Unraveling the Mysteries of Heparin Sodium

Abstract

Heparin Sodium, as an important anticoagulant drug, plays an irreplaceable role in clinical medicine. Its unique pharmacological mechanism has shown remarkable efficacy in the prevention and treatment of thrombosis, embolism and disseminated intravascular coagulation (DIC). In this paper, the basic information, pharmacological effects, clinical applications, adverse reactions, contraindications, and market prospects of heparin sodium are reviewed in order to provide references for researchers and clinicians in related fields.

Basic information

Heparin Sodium is a sodium salt of glucosamine sulfate extracted from the intestinal mucosa of pigs, cattle, sheep, and other animals. The drug is a white or white powder, has a strong wettability, easily soluble in water. As an anticoagulant, it mainly combines with antithrombin Ⅲ (AT-Ⅲ) to enhance the inhibitory effect of the latter on activated coagulation factors and achieve its anticoagulant effect.¹

Pharmacological effects

1. Anticoagulation mechanism

The anticoagulant mechanism of heparin sodium is complex and multi-link. It binds to AT-III to form a heparin AT-III complex, which significantly enhances the inhibitory effect of AT-III on activated coagulation factors II, IX, X, XI, and XII. This inhibition is specifically shown as preventing platelet aggregation and destruction, preventing the formation of thrombin-activating enzymes, preventing prothrombin from becoming thrombin and inhibiting thrombin, thereby preventing fibrinogen from becoming fibrin, and ultimately playing an anticoagulant role.²

2. Pharmacodynamic characteristics

Inhibition of prothrombin formation: Heparin sodium combined with AT-Ⅲ can inhibit the formation of prothrombin and counter the effect of the formed prothrombin kinase.

Interference with thrombin: After low-dose heparin is combined with AT-Ⅲ, the reaction site of AT-Ⅲ can more easily bind to the active center of thrombin, forming a stable thrombin-antithrombin complex, thus inactivating thrombin and inhibiting the transformation of fibrinogen into fibrin.

Interferes with the activation of factor ⅩⅢ by thrombin: affects the formation of non-soluble fibrin and prevents the normal activation of thrombin on factors Ⅷ and Ⅴ.

Inhibit platelet adhesion and aggregation: prevent platelet disintegration and release platelet factor 3 and 5-hydroxytryptamine, further preventing thrombosis.³

Pharmacokinetic characteristics

Heparin sodium is not absorbed orally but is well absorbed by subcutaneous, intramuscular, or intravenous injection. It is distributed in blood cells and plasma, and some of it can disperse into the extravascular tissue space. Due to the large size of the molecule, heparin cannot pass through the pleura and peritoneum, nor through placental tissue or into the milk. After intravenous injection, heparin sodium can be highly bound to plasma low-density lipoprotein to form a complex and also bound to globulin and fibrinogen, which is taken up by the mononuclear macrophage system, and partially broken down into urinary heparin by the action of intrahepatic heparinase. The metabolite is usually heparin, which is excreted through the kidney, and about 50% can be excreted in its original form when given in large quantities by intravenous injection.⁴

Clinical application

1. Prevent thrombosis and embolism

Heparin sodium is widely used to prevent deep venous thrombosis, myocardial infarction, pulmonary embolism, thrombophlebitis, and postoperative thrombosis. Its anticoagulant effect is significant, helping to reduce the serious complications caused by thrombosis.

2. Treatment of disseminated intravascular coagulation (DIC)

Heparin sodium can be used to treat DIC caused by bacterial sepsis, early placental dissection, and the dissolution of malignant tumor cells, but it is not suitable for DIC caused by snake bites. Early application of heparin sodium can prevent the depletion of fibrinogen and other clotting factors, thereby controlling the progression of the disease.

3. Other anticoagulants in vivo and in vitro

Heparin sodium is also used in cardiac catheterization, cardiopulmonary bypass, hemodialysis, and other anticoagulant treatments. In addition, heparin sodium can also be used as an anticoagulant for blood transfusion, extracorporeal circulation, peritoneal dialysis, and in vitro tests of blood samples.

4. Topical treatment

Heparin sodium cream (such as hyprin, and skin corning cream) can also be used for the treatment of early frostbite, chapping, ulcers, eczema, and superficial phlebitis, through its anticoagulant and anti-inflammatory effects, and promotes skin tissue repair.⁵

Adverse reactions

1. Bleeding tendency

The most common adverse effect of heparin sodium is bleeding, which can occur at any site. The risk of bleeding increases significantly when used in excess or in combination with other anticoagulants.

2. Allergic reactions

Patients may have chills, fever, urticaria, and other allergic reactions, severe cases may even appear as breathing difficulties, shock, and so on.

3. Other adverse reactions

Long-term use can cause hair loss and transient reversible alopecia, osteoporosis, and spontaneous fractures. Local irritation, erythema, slight headache, hematoma, ulcers, and so on can be seen in the injection area. In addition, heparin-induced thrombocytopenia (HIT) is a serious complication that can activate platelet aggregation, leading to small artery embolism and even death.

References

[1].Nachtmann, F.; Atzl, G.; Roth, W. D., Heparin sodium. In Analytical profiles of drug substances, Elsevier: 1983; Vol. 12, pp 215-276.

[2].Katrancioglu, N.; Karahan, O.; Kilic, A. T.; Altun, A.; Katrancioglu, O.; Polat, Z. A., Comparison of the antiangiogenic effects of heparin sodium, enoxaparin sodium, and tinzaparin sodium by using chorioallantoic membrane assay. Blood coagulation & fibrinolysis 2012,23(3), 218-221.

[3].Sommers, C. D.; Mans, D. J.; Mecker, L. C.; Keire, D. A., Sensitive detection of oversulfated chondroitin sulfate in heparin sodium or crude heparin with a colorimetric microplate based assay. Anal. Chem. 2011,83(9), 3422-3430.

[4].Baker, D. E.; Yost, G. S.; Craig, V. L.; Campbell, R. K., Compatibility of heparin sodium and morphine sulfate. American Journal of Hospital Pharmacy 1985,42(6), 1352-1355.

[5].Suzuki, T.; Ishii-Watabe, A.; Hashii, N.; Nakagawa, Y.; Takahashi, T.; Ebisawa, A.; Nishi, S.; Fujita, N.; Bando, A.; Sekimoto, Y., The establishment and validation of efficient assays for anti-IIa and anti-Xa activities of heparin sodium and heparin calcium. Biologicals 2013,41(6), 415-423.

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