Heparin

 

– Heparins are indirect thrombin inhibitors (IIa), acting by means of a plasma cofactor antithrombin III (AT III). The action of heparin-AT III complex is directed against thrombin (IIa) and against factor Xa (Stuart factor).

– This mode of action explains the inefficiency of heparin in patients with congenital or acquired deficiency in AT III.

– LMWHs are predominantly anti-Xa activity.

Mode of action of heparin

Mode of action of heparin

1- Unfractionated heparin:

– Heparin not reached the serous, meninges and placenta. No intestinal absorption.

– Degraded by the liver and excreted by the kidney in an inactive form. ½ life = 60-90 min.

– Curative treatment: heparin sodium => continuous venous infusion: loading dose = 50 IU / kg and infusion of 15 to 25 IU / kg / h (500 IU / kg / 24h). The first control of the TCA is made 4 to 6 hours after the start of infusion.

– Preventive treatment: Calciparine by subcutaneously every 8 hours or 12 hours (0.2 ml x3 / day)

– Biological Monitoring: TCA (1.5 to 3 times the control) 1 time a day; biweekly platelet count

– Absolute contraindications: pericarditis; aortic dissection; endocarditis; Hemorrhagic stroke; peptic ulcer recent;diabetic retinopathy; thrombocytopenia history to heparin.

– Relative contraindications: advanced age; Severe hypertension; moderate hepatic or renal impairment

– Side Effects: Heparin thrombocytopenia type 2 (immunoallergic) osteoporosis; eosinophilia; alopecia; liver enzymes; Hypoaldosteronism with hyperkalemia.

– Antidote: protamine sulphate IVL dose vis-à-vis heparin dose (last injection)

– Direct Antithrombin -> hirudin (in case of heparin-induced thrombocytopenia)

Chemical formula heparin

Chemical formula heparin

2- LMWH (low molecular weight heparin):

– LMWHs are characterized by a strong anti-factor Xa activity and low anti-factor IIa activity.

– Dosage in preventive treatment: 0.2 to 0.3 anti-Xa IU / ml.

– Dosage in curative treatment: 0.5 to 1 anti-Xa IU / ml.

– The measurement of anti-Xa activity is required in patients with moderate renal insufficiency, obesity, bleeding risk patient or use of high doses of LMWH.

– The lifetime of LMWH allows one injection every 24 hours.

– Molecules: nadroparin (Fraxiparine®) Enoxaparin (Fraxiparine®)

– Indications: Prophylaxis of thromboembolic disease; Curative treatment of venous thrombosis; pulmonary embolism low or medium severity (Inohep®) unstable angina and myocardial infarction without Q waves

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