Analysis of the prospective validation cohort (January 2017 to November 2019; n = 687): CLIA HIT-IgG testing with intermediate gray zone results according to Figure 2 (n = 111 of 687 [16.2%])
| CLIA HIT-IgG . | ID-PaGIA-H/PF4 . | 4T score . | Posttest probability . | Clinical prediction . | HIPA . | Conclusion (n) . | |||
|---|---|---|---|---|---|---|---|---|---|
| U/mL . | N . | Titer . | N . | Pretest probability . | n . | P (95% CI) . | HIT . | ||
| 0.13 to <0.33 | 62 | Negative | 30 | Low | 9 | 0% (0-0) | Excluded | 4 negative, 5 n.d. | Accurately excluded (4), excluded by algorithm (5) |
| Intermediate | 20 | 0% (0-2) | Excluded | 5 negative, 15 n.d. | Accurately excluded (5), excluded by algorithm (15) | ||||
| High | 1 | 0% (0-17) | Excluded | Negative | Accurately excluded (1) | ||||
| 1 | 19 | Low | 6 | 0% (0-0) | Excluded | Negative | Accurately excluded (6) | ||
| Intermediate | 12 | 0% (0-2) | Excluded | 11 negative, 1 n.d. | Accurately excluded (11), excluded by algorithm (1) | ||||
| High | 1 | 0% (0-17) | Excluded | Negative | Accurately excluded (1) | ||||
| 2 | 7 | Low | 3 | 0% (0-0) | Excluded | Negative | Accurately excluded (3) | ||
| Intermediate | 3 | 3% (0-18) | Excluded | Negative | Accurately excluded (3) | ||||
| High | 1 | 24% (4-70) | Undetermined | Negative | Solved by HIPA (1) | ||||
| 4 | 4 | Low | 1 | 0% (0-1) | Excluded | Negative | Accurately excluded (1) | ||
| Intermediate | 3 | 29% (13-53) | Undetermined | Negative | Solved by HIPA (3) | ||||
| 8 | 1 | Low | 1 | 4% (1-12) | Undetermined | Negative | Solved by HIPA (1) | ||
| 16 | 1 | High | 1 | 100% (96-100) | Predicted | Negative* | Possibly false-positive prediction (1) | ||
| 0.33 to <1.00 | 28 | Negative | 8 | Low | 4 | 0% (0-0) | Excluded | 3 negative, 1 n.d. | Accurately excluded (3), excluded by algorithm (1) |
| Intermediate | 4 | 0% (0-9) | Excluded | 2 negative, 2 n.d. | Accurately excluded (2), excluded by algorithm (2) | ||||
| 1 | 4 | Intermediate | 4 | 0% (0-9) | Excluded | Negative | Accurately excluded (4) | ||
| 2 | 6 | Low | 1 | 0% (0-0) | Excluded | Negative | Accurately excluded (1) | ||
| Intermediate | 4 | 14% (2-55) | Undetermined | 3 negative, 1 atypical† | Solved by HIPA (3), not solved by HIPA (1) | ||||
| High | 1 | 65% (20-93) | Undetermined | Negative | Solved by HIPA (1) | ||||
| 4 | 3 | Intermediate | 2 | 70% (46-86) | Undetermined | Negative | Solved by HIPA (2) | ||
| High | 1 | 96% (91-99) | Predicted | Positive‡ | Accurately predicted (1) | ||||
| 8 | 4 | Intermediate | 4 | 95% (80-99) | Predicted | 2 positive‡, 2 negative§ | Accurately predicted (2), probably accurate prediction (1), possible false-positive prediction (1) | ||
| 16 | 1 | Intermediate | 1 | 100% (93-100) | Predicted | Positive‡ | Accurately predicted (1) | ||
| >16 | 2 | Intermediate | 1 | 100% (93-100) | Predicted | Negativeǁ | Probably accurate prediction (1) | ||
| High | 1 | 100% (99-100) | Predicted | Negativeǁ | Probably accurate prediction (1) | ||||
| 1.00 to 3.00 | 21 | Negative | 1 | Low | 1 | 0% (0-2) | Excluded | Negative | Accurately excluded (1) |
| 1 | 5 | Low | 3 | 0% (0-2) | Excluded | Negative | Accurately excluded (3) | ||
| Intermediate | 1 | 0% (0-65) | Excluded | Negative | Accurately excluded (1) | ||||
| High | 1 | 0% (0-95%) | Undetermined | Negative | Solved by HIPA (1) | ||||
| 2 | 2 | Low | 1 | 4% (1-22) | Undetermined | Negative | Solved by HIPA (1) | ||
| Intermediate | 1 | 76% (30-96) | Predicted | Positive | Accurately predicted (1) | ||||
| 4 | 7 | Low | 3 | 35% (17-59) | Undetermined | 1 positive, 2 negative | Solved by HIPA (3) | ||
| Intermediate | 3 | 98% (94-99) | Predicted | 1 positive, 2 negativeǁ | Accurately predicted (1), probably accurate prediction (2) | ||||
| High | 1 | 100% (99-100%) | Predicted | Negativeǁ | Probably accurate prediction (1) | ||||
| 8 | 3 | Intermediate | 1 | 100% (99-100) | Predicted | Positive | Accurately predicted (1) | ||
| High | 2 | 100% (100-100) | Predicted | Negativeǁ | Probably accurate prediction (2) | ||||
| 16 | 2 | High | 2 | 100% (100-100) | Predicted | Positive | Accurately predicted (2) | ||
| >16 | 1 | High | 1 | 100% (100-100) | Predicted | Positive | Accurately predicted (1) | ||
| CLIA HIT-IgG . | ID-PaGIA-H/PF4 . | 4T score . | Posttest probability . | Clinical prediction . | HIPA . | Conclusion (n) . | |||
|---|---|---|---|---|---|---|---|---|---|
| U/mL . | N . | Titer . | N . | Pretest probability . | n . | P (95% CI) . | HIT . | ||
| 0.13 to <0.33 | 62 | Negative | 30 | Low | 9 | 0% (0-0) | Excluded | 4 negative, 5 n.d. | Accurately excluded (4), excluded by algorithm (5) |
| Intermediate | 20 | 0% (0-2) | Excluded | 5 negative, 15 n.d. | Accurately excluded (5), excluded by algorithm (15) | ||||
| High | 1 | 0% (0-17) | Excluded | Negative | Accurately excluded (1) | ||||
| 1 | 19 | Low | 6 | 0% (0-0) | Excluded | Negative | Accurately excluded (6) | ||
| Intermediate | 12 | 0% (0-2) | Excluded | 11 negative, 1 n.d. | Accurately excluded (11), excluded by algorithm (1) | ||||
| High | 1 | 0% (0-17) | Excluded | Negative | Accurately excluded (1) | ||||
| 2 | 7 | Low | 3 | 0% (0-0) | Excluded | Negative | Accurately excluded (3) | ||
| Intermediate | 3 | 3% (0-18) | Excluded | Negative | Accurately excluded (3) | ||||
| High | 1 | 24% (4-70) | Undetermined | Negative | Solved by HIPA (1) | ||||
| 4 | 4 | Low | 1 | 0% (0-1) | Excluded | Negative | Accurately excluded (1) | ||
| Intermediate | 3 | 29% (13-53) | Undetermined | Negative | Solved by HIPA (3) | ||||
| 8 | 1 | Low | 1 | 4% (1-12) | Undetermined | Negative | Solved by HIPA (1) | ||
| 16 | 1 | High | 1 | 100% (96-100) | Predicted | Negative* | Possibly false-positive prediction (1) | ||
| 0.33 to <1.00 | 28 | Negative | 8 | Low | 4 | 0% (0-0) | Excluded | 3 negative, 1 n.d. | Accurately excluded (3), excluded by algorithm (1) |
| Intermediate | 4 | 0% (0-9) | Excluded | 2 negative, 2 n.d. | Accurately excluded (2), excluded by algorithm (2) | ||||
| 1 | 4 | Intermediate | 4 | 0% (0-9) | Excluded | Negative | Accurately excluded (4) | ||
| 2 | 6 | Low | 1 | 0% (0-0) | Excluded | Negative | Accurately excluded (1) | ||
| Intermediate | 4 | 14% (2-55) | Undetermined | 3 negative, 1 atypical† | Solved by HIPA (3), not solved by HIPA (1) | ||||
| High | 1 | 65% (20-93) | Undetermined | Negative | Solved by HIPA (1) | ||||
| 4 | 3 | Intermediate | 2 | 70% (46-86) | Undetermined | Negative | Solved by HIPA (2) | ||
| High | 1 | 96% (91-99) | Predicted | Positive‡ | Accurately predicted (1) | ||||
| 8 | 4 | Intermediate | 4 | 95% (80-99) | Predicted | 2 positive‡, 2 negative§ | Accurately predicted (2), probably accurate prediction (1), possible false-positive prediction (1) | ||
| 16 | 1 | Intermediate | 1 | 100% (93-100) | Predicted | Positive‡ | Accurately predicted (1) | ||
| >16 | 2 | Intermediate | 1 | 100% (93-100) | Predicted | Negativeǁ | Probably accurate prediction (1) | ||
| High | 1 | 100% (99-100) | Predicted | Negativeǁ | Probably accurate prediction (1) | ||||
| 1.00 to 3.00 | 21 | Negative | 1 | Low | 1 | 0% (0-2) | Excluded | Negative | Accurately excluded (1) |
| 1 | 5 | Low | 3 | 0% (0-2) | Excluded | Negative | Accurately excluded (3) | ||
| Intermediate | 1 | 0% (0-65) | Excluded | Negative | Accurately excluded (1) | ||||
| High | 1 | 0% (0-95%) | Undetermined | Negative | Solved by HIPA (1) | ||||
| 2 | 2 | Low | 1 | 4% (1-22) | Undetermined | Negative | Solved by HIPA (1) | ||
| Intermediate | 1 | 76% (30-96) | Predicted | Positive | Accurately predicted (1) | ||||
| 4 | 7 | Low | 3 | 35% (17-59) | Undetermined | 1 positive, 2 negative | Solved by HIPA (3) | ||
| Intermediate | 3 | 98% (94-99) | Predicted | 1 positive, 2 negativeǁ | Accurately predicted (1), probably accurate prediction (2) | ||||
| High | 1 | 100% (99-100%) | Predicted | Negativeǁ | Probably accurate prediction (1) | ||||
| 8 | 3 | Intermediate | 1 | 100% (99-100) | Predicted | Positive | Accurately predicted (1) | ||
| High | 2 | 100% (100-100) | Predicted | Negativeǁ | Probably accurate prediction (2) | ||||
| 16 | 2 | High | 2 | 100% (100-100) | Predicted | Positive | Accurately predicted (2) | ||
| >16 | 1 | High | 1 | 100% (100-100) | Predicted | Positive | Accurately predicted (1) | ||
n.d., not done.
Negative HIPA and ELISA under ongoing combined therapy with acetylsalicylic acid and clopidogrel might have missed the diagnosis of HIT (PV-17.099; supplemental Table 5).
Heparin-dependent and independent aggregation.
False-negative CLIA HIT-IgG according to the recommended cutoff (supplemental Table 4).
One might be a false-negative HIPA test: positive ELISA inhibited by high-dose heparin, clinical course suggestive of HIT (PV-18.053; supplemental Table 5). The other might be a false-positive algorithm prediction: negative ELISA, negative HIPA (PV-19.295; supplemental Table 5).
ǁMight be a false-negative HIPA testing: positive ELISA inhibited by high-dose heparin, clinical course suggestive of HIT (PV-18.098, PV-18.123, PV-19.037, PV-19-111, PV-19.184, PV-19-230, and PV-19.264; supplemental Table 5).