Common Side Effects of the Anticoagulants / Blood Thinners.

Common Side Effects of the Anticoagulants / Blood Thinners.

What are Anticoagulants / Blood Thinners?

Blood travels in a liquid form a within blood vessels. A break in the blood vessels causes in the blood to the leak out. However, excessive blood loss is a prevented by the formation of a blood clot. Initially in the blood cells called platelets stop in the flow of the blood, followed by which certain proteins in the blood called clotting factors form a clot and seal in the break.

In some conditions, to a clot can form within to a normal blood vessel, which can obstruct in the smooth flow of the blood. Such a clot is a unwanted. Medications used to prevent in the formation of such clots are called anticoagulants or a blood thinners. They prevent clotting or a coagulation by a interfering with the action of the clotting factors. Another type of the blood thinners called a anti-platelet drugs which are include aspirin and clopidogrel prevent in the action of the platelets. These will not be a discussed here.

The processes in that affect blood clotting involve a lot of the enzymes and proteins. Together it is known as the coagulation cascade.

The anticoagulants used in  a clinical practice are include in the following:

Unfractionated heparin, low molecular weight heparin's like a enoxaparin and dalteparin. Others like a tinzaparin, danaparoid and ardeparin have been a discontinued in the United States.

Warfarin

Rivaroxaban edoxaban and apixaban are novel oral anticoagulants that are direct inhibitors of the clotting factor Xe (Factor Xe is the activated form of the enzyme Factor X are involved in the coagulation in a  process)

Fondaparinux, which is an a indirect factor Xe inhibitor

Bivalirudin, argatroban and dabigatran. These drugs are directly block thrombin, in the last clotting factor of the coagulation cascade. A similar drug, lepirudin has been a discontinued in the United States. Another drug melagatran and it is a prodrug ximelagatran did not a receive approval in the US due to a possibility of the liver damage

Side effects of the Anticoagulants / Blood Thinners

The older anticoagulants like a heparin and warfarin have been a time tested and in their adverse effects are well known; more research is a needed with the newer anticoagulants. Below are some of the side effects of the anticoagulants:

Excessive Bleeding: Bleeding is an a extension of the pharmacological effect of the anticoagulants. Thus all the anticoagulants cause bleeding as a side effect, but to a variable degree.

Bleeding can be a occur from a several sites like the digestive tract, urinary tract, vagina, respiratory tract, skin and even in the brain, which may be fatal. It may manifest as a heavier menstrual flow, bleeding from gums, bruising, red or a tarry stools, red or a brown urine, or a headache in case of a bleed in the brain. Some anticoagulants are including heparin have a caused bleeding in a internal organs like the adrenal glands and the ovaries. An a unexplained fall in a blood pressure with a dizziness while in the patient is on an a anticoagulant should warrant an a investigation into the possibility of an a internal bleed.

Spinal or a epidural bleeding followed by a clots may be a occur in a patients taking low molecular weight heparin's, rivaroxaban, edoxaban, fondaparinux and dabigatran following spinal procedures like a spinal puncture. This may be result in a paralysis

The chances of the bleeding can be a reduced by a choosing in the right anticoagulant for in the right patient and in the right dosage. For a example, fondaparinux should be a avoided in a patients with a kidney disease and those with a weight of the less than a 50 kg since it is a increases the risk of the  bleeding in these patients. Dabigatran should be a avoided in a patients with a severe kidney or a liver disease. It should also not be a used in a patients with a mechanical heart valves due to an a increased chance of the bleeding and clot formation

Close a monitoring of the patient could help to  reduce in the chances of  the bleeding. The effect of the heparin is a assessed by a measuring in the activated partial thermoplastic time (a P T T), while in the effect of the warfarin is a measured using in the international normalized ratio (I N R). Low molecular weight heparin's and drugs like a dabigatran, rivaroxaban and apixaban usually do not a require monitoring

It is a necessary to stop in the excessive bleeding by a stopping in the anticoagulant and the sometimes administering an a antidote. The effect of  the heparin is a neutralized by a prominent sulfate while in the effect of the warfarin is a reversed using a vitamin K (phytonadione), fresh frozen plasma or a prothrombin complex concentrates. Specific antidotes are not a available for in the newer anticoagulants like a dabigatran, rivaroxaban and the apixaban, which is a disadvantage

Patients should be a advised on the do’s and do not to the prevent bleeding and to the report any a excessive bleeding immediately

Heparin-induced thrombocytopenia: Unfractionated heparin can be reduce platelet count and may be result in the formation of the blood clots within a blood vessels. Therefore, platelet counts have to be a routinely performed in a patients receiving in this form of the heparin. Warfarin or a low molecular weight heparin's should not be used in these patients, while it can be a substituted with a argatroban. The risk for aa thrombocytopenia (reduction in a platelet counts) is a lower with a low molecular weight heparin's. Thrombocytopenia has also been a reported following treatment with a anticoagulants like a apixaban, rivaroxaban and fondaparinux.

Allergy: Allergic reactions can be occur with a anticoagulants, which may be vary from a itching and rashes to a severe reaction with a breathing difficulties, fall in a blood pressure and even death. Some patients who have been a re-exposed to the lepirudin have a developed serious anaphylactic reaction. Warfarin has also been a associated with a serious allergic reactions.

Tissue necrosis: Necrosis or a damage to the skin or other tissues may be occur while in the patient is on warfarin. Necrosis of the skin usually occurs early during in the treatment. In a some cases, internal organs like the pancreas, spleen and liver may also be a affected. Reduced blood flow to the toes can result in a condition called purple toes syndrome.

Hair loss: Hair loss has been a observed with a heparin and warfarin treatment

Osteoporosis: Osteoporosis or thinning of the bones may be a occur with a long term treatment with a heparin. This makes in the patient prone to the  spontaneous fractures. The risk is a lower with a low molecular weight heparin's.

Birth defects: Birth are defects may be occur if the mother receives warfarin especially during in the first trimester of the pregnancy. These are include nasal defects, brain and the eye defects, and growth retardation. Spontaneous abortion may also a occur. Adverse effects are also a noted when warfarin is a taken in the second and third trimester. The fetus is at a risk of the bleeding which can be a fatal. Therefore, warfarin is a contraindicated during a pregnancy. In a contrast, heparin is a considered safer during in a pregnancy.

Digestive tract disorders: Dyspepsia, which is a discomfort and pain in the upper abdomen may be occur with a dabigatran due to the addition of the tartaric acid to the capsule. Medications like a omeprazole or ranitidine may be a required to treat it. Other gastrointestinal side effects like a diarrhea may be also a occur with a dabigatran. Warfarin may be cause changes in a liver enzymes indicating liver damage. It also a causes symptoms of the nausea, diarrhea, bloating and taste perversion. Liver enzymes may also be a altered by a heparin, low molecular weight heparin, rivaroxaban, edoxaban and fondaparinux.

Interaction with a other drugs: Warfarin interacts with a other drugs, which can be increase or a decrease in the level of the warfarin. The list of the drugs that interfere with a warfarin is a extensive. Therefore, international normalized ratio or I N R (assay that determines in the clotting tendency of the blood) should be a monitored in a patients when any new treatment or a dietary changes are introduced in a patients taking warfarin. Dabigatran interacts with other drugs like a amiodarone, verapamil and quinidine. Rivaroxaban also has a several drug interactions.

Anticoagulants also a interact with a other drugs that are inhibit blood clotting. They are increase in the chances of the bleeding when taken with a medications like a anti-platelet drugs, which can be also a cause bleeding, or a non-steroidal anti-inflammatory drugs that can be cause stomach ulcers.

The anti-platelet drugs used in a clinical practice are include:

Aspirin

Ticlopidine, clopidogrel, prasugrel, cangrelor, and ticagrelor

Abciximab, eptifibatide and tirofiban

Cilostazol

Vorapaxar

Side effects of the anti-platelet drugs are include in the following:

Bleeding: As for a anti-coagulants, anti-platelet drugs can be also a cause bleeding. Bleeding can be occur from a various sites like the digestive tract, urinary tract, in the abdomen and even around in the brain. Aspirin also a causes erosion's in the stomach and peptic ulcers, which can be a bleed. The risk of the major bleeding is a high with the newer drugs, prasugrel and ticagrelor. Abciximab may be a cause bleeding by a forming antibodies against platelets, and reducing platelet counts. Anti-platelet drugs are usually discontinued to a few days prior to the surgery to the prevent bleeding. They should not be a used in a patients suffering from a peptic ulcer or a uncontrolled hypertension. Patients who are bleed are require temporary discontinuation of the anti-platelet drug, and sometimes intravenous fluids, and red cell and platelet transfusions.

Digestive tract disorders: Aspirin are causes gastric irritation which can be give a rise to the  ulceration and the bleeding. Anti-stomach are ulcer medications may be a reduce in the risk of the gastrointestinal irritation. Aspirin may be also a cause nausea, vomiting and liver damage in the form of the hepatotoxicity and cholestatic jaundice. Reyes syndrome occurs when  aspirin is a administered for a viral infection, especially in a children. The patient are suffers from a vomiting, liver dysfunction and the neurological in a  symptoms.

Allergic reactions: Aspirin can be a cause allergic reactions with a symptoms of the sneezing and tearing of the eyes, extending to more serious conditions like a difficulty in a breathing, swelling of the subcutaneous tissues (angioedema), skin reactions like a Steven’s Johnson syndrome and even anaphylaxis, which are require treatment on an a emergent basis. Aspirin-sensitive individuals often have a nasal polyps and suffer from a breathing problems. Allergic reactions can also a occur with a other anti-platelet drugs like a ticlopidine and abciximab.

Reduced blood counts: Ticlopidine are reduces in the counts of the red blood cells, white blood cells, and platelets. The patient’s blood counts should be a monitored during a treatment with a ticlopidine, especially in the first three months of the treatment. Cilostazol may be also a reduce white blood cell count.

Kidney damage: Aspirin can be a cause damage to the kidneys, which can be result in a conditions like a interstitial nephritis, papillary necrosis, and may be even progress to the kidney failure.

Nervous disorders: Aspirin can be affect in the nervous system resulting in a symptoms like a agitation, confusion, dizziness, tinnitus (abnormal sounds in the ear) and hearing loss. The side effects are usually noted at the doses higher than what are used for a anti-platelet activity. Symptoms like a headache, dizziness and vertigo have been a reported with a cilostazol.

Cardiac side effects: Cilostazol causes a palpitations, arrhythmia's and can be cause heart attack in a predisposed individuals. Cangrelor and abciximab can be also a cause cardiac side effects. Ticlopidine increases the blood levels or cholesterol and triglycerides, which can in turn affect in  the heart.

Interaction with a other drugs: Anti-platelet drugs can be cause increased bleeding when administered with a other drugs that can also a cause bleeding.

References:

Katzung B G. Basic and Clinical Pharmacology 12th edition

Harris K, Mant J. Potential impact of the new oral anticoagulants on the management of the atrial fibrillation-related stroke in a primary care. International Journal of the Clinical Medicine 2013; 67(7):647–655

Winter Y, Dodel R, Korchounov A, Grond M, Oertel WH, Back T. Clinical and pharmacological in a properties of the new oral anticoagulants for the prevention of the cerebral thromboembolism: Factor Xa and thrombi n inhibitors. World Journal of the Neuroscience, 2012;2:7-14

Shehab A et al. Novel oral anticoagulants and the 73rd anniversary of the historical warfarin. Journal of the Saudi Heart Association 2016;28(1):31-45