Hirudin monitoring

The prototype of this class is hirudin, which was originally isolated from the salivary glands of the medicinal leech, Hirudo medicinalis. Hirudin itself is not commercially available, but recombinant technology has permitted production of hirudin derivatives, namely lepirudin and desirudin.29,38,41 Lepirudin has a short half-life of approximately 40 minutes after IV administration and 120 minutes when given SC. Elimination of lepirudin is primarily renal therefore, doses must be adjusted based on the patient s renal function. The dose should be monitored and adjusted to achieve an aPTT ratio of 1.5 to 2.5 times the baseline measurement. Lepirudin is currently approved for use in patients with HIT and related thrombosis. Up to 40% of patients treated with lepirudin will develop antibodies to the drug.29,38,41... 

Nowak G., Bucha E. A new method for the therapeutical monitoring of hirudin. Thromb Haemost 1993 69, 1306. 

Some evidence suggests that monitoring these agents with the ecarin clotting time (ECT) may be more appropriate. Measurements based on this test appear to better correlate with bivalirudin and hirudin levels (14). Whether levels based on this assay evolve to recommended targets for therapy remains to be established. 

Hirudin treatment has been monitored by aPTT and frequent aPTT monitoring is required in patients with renal impairment, serious liver injury, or an increased risk of bleeding (56). Stricter dose adjustment is required in renal impairment patients. ECT may be a more appropriate marker, particularly for high-dose hirudin (57). 

Potzsch B, Hund S, Madlener K, et al. Monitoring of recombinant hirudin assessment of a plasma-based ecarin clotting time assay. Thromb Res 1997 86 373-383. 

Bivalirudin is a direct thrombin inhibitor that has found utility for reducing the rate of acute reocclusion in patients treated with PCI. It is preferential to heparin in PCI when HIT is present. This drug is a derivative of hirudin, which is a dedicated thrombin inhibitor with no other in vivo activities of significance. The molecule is semisynthetic the C-terminal of hirudin is linked by a polyglycine spacer to the tetrapeptide region of the N-terminal that reacts with the thrombin active site (22). It is monitored by the activated clotting time test. Its pharmacologic properties are shown in Table I. 

Matsuno et al. (1991) reports a method to induce thrombosis in the rat femoral artery by means of a photochemical reaction after injection of a fluorescent dye (rose Bengal, 10 mg/kg i.v.) and transillumination with a filtered xenon lamp (wave length 540 nm). Blood flow is monitored by a pulsed Doppler flow meter. Occlusion is achieved after approximately 5-6 min. Pretreatment with heparin dose-dependently prolongs the time required to interrupt the blood flow. The model also enables the study of thrombolytic mechanisms, which had been evaluated with t-PA. A comparative data for hirudin in various models was carried out by Just et al. (1991). 

Platelet counts should be carefully monitored for any decline. If thrombocytopenia develops, the time course and severity should help differentiate which type of HIT exists. If HIT I is suspected, heparin may be continued with caution. If HIT II is suspected, heparin therapy should be discontinued and an alternate form of anticoagulation therapy begun. If a low platelet count is encountered with a thrombotic complication, heparin should be discontinued immediately. Thrombolytic therapy or embolectomy may be necessary. Lepirudin (recombinant hirudin) is... 

Nowak G. 2001. Clinical monitoring of hirudin and direct thrombin inhibitors. Semin. Thromb. Hemos-tas. 27 537-541. 

Pivalizza EG. Monitoring of hirudin therapy with the Thrombelastograph. J Clin Anesth 2002 14 456-8. 

---