April
24
23:00
Hematology

Anticoagulants direct action: indications and contraindications.

Anticoagulants - that's one of the groups of drugs that affect blood clotting, prevent the formation of blood clots in the vessels.Depending on the mechanism of action of these drugs can be divided into 2 groups: anticoagulants of direct and indirect action.Below we talk about the first group of anticoagulants - direct action.

Content

  • 1 clotting systems: basic physiology
    • 1.1 primary hemostasis
    • 1.2 Enzymatic coagulation
  • 2 Indications and contraindications to the use of anticoagulants of direct action
  • 3 Classification of anticoagulants of direct action
    • 3.1 unfractionated heparin preparations
    • 3.2 low molecular weight heparin preparations
      • 3.2.1 dalteparin (Fragmin)
      • 3.2.2 Enoxaparin (Clexane, Novoparin, Flenoks)
      • 3.2.3 Nadroparin (Fraksiparin)
      • 3.2.4 Bemiparin (Tsibor)
    • 3.3 Heparinoids
      • 3.3.1 Sulodeksin (Vessel Due F)
      • 3.3.2 Pentosan polysulfate
    • 3.4 Preparations hirudin
    • 3.5 Fondaparinux (Arixtra)
    • 3.6 Rivaroxaban (Ksarelto)

Blood clotting - a combination of physiological and biochemical processes to start-stop earlierbleeding.It is a defensive reaction, warning of massive blood loss.

Blood clotting takes place in 2 stages:

In this complex physiological process involved three structures: the vascular wall, the central nervous system, and platelets.When a vessel wall is damaged and bleeding starts, smooth muscles located therein around the perforation, are compressed, and the vessels spazmiruyutsya.The nature of this event reflex, i.e. it takes place spontaneously after the corresponding signal of the nervous system.Anticoagulants direct action: indications and contraindications.

The next step is the adhesion (adhesion) of platelets to the site of damage to the vascular wall and aggregation (sticking) of each other.Within 2-3 minutes the bleeding stopped, because the injury is clogged by a thrombus.However, this is still soft thrombus, and blood plasma into the site of damage is still liquid, however, under certain conditions, may develop bleeding anew.The essence of the next phase of primary hemostasis is that platelets undergo a series of metamorphoses, which resulted in three of them released clotting factor: their interaction leads to thrombin and triggers a series of chemical reactions - enzymatic coagulation.

When the damaged area of ​​the vessel wall with traces of thrombin triggers a cascade of reactions between tissue with blood coagulation factors, there is another factor - the thromboplastin, which interacts with a particular substance prothrombin to form active thrombin.This reaction takes place with the participation of salts kaltsiya.Trombin interacts with fibrinogen and fibrin is formed, which is insoluble substance - its thread precipitate.

Anticoagulants direct action: indications and contraindications.

next stage - compression or retraction of a blood clot, which is achieved by compacting, compressing it, resulting in a separated transparent, liquid serum.
And the last stage - the dissolution or lysis of preformed thrombus.In the process, they interact with each other a number of substances, and the result is the appearance of blood enzyme fibrinolizina destroying strands of fibrin and fibrinogen converting it into.
It is worth noting that some of the substances involved in the clotting process, is formed in the liver with the direct involvement of vitamin K: deficiency of this vitamin leads to violations of the processes of coagulation.

use the drugs in this group in the following situations:

Each of anticoagulants of direct action has its contraindications, mainly:

recommended to be careful in appointing these drugs is very malnourished patients during pregnancy, in the first 38 days after childbirth or surgical intervention, in the case of high blood pressure.

Depending on the characteristics of the structure and mechanism of action of drugs in this group are divided into 3 subgroups:

Anticoagulants direct action: indications and contraindications. main representative of this class of drugs is directly Heparin.
antithrombotic effect of this drug is its ability to inhibit the main circuit clotting enzyme thrombin.Heparin binds to the coenzyme - antithrombin III, whereby the latter is associated with a group of active plasma coagulation factors, reducing their activity.Heparin when administered in high doses, it also inhibits the process of transformation of fibrinogen to fibrin.

addition to the above, this substance has a number of other effects:

heparin produced in the form of solution for injection (1 mL of solution contains 5000 IU of active substance) and also in the form of gels and ointments for topical application.

Enter heparin subcutaneously, intramuscularly and intravenously.

fast action of the drug, but, unfortunately, a relatively short time - after a single intravenous administration to act, he starts almost immediately and continues the effect for 4-5 hours.When administered into the muscle effect occurs in half an hour and continued until 6 hours after subcutaneous same - 45-60 minutes and 8 hours, respectively.

often prescribe heparin are not alone, and in combination with fibrinolytic and antiplatelet.
Dosages are individual and depend on the nature and severity of the disease, as well as its clinical manifestations and laboratory parameters.

effect of heparin must be monitored by determining the APTT - activated partial thromboplastin time - at least 1 every 2 days during the first week of therapy, and then at least - 1 time in 3 days.

Anticoagulants direct action: indications and contraindications. As with administration of the drug may develop hemorrhagic syndrome, it should be administered only in a hospital under the constant supervision of medical staff.
addition hemorrhages heparin may trigger the development of alopecia, thrombocytopenia, hyperaldosteronism, hyperkalemia and osteoporosis.

heparin for topical application are Lioton, Linova, Trombofob and others.They are used for prevention and in treatment of chronic venous insufficiency: prevent the formation in saphenous veins of the lower extremities blood clots and reduce the swelling of the extremities, eliminate the severity of them and reduce the severity of pain.

This new generation of drugs that have the properties of heparin, but having a number of advantageous features.By inactivation of factor Xa are largely reduce the risk of thrombus formation, while their anticoagulant activity is expressed to a lesser extent, and therefore less likely to occur hemorrhage.In addition, low molecular weight heparins are absorbed better, and operate longer, that is, to achieve the effect required a smaller dose and less multiplicity of its introduction.In addition, osteoporosis and thrombocytopenia they cause only in exceptional cases are extremely rare.

main representatives of the low molecular weight heparins are dalteparin, enoxaparin, Nadroparin, Bemiparin.Let us consider each of these in more detail.

Anticoagulants direct action: indications and contraindications. Blood clotting slows slightly.Inhibits aggregation, adhesion is practically not affected.Also, to a certain extent it has immunosuppressive and anti-inflammatory properties.
issued in the form of solution for injection.

drug is injected into a vein or subcutaneously.Intramuscularly administered prohibited.Dosing scheme, depending on the severity of the disease and the patient's condition.When using dalteparin possible lowering of blood platelets, the development of hemorrhages, as well as local and systemic allergic reactions.
Contraindications are similar to those of other drugs of anticoagulants of direct action (listed above).

Anticoagulants direct action: indications and contraindications. rapidly and completely absorbed into the blood stream when administered subcutaneously.The maximum concentration observed after 3-5 hours.The half-life is more than the 2nd day.Excreted in the urine.

issued in the form of solution for injection.Is introduced, usually subcutaneously in the abdominal wall.The administered dose depends on the disease.
side effects of the standard.
Do not use this medication to patients prone to bronchospasm.

Anticoagulants direct action: indications and contraindications. addition to the direct anticoagulant action has also immunosuppressive and anti-inflammatory properties.In addition, it reduces β-lipoprotein and cholesterol levels.
When subcutaneous injection is almost completely absorbed, the maximum concentration of drug in the blood observed after 4-6 hours, half-life of 3.5 hours in primary and 8-10 hours with repeated administration of nadroparin.

usually administered in abdominal fat: subcutaneously.Multiplicity of administration is 1-2 times a day.In some cases, the intravenous route is used, under the control of blood coagulation parameters.
dosages prescribed, depending on the pathology.
side effects and contraindications are similar to those of other drugs in this group.

Has a pronounced anticoagulant and moderate haemorrhagic effect.

Anticoagulants direct action: indications and contraindications. Subcutaneous administration of the drug is rapidly and completely absorbed into the blood, where the maximum concentration observed in 2-3 hours.The half-life of the drug is 5-6 hours.Regarding the method of elimination to date there is no information.

release form - injection.The route of administration - subcutaneous.
dosage and duration of treatment depend on the severity of the disease.
side effects and contraindications are listed above.

not recommended to use the drug in conjunction with other anticoagulants, nonsteroidal anti-inflammatory agents, systemic glucocorticoids and dextran: All these drugs enhance the effect of bemiparin, which can cause bleeding.

This group mucopolysaccharides semi-synthetic origin, having the properties of heparin.
Drugs of this class acts exclusively on factor Xa, regardless of angiotensin III.It turns anticoagulant, fibrinolytic, and lipid-lowering effect.

are usually used for the treatment of patients with angiopathy, caused by elevated levels of blood glucose: diabetes.Also applied to prevent thrombus formation during hemodialysis and for surgical operations.They are also used in acute, subacute and chronic atherosclerotic, thrombotic and thromboembolic nature.Strengthen antianginal effect of therapy in patients with angina pectoris (ie, reduce the severity of pain).The main representatives of this group of drugs are sulodeksin and pentosan polysulfate.

issued in the form of capsules and injectable solution.It is recommended to be administered within 2-3 weeks intramuscularly, then taken orally for another 30-40 days.The course of treatment - 2 times a year and more frequently.
While taking the drug may nausea, vomiting, stomach pain, hematoma at the injection site, and allergic reactions.
Contraindications - common drugs heparin.

Anticoagulants direct action: indications and contraindications. release form - coated tablets and solution for injection.
route of administration and dosage vary depending on the particular disease.
ingestion is absorbed in small quantities: its bioavailability is only 10% in the case of subcutaneous or intramuscular injection bioavailability approaches 100%.The maximum concentration in the blood was 1-2 hours after ingestion, the half-life is equal to a day or more.
The rest of the preparation is similar to other drugs anticoagulant.

substance secreted by the salivary glands of leeches - Hirudin - similar to heparin has antithrombotic properties.Its mechanism of action is to bind directly and irreversibly to thrombin inhibiting it.It has a partial effect on other clotting factors.

Recently developed drugs based on hirudin - Piyavit, Revask, Girolog, argatroban, but widespread use, they have not received, so the clinical experience of their use to date is not collected.

We want to say a few words about the two relatively new drugs with anticoagulant action - is fondaparinux and rivaroxaban.

Anticoagulants direct action: indications and contraindications. The drug has antithrombotic effect by selective inhibition of Factor Xa.Once in the body, fondaparinux binds to antithrombin III and several hundred times it enhances neutralization of factor Xa.As a result, the coagulation process is interrupted, thrombin is formed, therefore, may not form thrombi.

rapidly and completely absorbed after subcutaneous injection.After single administration the maximum concentration in the blood was 2.5 hours.The blood is associated with antithrombin II, which is responsible for its effect.

Write mainly with urine in unchanged form.The half-life of 17 to 21 hours, depending on the age of the patient.

issued in the form of solution for injection.

route of administration - subcutaneously or intravenously.Intramuscular not apply.

Dosage depends on the type of pathology.

Patients with impaired renal function dose adjustment is necessary ARIXTRA according to creatinine clearance.

patients with severe reduction in liver function the drug is used very carefully.
should not be used concurrently with drugs that increase the risk of bleeding.

Anticoagulants direct action: indications and contraindications. This drug is highly selective actions against factor Xa, depressing its activity.It characterized by high bioavailability (80-100%) when administered orally (i.e., well absorbed in the gastrointestinal tract by ingestion).

maximum concentration in the blood was rivaroxaban 2-4 hours after single oral administration.

eliminated from the body in urine half and half with feces.The half-life is from 5-9 to 11-13 hours, depending on the age of the patient.

release form - pill.
Inside, regardless of meals.As with other anticoagulants direct acting drug dosage will vary depending on the type of disease and its severity.

receiving rivaroxaban is not recommended in patients receiving therapy with certain anti-fungal drugs and anti-HIV drugs because they can increase the concentration of Ksarelto in the blood, which can cause bleeding.

patients with severe renal impairment require dose adjustment of rivaroxaban.
women of reproductive age should be securely protected from pregnancy during treatment with this drug.

As you can see, the modern pharmaceutical industry offers significant choice of drugs, anticoagulants of direct action.In no case, of course, can not engage in self, all drugs, their dosage and duration of use of a doctor determines, based on the severity of the illness, the patient's age and other relevant factors.

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