Assessment of Study Drug-Related
Definitions
For SRA+ patients, the day of onset of HIT was the first day of HIT-related platelet count decline or of HIT-associated thrombosis, assessed in relation to the presumed immunizing heparin exposure (generally, the first in-hospital heparin exposure, whether open label or study drug [ = day 0]). HIT-associated thrombosis was any proven venous or arterial thrombosis that occurred in an SRA+ patient on/after day 5 after immunizing heparin exposure. An HIT-associated anaphylactoid reaction was defined as any of the following occurring within 30 min of an IV bolus of heparin: chills/fever, flushing, dyspnea, or cardiorespiratory arrest.
Plausible study drug-related seroconversion was defined as SRA+ status that could reasonably have been associated with the administration of the study drug (ie, administration of the study drug occurred > 5 days prior to the SRA+ status and associated onset of HIT). Confounding heparin was defined as any documented open-label prophylactic or therapeutic-dose heparin that could have also plausibly explained the patient’s SRA+ status. Plausible study drug-related breakthrough of thrombocytopenia and/or thrombosis was defined by an HIT-associated platelet count fall and/or by thrombosis that occurred while receiving the study drug.
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Data Analysis
Table 1 describes how the study drug-related seroconversion and study drug-related thrombocytopenia/thrombosis breakthrough of HIT were analyzed. To examine whether there may have been a lower risk of anti-PF4/heparin antibody seroconversion with dalteparin vs UFH, we determined the frequency of anti-PF4/hep-arm antibodies by SRA and both ELISAs among all 409 patients
Table 1—Assessment of Study Drug-Related Seroconversion to SRA+ Status and Study Drug-Related Breakthrough of Thrombocytopenia and/or Thrombosis tested in the central laboratory. UFH exposure in catheters (eg, heparin flushes) was not considered when evaluating study-drug related seroconversion and breakthrough of HIT because of its minor expected contributory role compared Viagra in Canada with the substantially larger exposures through prophylactic- and therapeutic-dose exposures required to reach stoichiometrically optimal immunizing concentrations of heparin.
Points | Definition |
Seroconversion | |
0 | No possible role of study drug in seroconversion (ie, SRA+ status and associated HIT onset occurred < 5 d after first administration of study drug) |
1 | Plausible role of study drug in explaining seroconversion but was confounded by open-label heparin that could also plausibly explain seroconversion |
2 | Plausible role of study drug in explaining seroconversion and associated onset of HIT, with no confounding by open-label heparin. |
Breakthrough | |
0 | Unlikely role of study drug in explaining breakthrough (eg, study drug had already been stopped for > 24 h when HIT-related event began) |
1 | Plausible role of study drug in explaining breakthrough (ie, platelet count fall and/or thrombotic event[s] occurred while receiving study drug, but was confounded by administration of open-label heparin) |
2 | Plausible role of study drug in explaining breakthrough, but with no confounding by open-label heparin |
HIT = heparin-induced thrombocytopenia; SRA+ = serotonin-release assay positive.