Argatroban anticoagulation for heparin-induced thrombocytopenia in elderly patients.
BACKGROUND
Argatroban, a direct thrombin inhibitor that has reduced clearance in elderly versus younger volunteers, is used for thromboprophylaxis or treatment in heparin-induced thrombocytopenia (HIT).


OBJECTIVE
To evaluate the effect of aging on argatroban therapy, including dosage, anticoagulant responses, clinical outcomes and factors influencing those responses, in elderly patients with HIT or a history of HIT.


METHODS
This was a retrospective multicentre database analysis of 118 inpatients treated with argatroban at six medical centres between August 2001 and January 2005. Sixty-two adults aged >/=65 years were administered argatroban for clinically diagnosed HIT (n = 54) or a history of HIT (n = 8). Argatroban infusion was adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline. All study measures and analyses were prospectively defined. Argatroban dosage patterns, aPTTs and platelet count responses, and 37-day outcomes (death, amputation, new thrombosis, major bleeding) were summarised for patients stratified by age (65-74 years [n = 31]; 75-84 years [n = 26]; >/=85 years [n = 5]) to identify possible age-related trends. Regression analyses explored relationships between dose and patient age, liver function and renal function. Cox proportional hazards models evaluated the effect of age, dose, gender, aPTT and platelet count on the risk of new thrombosis.


RESULTS
In each age group, the median argatroban dosage was initially 1.0 microg/kg/min and was generally maintained at or near that dose during therapy (median, 5-7 days). Therapeutic aPTTs occurred within 11.5 hours; the median aPTT during therapy was 54.7 seconds, without obvious trend by age. By regression analysis, the initial and mean argatroban dosages decreased 0.08-0.09 microg/kg/min with each 0.2 mg/dL increase in serum creatinine, but no association was detected between dose and patient age, serum total bilirubin, calculated creatinine clearance or blood urea nitrogen. Platelet counts recovered within 6-7 days of initiating therapy, without apparent trend by age. No patient experienced amputation or major bleeding, and no patient in the oldest group died or had new thrombosis. Overall, 13 (21%) patients died (9 in the 65-74 years group; 1 receiving argatroban) and 5 (8%) had new thrombosis (4 in the 65-74 years group; 2 receiving argatroban), comparing favourably with previously reported rates, irrespective of patient age. By univariate (but not multivariate) analysis, the risk of new thrombosis decreased with increasing argatroban dose (hazard ratio 0.020; 95% CI 0.001, 0.757; p = 0.035). No effect of age or the other covariates considered on thrombotic risk was detected.


CONCLUSIONS
Argatroban at a median initial dosage of 1.0 microg/kg/min, adjusted to achieve median aPTTs of 54.7 seconds during therapy, generally provided safe, adequate anticoagulation across a wide age range in elderly patients with HIT or a history of HIT. In these elderly patients, age was not a significant determinant of argatroban dosage or thrombotic risk. Prospective evaluation of this initial dose of argatroban in the elderly is warranted.
Bartholomew
John R
JR
The Cleveland Clinic, Cleveland, Ohio 44195, USA. barthoj@ccf.org
Pietrangeli
Carolynn E
CE
Hursting
Marcie J
MJ
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D003401:Creatine / Q000097:blood; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D010976:Platelet Count; D012307:Risk Factors; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D016896:Treatment Outcome
D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban; D003401:Creatine