Heparin
Regulatory sources consulted
Approved indications
- Local symptomatic relief in adults of superficial venous disorders, such as heaviness and tightness of legs with varicose veins, and of superficial bruises caused by blows.
Contraindications
Absolute
- Hypersensitivity to sodium heparin or any excipient.
- Application to mucosae, ulcers, or open or infected wounds.
Clinical warnings
- Major warning · Use only on intact skin, avoid the eyes, and do not use for prolonged periods or over large areas; prolonged use may cause sensitization. — https://cima.aemps.es/cima/dochtml/ft/58678/FT_58678.html
- Major warning · For thrombotic venous disorders, apply gently without massage. Use particular caution or avoid according to clinical judgment in patients with bleeding manifestations or major hemostatic disorders. — https://cima.aemps.es/cima/dochtml/ft/58678/FT_58678.html
- Major warning · Use particular caution because bleeding risk is increased with severe hypertension, gastroduodenal ulcer, congenital or acquired bleeding disorders—such as hemophilia, thrombocytopenia or certain vascular purpuras—and during menstruation. — https://cima.aemps.es/cima/dochtml/ft/58678/FT_58678.html
Drug interactions
- ModerateNSAIDs, dextran, dipyridamole and other drugs affecting platelet function
Mechanism: They may increase the bleeding effect of heparin.
Recommendation: Use with caution and monitor for signs of bleeding.
https://cima.aemps.es/cima/dochtml/ft/58678/FT_58678.html
- ModerateNitroglycerin, cardiac glycosides, nicotine, quinine and tetracyclines
Mechanism: They may interfere with the anticoagulant effect of heparin.
Recommendation: Assess the combination and monitor the clinical response.
https://cima.aemps.es/cima/dochtml/ft/58678/FT_58678.html
Adverse events
Common (≥1%)
Contact dermatitis · Local irritation · Local allergic reactions · Pruritus
Rare but serious
Very rare: skin necrosis at the application site
Pregnancy and lactation
During pregnancy or breastfeeding, use only when strictly necessary and after professional assessment; heparin does not cross the placenta or distribute into human milk.
Recent literature (PubMed)
Critically ill adults are at increased risk of VTE, including DVT, and pulmonary embolism. Various agents exist for venous thromboprophylaxis in this population. What is the comparative efficacy and safety of prophylaxis agents for prevention of VTE in critically ill adults? Systematic review and network meta-analysis of randomized clinical trials (RCTs) evaluating efficacy of thromboprophylaxis agents among critically ill patients. We searched six databases (including PubMed, EMBASE, and Medline) from inception through January 2021 for RCTs of patients in the ICU receiving pharmacologic, mechanical, or combination therapy (pharmacologic agents and mechanical devices) for thromboprophylaxis. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates. We included 13 RCTs (9,619 patients). Compared with control treatment (a composite of no prophylaxis, placebo, or compression stockings only), low-molecular-weight heparin (LMWH) reduced the incidence of DVT (OR, 0.59 [95% credible interval [CrI], 0.33-0.90]; high certainty) and unfractionated heparin (UFH) may reduce the incidence of DVT (OR, 0.82 [95% CrI, 0.47-1.37]; low certainty). LMWH probably reduces DVT compared with UFH (OR, 0.72 [95% CrI, 0.46-0.98]; moderate certainty). Compressive devices may reduce risk of DVT compared with control treatments; however, this is based on low-certainty evidence (OR, 0.85 [95% CrI, 0.50-1.50]). Combination therapy showed unclear effect on DVT compared with either therapy alone (very low certainty). Among critically ill adults, compared with control treatment, LMWH reduces incidence of DVT, whereas UFH and mechanical compressive devices may reduce the risk of DVT. LMWH is probably more effective than UFH in reducing incidence of DVT and should be considered the primary pharmacologic agent for thromboprophylaxis. The efficacy and safety of combination pha
Heparin has been used extensively as an antithrombotic and anticoagulant for close to 100 years. This anticoagulant activity is attributed mainly to the pentasaccharide sequence, which potentiates the inhibitory action of antithrombin, a major inhibitor of the coagulation cascade. More recently it has been elucidated that heparin exhibits anti-inflammatory effect via interference of the formation of neutrophil extracellular traps and this may also contribute to heparin's antithrombotic activity. This illustrates that heparin interacts with a broad range of biomolecules, exerting both anticoagulant and nonanticoagulant actions. Since our previous review, there has been an increased interest in these nonanticoagulant effects of heparin, with the beneficial role in patients infected with SARS2-coronavirus a highly topical example. This article provides an update on our previous review with more recent developments and observations made for these novel uses of heparin and an overview of the development status of heparin-based drugs. SIGNIFICANCE STATEMENT: This state-of-the-art review covers recent developments in the use of heparin and heparin-like materials as anticoagulant, now including immunothrombosis observations, and as nonanticoagulant including a role in the treatment of SARS-coronavirus and inflammatory conditions.
Haemodialysis (HD) requires safe and effective anticoagulation to prevent clot formation within the extracorporeal circuit during dialysis treatments to enable adequate dialysis and minimise adverse events, including major bleeding. Low molecular weight heparin (LMWH) may provide a more predictable dose, reliable anticoagulant effects and be simpler to administer than unfractionated heparin (UFH) for HD anticoagulation, but may accumulate in the kidneys and lead to bleeding. To assess the efficacy and safety of anticoagulation strategies (including both heparin and non-heparin drugs) for long-term HD in people with kidney failure. Any intervention preventing clotting within the extracorporeal circuit without establishing anticoagulation within the patient, such as regional citrate, citrate enriched dialysate, heparin-coated dialysers, pre-dilution haemodiafiltration (HDF), and saline flushes were also included. We searched the Cochrane Kidney and Transplant Register of Studies up to November 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating anticoagulant agents administered during HD treatment in adults and children with kidney failure. Two authors independently assessed the risk of bias using the Cochrane tool and extracted data. Treatment effects were estimated using random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach (GRADE). We included 113 studies randomising 4535 participants. The risk of bias in each study was adjudicated
Heparin, an old but first-line anticoagulant, has been used over a century. It is a heterogeneous, linear, highly sulfated, anionic glycosaminoglycan with a broad distribution in relative molecular weight and charge density. These structural properties allow heparin to selectively interact with multiple proteins, leading to heparin's various pharmacological functions, such as anticoagulant, anti-viral, anti-tumor and anti-inflammatory activities. Clinical data suggest that unfractionated heparin or low molecule weight heparin could decrease mortality in COVID-19 patients with sepsis-induced hypercoagulation through the anticoagulant, anti-viral and anti-inflammatory activities of these drugs. Thus, the non-anticoagulant activity of heparin has again aroused attention. This review highlights recent advances in the preparation of heparin-derived drugs and clinical research on its non-anticoagulant properties over the past decade, to further the development and utilization of these important drugs.