What are the advantages of low molecular weight heparin?

Unfractionated Heparin and Low Molecular Weight Heparin: Commonly Used Non-Oral Anticoagulants in Clinical Practice

Unfractionated heparin and low molecular weight heparin are commonly used non-oral anticoagulants in clinical settings, mainly for the prevention and treatment of thrombotic diseases such as myocardial infarction, stroke, thrombophlebitis, pulmonary embolism, etc. They are also used in procedures like hemodialysis, extracorporeal circulation, catheterization, and microvascular surgery. Many people clinically do not distinguish clearly between unfractionated heparin and low molecular weight heparin. Today, let’s understand the differences between them.

Differences Between Unfractionated Heparin and Low Molecular Weight Heparin:

Adverse Reactions:

1.Risk of Bleeding:

Both unfractionated heparin and low molecular weight heparin can induce severe adverse drug reactions, namely heparin-induced thrombocytopenia. According to the “Chinese Consensus on Heparin-Induced Thrombocytopenia,” unfractionated heparin is more likely to cause heparin-induced thrombocytopenia than low molecular weight heparin, necessitating platelet count monitoring in clinical practice. The smaller the molecular weight, the lower the risk of bleeding. Compared to low molecular weight heparin, unfractionated heparin has a higher risk of bleeding, requiring monitoring of activated partial thromboplastin time (APTT) for intravenous administration.


Large doses or long-term use of heparin may occasionally cause osteoporosis, while low molecular weight heparin rarely causes osteoporosis.


Both unfractionated heparin and low molecular weight heparin can cause hyperkalemia, warranting monitoring of potassium levels.

Source Differences: Unfractionated heparin is extracted and refined from pig intestinal mucosa or bovine lungs, consisting of a mixture with a molecular weight range of 3,000 to 30,000 KD. Low molecular weight heparin consists of fragments of unfractionated heparin, also a mixture, with a molecular weight range of 3,000 to 5,000 KD, including enoxaparin, nadroparin, dalteparin, etc.

Calcium Salts and Sodium Salts, Minor Differences:

Both unfractionated heparin and low molecular weight heparin come in sodium and calcium salt forms. When administered subcutaneously, calcium salts have lower anticoagulant activity than sodium salts, but this does not affect clinical efficacy. Calcium salts are less likely to cause skin bruising, but other bleeding symptoms are not significantly different.

Differences in Anticoagulant Action:

Antithrombin III, a plasma anticoagulant, can inhibit activated coagulation factors Xa, IIa (thrombin), XIIa, etc., where plasma factor IIa is closely related to coagulation, and factor Xa is closely related to thrombus formation.

Unfractionated heparin and low molecular weight heparin, upon binding with antithrombin III, can increase the affinity of antithrombin III for coagulation factor Xa, exerting an anti-factor Xa effect. However, only heparin with a larger molecular weight (>5400KD) can bind simultaneously with antithrombin III and factor IIa, exerting an anti-factor IIa effect. Anti-factor IIa effect: Unfractionated heparin > Low molecular weight heparin. Anti-factor Xa effect: Low molecular weight heparin > Unfractionated heparin. The anti-Xa/IIa ratio for heparin is 1:1, while for low molecular weight heparin, this ratio is (2-4):1. Therefore, low molecular weight heparin has a stronger antithrombotic effect.

Pharmacokinetics Differences:

The smaller the molecular weight, the longer the half-life. The plasma half-life of unfractionated heparin is about 1-2 hours; the plasma half-life of low molecular weight heparin is about 5-7 hours; the plasma half-life of fondaparinux is about 17-21 hours, allowing for once-daily subcutaneous injection.

Unfractionated heparin can be cleared and degraded by the reticuloendothelial system, with a small amount excreted by the kidneys; low molecular weight heparin and fondaparinux are mainly excreted by the kidneys, and accumulation can occur in patients with renal insufficiency, potentially leading to bleeding.

The bioavailability of unfractionated heparin via subcutaneous injection is only 30%; the bioavailability of low molecular weight heparin and fondaparinux via subcutaneous injection is ≥90%. Unfractionated heparin, low molecular weight heparin, and fondaparinux can all be administered intravenously or subcutaneously, but intramuscular injections are contraindicated.


  1. Low molecular weight heparin cannot be interchanged with unfractionated heparin on a unit-for-unit basis, nor can different low molecular weight heparins be interchanged in this manner, due to differences in the preparations, molecular weight distributions, and anti-Xa/IIa activity ratios of each formulation. Each medication must be used according to its own instructions.
  2. Heparin and low molecular weight heparin should not be used for intramuscular injections.
  3. Heparin or low molecular weight heparin should not be combined with nonsteroidal anti-inflammatory drugs (NSAIDs), as this increases the risk of bleeding.
  4. Subcutaneous injections: The patient should be in a lying position, with the injection site in the subcutaneous tissue of the anterior lateral or posterior lateral abdominal wall, alternating sides. The injection needle should be inserted perpendicularly and completely into the skin fold pinched by the thumb and index finger of the injector, rather than at an angle, and the skin fold should be maintained throughout the injection process.

Background on the Development of Heparin:

Heparin is a potent anticoagulant drug, and its discovery and application are filled with surprises and drama. The discovery of heparin dates back to 1916 when a second-year medical student named Jay McLean, under the guidance of his mentor W. H. Howell, attempted to extract a substance from dog organs that would promote coagulation. Instead, he accidentally discovered a substance extracted from the liver that not only failed to promote coagulation but actually inhibited it. This was the initial form of heparin.

McLean reported his findings to Howell, who after verification, considered it an important discovery and named the substance “heparin,” as it was extracted from the liver. “Hepar” is Greek for liver, hence the name “Heparin.” McLean published his paper as an independent author in 1922, introducing the anticoagulant effects and extraction methods of heparin.

However, McLean did not receive the recognition and reputation he deserved for this discovery, as the outside world generally believed it was his mentor Howell who discovered heparin. This led to discord and controversy between the mentor and student. It was not until 1965, when the Journal of the American Medical Association (JAMA) published an editorial “Jay McLean (1890-1957): Discoverer of Heparin,” that the controversy was somewhat resolved.

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