(Circulation. 2001;103:1838.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Argatroban Anticoagulant Therapy in Patients With Heparin-Induced Thrombocytopenia
From Loyola University Medical Center, Maywood, Ill (B.E.L., J.F., J.M.W., J.M.); Midwest Heart Specialists, Downers Grove, Ill (D.E.W.); Duke University Medical Center, Durham, NC (S.D.B.); University of Pennsylvania, Philadelphia (W.H.M.); the Cleveland Clinic, Cleveland, Ohio (J.B.); Rochester General Hospital, Rochester, NY (R.S.); Westchester Medical Center, Valhalla, NY (R.G.L.); West Pennsylvania Hospital, Pittsburgh (Z.R.Z.); University of Alabama, Birmingham (P.K.R.); Massachusetts General Hospital, Boston (I.K.J.); Northwest Medical Specialists, Arlington Heights, Ill (S.D.R.); Texas Biotechnology Corporation, Houston (M.J.H., as consultant); and McMaster University, Hamilton, Ontario, Canada (J.G.K.).
Correspondence to Dr Bruce E. Lewis, Loyola University Medical Center, 2160 S First Ave, Maywood, IL 60153. E-mail blewis{at}LUMC.edu
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionAppendix 1References |
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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).
Methods and Results—Patients with HIT (isolated thrombocytopenia, n=160) or HITTS (n=144) received 2 µg · 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.
Key Words: anticoagulants • inhibitors • heparin • thrombosis • platelets
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
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Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome characterized by thrombocytopenia, which can be isolated or associated with thrombotic events. For patients with isolated HIT, >50% are at risk for developing thrombosis.1 Furthermore, the mortality rate associated with HIT is
10% to
30%.1 2 3 4
HIT is caused by the binding of antibodies (most frequently IgG) to a
complex of heparin and platelet factor
4.5 These antibodies
activate platelets through their Fc receptors, causing
platelet destruction and the release of prothrombotic
platelet-derived
microparticles.6
Microparticles in turn promote thrombin generation and contribute to a
hypercoagulable state.7
Although certain clinical situations are more likely to be associated
with thrombosis, no specific laboratory or clinical characteristic can
predict which patient will have isolated thrombocytopenia or have
thrombocytopenia with thrombotic
complications.8 Thrombotic
events are most frequently venous, but arterial thrombosis
leading to myocardial infarction and ischemic limb damage
requiring amputation also
occur.1 2 3 4 The discontinuation of heparin is recommended for managing HIT2 9 ; however, treatment strategies such as alternate anticoagulants should be considered. Approximately 40% to 50% of HIT patients will have a thrombotic event when heparin is discontinued.1 9 Additionally, many patients require ongoing anticoagulation for underlying medical conditions. Alternative agents that have been used in this setting include warfarin,10 ancrod,11 low-molecular-weight heparin,12 danaparoid,13 and recombinant hirudin (lepirudin).4 14 Thrombotic event rates, however, have generally remained high, and there are disadvantages associated with these agents. For example, warfarin has been associated with worsening of the thrombotic event in patients with HIT.15 The defibrinogenating agent ancrod does not inhibit thrombin, which is a significant problem for patients with HIT. Low-molecular-weight heparin and, to a lesser extent, danaparoid, cross-react with HIT antibodies.16
Direct thrombin inhibition may be beneficial in managing
HIT. In 1 of 2 trials, lepirudin significantly improved clinical
outcomes in HIT patients, relative to historical control
subjects.4 14
Lepirudin is renally cleared, and 50% of lepirudin-treated patients
develop drug-specific antibodies that can alter its anticoagulant
effects, hence complicating monitoring and dosing, particularly in
patients with renal failure or
insufficiency.17 Argatroban,
also a direct thrombin inhibitor, is a small, synthetic
molecule that binds reversibly and specifically to the catalytic domain
of thrombin.18 Argatroban is
hepatically metabolized but not renally cleared, and drug-specific
antibodies have not been known to develop.
We report a prospective study evaluating the efficacy and safety of argatroban as an anticoagulant in patients with HIT or HIT with thrombosis syndrome (HITTS). When this study was initiated, no approved alternative agent was available for use as an active comparator, and a randomized, placebo-controlled design was deemed unethical. Therefore, historical control subjects were studied for comparison.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
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Study Design
The institutional review board at each participating center approved this multicenter, nonrandomized, open-label, historical-controlled trial before its initiation, and patient informed consent was obtained. Men and nonpregnant, nonbreastfeeding women 18 to 80 years old were eligible. Patients were assigned at enrollment to either the HIT study arm (for those with isolated HIT) or HITTS study arm (for those with HIT complicated by thrombosis that occurred after heparin initiation). Eligible patients had thrombocytopenia, defined as a platelet count <100x109/L, or a 50% reduction in count after heparin therapy with no explanation besides HIT. Patients who had documented history of positive HIT antibody (ie, latent disease) and who required anticoagulation were eligible for the HIT arm, in the absence of thrombocytopenia or heparin challenge. Any patient with an unexplained activated partial thromboplastin time (aPTT) >2 times control at baseline, documented coagulation disorder or bleeding diathesis unrelated to HITTS, a lumbar puncture within the past 7 days, or a history of previous aneurysm, hemorrhagic stroke, or recent (within 6 months) thrombotic stroke unrelated to HITTS was excluded. Patients underwent a 2-tier medical review with adjudication, with differences in attribution adjudicated by a panel of physicians not related to the trial. Study baseline was the date argatroban therapy was initiated.
Potential historical control cases were identified by means of prospectively agreed on, documented approaches, which included a review of laboratory logs of patients who were tested for HIT or were thrombocytopenic. Potential control subjects were seen typically within 4 years before study initiation at participating centers and met these same inclusion/exclusion criteria per chart review by the investigator. Control subjects were treated according to the local standard of practice at the time of HIT diagnosis, with typical treatments being heparin discontinuation and/or oral anticoagulation. To minimize site-specific, nongeneralizable outcomes, a center could enroll up to 3 control subjects, in chronological order of their identification, per prospective patient enrolled. Case report forms were completed for 215 potential control patients. Case information underwent a 2-tier medical review with adjudication as described above. Patients found eligible made up the control group (n=193). Study baseline for control subjects was the date that heparin was discontinued after the platelet count met inclusion criteria or that the count met inclusion criteria after heparin initiation.
Treatment and Assessments
Heparin was discontinued for prospective patients,
and continuous intravenous argatroban (Texas Biotechnology
Corporation; Smith-Kline Beecham Pharmaceuticals) was initiated at 2
µg · kg-1 ·
min-1. The aPTT was determined 2 hours
later at each site, and dosage was adjusted (up to 10 µg ·
kg-1 ·
min-1, maximum) until the aPTT was 1.5 to
3.0 times the baseline aPTT value (not to exceed 100 seconds). The aPTT
was measured daily and 2 hours after each dosage adjustment. Patients
received argatroban until the underlying condition was clinically
resolved, appropriate anticoagulation was provided with other agents,
or treatment was continued for 14 days.
Patients were followed from baseline, during treatment, and
for 30 days after therapy cessation. Control subjects were followed for
37 days from baseline. Death (all causes), death caused by thrombosis
(per investigator’s assessment), amputation (all causes), new
thrombosis, and bleeding events were recorded. Major bleeding was
defined as overt and associated with a hemoglobin decrease 
2 g/dL
that led to a transfusion of 2 U or that was intracranial,
retroperitoneal, or into a prosthetic joint. Other bleeding was
considered minor. The primary efficacy assessment was a composite end
point of all-cause death, all-cause amputation, or new thrombosis
within 37 days of baseline. Secondary efficacy assessments included the
individual components of the composite end point, death caused by
thrombosis, any new thrombosis, achievement of adequate anticoagulation
(ie, aPTT 1.5 times baseline aPTT value), and resolution of
thrombocytopenia. Thrombocytopenia was resolved during treatment if at
any time during argatroban infusion (or within 7 days of baseline for
control subjects) a baseline platelet count of
<100x109/L increased to
100x109/L or if a baseline platelet
count of 100x109/L remained at the same
level or increased during treatment. Thrombocytopenia was resolved
within 3 days of baseline if the platelet count was
>100x109/L or >1.5 times baseline
value.
Data Analyses and Statistics
Using literature estimates of composite end point
rates for HIT/HITTS (30% to
50%),3 19 we
estimated20 that 150
argatroban-treated patients per arm, at least 60 HIT control subjects,
and 50 HITTS control subjects would allow detection (ß=0.10,
=0.01) of a significant treatment effect (absolute difference in
composite end point rate of 20%).
Analyses were conducted separately for the study
arms. Hypothesis testing was 2-sided, with significance at a level of
P
0.05. No adjustments were
made for multiple comparisons. Demographic and baseline characteristics
were compared between groups by means of the Student’s
t test (age, weight) or
Fisher’s exact test (sex, percent test positive by heparin-induced
platelet aggregation
test21 or
serotonin release
assay22 ). Between-group
analysis of the composite end point was performed by
categorical and time-to-event (Kaplan-Meier lifetime tables) methods,
with statistical significance assessed by means of the
2 test and log-rank test, respectively.
For time-to-event analysis, patients were censored on their
last day of follow-up or on day 37, whichever came first. Hazard ratios
and 95% CIs were estimated by proportional hazards regression
analysis. Between-group comparisons for the composite end
point’s individual components (distributed by severity), death caused
by thrombosis, and any new thrombosis were performed by means of
Fisher’s exact test. ANCOVA was performed on the change in
platelet count by study day 3, with baseline platelet count
taken as covariate.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
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This trial enrolled 304 argatroban-treated patients (n=160, HIT arm; n=144, HITTS arm) for comparison with 193 historical control subjects (n=147, HIT arm; n=46, HITTS arm). The HIT study arm included 31 argatroban-treated patients and 8 historical control subjects without thrombocytopenia yet with a history of a positive HIT antibody test and requiring anticoagulation. Table 1
summarizes patient demographic and baseline
characteristics. Between-group differences were detected in both arms
for age and in the HIT arm for sex and test positivity. Median baseline
platelet counts were lower among argatroban-treated patients than
control subjects.
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The mean (±SE) argatroban dose in the HIT and HITTS arm, respectively, was 2.0±0.1 µg · kg-1 · min-1 and 1.9±0.1 µg · kg-1 · min-1, and the duration of therapy was 5.3±0.3 days and 5.9±0.2 days, respectively. Of 304 argatroban-treated patients, 252 (83%) completed the protocol-specified treatment period; 30 (10%) prematurely discontinued infusion because of surgery (6), patient request (3), or other reasons (21; eg, increased aPTT, positive blood culture, decision to withdraw life support); and 22 (7%) were withdrawn because of adverse events. Events leading to withdrawal of >1 patient were coagulopathy, anemia, and gastrointestinal hemorrhage (2 patients each) and unspecified hemorrhage (3 patients).
Primary Efficacy End Point
The incidence of the composite end point was reduced
significantly in argatroban-treated patients versus control subjects
with HIT (25.6% versus 38.8%,
P=0.014). In HITTS, the
composite end point occurred in 43.8% of argatroban-treated patients
compared with 56.5% of control subjects
(P=0.13). Significant
between-group differences by time-to-event analysis of the
composite end point favored argatroban treatment in both the HIT arm
(P=0.010, hazard ratio=0.60,
95% CI=0.40 to 0.89;
Figure 1) and HITTS arm
(P=0.014, hazard ratio=0.57,
95% CI=0.36 to 0.90;
Figure 2). Treatment effect remained a significant predictor
of the time-to-first event also after adjusting for patient age, test
positivity, race, and baseline medical conditions (HIT,
P=0.001; HITTS,
P=0.027).
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Secondary Efficacy End Points
Table 2 summarizes the between-group comparative
analyses for the incidence of death caused by thrombosis, new
thrombosis, and each individual component of the composite end point.
In both arms, argatroban-treated patients compared with control
subjects had significantly reduced death caused by thrombosis
(P0.005). There were no
between-group differences in all-cause mortality. The incidence of
amputation (as the most severe outcome) was similar between groups.
Argatroban therapy significantly reduced the percentage of patients
with new thrombosis in both study arms
(P0.044). New thrombotic
events occurring in argatroban-treated patients were primarily (86%)
in the venous circulation.
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Thrombocytopenia was resolved in 69% of
argatroban-treated patients (compared with 50% of control subjects)
during the treatment interval and in 53% of argatroban-treated
patients by day 3
(Table 3). For the HIT and HITTS arms, mean (±SE) changes
in platelet count by day 3 were +54 (±7)
x109/L and +52 (±7)
x109/L, respectively, for
argatroban-treated patients, compared with -33 (±10)
x109/L and -21 (±19)
x109/L, respectively, for control subjects
(P=0.0001, each arm). By
conclusion of treatment, median platelet counts for
argatroban-treated patients were
185.5x109/L in the HIT arm and
198x109/L in the HITTS arm.
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Adequate anticoagulation with argatroban was achieved in
83% of patients during the study and generally within 4 to 5 hours
of initiation of infusion
(Table 4). Median aPTTs increased from 29.9 seconds at
baseline in the HIT and HITTS arms to 60.4 (interquartile range, 51.0
to 71.8) seconds and 67.5 (53.9 to 83.4) seconds, respectively, within
12 hours of argatroban initiation. During infusion, aPTTs remained
steady, with median daily values of 52.2 to 62.6 seconds in the HIT arm
and 52.4 to 68.0 seconds in the HITTS arm.
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Safety
Major bleeding rates were not different between the
argatroban-treated patients and control subjects in either study arm
(Table 5). One argatroban-treated patient had an
intracranial hemorrhage, which the investigator deemed
unrelated to study medication, 4 days after discontinuing argatroban
and after warfarin and urokinase therapy. Another patient developed
disseminated intravascular coagulation while receiving argatroban,
warfarin, citrate, aspirin, and streptokinase and died of multisystem
hemorrhage. Two fatal bleeding events, including 1 intracranial
hemorrhage, occurred in the control subjects 3 days and 16 days
after heparin cessation and in the absence of additional anticoagulants
or thrombolytics. Minor bleeding rates were similar
between groups
(Table 5).
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The most common adverse events among argatroban-treated patients in the HIT and HITTS arms, respectively, were diarrhea (11%) and pain (9%). The most common drug-related adverse events were rash, unspecified hemorrhage, and purpura in HIT patients (2% each) and thrombophlebitis in HITTS patients (4%).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
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Heparin-induced thrombocytopenia, presenting as isolated thrombocytopenia (HIT) or thrombocytopenia with thrombotic complications (HITTS), is a potentially catastrophic complication of heparin therapy. For treatment of HIT/HITTS, heparin discontinuation is necessary but may not be sufficient; these patients may also require continued anticoagulation.1 9 Consequently, a safe, effective and rapidly active anticoagulant is needed for use in this setting. Argatroban, a direct thrombin inhibitor, offers several theoretical advantages as an anticoagulant for HIT/HITTS patients. It is a small, synthetic molecule that inactivates clot-bound and free thrombin and achieves steady state rapidly when administered intravenously, with a predictable dose-response effect.18 23 24 Its anticoagulant effects are rapidly reversible (elimination half-life of 39 to 51 minutes).23 Because argatroban does not resemble heparin, it does not cross-react with HIT antibodies,25 a disadvantage of low-molecular-weight heparin and danaparoid. Furthermore, being small and synthetic, argatroban does not induce formation of antibodies that can alter its clearance, a disadvantage of lepirudin.
This report describes the results of a historical-controlled trial of argatroban therapy in patients with clinically diagnosed heparin-induced thrombocytopenia. In the trial, 304 prospectively studied patients were compared with 193 historical control subjects who were accrued from the same centers and met the same inclusion/exclusion criteria as the treated patients, were deemed eligible by independent medical review, and closely matched the treated patients. By design, the trial included two separately analyzed study arms (ie, HIT and HITTS) because of uncertainty in the literature about whether patients with isolated thrombocytopenia (HIT) have different outcomes than patients with thrombocytopenia and thrombotic complications (HITTS). The primary efficacy end point, a composite of death, amputation, or new thrombosis, was selected to reflect major morbidity and mortality associated with the disease. Also, the time required for resolution of thrombocytopenia, an important marker of ongoing HIT activity, was monitored.
Although not ideal, a historical-control study design may be necessary when it is important to compare treatments, but a comparative treatment is not available. Furthermore, the participants in our trial believed that it would be unethical to use a placebo or withhold a treatment that has been shown in preliminary studies to be effective. For example, >50% of patients with isolated HIT who are treated simply by stopping heparin will have thrombosis within 30 days.1 Hence, treatment by observation or placebo was considered unacceptable, and comparison with a historical control group was used.
There are known scientific limitations with a historical comparator, including different methods of event ascertainment for historical control subjects and treated patients. Among control subjects, events may be underreported because data are initially collected for different purposes or possibly overreported because cases may have been specifically recognized as a result of their events. We attempted to minimize such bias by identifying potential control subjects by approaches such as reviewing laboratory logs of patients who were tested for HIT and were thrombocytopenic and by having control subjects (and treated patients) independently adjudicated. We also tried to limit possible event underreporting in the unblinded treatment group by having duplex Doppler examinations and ventilation/perfusion scans performed at baseline and end of the study.
Another possible concern of historical comparators is referral bias, wherein prospective patients may have more advanced illness than control subjects because of the potential for medical "watchful waiting" when an investigational agent is available. However, this bias would favor control. To try to minimize this problem, we applied the same inclusion and exclusion criteria to both groups. Changing management practices may also be an issue with historical control subjects. Herein, control subjects typically were seen within 4 years before study initiation at participating sites, and we aimed to minimize variability in practice by limiting each site to 3 control subjects per treated patient. Our overall impression is that these biases, if operational, would tend to mask, not exaggerate, the true differences between the groups.
Our study demonstrated that argatroban treatment of patients with HIT produced significant benefits in clinical outcomes and disease progression compared with historical control subjects. Specifically, argatroban therapy significantly reduced the risk of a composite of death, amputation, or new thrombosis; the risk of death caused by thrombosis; and the risk of new thrombosis. Additionally, argatroban-treated patients had a more rapid recovery of the platelet count. These benefits were realized without increased bleeding risk, compared with control subjects. Therefore, in patients with heparin-induced thrombocytopenia, argatroban is effective in lowering mortality rates from thrombosis and preventing new thrombotic events with an acceptable risk-benefit ratio. Hence, argatroban offers a therapeutic alternative for these patients in whom current options are limited.
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Appendix 1 |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
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Principal Investigator was B. Lewis.
Investigators
Y. Ahn, D. Akers, B. Alving, W. Andes, F.
Arabia, K. Ayala, H. Azar, J. Bartholomew, J. Barton, R. Baynes, J.
Bengston, S. Berkman, S.D. Berkowitz, U. Bhanja, A. Bianco, L.
Blaszkowsky, R. Bona, M. Boxer, A. Brown, J. Chang, J.
Chediak, D. Cochran, A. Cohen, M. Cohen, M. Cushman, D. Diuguid, C.
Eby, G. Elliot, D. Faig, C. Francis, J. Francis, W. Fried, D. Gabriel,
T. Gernsheimer, E. Greeno, T. Hack, W. Haire, K. Hassell, D. Hild, M.
Horne, M. Hutchins, M. Irani, I.K. Jang, S. Jubelirer, M. Juckett, C.
Kessler, A. Khan, B. Konkle, R. Lerner, L. Levitt, F. Leya, A.
Luterman, R. Lyons, D. MacFarlane, A. Makary, W. Matthai, J. McClurken,
W. McGehee, R. McKenna, R. Mena, J. Moran, G. Ortega, R. Paulson, J.
Penner, J. Perry, J. Reeves, K. Rehman, L. Rice, E. Richman, S. Rifkin,
J. Rubin, P. Rustagi, M. Santiago, N. Schacht, A. Schmaier, R. Sham, R.
Shopnick, M. Shuman, M. Shurafa, J. Siegel, M. Sobel, G. Soff, H.
Staszewski, J. Strony, M. Telfer, A. Trowbridge, D. Wallis, T. Warr, E.
Williams, A. Wiseman, J. Zehnder, Z. Zeigler, and M.
Zimmerman.
Hemostasis Core Laboratory
J. Fareed and J. Walenga.
Independent Medical Reviewers
J. Ferguson, J. Hinson, B. Khandheria, H. Kwaan, H.
Messmore, G. Pineo, and R.
Pruthi.
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Acknowledgments |
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This study was supported by Texas Biotechnology Corporation, Houston, Tex.
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Footnotes |
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Drs Lewis and Matthai received grant support from Texas Biotechnology Corporation, and both serve as consultants to SmithKline Beecham; Dr Hursting currently serves as a consultant to Texas Biotechnology Corporation, and Dr Wallis served as a consultant to Texas Biotechnology Corporation in 1988; Dr Lerner owns 1000 shares of Texas Biotechnology Corporation; and Dr Jang has previously received honoraria for giving talks about Argatroban, a drug developed and marketed by Texas Biotechnology Corporation, in conjunction with SmithKline Beecham.
Guest Editor for this article was Carl J. Pepine, MD, University of Florida College of Medicine, Gainesville.
Received September 26, 2000; revision received December 6, 2000; accepted December 29, 2000.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionAppendix 1References |
|---|
1. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101:502–507.[Medline] [Order article via Infotrieve]
2.
Brieger DB, Mak
K-H, Kottke-Marchant K, et al. Heparin-induced thrombocytopenia.
J Am Coll Cardiol. 1998;31:1449–1459.
3. Nand S, Wong W, Yuen B, et al. Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution. Am J Hematol. 1997;56:12–16.[Medline] [Order article via Infotrieve]
4.
Greinacher A,
Volpel H, Janssens U, et al, for the HIT investigators group.
Recombinant hirudin (lepirudin) provides safe and effective
anticoagulation in patients with heparin-induced thrombocytopenia: a
prospective study. Circulation. 1999;99:73–80.
5. Horsewood P, Warkentin TE, Hayward CPM, et al. The epitope specificity of heparin-induced thrombocytopenia. Br J Haematol. 1996;95:161–167.[Medline] [Order article via Infotrieve]
6. Chong BH, Fawaz I, Chesterman CN, et al. Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol. 1989;73:235–240.[Medline] [Order article via Infotrieve]
7.
Warkentin TE,
Hayward CPM, Boshkov LK, et al. Sera from patients with heparin-induced
thrombocytopenia generate platelet-derived microparticles with
procoagulant activity: an explanation for the thrombotic complications
of heparin-induced thrombocytopenia.
Blood. 1994;84:3691–3699.
8. Boshkov LK, Warkentin TE, Haywood CPM, et al. Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies. Br J Haematol. 1993;84:322–328.[Medline] [Order article via Infotrieve]
9. Wallis DE, Workman DL, Lewis BE, et al. Failure of early heparin cessation as treatment for heparin-induced thrombocytopenia. Am J Med. 1999;106:629–635.[Medline] [Order article via Infotrieve]
10. King D, Kelton JG. Heparin-induced thrombocytopenia. Ann Intern Med. 1984;100:535–540.
11.
Demers C,
Ginsberg JS, Brill-Edwards P, et al. Rapid anticoagulation using ancrod
for heparin-induced thrombocytopenia.
Blood. 1991;78:2194–2197.
12. Leroy J, Leclerc MH, Delahousse B, et al. Treatment of heparin-associated thrombocytopenia and thrombosis with low molecular weight heparin (CY216). Semin Thromb Hemost. 1985;11:326–329.[Medline] [Order article via Infotrieve]
13. Magnani HN. Heparin-induced thrombocytopenia (HIT): an overview of 230 patients treated with Orgaron (Org 10172). Thromb Haemost. 1993;70:554–561.[Medline] [Order article via Infotrieve]
14.
Greinacher A,
Janssens U, Berg G, et al, for the Heparin-Associated Thrombocytopenia
Study (HAT) investigators. Lepirudin (recombinant hirudin) for
parenteral anticoagulation in patients with heparin-induced
thrombocytopenia. Circulation. 1999;100:587–593.
15.
Warkentin TE,
Elavathil LJ, Hayward CPM, et al. The pathogenesis of venous limb
gangrene associated with heparin-induced thrombocytopenia.
Ann Intern Med. 1997;127:804–812.
16. Amiral J, Bridey F, Wolf M, et al. Antibodies to macromolecular platelet factor 4-heparin complexes in heparin-induced thrombocytopenia: a study of 44 cases. Thromb Haemost. 1995;73:21–28.[Medline] [Order article via Infotrieve]
17.
Song X, Huhle G,
Wang L, et al. Generation of anti-hirudin antibodies in heparin-induced
thrombocytopenic patients treated with r-hirudin.
Circulation. 1999;100:1528–1532.
18. Hursting MJ, Alford KL, Becker JCP, et al. NOVASTAN (brand of argatroban): a small-molecule, direct thrombin inhibitor. Semin Thromb Hemost. 1997;23:503–516.[Medline] [Order article via Infotrieve]
19. Walls JT, Curtis JJ, Silver D, et al. Heparin-induced thrombocytopenia in open heart surgical patients: sequelae of late recognition. Ann Thorac Surg. 1992;53:787–791.[Abstract]
20. Kraemer HC, Thiemann S. How Many Subjects? Statistical Power Analysis in Research. Newberry Park, Calif: Sage Publishing; 1987.
21. Pfueller SL, David R. Different platelet specificities of heparin-dependent platelet aggregating factors in heparin-associated immune thrombocytopenia. Br J Haematol. 1986;64:149–159.[Medline] [Order article via Infotrieve]
22.
Sheridan D,
Carter C, Kelton JG. A diagnostic test for heparin-induced
thrombocytopenia. Blood. 1986;67:27–30.
23. Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy. 2000;20:318–329.[Medline] [Order article via Infotrieve]
24.
Hantgan RR,
Jerome WG, Hursting MJ. No effect of clot age or
thrombolysis on argatroban’s inhibition of thrombin.
Blood. 1998;92:2064–2074.
25. Walenga JM, Koza MJ, Lewis BE, et al. Relative heparin-induced thrombocytopenic potential of low molecular weight heparins and new antithrombotic agents. Clin Appl Thromb Hemost. 1996;2(suppl 1):S21–S27.
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 A. J Ansara, S. Arif, and R. D Warhurst Weight-Based Argatroban Dosing Nomogram for Treatment of Heparin-Induced Thrombocytopenia Ann. Pharmacother., January 1, 2009; 43(1): 9 - 18. [Abstract] [Full Text] [PDF]
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S. P Keegan, E. M Gallagher, N. E Ernst, E. J Young, and E. W Mueller Effects of Critical Illness and Organ Failure on Therapeutic Argatroban Dosage Requirements in Patients with Suspected or Confirmed Heparin-Induced Thrombocytopenia Ann. Pharmacother., January 1, 2009; 43(1): 19 - 27. [Abstract] [Full Text] [PDF]
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 J. G. Kelton and T. E. Warkentin Heparin-induced thrombocytopenia: a historical perspective Blood, October 1, 2008; 112(7): 2607 - 2616. [Full Text] [PDF]
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 S. M. Begelman, S. B. Baghdasarian, I. M. Singh, M. A. Militello, M. J. Hursting, and J. R. Bartholomew Argatroban Anticoagulation in Intensive Care Patients: Effects of Heart Failure and Multiple Organ System Failure J Intensive Care Med, September 1, 2008; 23(5): 313 - 320. [Abstract] [PDF]
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 M. A. Smythe, J. M. Koerber, M. Fitzgerald, and J. C. Mattson The Financial Impact of Heparin-Induced Thrombocytopenia Chest, September 1, 2008; 134(3): 568 - 573. [Abstract] [Full Text] [PDF]
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 J. M. Walenga, A. F. Drenth, M. Mayuga, D. A. Hoppensteadt, M. Prechel, S. Harder, H. Watanabe, M. Osakabe, and H.-K. Breddin Transition From Argatroban to Oral Anticoagulation With Phenprocoumon or Acenocoumarol: Effect on Coagulation Factor Testing Clinical and Applied Thrombosis/Hemostasis, July 1, 2008; 14(3): 325 - 331. [Abstract] [PDF]
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T. E. Warkentin, A. Greinacher, A. Koster, and A. M. Lincoff Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 340S - 380S. [Abstract] [Full Text] [PDF]
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M. A. Crowther and T. E. Warkentin Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents Blood, May 15, 2008; 111(10): 4871 - 4879. [Abstract] [Full Text] [PDF]
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W. D Hoffman, Y. Czyz, D. A McCollum, and M. J Hursting Reduced Argatroban Doses After Coronary Artery Bypass Graft Surgery Ann. Pharmacother., March 1, 2008; 42(3): 309 - 316. [Abstract] [Full Text] [PDF]
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 S. Fugate and J. Chiappe Standardizing the management of heparin-induced thrombocytopenia Am. J. Health Syst. Pharm., February 15, 2008; 65(4): 334 - 339. [Abstract] [Full Text] [PDF]
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A. Gray, D. E. Wallis, M. J. Hursting, E. Katz, and B. E. Lewis Argatroban Therapy for Heparin-Induced Thrombocytopenia in Acutely Ill Patients Clinical and Applied Thrombosis/Hemostasis, October 1, 2007; 13(4): 353 - 361. [Abstract] [PDF]
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 J. H. Levy, K. A. Tanaka, and M. J. Hursting Reducing Thrombotic Complications in the Perioperative Setting: An Update on Heparin-Induced Thrombocytopenia Anesth. Analg., September 1, 2007; 105(3): 570 - 582. [Abstract] [Full Text] [PDF]
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 I Ahmed, A Majeed, and R Powell Heparin induced thrombocytopenia: diagnosis and management update Postgrad. Med. J., September 1, 2007; 83(983): 575 - 582. [Abstract] [Full Text] [PDF]
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 L. Rice, M. J. Hursting, G. M. Baillie, and D. A. McCollum Argatroban Anticoagulation in Obese Versus Nonobese Patients: Implications for Treating Heparin-induced Thrombocytopenia J. Clin. Pharmacol., August 1, 2007; 47(8): 1028 - 1034. [Full Text] [PDF]
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 B. P. Dickinson and P. F. Lawrence Bilateral Lower Extremity Gangrene Requiring Amputation Associated With Heparin-Induced Thrombocytopenia: A Case Report Angiology, April 1, 2007; 58(2): 234 - 237. [Abstract] [PDF]
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 H. G Watson and M. Greaves Review: New anticoagulants: a story of promise and disappointment The British Journal of Diabetes & Vascular Disease, March 1, 2007; 7(2): 51 - 58. [Abstract] [PDF]
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R. L. Levine, D. McCollum, and M. J. Hursting How frequently is venous thromboembolism in heparin-treated patients associated with heparin-induced thrombocytopenia? Chest, September 1, 2006; 130(3): 681 - 687. [Abstract] [Full Text] [PDF]
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 G. M. Arepally and T. L. Ortel Heparin-Induced Thrombocytopenia N. Engl. J. Med., August 24, 2006; 355(8): 809 - 817. [Full Text] [PDF]
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T. W. Warkentin Thrombotic End Point for Assessing Argatroban Therapy for Heparin-Induced Thrombocytopenia: Learning From Secondary Analyses of Prospective Studies Chest, June 1, 2006; 129(6): 1396 - 1398. [Full Text] [PDF]
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B. E. Lewis, D. E. Wallis, M. J. Hursting, R. L. Levine, and F. Leya Effects of Argatroban Therapy, Demographic Variables, and Platelet Count on Thrombotic Risks in Heparin-Induced Thrombocytopenia Chest, June 1, 2006; 129(6): 1407 - 1416. [Abstract] [Full Text] [PDF]
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R. L. Levine, M. J. Hursting, and D. McCollum Argatroban Therapy in Heparin-Induced Thrombocytopenia With Hepatic Dysfunction Chest, May 1, 2006; 129(5): 1167 - 1175. [Abstract] [Full Text] [PDF]
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S. Kodityal, P. H. Nguyen, A. Kodityal, J. Sherer, M. J. Hursting, and L. Rice Argatroban for Suspected Heparin-Induced Thrombocytopenia: Contemporary Experience at a Large Teaching Hospital J Intensive Care Med, March 1, 2006; 21(2): 86 - 92. [Abstract] [PDF]
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B. P. Dickinson, D. A. De Ugarte, T. D. Reil, B. D. Beseth, and P. F. Lawrence Bilateral Lower Extremity Gangrene Requiring Amputation Associated with Heparin-Induced Thrombocytopenia: A Case Report Vascular and Endovascular Surgery, March 1, 2006; 40(2): 161 - 164. [Abstract] [PDF]
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M. A. Smythe, J. L. Stephens, J. M. Koerber, and J. C. Mattson A Comparison of Lepirudin and Argatroban Outcomes Clinical and Applied Thrombosis/Hemostasis, October 1, 2005; 11(4): 371 - 374. [Abstract] [PDF]
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B. V Reddy, E. J Grossman, S. A Trevino, M. J Hursting, and P. T Murray Argatroban Anticoagulation in Patients with Heparin-Induced Thrombocytopenia Requiring Renal Replacement Therapy Ann. Pharmacother., October 1, 2005; 39(10): 1601 - 1605. [Abstract] [Full Text] [PDF]
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M. Di Nisio, S. Middeldorp, and H. R. Buller Direct Thrombin Inhibitors N. Engl. J. Med., September 8, 2005; 353(10): 1028 - 1040. [Full Text] [PDF]
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M. J. Hursting, B. E. Lewis, and D. E. Macfarlane Transitioning from Argatroban to Warfarin Therapy in Patients with Heparin-induced Thrombocytopenia Clinical and Applied Thrombosis/Hemostasis, July 1, 2005; 11(3): 279 - 287. [Abstract] [PDF]
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 I.-K. Jang and M. J. Hursting When Heparins Promote Thrombosis: Review of Heparin-Induced Thrombocytopenia Circulation, May 24, 2005; 111(20): 2671 - 2683. [Full Text] [PDF]
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R. L. Levine Finding Haystacks Full of Needles: From Opus to Osler Chest, May 1, 2005; 127(5): 1488 - 1490. [Full Text] [PDF]
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 F. G. Bakaeen, J.-C. M. Walkes, and M. J. Reardon Heparin-Induced Thrombocytopenia Associated With Bilateral Adrenal Hemorrhage After Coronary Artery Bypass Surgery Ann. Thorac. Surg., April 1, 2005; 79(4): 1388 - 1390. [Abstract] [Full Text] [PDF]
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C. Verme-Gibboney, J. W. Dubb, S. A. Spinler, and A. Greinacher Direct thrombin inhibitors in heparin-induced thrombocytopenia Am. J. Health Syst. Pharm., February 1, 2005; 62(3): 247 - 250. [Full Text] [PDF]
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K. Hassell The Management of Patients With Heparin-Induced Thrombocytopenia Who Require Anticoagulant Therapy Chest, February 1, 2005; 127(2_suppl): 1S - 8S. [Abstract] [Full Text] [PDF]
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J. G. Kelton The Pathophysiology of Heparin-Induced Thrombocytopenia: Biological Basis for Treatment Chest, February 1, 2005; 127(2_suppl): 9S - 20S. [Full Text] [PDF]
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L. Rice Cases of Heparin-Induced Thrombocytopenia Elucidate the Syndrome Chest, February 1, 2005; 127(2_suppl): 21S - 26S. [Abstract] [Full Text] [PDF]
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W. H. Matthai Jr Thrombocytopenia in Cardiovascular Patients: Diagnosis and Management Chest, February 1, 2005; 127(2_suppl): 46S - 52S. [Abstract] [Full Text] [PDF]
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I. Y Tang, D. S Cox, K. Patel, B. V Reddy, L. Nahlik, S. Trevino, and P. T Murray Argatroban and Renal Replacement Therapy in Patients with Heparin-Induced Thrombocytopenia Ann. Pharmacother., February 1, 2005; 39(2): 231 - 236. [Abstract] [Full Text] [PDF]
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J. Hirsh, M. O'Donnell, and J. I. Weitz New anticoagulants Blood, January 15, 2005; 105(2): 453 - 463. [Abstract] [Full Text] [PDF]
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B. Kemkes-Matthes, J. M. Walenga, J. Harenberg, and J. Fareed Argatroban Treatment for Patients with Intoleranceto Heparin and Hirudin Clinical and Applied Thrombosis/Hemostasis, January 1, 2005; 11(1): 99 - 103. [Abstract] [PDF]
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 A. T. Gurbuz, W. G. Elliott, and A. A. Zia Heparin-induced thrombocytopenia in the cardiovascular patient: diagnostic and treatment guidelines Eur. J. Cardiothorac. Surg., January 1, 2005; 27(1): 138 - 149. [Abstract] [Full Text] [PDF]
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K. A. Tanaka, F. Szlam, N. Katori, N. Sato, J. D. Vega, and J. H. Levy The Effects of Argatroban on Thrombin Generation and Hemostatic Activation In Vitro Anesth. Analg., November 1, 2004; 99(5): 1283 - 1289. [Abstract] [Full Text] [PDF]
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 L. Rice Heparin-Induced Thrombocytopenia: Myths and Misconceptions (That Will Cause Trouble for You and Your Patient) Arch Intern Med, October 11, 2004; 164(18): 1961 - 1964. [Full Text] [PDF]
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M. A. Smythe and A. Caffee Anticoagulation Monitoring Journal of Pharmacy Practice, October 1, 2004; 17(5): 317 - 326. [Abstract] [PDF]
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M. A. Smythe, W. E. Dager, and N. M. Patel Managing Complications of Anticoagulant Therapy Journal of Pharmacy Practice, October 1, 2004; 17(5): 327 - 346. [Abstract] [PDF]
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 G. Young, K. E Yonekawa, P. Nakagawa, and D. J Nugent Argatroban as an alternative to heparin in extracorporeal membrane oxygenation circuits Perfusion, September 1, 2004; 19(5): 283 - 288. [Abstract] [PDF]
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D. S. Cox, N. S. Kleiman, D. A. Boyle, J. Aluri, L. G. Parchman, F. Holdbrook, and M. J. Fossler Pharmacokinetics and Pharmacodynamics of Argatroban in Combination With a Platelet Glycoprotein IIB/IIIA Receptor Antagonist in Patients Undergoing Percutaneous Coronary Intervention J. Clin. Pharmacol., September 1, 2004; 44(9): 981 - 990. [Abstract] [Full Text] [PDF]
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T. E. Warkentin and A. Greinacher Heparin-Induced Thrombocytopenia: Recognition, Treatment, and Prevention: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 311S - 337S. [Abstract] [Full Text] [PDF]
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R. A. Harrington, R. C. Becker, M. Ezekowitz, T. W. Meade, C. M. O'Connor, D. A. Vorchheimer, and G. H. Guyatt Antithrombotic Therapy for Coronary Artery Disease: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 513S - 548S. [Abstract] [Full Text] [PDF]
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 M. P. LaMonte, M. L. Nash, D. Z. Wang, A. R. Woolfenden, J. Schultz, M. J. Hursting, P. M. Brown, and for the ARGIS-1 Investigators Argatroban Anticoagulation in Patients With Acute Ischemic Stroke (ARGIS-1): A Randomized, Placebo-Controlled Safety Study Stroke, July 1, 2004; 35(7): 1677 - 1682. [Abstract] [Full Text] [PDF]
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K. Rikitake, Y. Okazaki, K. Naito, S. Ohtsubo, M. Natsuaki, and T. Itoh Heparinless cardiopulmonary bypass with argatroban in dogs Eur. J. Cardiothorac. Surg., May 1, 2004; 25(5): 819 - 824. [Abstract] [Full Text] [PDF]
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J. Hirsh, N. Heddle, and J. G. Kelton Treatment of Heparin-Induced Thrombocytopenia: A Critical Review Arch Intern Med, February 23, 2004; 164(4): 361 - 369. [Abstract] [Full Text] [PDF]
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 J. Martchenke, M. F. D. Pate, M. Cruz, and S. Phromsivarak What is the incidence of heparin-induced thrombocytopenia (HIT) in children? Crit. Care Nurse, February 1, 2004; 24(1): 66 - 67. [Full Text] [PDF]
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E. A Nutescu and A. K Wittkowsky Direct Thrombin Inhibitors for Anticoagulation Ann. Pharmacother., January 1, 2004; 38(1): 99 - 109. [Abstract] [Full Text] [PDF]
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S. Z. Goldhaber and C. G. Elliott Acute Pulmonary Embolism: Part II: Risk Stratification, Treatment, and Prevention Circulation, December 9, 2003; 108(23): 2834 - 2838. [Full Text] [PDF]
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K. W. Cleveland Argatroban: A New Treatment Option for Heparin-Induced Thrombocytopenia Crit. Care Nurse, December 1, 2003; 23(6): 61 - 66. [Full Text] [PDF]
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 A. Koster and T. Fischer Management of Patients with Heparin-Induced Thrombocytopenia During Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, December 1, 2003; 7(4): 411 - 416. [Abstract] [PDF]
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 A. Leo and S. Winteroll Laboratory Diagnosis of Heparin-Induced Thrombocytopenia and Monitoring of Alternative Anticoagulants Clin. Vaccine Immunol., September 1, 2003; 10(5): 731 - 740. [Full Text] [PDF]
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W. E Dager and R. H White Argatroban for Heparin-Induced Thrombocytopenia in Hepato-Renal Failure and CVVHD Ann. Pharmacother., September 1, 2003; 37(9): 1232 - 1236. [Abstract] [Full Text] [PDF]
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B. E. Lewis, D. E. Wallis, F. Leya, M. J. Hursting, and J. G. Kelton Argatroban Anticoagulation in Patients With Heparin-Induced Thrombocytopenia Arch Intern Med, August 11, 2003; 163(15): 1849 - 1856. [Abstract] [Full Text] [PDF]
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 K. Ota, T. Akizawa, Y. Hirasawa, T. Agishi, and N. Matsui Effects of argatroban as an anticoagulant for haemodialysis in patients with antithrombin III deficiency Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1623 - 1630. [Abstract] [Full Text] [PDF]
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C. N Verme-Gibboney and M. J Hursting Argatroban Dosing in Patients with Heparin-Induced Thrombocytopenia Ann. Pharmacother., July 1, 2003; 37(7): 970 - 975. [Abstract] [Full Text] [PDF]
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 E. Pravinkumar and N. R. Webster HIT/HITT and alternative anticoagulation: current concepts Br. J. Anaesth., May 1, 2003; 90(5): 676 - 685. [Abstract] [Full Text] [PDF]
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J. F. Schenk, G. Pindur, B. Stephan, S. Mursdorf, F. Mertzlufft, H. Kroll, E. Wenzel, and U. T. Seyfert On the Prophylactic and Therapeutic Use of Danaparoid Sodium (Orgaran(R)) in Patients With Heparin-Induced Thrombocytopenia Clinical and Applied Thrombosis/Hemostasis, January 1, 2003; 9(1): 25 - 32. [Abstract] [PDF]
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W. J DeBois, J. Liu, L. Y Lee, L. N Girardi, C. Mack, A. Tortolani, K. H Krieger, and O W. Isom Diagnosis and treatment of heparin-induced thrombocytopenia Perfusion, January 1, 2003; 18(1): 47 - 53. [Abstract] [PDF]
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 T. E. Warkentin, W. C. Aird, and J. H. Rand Platelet-Endothelial Interactions: Sepsis, HIT, and Antiphospholipid Syndrome Hematology, January 1, 2003; 2003(1): 497 - 519. [Abstract] [Full Text] [PDF]
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B. M. Alving, C. W. Francis, W. R. Hiatt, and M. R. Jackson Consultations on Patients with Venous or Arterial Diseases Hematology, January 1, 2003; 2003(1): 540 - 558. [Abstract] [Full Text] [PDF]
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B. M. Alving How I treat heparin-induced thrombocytopenia and thrombosis Blood, January 1, 2003; 101(1): 31 - 37. [Full Text] [PDF]
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 T. Fenyvesi, I. Joerg, and J. Harenberg Influence of Lepirudin, Argatroban, and Melagatran on Prothrombin Time and Additional Effect of Oral Anticoagulation Clin. Chem., October 1, 2002; 48(10): 1791 - 1794. [Full Text] [PDF]
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S. K. Young New Treatment Options for Heparin-Induced Thrombocytopenia Journal of Pharmacy Practice, August 1, 2002; 15(4): 305 - 317. [Abstract] [PDF]
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O. Iqbal, S. Ahmad, B. E. Lewis, J. M. Walenga, Y. Rangel, and J. Fareed Monitoring of Argatroban in ARG310 Study: Potential Recommendations for its Use in Interventional Cardiology Clinical and Applied Thrombosis/Hemostasis, July 1, 2002; 8(3): 217 - 224. [Abstract] [PDF]
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N. Lubenow, R. Kempf, A. Eichner, P. Eichler, L. E. Carlsson, and A. Greinacher Heparin-Induced Thrombocytopenia* : Temporal Pattern of Thrombocytopenia in Relation to Initial Use or Reexposure to Heparin Chest, July 1, 2002; 122(1): 37 - 42. [Abstract] [Full Text] [PDF]
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L. Mureebe and D. Silver Heparin-Induced Thrombocytopenia: Pathophysiology and Management Vascular and Endovascular Surgery, May 1, 2002; 36(3): 163 - 170. [Abstract] [PDF]
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K. R. McCrae, J. B. Bussel, P. M. Mannucci, G. Remuzzi, and D. B. Cines Platelets: An Update on Diagnosis and Management of Thrombocytopenic Disorders Hematology, January 1, 2001; 2001(1): 282 - 305. [Abstract] [Full Text] [PDF]
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