heparin mechanism of action #simple & easy

heparin-mechanism-of-action
mechanism of action heparin


Heparin is anticoagulant drugs. it used to prevent the blood clot, thrombus and embolism in blood. 

When natural heparin is not generating their significant effect in body. This time needs to heparin injection. 

Here, I will discuss the heparin mechanism of action, but before discussing it, firstly understand the basic details of heparin.  

Mclean is a medical student he found one liver containing substance produce a powerful anticoagulant effect. After some years, Howell and holt in 1918 given named to “heparin” because it extracts from the liver. Firstly, used clinically in 1937 when sufficient purification was achieved.

It is a straight chain of mucopolysaccharide. Molecular weight is 10000 to 20000. 

It present in all tissue containing mast cells. More amount in lungs, liver and intestinal mucosa. Thus, commercially produce heparin from ox lungs and pig intestinal mucosa.

Heparin release from the mast cell and degraded by the macrophages. in this article I will discuss a brief overview of heparin include Mao, side effect, contraindication, low molecular heparin, example etc. so, stay tuned.

Let’s start


heparin mechanism of action 

First of all understand the mechanism of action of heparin, why heparin used?

Sometime in body rupture the cell and leakage the blood through the rupture site. Then formed a clot to prevent bleeding. This clot formation is beneficial for the bleeding. But, this clot is delivering inside the blood vessel and do not dissolve properly. So, this time it develops thrombosis and embolism action.

Our body produce natural heparin like anticoagulant to dissolve this type of clot. This heparin stimulates antithrombin 3. Antithrombin is an antagonist of thrombosis & dissolve this type of clot. It also inhibits other factors that stimulate thrombin.

Naturally heparin is work well but, sometimes this naturally physiologically system imbalance. So, this time artificial heparin is used.

heparin-mechanism-of-action
mechanism of action heparin

Artificial heparin is 1000 times beneficial then naturally heparin

This heparin is powerful & instantaneously acting and also effective both in-vivo and in-vitro.

This heparin indirectly acting on antithrombin 3 (serine protease inhibitor) and some other cofactors that useful in inducing the clot formation.

As per above mention, this heparin-antithrombin complex improves the efficacy of antithrombin 1000 times & prolonged clotting time.

This heparin-antithrombin 3 complex binds to other clotting factors like 10a, 9a, 11a, 12a and 13a and inactivate them.

At the lower concentration of heparin, factor 10a mediated conversion prothrombin to thrombin is selectively affected. This anticoagulant action mainly produced by inhibiting the 10a factors, as well as thrombin (2a), mediated conversion of fibrinogen to fibrin.


Heparin enhance the action of antithrombin 3 by the two ways.

➟ Long molecule heparin provides a scaffolding for the clotting factors (mainly 2a and 10a) as well as antithrombin 3 to get bound and interact with each other.

➟ Heparin increase it’s conformation changes to increase binding affinity to other sites.


Sometimes, the higher dose of heparin causes a reduction of antithrombin 3 levels. It’s reversible when given high amount.

To sudden stop this therapy leads to again increase coagulation within a few days.

Antiplatelet. The higher dose of heparin inhibits the platelet aggregation and also prolongs the bleeding time.

Lipemia clearing. Heparin also clears the turbid post-prandial lipemic plasma. When heparin was given, it releases a lipoprotein lipase enzyme in a blood vessel and tissue. This enzyme helps to hydrolyses triglyceride of chylomicra and low-density lipoprotein to the fatty acid. After plasma looks a clear not a turbid.

This proper heparin mechanism required only a lower concentration of heparin. This is a physiological function of heparin but, not found a much in tissue and blood. So, seems only conjectural.

Heparin is a largely ionized molecule, not used for orally or intramuscular, it given through intravenous and subcutaneous. When intramuscular used it to develop skin irritation and itching.

Intravenous heparin act as an instantaneously, but when subcutaneous given anticoagulant effect develop after one hour. Also, bioavailability is also inconsistency.

It metabolized by fragments and heparinase in the liver and eliminate through urine.

It safe during pregnancy because it doesn’t cross blood-brain barrier or placental barrier.


Low molecular heparin

Generally, low molecular heparin is developed by heparin. Actually, heparin (10,000 to 20,000 MW) fractionated into LMW (3000 TO 7000 MW) by the different techniques.

It is different anticoagulant profile action, it inhibits the factor 10a and produce little effect on factor 2a. it acts as an anticoagulant effect by increase the conformation of antithrombin 3. And do not by bringing together antithrombin 3.

The very slower effect produced on PPT and whole blood clotting time.

It also has a lesser anti-platelet action and less interference with the haemostasis. Also, less frequent thrombocytopenia.


Why low molecular heparin used?

It produced a better subcutaneous bioavailability (70 to 80%) than normal heparin (20 to 30%).

To longer and more consistence exponential half-life. Once a daily subcutaneous administration.

As per above mention PPT/blood clotting time not prolonged or less effect.

Also, laboratory monitoring is not needed. And dose is circulated depend on body weight. 

 

➣ Which condition low molecular heparin beneficial?                                                                                    

To prophylaxis of pulmonary embolism and deep vein thrombosis in the patients undergoing surgery.

Useful in stroke and other immobilized patients.

To the treatment of deep vein thrombosis.

To the treatment of unstable angina.

To maintain the potency of cannulae and shunts in dialysis patients.


➣ Example of low molecular heparin

⇨ Enoxaparin (Clexane 20 mg or 40 mg)

⇨ Reviparin (Clivarine 13.8 mg)

⇨ Nadroparin (Fraxiparine 3075 and 4100 IU)

⇨ Dalteparin (Fragmin 2500 and 5000 IU)

⇨ Pamparin (Fluxum 3200 IU)

⇨ Ardeparin (Indeparin 2500 and 5000 IU)


Heparin agonist

➦ Heparin sulphate. It is a natural structure same as heparin. Found on the cell surface and intracellular matrix in many tissues. Generally, it’s less potent anticoagulant than heparin. But, it’s more favourable compound.

➦ Danaparoid. It is obtained from pig gut mucosa. When heparin produces thrombocytopenia. In this condition, danaparoid is a drug of choice.

➦ Lepirudin. It’s a recombinant preparation of hirudin. (Generally, hirudin secreted through salivary gland) it acts as thrombin inhibiting agents. When heparin induces thrombocytopenia. In this condition, lepirudin is also used.

➦ Ancord. It is obtained from Malayan vit viper venom. It degrades fibrinogen to unstable fibrin. It produced a heparin-like effect. When heparin-induced thrombocytopenia or any severe hypersensitivity reaction. In this condition this drugs more beneficial. (other lists of heparin drugs heparin drug list)

Please, take note if you suffering any disease or anything. Consult your doctor. I humble request to all of you do not take medicine on your decision. Our motive to give information of medicine. Not to self-medication. 

Heparin antagonist (protamine sulphate)

Protamine sulphate is a strongly basic, low molecular weight protein obtained from the sperm of certain fish. It administered through intravenous.

Protamine sulphate is neutralizing the heparin. (1 mg needed for the every 100 U heparin) generally, it is given by infrequently, because the mechanism of action heparin disappears by itself in a few hours.

In the heparin termination condition, protamine sulphate is more common usage. Like cardiac or vascular surgeries.

Sometimes used itself as an anticoagulant effect in the absence of heparin by interacting with fibrinogen and platelets.

It produced some hypersensitivity reaction. The rapid intravenous injection causes breathing difficulty or flushing.

 

Use of heparin

As per known in heparin mechanism of action, it's used as an anticoagulant to prevent the thrombus and embolism and also reduce the fibrin formation rate. Specially heparin is used for rapid and short live-action. But, other anticoagulant drugs used as maintenance therapy of coagulation.

Heparin is used for initial treatment. generally, heparin drug is discontinued after 4 to 8 days after warfarin continued.

Deep vein thrombosis.

Heparin and other anticoagulant drugs used in deep vein thrombosis and pulmonary embolism.

Low molecules heparin or low dose prophylaxis for the patients undergoing elective surgery has considerably reduced to vein thrombus and pulmonary embolism in the postoperative period.

Myocardial infarction.

Arterial thrombus mainly due to platelet thrombus. And it’s causes of myocardial infarction.

In this condition heparin discontinued after 2 to 8 days and followed other anticoagulant drugs for 3 months or low dose. Generally, heparin is given after recanalization of a coronary artery by fibrinolytic therapy.

Heparin also used during the stent and angioplasty treatment.

Unstable angina.

Heparin used as a short term in unstable angina patients. Also, aspirin is equally effective. Commonly used combination of aspirin and heparin. Then followed warfarin.

Rheumatic heart disease.

Combination of a low dose of heparin and aspirin & warfarin is used to prevent the stroke. Generally, warfarin is most suitable for preventing stroke in atrial fibrillation. (if you know stroke disease visit this article stroke)

Also, heparin and anticoagulant used many diseases include cerebrovascular disease, vascular surgeries, haemodialysis, retinal vessel thrombosis and defibrillation syndromes.

 

Adverse effect of heparin

as per understand in heparin mechanism it used to stop clotting in blood but, in overdose or high dose it develops various adverse effect.

bleeding. When heparin is given in overdose or high dose it causes severe bleeding. Hematuria is the first sign of bleeding.

Thrombocytopenia. Another effect produce is thrombocytopenia because aggregation of platelets. In this condition, heparin should be discontinued. But, some patient low molecular heparin is safe. not all patients.

Osteoporosis. High dose of heparin in a long time used it produces osteoporosis.

Alopecia. Transient and reversible alopecia is infrequent. Increase Serum transaminase level.

Hypersensitivity reaction. Some rare reaction includes urticaria, rigour, fever and anaphylaxis.    

Antiplatelet drugs. Aspirin and some other antiplatelet drugs should be used very cautiously during heparin therapy.

 

Heparin versus warfarin

Heparin. Heparin is anticoagulant drugs. It blocks the factors X and thrombin. It dissolves formed a clot in the blood vessel.  Antagonized by protamine sulphate. (if you know heparin injection in details visit this article - heparin injection)


Warfarin. Warfarin is an anticoagulant drug. it prevents the blood coagulation. It decreases clot formation and thrombosis. Also called a “blood thinner”. It prevents the blood stroke in congestive heart patients because it decreases blood clot in vein & arteries. It inhibits some coagulation factors as well as vitamin K. that’s why called a vitamin K antagonist.

(if you know details in heparin visit this article – warfarin)

 

Difference between heparin and warfarin

Heparin

 

Warfarin

It obtains from hog lung and pig intestine.

 

it obtains by synthetically.

It blocks the factors X and thrombin

 

It inhibits the clotting factors.

Chemistry is mucopolysaccharide

Chemistry is a coumarin derivatives

 

Administered by the parenteral route (intravenous and subcutaneous)

Administered by oral route.

 

Immediate onset of action

 

Delayed onset of action (1 -3 days)

Activity is in-vivo or in-vitro

Activity is only in-vivo

 

Antagonized by protamine sulphate

Antagonized by vitamin K

 

Drug interaction is few and significant

 

Drug interaction is many and significant

Use for initial therapy

 

Use for maintenance therapy

 

Conclusion. In this article, I will discuss the basic overview of heparin include the heparin mechanism of action, use, drugs, side effect, antidote etc. if you like it please comment out.