have been available, so-called NOAK's or DOAK's. Rivaroxaban, apixaban and edoxaban (also called Xabane) are inhibitors of activated factor X (Xa). Dabigatran inhibits thrombin (factor IIa).
The substances unfold their full effect just a few hours after taking the tablets, comparable to heparins and fondaparinux, but with the advantage of being taken as tablets.
Other advantages of these substances are mainly the following:
- The effect is easier to control than with vitamin K opponents. It begins quickly (a few hours) after taking the active ingredient and ends just as quickly after stopping treatment.
- Food has no effect on the effect.
- No routine laboratory controls are necessary to check effectiveness.
- The frequency of severe cerebral hemorrhage is lower.
The new active ingredients are approved with the appropriate dosage for the following areas of application:
- Atrial fibrillation with an increased risk of stroke or embolism without valve involvement (all four substances currently available)
- Thrombosis prevention after hip and knee replacement (currently rivaroxaban, dabigatran, apixaban)
- Treatment of deep vein thrombosis or pulmonary embolism
Disadvantages of the new anticoagulants compared to the coumarins are:
- They carry an increased risk of an overdose and thus an increased risk of bleeding with increasing renal impairment (to be observed most with dabigatran), since they are all excreted to a greater or lesser extent via the kidneys. If the kidneys are weak, the dose should be reduced. Pronounced kidney weakness is one of the contraindications here, but also with the vitamin K opponents.
- They should not be used during pregnancy; however, there are also restrictions for pregnant women in the case of vitamin K inhibitors.
- They are not effective enough for artificial mechanical heart valves and must not be used here. Vitamin K inhibitors are then the therapy of choice.
- In the event of severe or life-threatening bleeding, dabigatran has a direct antidote (idarucizumab). Global coagulants are available for the Xabane (PPSB concentrates), which are also administered under coumarins in the event of bleeding (see section "Vitamin K opponents"). A specifically effective antidote is in the trial phase (Adexanet).
Vitamin K antagonists or direct anticoagulants to thin the blood?
There is no general answer to this question. It seems advisable to continue treatment with phenprocoumon or warfarin, which can achieve stable anticoagulation without major fluctuations. For this, at least 70 percent of the measured values should be in the target range (usually an INR of 2-3).
In situations in which it is difficult to stop using phenprocoumon, the doctor may consider switching to one of the new substances, taking into account the indication and the risk factors (including impairment of kidney or liver function).
Even for patients who only need short-term anticoagulation or for whom the anticoagulant has to be interrupted more frequently, for example for polyp removal in the intestine or for major dental interventions, treatment with a direct anticoagulant is ideal because of its good controllability.
What should you watch out for if you are taking anticoagulant medication?
It is evident that treatment with all anticoagulant drugs increases the risk of bleeding. In everyday life, this is often not immediately noticeable, because the drugs do not completely stop the blood clotting, they only weaken it.
However, even with the correct dosage, increased or prolonged bleeding in injuries can occur.
Therefore, when taking anticoagulant drugs, certain precautions are important:
- Always carry ID in your wallet stating that you are taking an anticoagulant, why, what it is and what dose.
- Let all attending physicians know that you are taking anticoagulant medication. This is especially important when operations, catheter examinations, gastrointestinal reflections or dental treatments are due. It may be necessary to change or even discontinue the anticoagulant before treatment. The treating physicians decide on this, also in consultation with your family doctor.
- There are numerous drugs that change the effectiveness of anticoagulant drugs, for example several antibiotics in the case of phenprocoumon or warfarin. Some of them can significantly increase the risk of bleeding. It may then be necessary to briefly determine the INR value several times or to reduce the dose.
- With all anticoagulants, the simultaneous use of anti-inflammatory drugs such as ibuprofen, diclofenac or ASA increases the risk of bleeding.
- Over-the-counter drugs can also influence the effect, for example the substances gingko and St. John's wort. Before taking any other medication, ask your doctor or pharmacist about possible interactions and read the package insert.
In particular, when taking phenprocoumon or a new, direct anticoagulant, the following information applies:
- Do not have injections into the gluteal muscles or joints unless the measures are taken after a doctor-prescribed pause in treatment.
- Do not change the dose of tablet intake without consulting your doctor (exception: self-management of therapy with a vitamin K inhibitor, i.e. self-measurement of blood coagulation (INR values) and independent adjustment of the drug dose, medical check-ups by arrangement).
Both underdosing and overdosing blood thinning can have serious consequences.
- During treatment with blood-thinning medication, one should avoid sports that are associated with an increased risk of injury, for example contact sports such as handball or boxing.This is especially true if combinations of different anticoagulant drugs are necessary for certain diseases.
- Contact your doctor or the emergency services immediately (emergency number: 112) if you experience visual disturbances, sudden difficulty finding words, paralysis or headaches.
- The same applies if there is spontaneous, visible bleeding (without previous injury), including bleeding from the gums, heavy nosebleeds, increased menstrual bleeding, blood leakage through the urine or from the rectum, and if there is blood in the sputum. Or if bleeding does not stop after an injury despite a pressure bandage.
Prof. Dr. med. Viola Hach-Wunderle
© W & B / Bert Bostelmann
Consulting expert: Professor Dr. med. Viola Hach-Wunderle is a specialist in internal medicine and vascular diseases (angiology). Since 1998 she has been teaching at the Medical University Clinic in Frankfurt am Main, where she also qualified as an associate professor for internal medicine. The vascular specialist heads the vascular center of the Northwest Hospital (academic teaching hospital) and runs her own practice in Frankfurt. Professor Hach-Wunderle has been an active board member of the Hessian Medical Association for years. She was responsible for editing the guidelines on venous thrombosis and pulmonary embolism.
Sources for this guide:
1. New anticoagulants in the therapy of atrial fibrillation, further training event of the AKdÄ in cooperation with the ÄK Sachsen and the KV Sachsen, as of October 2013. Online: https://www.akdae.de/Fortbildung/Vortraege/TS/2013/Neue- Anticoagulants.pdf (accessed on April 15, 2019)
2. German Society for Angiology - Society for Vascular Medicine e.V .: Arterial diseases.
Online: https://www.dga-gefaessmedizin.de/patienten/arterielle- Krankungen.html (accessed on April 15, 2019)
3. Patient information from the University Heart Center Freiburg, Bad Krozingen on anticoagulation. Status: May 2012. Online: https://www.herzzentrum.de/fileadmin/mediapool/08_haben/pdf/piz_gerinnungshemmung-fact-sheet.pdf
(Accessed on April 15, 2019)
4. Gawaz M, Geisler T, update oral platelet inhibitors. In: Kardiologie 2012, 6: 195-209. Online: https: //leitlinien.dgk.org/files/2012_Positionspapier_Orale_Plaettchenhemmer.pdf (accessed on April 15, 2019)
5. Guidelines of the German Society for Angiology: Diagnosis and therapy of venous thrombosis and pulmonary embolism. AWMF guidelines register No. 065/002. Online (pocket version): https://www.awmf.org/uploads/tx_szleitlinien/065-002k_S2k_VTE_Venenthrombose-Lungenembolie_2017-04.pdf
(Accessed on April 15, 2019)
6. Altiok E, Marx N: Oral anticoagulation. Deutsches Ärzteblatt, vol. 115, issue 46, Nov. 16, 2018, 776-83. DOI: 10.3238 / arztebl.2018.0776
This article is for general guidance only and is not intended to be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor. Unfortunately, our experts cannot answer individual questions.