title: A new therapeutic option by subcutaneous recombinant hirudin in patients with heparin-induced thrombocytopenia type II: a pilot study.
abstract: We prospectively studied 15 patients suffering from acute heparin-induced thrombocytopenia (HIT) type II with and without thromboembolic events and 4 patients with anamnestically known HIT type II recurrently requiring thromboprophylaxis in order to develop new therapeutic strategies by subcutaneous recombinant hirudin administration. Patients with acute venous or arterial thromboembolism were treated with aPTT-controlled intravenous (mean: 19.3 days) followed by subcutaneous r-hirudin (mean: 22.5 days). Patients without thromboembolism were treated with subcutaneous r-hirudin (mean: 25.9 days). Four patients were readmitted to subcutaneous r-hirudin (mean: 32 days). When r-hirudin was administered subcutaneously following intravenous treatment, mean baseline (prior to the injection) and mean peak (1.5-2.5 hours after the injection) aPTT ratios were 1.1 (+/-0.2) to 1.7 (+/-0.48) and 2. 48 (+/-0.43) to 2.52 (+/-0.4) times normal value, respectively. Mean baseline and mean peak ECT ratios were 1.2 (+/-0.12) to 1.9 (+/-0. 22) and 2.2 (+/-0.25) to 2.6 (+/-0.11) times the upper normal value, respectively. When r-hirudin was initially administered subcutaneously, mean baseline and mean peak aPTT ratios were 1.41 (+/-0.25) to 1.61 (+/-00.28) and 1.88 (+/-0.26) to 2.06 (+/-0.09) times the normal value, respectively. Mean baseline and mean peak ECT ratios were 1.25 (+/-0.2) to 1.5 (+/-0.38) and 2.01 (+/-0.21) to 2.23 (+/-0.25) times the upper limit of normal, respectively. Patients who received recurrent subcutaneous r-hirudin had mean baseline and peak aPTT values of 1.5 (+/-0.35) to 1.75 (+/-0.156) and 2.0 (+/-0.33) to 2.1 (+/-0.18) times the normal value, respectively. Mean baseline and peak ECT ratios were 1.3 (+/-0.26) to 1.65 (+/-0.09) and 1.94 (+/-0.256) to 2.7 (+/-0.23) times the upper limit of normal, respectively. The overall cumulative incidence of r-hirudin antibodies was 12/19 (63%) with a significant accumulation of r-hirudin in antibody-positive patients compared to antibody-negative patients (p<0.05). No patient suffered a new thromboembolic or major bleeding event. Subcutaneous administration of recombinant hirudin provides a long-term thromboprophylaxis regimen in HIT type II patients after passivation of acute thromboembolism.
authors.affiliation: Department of Medicine I., Faculty of Clinical Medicine, University Clinic of the University of Heidelberg, Heidelberg, Germany. Ghuhle@aol.com
authors.forename: G
authors.initials: G
authors.lastname: Huhle
authors.forename: U
authors.initials: U
authors.lastname: Hoffmann
authors.forename: I
authors.initials: I
authors.lastname: Hoffmann
authors.forename: V
authors.initials: V
authors.lastname: Liebe
authors.forename: J F
authors.initials: JF
authors.lastname: Harenberg
authors.forename: D L
authors.initials: DL
authors.lastname: Heene
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000097:blood; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D003401:Creatine / Q000097:blood; D005260:Female; D006406:Hematoma / Q000209:etiology; D006493:Heparin / Q000009:adverse effects*; D024764:Hirudin Therapy; D006629:Hirudins / Q000276:immunology; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010865:Pilot Projects; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy*; D013923:Thromboembolism / Q000188:drug therapy; D013997:Time Factors
chemical_list: D000906:Antibodies; D006629:Hirudins; D011994:Recombinant Proteins; D006493:Heparin; D003401:Creatine