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Low Molecular Weight Heparin – Uses And Its Mechanism Of Action

Anticoagulants belonging to the class known as low molecular weight heparin (LMWH) are put to use therapeutically for the treatment of thrombosis and prophylactically in situations with a high risk of thrombosis.

As its name indicates, low molecular weight heparin is generated from unfractionated heparin (UFH) by digestion or depolymerizing larger chains of heparin into shorter chains using chemical or enzymatic techniques.

This results in low molecular weight heparin having a lower molecular weight. Because of the tiny strands, low molecular weight heparin has a longer half-life than unfractionated heparin and acts more predictably in the body.

Low molecular weight heparin and unfractionated heparin both suppress clotting factors. However, low molecular weight heparin may be self-administered at home by a subcutaneous (under the skin) injection, but unfractionated heparin therapy requires frequent blood testing.

Although both low molecular weight heparin and unfractionated heparin function similarly, they block clotting factors differently. The dosage of low molecular weight heparin is determined by the patient's weight, just as it is for all other types of heparin.

Dalteparin (brand name: Fragmin®) and enoxaparin (brand name: Lovenox®) are examples of low molecular weight heparin that may be purchased in the United States.

What Is Low Molecular Weight Heparin?

Anticoagulants are medications that belong to the class known as low molecular weight heparin. They are employed in treating myocardial infarction and preventing blood clots and venous thromboembolism (deep vein thrombosis and pulmonary embolism), both types of venous thromboembolism.

Heparin is a polysaccharide that occurs naturally and slows the process of coagulation, which is the first step in the development of thrombosis. The molecular chains that make up natural heparin vary in terms of both their length and their molecular weight.

Polydisperse pharmaceutical-grade heparin is composed of chains with a wide range of molecular weights, ranging from 5,000 to over 40,000 Daltons. On the other hand, low molecular weight heparins are made up entirely of relatively short polysaccharide chains.

Low molecular weight heparins are defined as heparin salts with an average molecular weight of less than 8000 Da and for which at least 60 percent of all chains have a molecular weight of less than 8000 Da.

In addition, low molecular weight heparins must not include chains with a molecular weight of more than 8000 Da. The polymeric heparin is subjected to a variety of fractionation and depolymerization processes in order to produce these.

Therapeutic doses of heparin obtained from natural sources, most often the intestines of pigs or the lungs of cattle, may be given to patients to reduce the risk of thrombosis. On the other hand, the effects of natural heparin, also known as unfractionated heparin, are less predictable than those of low molecular weight heparin.

A nurse with blue surgical gloves is making an injection.
A nurse with blue surgical gloves is making an injection.

Low Molecular Weight Heparin Indications

Anticoagulants include low molecular weight heparins such as dalteparin and enoxaparin. These medications are used in the prevention of venous thromboembolic illness (VTE) during acute or elective hospitalization, as well as in the treatment of deep vein thromboses and pulmonary embolism (PE).

The British National Formulary (BNF) and the National Institute for Health and Care Excellence (NICE) have approved the use of low molecular weight heparins for the following indications:

  • Deep vein thromboses prevention in the middle and high-risk populations (surgical, orthopedic, and medical patients)
  • Pregnancy venous thromboembolism treatment
  • Nonpregnant women's deep vein thromboses and pulmonary embolism treatment (those with both high and low risk of recurrence)
  • STEMI treatment (in both those undergoing percutaneous coronary intervention and those not)
  • Angina pectoris
  • Clotting prevention in extracorporeal circuits

Because low molecular weight heparins are not the only drugs used for these objectives, a complete grasp of the different anticoagulants and their pros and downsides is required for a suitable prescription.

Low Molecular Weight Heparin Mechanism Of Action

Low molecular weight heparins are anticoagulants that work by inhibiting the coagulation cascade's last common route. The coagulation cascade aims to convert blood into a clot, avoiding bleeding.

The previous common process is the conversion of fibrinogen to fibrin by thrombin activity. Antithrombin III is activated by low molecular weight heparins, which reduces coagulation.

Factor Xa is inhibited by antithrombin III. In doing so, it blocks activation of the last common route; Xa inactivation implies that prothrombin is not activated to thrombin, so fibrinogen is not converted into fibrin for clot formation.

Low molecular weight heparins are tiny fragments of heparin, a bigger mucopolysaccharide. Heparin acts similarly by attaching to and activating antithrombin III.

Heparin also possesses a thrombin binding site, allowing thrombin to interact with antithrombin III and heparin, preventing coagulation. Heparin has a quicker beginning of anticoagulant activity because it inhibits both Xa and thrombin, while low molecular weight heparins solely inhibit Xa.

Low Molecular Weight Heparin Uses

LMWH allows outpatient treatment of illnesses such as deep vein thrombosis or pulmonary embolism that traditionally required inpatient hospitalization for unfractionated heparin administration since it may be administered subcutaneously and does not need activated thromboplastin time (APTT) monitoring.

Because LMWH has better predictable pharmacokinetics and anticoagulant efficacy than unfractionated heparin, it is preferred for patients with severe pulmonary embolism and the first therapy of deep vein thrombosis.

Prophylactic treatment of hospitalized medical patients with LMWH and comparable anticoagulants lowers the incidence of venous thromboembolism, particularly pulmonary embolism, compared to placebo or no intervention.

Recently, these medicines have been studied as anticoagulants in patients with the acute coronary syndrome (ACS) treated with percutaneous intervention (PCI).

In individuals at extremes of weight or in patients with renal impairment, the usage of LMWH must be continuously managed. Anti-factor Xa activity might be used to monitor anticoagulation.

Because of its renal clearance, LMWH may be ineffective in people with an end-stage renal illness. LMWH may also be administered to dialysis patients to keep the open cannulae and shunts.

Cancer patients are more likely to develop venous thromboembolism, and LMWHs are used to minimize this risk. The CLOT research, published in 2003, found that dalteparin was more effective than warfarin in lowering the incidence of recurrent embolic events in patients with cancer and acute venous thromboembolism.

Numerous recommendations urge using LMWH in cancer patients for at least the first 3 to 6 months of long-term therapy, which is currently considered standard of care.

A doctor is administering an injection to the belly of a patient
A doctor is administering an injection to the belly of a patient

Low Molecular Weight Heparin Advantages

  • Longer and more regular exercise than UFH
  • Subcutaneous injections are self-administered at home, decreasing or eliminating hospital visits.
  • There is no need for routine blood testing.

Low Molecular Weight Heparin Disadvantages

  • Expensive
  • It might be challenging to give, mainly if the patient is afraid of needles.
  • Longer activity may make reversal more difficult if required.

Low Molecular Weight Heparin Side Effects

  • Uncontrollable bruising (most serious side effect)
  • Redness, discomfort, and bruising at the injection site
  • Bone strength deterioration (less than UFH)
  • Increased liver enzymes
  • Heparin-induced thrombocytopenia (HIT)

Low Molecular Weight Heparin Contraindications

LMWHs should be avoided in patients with known allergies to LMWHs, heparin, sulfites, or benzyl alcohol, in patients with current severe bleeding, or patients with a history of heparin-induced low blood platelet count (also known as heparin-induced thrombocytopenia or HIT).

High therapeutic dosages are not recommended in severe bleeding, such as brain or gastrointestinal hemorrhage. Because LMWHs are more reliant on renal function for excretion than unfractionated heparin, their biological half-life may be extended in patients with kidney failure, and their usage in the context of CrCl 30 mL/min may be contraindicated.

Aside from using unfractionated heparin instead, it may be able to lower the dosage and/or monitor anti-Xa activity to guide therapy.

The most frequent adverse effects include bleeding, which may be severe or even deadly, allergic responses, injection site reactions, and elevations in liver enzyme testing, which generally occur without symptoms.

Heparin and LMWH usage may occasionally be compounded by a reduction in platelet count, a problem known as Heparin Induced Thrombocytopenia. There are two types: a clinically benign, non-immune, and reversible variant (Type I) and a rare, more dangerous immune-mediated version (Type II).

HIT Type II is caused by the production of autoantibodies that identify complexes between heparin and platelet factor 4 (PF4) and is therefore linked with a significant risk of thrombotic events. The incidence is difficult to determine. However, it might reach up to 5% of UFH patients or roughly 1% of LMWH patients.

Low Molecular Weight Heparin Administration

Subcutaneous injection is used to provide LMWH; this has long-term ramifications for the choice of anticoagulant for prophylaxis, such as in orthopedic patients recuperating from joint replacement surgery or in the treatment of DVT/PE.

Patients often detest injections, particularly self-administered ones, and prefer an oral alternative. There are oral solutions for anticoagulation in the non-pregnant population, which commonly chooses this choice. The oral route has fewer needle and sharps dangers.

These oral alternatives are inappropriate outside pregnancy due to placental transfer and hazards to the embryo/fetus. Because LMWHs have a longer half-life than heparin, the dosage is more predictable and may be less frequent, most often once per day. Patients with high body weight, on the other hand, will need greater dosages, and in some cases, two doses daily, depending on local administration guidelines.

People Also Ask

What Is The Advantage Of LMWH?

LMWHs offer several benefits over UFH. These medicines have a higher bioavailability, may be taken subcutaneously, and have a longer anticoagulant action duration. A set dosage of LMWH may be administered, and activated thromboplastin time laboratory monitoring is not required.

What Is The Action Of Low-Molecular-Weight Heparin?

Heparin and LMWH work as anticoagulants by activating antithrombin (formerly known as antithrombin III), which speeds up the inactivation of the coagulation enzymes thrombin (factor IIA), factor Xa, and factor IXA.

What Is The Difference Between Heparin And Low-Molecular-Weight Heparin Drugs?

Polymeric heparin is fractionated to produce LMWH. The average molecular weight of LMWH varies from that of unfractionated heparin, as does the necessity for just a once or twice daily dose, the lack of activated thromboplastin time monitoring, and the decreased risk of bleeding, osteoporosis, and HIT.

What Drugs Are Low-Molecular-Weight Heparin?

Rivaroxaban - xarelto ®, Fondaparinux (arixtra ®), Edoxaban tosylate - savaysa ™, Apixaban - eliquis®, Tinzaparin (innohep ®), Enoxaparin (lovenox ®), Danaparoid (orgaran ®) and Dalteparin (fragmin ®)

Conclusion

Low molecular weight heparin (LMWH) offers several benefits over unfractionated heparin (UFH). These medicines have a higher bioavailability, may be taken subcutaneously, and have a longer anticoagulant action duration. LMWH provide several benefits. These have a higher bioavailability, may be taken subcutaneously, and have a longer anticoagulant action duration. LMWH has no known food interactions or dietary restrictions.

About The Authors

Suleman Shah

Suleman Shah - Suleman Shah is a researcher and freelance writer. As a researcher, he has worked with MNS University of Agriculture, Multan (Pakistan) and Texas A & M University (USA). He regularly writes science articles and blogs for science news website immersse.com and open access publishers OA Publishing London and Scientific Times. He loves to keep himself updated on scientific developments and convert these developments into everyday language to update the readers about the developments in the scientific era. His primary research focus is Plant sciences, and he contributed to this field by publishing his research in scientific journals and presenting his work at many Conferences. Shah graduated from the University of Agriculture Faisalabad (Pakistan) and started his professional carrier with Jaffer Agro Services and later with the Agriculture Department of the Government of Pakistan. His research interest compelled and attracted him to proceed with his carrier in Plant sciences research. So, he started his Ph.D. in Soil Science at MNS University of Agriculture Multan (Pakistan). Later, he started working as a visiting scholar with Texas A&M University (USA). Shah’s experience with big Open Excess publishers like Springers, Frontiers, MDPI, etc., testified to his belief in Open Access as a barrier-removing mechanism between researchers and the readers of their research. Shah believes that Open Access is revolutionizing the publication process and benefitting research in all fields.

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