title: Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.
abstract: BACKGROUND
  Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome caused by heparin. Complications range from thrombocytopenia to thrombocytopenia with thrombosis. We report a prospective, historical- controlled study evaluating the efficacy and safety of argatroban, a direct thrombin inhibitor, as anticoagulant therapy in patients with HIT or HIT with thrombosis syndrome (HITTS).
  
  
  RESULTS
  Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 microgram. kg(-1). min(-1) IV argatroban, adjusted to maintain the activated partial thromboplastin time 1.5 to 3.0 times baseline value. Treatment was maintained for 6 days, on average. Clinical outcomes over 37 days were compared with those of 193 historical control subjects with HIT (n=147) or HITTS (n=46). The incidence of the primary efficacy end point, a composite of all-cause death, all-cause amputation, or new thrombosis, was reduced significantly in argatroban-treated patients versus control subjects with HIT (25.6% versus 38.8%, P=0.014). In HITTS, the composite incidence in argatroban-treated patients was 43.8% versus 56.5% in control subjects (P=0.13). Significant between-group differences by time-to-event analysis of the composite end point favored argatroban treatment in HIT (P=0.010) and HITTS (P=0.014). Argatroban therapy, relative to control subjects, also significantly reduced new thrombosis and death caused by thrombosis (P<0.05). Argatroban-treated patients achieved therapeutic activated partial thromboplastin times generally within 4 to 5 hours of starting therapy and, compared with control subjects, had a significantly more rapid rise in platelet counts (P=0.0001). Bleeding events were similar between groups.
  
  
  CONCLUSIONS
  Argatroban anticoagulation, compared with historical control subjects, improves clinical outcomes in patients who have heparin-induced thrombocytopenia, without increasing bleeding risk.
authors: Loyola University Medical Center, Maywood, Illinois, USA. blewis@LUMC.edu
authors: B E
authors: BE
authors: Lewis
authors: D E
authors: DE
authors: Wallis
authors: S D
authors: SD
authors: Berkowitz
authors: W H
authors: WH
authors: Matthai
authors: J
authors: J
authors: Fareed
authors: J M
authors: JM
authors: Walenga
authors: J
authors: J
authors: Bartholomew
authors: R
authors: R
authors: Sham
authors: R G
authors: RG
authors: Lerner
authors: Z R
authors: ZR
authors: Zeigler
authors: P K
authors: PK
authors: Rustagi
authors: I K
authors: IK
authors: Jang
authors: S D
authors: SD
authors: Rifkin
authors: J
authors: J
authors: Moran
authors: M J
authors: MJ
authors: Hursting
authors: J G
authors: JG
authors: Kelton
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D003967:Diarrhea / Q000139:chemically induced; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D010875:Pipecolic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D011693:Purpura / Q000139:chemically induced; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban