Stroke in patients with heparin-induced thrombocytopenia and the effect of argatroban therapy.
OBJECTIVE
To investigate the frequency, mortality rate, and characteristics of stroke in heparin-induced thrombocytopenia and the effect of argatroban therapy in that setting.


METHODS
Retrospective analysis of two prospective studies of argatroban therapy in heparin-induced thrombocytopenia.


METHODS
Hospitalized care.


METHODS
Patients were 960 patients with heparin-induced thrombocytopenia (767 argatroban-treated patients, 193 historical controls).


METHODS
Argatroban 2 microg x kg x min, adjusted to achieve activated partial thromboplastin times 1.5-3 times baseline


RESULTS
Case records were reviewed to identify patients with stroke present at or within 37 days of study entry and to assess 37-day outcomes. Stroke occurred in 30 (3.1%) patients (stroke at entry, n = 9; new stroke during follow-up, n = 24; more than one stroke, n = 4). By logistic regression with treatment, protocol, age, and gender as covariates, females were significantly more likely to suffer stroke (odds ratio, 2.48; 95% confidence interval, 1.11-5.53; p =.026) and stroke-associated mortality (odds ratio, 4.10; 95% CI, 1.12-15.01; p =.033), and argatroban-treated patients had significantly reduced odds, vs. control, of new stroke (odds ratio, 0.31; 95% confidence interval, 0.10-0.96; p =.041) and stroke-associated mortality (odds ratio, 0.18; 95% confidence interval, 0.03-0.92; p =.039). Stroke (odds ratio, 3.66; 95% confidence interval, 1.73-7.73; p <.001) and age (odds ratio per year, 1.017; 95% confidence interval, 1.004-1.029; p =.008) were significant predictors of all-cause death. In the argatroban group, baseline platelet counts were significantly less in patients with, vs. without, stroke (medians, 42 x 10/L vs. 72 x 10/L; p =.006). Of 35 stroke events, 33 (94%) were ischemic and two (6%) were hemorrhagic (one per group, none during argatroban infusion); 30 (86%) were present at or within 13 days of entry.


CONCLUSIONS
Stroke, particularly ischemic stroke, is common in heparin-induced thrombocytopenia and significantly increases mortality risk. Stroke in heparin-induced thrombocytopenia occurs most often in females, in patients with more severe thrombocytopenia, and within 2 wks of heparin-induced thrombocytopenia presentation. Argatroban therapy vs. control significantly reduces the likelihood of new stroke and stroke-associated mortality in heparin-induced thrombocytopenia without increasing intracranial hemorrhage.
LaMonte
Marian P
MP
University of Maryland School of Medicine (MPL), Baltimore, MD, USA. mlamonte@umm.edu
Brown
Philip M
PM
Hursting
Marcie J
MJ
D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001120:Arginine / Q000031:analogs & derivatives; D002544:Cerebral Infarction / Q000209:etiology* / Q000401:mortality; D003422:Critical Care; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000627:therapeutic use; D017052:Hospital Mortality; D006801:Humans; D020766:Intracranial Embolism / Q000139:chemically induced* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010314:Partial Thromboplastin Time; D010875:Pipecolic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013449:Sulfonamides; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy*
D000925:Anticoagulants; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban