The Classification of Heparin
Heparin is a glycosaminoglycan that functions as an anticoagulant. It is primarily classified based on molecular size into unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). Synthetic drugs like fondaparinux are also important related anticoagulants.
Unfractionated Heparin (UFH)
UFH is the original form of heparin with a wide range of molecular weights (3,000 to 30,000 Da). It activates antithrombin (AT) which then inhibits clotting factors, especially Factor Xa and thrombin (Factor IIa).
- Administration: UFH can be given intravenously for rapid anticoagulation or subcutaneously for prevention.
- Monitoring: Due to variable effects, UFH requires monitoring with tests like aPTT.
- Reversibility: Protamine sulfate can quickly reverse UFH's effects.
Low-Molecular-Weight Heparin (LMWH)
LMWHs are smaller heparin molecules (4,000 to 6,500 Da) produced from UFH. This smaller size leads to more predictable effects.
Common LMWHs include:
- Enoxaparin (Lovenox)
- Dalteparin (Fragmin)
- Tinzaparin (Innohep)
Key features of LMWH:
- Mechanism: Primarily inhibits Factor Xa, with less effect on thrombin compared to UFH.
- Administration: Given subcutaneously, often in a fixed dose, allowing for outpatient use.
- Monitoring: Routine lab monitoring is typically not needed, though anti-Xa assays may be used in specific cases.
- Reversibility: Protamine sulfate can partially reverse LMWH's effects.
Heparinoids and Synthetic Pentasaccharides
These agents are related anticoagulants. Fondaparinux (Arixtra) is a synthetic drug based on a key sequence in heparin.
- Mechanism: Fondaparinux is a specific inhibitor of Factor Xa and does not inhibit thrombin.
- Administration: Given subcutaneously with predictable effects.
- Monitoring: Routine monitoring is not required.
- Reversibility: No specific reversal agent exists for fondaparinux.
Comparing the Types of Heparin
| Feature | Unfractionated Heparin (UFH) | Low-Molecular-Weight Heparin (LMWH) | Fondaparinux |
|---|---|---|---|
| Molecular Weight | High (5,000-30,000 Da) | Low (4,000-6,500 Da) | Very Low (Synthetic Pentasaccharide) |
| Mechanism | Inhibits both Factor Xa and Factor IIa (thrombin) | Primarily inhibits Factor Xa | Highly specific inhibitor of Factor Xa |
| Administration | IV infusion or SC injection | SC injection | SC injection |
| Half-Life | Short (60-90 minutes) | Longer than UFH | Longest half-life |
| Monitoring | Frequent aPTT monitoring required | Routine monitoring not needed (except for specific cases) | No routine monitoring required |
| Predictability | Low, due to protein binding | High, due to less protein binding | High |
| Reversal Agent | Completely reversible with protamine sulfate | Partially reversible with protamine sulfate | No specific reversal agent |
Clinical Applications and Side Effects
Clinical Uses
The choice of heparin type depends on the specific clinical need. UFH is used when rapid, short-acting anticoagulation is needed, like during surgery or in unstable patients. LMWHs are often used for preventing and treating DVT and PE, offering convenience for outpatient use. Fondaparinux is used for similar reasons, especially if a patient has a history of HIT.
Potential Side Effects
Bleeding is the most common and serious side effect of all heparins. Other potential side effects include:
- Heparin-Induced Thrombocytopenia (HIT): A rare, severe reaction causing low platelets and increased thrombosis risk. It's more likely with UFH.
- Osteoporosis: Long-term use, particularly of UFH, can weaken bones.
- Injection Site Reactions: Pain or bruising at the site of subcutaneous injections.
- Allergic Reactions: Though uncommon, allergic responses are possible.
Conclusion
The different types of heparin vary mainly in molecular size, which affects how they work and their properties. UFH is the traditional option offering quick, controlled anticoagulation but requiring close monitoring. LMWHs are more predictable and convenient for both hospital and home use. Fondaparinux is a synthetic alternative that specifically targets Factor Xa with a low risk of HIT. Healthcare providers choose the best agent by considering its mechanism, how it's given, the need for monitoring, and if its effects can be reversed, to effectively prevent or treat blood clots. For more information, the National Institutes of Health provides an authoritative resource: Heparin: A Clinical Overview.
