What is the difference between unfractionated heparin, low molecular weight heparin and fondaparinux❓❓❓

Heparins are one type of the most commonly used anticoagulant drugs in clinical practice. Unfractionated heparin, low molecular weight heparin and fondaparinux are very commonly used heparins. Thrombosis or embolic diseases such as myocardial infarction, vascular embolism and pulmonary embolism can be prevented and treated with these drugs. They have similar therapeutic uses and belong to the same type of drug, so what is the difference between them?

Thrombotic disease.

Thrombotic disorders can be divided into venous thromboembolism and arterial thromboembolism. Common venous thromboembolisms include deep vein thrombosis and pulmonary embolism. Common arterial thromboembolisms include myocardial infarction and acute cerebral infarction.

Mechanisms of heparin anticoagulants.

The liver can synthesize antithrombin which is a natural anticoagulant. Its anticoagulant effect is by binding to coagulation factors Xa and IIa and inhibiting their activity. However, heparin has no direct anticoagulant ability. Its anticoagulant effect is through binding to antithrombin, thereby enhancing the inhibitory ability of antithrombin on coagulation factors Xa and IIa. 

Unfractionated heparin has a longer molecular chain. The molecular weight range is about 3000 to 30000KD. Heparin with a molecular weight greater than 5400KD can be combined with thrombin and antithrombin. It inhibits coagulation factors Xa and IIa.

Enoxaparin, nadroparin and dalteparin are commonly used low molecular weight heparins. Their molecular weight is less than 8000KD. They mainly inhibit coagulation factor Xa. They inhibit coagulation factor Xa and IIa in a ratio of (2 to 4):1.

The molecular chain of fondaparinux is very short. Its molecular weight is 1728. It only inhibits coagulation factor Xa.

Pharmacokinetics of unfractionated heparin, low molecular weight heparin and fondaparinux.

The smaller the molecular weight of heparins, the longer their half-life.

• Unfractionated heparin: Only a small amount of unfractionated heparin is excreted by the kidneys, so patients with creatinine clearance less than 30ml/min can also use it. It can be administered by intravenous or subcutaneous injection, but the bioavailability of subcutaneous injection is only 30% and the intravenous administration has immediate effect. Its half-life is about 1 to 2 hours.
• Low molecular weight heparin: Because it is excreted by the kidneys, it should be used with caution in patients with renal insufficiency. It can be administered intravenously or subcutaneously, but subcutaneous injection has better bioavailability (about 90%). It works 3 to 4 hours after subcutaneous injection. Its half-life is about 5 to 7 hours.
• Fondaparinux: The kidneys are its main route of excretion. In patients with creatinine clearance of 30 to 50 ml/min, the dose should be halved. It is contraindicated in patients with creatinine clearance less than 30. It can be given by intravenous or subcutaneous injection. The bioavailability of subcutaneous injection can reach 100%. It works 2 to 3 hours after subcutaneous injection. It has a half-life of 17 to 21 hours, so only one subcutaneous injection per day is required.

They can be administered intravenously or subcutaneously, but intramuscular injection is prohibited. They cannot penetrate the placenta, so they do not cause teratogenicity. Protamine can completely eliminate the anticoagulant effect of unfractionated heparin with larger molecular weight. However, it can only eliminate part of the anticoagulant effect of low molecular weight heparin and is ineffective against fondaparinux.

Indications.

In the thrombosis process of ST elevation myocardial infarction, coagulation factor IIa plays an important role. Unfractionated heparin has a strong inhibitory effect on coagulation factor IIa. It can effectively and rapidly inhibit coagulation and prevent the expansion of infarct size. Therefore, unfractionated heparin is an important basic treatment for the thrombolysis of ST elevation myocardial infarction and before percutaneous coronary intervention.

Unfractionated heparin: It can be used to prevent venous thromboembolic disease associated with surgery, treat established deep vein thrombosis, treat unstable angina pectoris and acute phase of non-Q-wave myocardial infarction, treat acute ST elevation myocardial infarction, combined use with thrombolytic agents or concurrent use with percutaneous coronary intervention, treatment of disseminated intravascular coagulation of various causes, prevention of clot formation in extracorporeal circulation during hemodialysis.

Low molecular weight heparin (nadroparin, enoxaparin, dalteparin): it can be used to prevent venous thromboembolic disease associated with surgery, treat established deep vein thrombosis, treat unstable angina and non-Q-wave myocardium In the acute phase of infarction, prevention of clot formation in cardiopulmonary bypass during hemodialysis. Only enoxaparin can be used to treat acute ST elevation myocardial infarction, in combination with thrombolytics, or concomitantly with percutaneous coronary intervention.

Fondaparinux: It is used to prevent venous thromboembolic events in patients undergoing major orthopedic surgery of the lower extremity, such as hip fractures, major knee surgery, or hip replacements. It treats unstable angina pectoris or non-ST elevation myocardial infarction for not indicated urgent (less than 120 minutes) percutaneous coronary intervention. It is used to treat patients with ST elevation myocardial infarction who are on thrombolytics or who are not initially receiving other forms of reperfusion therapy. It significantly increases the risk of catheter thrombosis, so it is not suitable for patients undergoing percutaneous coronary intervention.

Adverse effects.

Although they have similar side effects, they occur at different rates. In general, lower molecular weight heparins are safer.

Hyperkalemia: Heparin drugs inhibit the synthesis of aldosterone. Therefore, even in small doses, it may cause an increase in serum potassium.

Bleeding: The higher the molecular weight of heparin, the higher the risk of bleeding. Therefore, unfractionated heparin has the highest bleeding risk. Activated partial thrombin time should be monitored when using it.

Thrombocytopenia: Unfractionated heparin may cause fatal thrombocytopenia. Low molecular weight heparin has a low incidence of thrombocytopenia. Patients should have their platelet counts monitored when using both of them. Thrombocytopenia caused by fondaparinux is rare.

Osteoporosis: Patients receiving long-term (3 to 6 months) or high-dose (>20,000 units/day) unfractionated heparin are at risk for spontaneous vertebral fractures or osteoporosis. Low molecular weight heparin and fondaparinux are less risky.