Pooled diagnostic accuracy measures of different classes of immunoassays for diagnosis of HIT
| Type of test . | No. studies; no. patients* . | Statistical model . | Sens. (%) . | Spec. (%) . | LR . | Posttest probability of pos. test result . | Posttest probability of neg. test result . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pos. (95% CI) . | Neg. (95% CI) . | 1% Prev. . | 7% Prev. . | 15% Prev. . | 1% Prev. . | 7% Prev. . | 15% Prev. . | |||||
| Polyspecific ELISA | ||||||||||||
| LT16,19,20,28,39,41,43,44,46,47,49-54,59-61,63,64,68,69,71,74,75,77-79 | 31; 8933 | Unified† | 96.7 (89.7, 99.0) | 86.8 (82.0, 90.5) | 7.3 (5.4-10.0) | 0.04 (0.01- 0.12) | 6.9 (5.1, 9.2) | 35.5 (28.9, 42.9) | 56.3 (48.9, 63.8) | 0.0 (0.0, 0.1) | 0.3 (0.1, 0.9) | 0.7 (0.2, 2.1) |
| IT19,47,61,65,77 | 5; 2334 | Unified† | 98.4 (90.8, 99.7) | 94.9 (90.5, 97.3) | 19.3 (10.4-36.0) | 0.02 (0.00-0.1) | 16.3 (9.5, 26.7) | 59.2 (43.9, 73.0) | 77.3 (64.7, 86.4) | 0.0 (0.0, 0.1) | 0.1 (0.0, 0.7) | 0.4 (0.0, 1.7) |
| HT19,39,47 | 3; 1014 | Fixed effects‡ | 15.0 (14.5, 15.5) | 100 (99.3, 100) | 73.4 (28.2-190.9) | 0.3 (0.2-0.5) | 42.6 (22.2, 65.9) | 84.7 (68.0, 93.5) | 92.8 (83.3, 97.1) | 0.3 (0.2, 0.5) | 2.2 (1.5, 3.6) | 5.0 (3.4, 8.1) |
| IgG-specific ELISA | ||||||||||||
| LT19,20,44,55,63,64,66,69-72,77 | 12; 3116 | Unified† | 98.3 (95.1, 99.4) | 85.4 (78.2, 90.6) | 6.7 (4.5-10.2) | 0.02 (0.01-0.05) | 6.3 (4.3, 9.3) | 33.5 (25.3, 43.4) | 54.2 (44.3, 64.3) | 0.0 (0.0, 0.1) | 0.2 (0.1, 0.4) | 0.4 (0.2, 0.9) |
| IT19,20,77 | 4; 2545 | Unified† | 91.2 (86.2, 94.5) | 93.5 (89.1-96.2) | 14.1 (8.1-24.5) | 0.09 (0.05-0.15) | 12.5 (7.6, 19.8) | 51.5 (38.0, 64.8) | 71.3 (58.9, 81.2) | 0.1 (0.1, 0.2) | 0.7 (0.4, 1.1) | 1.6 (1.0, 2.6) |
| HT19 | 2; 1958 | Fixed effects‡ | 60.9 (59.7, 62.1) | 99.4 (97.6-100) | 97.0 (53.0-177.6) | 0.4 (0.3-0.5) | 49.5 (34.9, 64.2) | 88.0 (80.0, 93.0) | 94.5 (90.3, 96.9) | 0.4 (0.3, 0.5) | 2.9 (2.2, 3.6) | 6.6 (5.0, 8.1) |
| PaGIA | ||||||||||||
| LT20,36,42,45,46,53,58,64,68,70,72,75,79 | 12; 2205 | Unified† | 96.5 (89.8, 98.9) | 93.7 (83.1, 97.8) | 15.3 (5.5, 42.3) | 0.04 (0.01, 0.11) | 13.4 (5.3, 29.9) | 53.5 (29.3, 76.1) | 73.0 (49.3, 88.2) | 0.0 (0.0, 0.1) | 0.3 (0.1, 0.8) | 0.7 (0.2, 1.8) |
| IT65 | 1; 1291 | None§ | 98.9 | 95.9 | 24.1 | 0.01 | 19.6 | 64.5 | 81.0 | 0.0 | 0.1 | 0.2 |
| Lateral flow immunoassay54-56,58,66,70,72 | 7; 1163 | Unified† | 98.4 (85.3, 99.9) | 90.3 (84.4, 94.1) | 10.1 (6.2, 16.5) | 0.02 (0.00, 0.18) | 9.3 (5.9, 14.3) | 43.3 (31.9, 55.4) | 64.2 (52.4, 74.5) | 0.0 (0.0, 0.2) | 0.1 (0.0, 1.3) | 0.3 (0.0, 3.0) |
| PIFA28 | 1; 88 | None§ | 0.0 | 70.1 | 2.3 | 0.5 | 2.3 | 14.8 | 28.9 | 0.5 | 3.6 | 8.1 |
| Latex agglutination assay37 | 1; 119 | None§ | 100.0 | 84.3 | 3.7 | 0.0 | 3.6 | 21.8 | 39.5 | 0.0 | 0.0 | 0.0 |
| Polyspecific CLIA | ||||||||||||
| LT37,38,57,61,62,77 | 7; 1008 | Unified† | 98.9 (92.7, 99.8) | 85.6 (79.3, 90.3) | 6.9 (4.7-10.0) | 0.01 (0.00-0.09) | 6.5 (4.5, 9.2) | 34.2 (26.1, 42.9) | 54.9 (45.4, 63.8) | 0.0 (0.0, 0.1) | 0.1 (0.0, 0.7) | 0.2 (0.0, 1.6) |
| IT37 | 2; 448 | Fixed effects‡ | 97.9 (94.6, 100.0) | 93.1 (90.4, 95.8) | 13.5 (9.5-18.9) | 0.0 (0.0-0.1) | 12.0 (8.8, 16.0) | 50.4 (41.7, 58.7) | 70.4 (62.6, 76.9) | 0.0 (0.0, 0.1) | 0.0 (0.0, 0.7) | 0.0 (0.0, 1.7) |
| HT37,61,62,77 | 5; 755 | Unified† | 98.3 (69.5, 99.9) | 97.5 (94.4, 98.9) | 39.5 (17.5-89.2) | 0.0 (0.0-0.40) | 28.5 (15.0, 47.6) | 74.8 (56.8, 87.1) | 87.5 (75.5, 94.1) | 0.0 (0.0, 0.4) | 0.1 (0.0, 2.9) | 0.2 (0.0, 6.6) |
| IgG-specific CLIA | ||||||||||||
| LT37,57,61,77 | 5; 741 | Unified† | 98.8 (69.2, 100.0) | 94.6 (90.7, 96.9) | 18.3 (10.6-31.5) | 0.01 (0.00- 0.40) | 15.6 (9.7, 24.1) | 57.9 (44.4, 70.3) | 76.3 (65.2, 84.8) | 0.0 (0.0, 0.4) | 0.1 (0.0, 3.2) | 0.2 (0.0, 7.2) |
| IT37 | 2; 448 | Fixed effects‡ | 78.6 (75.9, 81.2) | 98.7 (94.6, 100) | 42.3 (20.1-88.7) | 0.2 (0.1-0.3) | 29.9 (16.9, 47.3) | 76.1 (60.2, 87.0) | 88.2 (78.0, 94.0) | 0.2 (0.1, 0.3) | 1.5 (0.7, 2.2) | 3.4 (1.7, 5.0) |
| HT37,61 | 3; 552 | Fixed effects‡ | 74.2 (71.9, 76.5) | 99.1 (95.4, 100) | 47.8 (23.2-98.7) | 0.2 (0.1-0.4) | 32.6 (19.0, 49.9) | 78.3 (63.6, 88.1) | 89.4 (80.4, 94.6) | 0.2 (0.1, 0.4) | 1.5 (0.7, 2.9) | 3.4 (1.7, 6.6) |
| High-dose heparin confirmation step | ||||||||||||
| Polyspecific ELISA, LT21,40 | 2; 116 | Fixed effects‡ | 99.4 (94.7, 100)|| | 85.8 (83.1, 88.5) | 2.7 (1.6-4.7) | 0.3 (0.1-1.3) | 2.7 (1.6, 4.5) | 16.9 (10.7, 26.1) | 32.3 (22.0, 45.3) | 0.3 (0.1, 1.3) | 2.2 (0.7, 8.9) | 5.0 (1.7, 18.7) |
| IgG-specific ELISA, LT21 | 3; 1459 | Fixed effects‡ | 88.3 (87.0, 89.8) | 90.7 (89.2, 92.1) | 9.3 (7.8-11.1) | 0.1 (0.1-0.2) | 8.6 (7.3, 10.1) | 41.2 (37.0, 45.5) | 62.2 (57.9, 66.2) | 0.1 (0.1, 0.2) | 0.7 (0.7, 1.5) | 1.7 (1.7, 3.4) |
| IgG-specific ELISA, IT21 | 2; 1000 | Fixed effects‡ | 69.7 (68.2, 71.3) | 96.2 (94.7, 97.8) | 18.2 (12.8-25.8) | 0.3 (0.2-0.4) | 15.5 (11.4, 20.7) | 57.8 (49.1, 66.0) | 76.3 (69.3, 82.0) | 0.3 (0.2, 0.4) | 2.2 (1.5, 2.9) | 5.0 (3.4, 6.6) |
| Type of test . | No. studies; no. patients* . | Statistical model . | Sens. (%) . | Spec. (%) . | LR . | Posttest probability of pos. test result . | Posttest probability of neg. test result . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pos. (95% CI) . | Neg. (95% CI) . | 1% Prev. . | 7% Prev. . | 15% Prev. . | 1% Prev. . | 7% Prev. . | 15% Prev. . | |||||
| Polyspecific ELISA | ||||||||||||
| LT16,19,20,28,39,41,43,44,46,47,49-54,59-61,63,64,68,69,71,74,75,77-79 | 31; 8933 | Unified† | 96.7 (89.7, 99.0) | 86.8 (82.0, 90.5) | 7.3 (5.4-10.0) | 0.04 (0.01- 0.12) | 6.9 (5.1, 9.2) | 35.5 (28.9, 42.9) | 56.3 (48.9, 63.8) | 0.0 (0.0, 0.1) | 0.3 (0.1, 0.9) | 0.7 (0.2, 2.1) |
| IT19,47,61,65,77 | 5; 2334 | Unified† | 98.4 (90.8, 99.7) | 94.9 (90.5, 97.3) | 19.3 (10.4-36.0) | 0.02 (0.00-0.1) | 16.3 (9.5, 26.7) | 59.2 (43.9, 73.0) | 77.3 (64.7, 86.4) | 0.0 (0.0, 0.1) | 0.1 (0.0, 0.7) | 0.4 (0.0, 1.7) |
| HT19,39,47 | 3; 1014 | Fixed effects‡ | 15.0 (14.5, 15.5) | 100 (99.3, 100) | 73.4 (28.2-190.9) | 0.3 (0.2-0.5) | 42.6 (22.2, 65.9) | 84.7 (68.0, 93.5) | 92.8 (83.3, 97.1) | 0.3 (0.2, 0.5) | 2.2 (1.5, 3.6) | 5.0 (3.4, 8.1) |
| IgG-specific ELISA | ||||||||||||
| LT19,20,44,55,63,64,66,69-72,77 | 12; 3116 | Unified† | 98.3 (95.1, 99.4) | 85.4 (78.2, 90.6) | 6.7 (4.5-10.2) | 0.02 (0.01-0.05) | 6.3 (4.3, 9.3) | 33.5 (25.3, 43.4) | 54.2 (44.3, 64.3) | 0.0 (0.0, 0.1) | 0.2 (0.1, 0.4) | 0.4 (0.2, 0.9) |
| IT19,20,77 | 4; 2545 | Unified† | 91.2 (86.2, 94.5) | 93.5 (89.1-96.2) | 14.1 (8.1-24.5) | 0.09 (0.05-0.15) | 12.5 (7.6, 19.8) | 51.5 (38.0, 64.8) | 71.3 (58.9, 81.2) | 0.1 (0.1, 0.2) | 0.7 (0.4, 1.1) | 1.6 (1.0, 2.6) |
| HT19 | 2; 1958 | Fixed effects‡ | 60.9 (59.7, 62.1) | 99.4 (97.6-100) | 97.0 (53.0-177.6) | 0.4 (0.3-0.5) | 49.5 (34.9, 64.2) | 88.0 (80.0, 93.0) | 94.5 (90.3, 96.9) | 0.4 (0.3, 0.5) | 2.9 (2.2, 3.6) | 6.6 (5.0, 8.1) |
| PaGIA | ||||||||||||
| LT20,36,42,45,46,53,58,64,68,70,72,75,79 | 12; 2205 | Unified† | 96.5 (89.8, 98.9) | 93.7 (83.1, 97.8) | 15.3 (5.5, 42.3) | 0.04 (0.01, 0.11) | 13.4 (5.3, 29.9) | 53.5 (29.3, 76.1) | 73.0 (49.3, 88.2) | 0.0 (0.0, 0.1) | 0.3 (0.1, 0.8) | 0.7 (0.2, 1.8) |
| IT65 | 1; 1291 | None§ | 98.9 | 95.9 | 24.1 | 0.01 | 19.6 | 64.5 | 81.0 | 0.0 | 0.1 | 0.2 |
| Lateral flow immunoassay54-56,58,66,70,72 | 7; 1163 | Unified† | 98.4 (85.3, 99.9) | 90.3 (84.4, 94.1) | 10.1 (6.2, 16.5) | 0.02 (0.00, 0.18) | 9.3 (5.9, 14.3) | 43.3 (31.9, 55.4) | 64.2 (52.4, 74.5) | 0.0 (0.0, 0.2) | 0.1 (0.0, 1.3) | 0.3 (0.0, 3.0) |
| PIFA28 | 1; 88 | None§ | 0.0 | 70.1 | 2.3 | 0.5 | 2.3 | 14.8 | 28.9 | 0.5 | 3.6 | 8.1 |
| Latex agglutination assay37 | 1; 119 | None§ | 100.0 | 84.3 | 3.7 | 0.0 | 3.6 | 21.8 | 39.5 | 0.0 | 0.0 | 0.0 |
| Polyspecific CLIA | ||||||||||||
| LT37,38,57,61,62,77 | 7; 1008 | Unified† | 98.9 (92.7, 99.8) | 85.6 (79.3, 90.3) | 6.9 (4.7-10.0) | 0.01 (0.00-0.09) | 6.5 (4.5, 9.2) | 34.2 (26.1, 42.9) | 54.9 (45.4, 63.8) | 0.0 (0.0, 0.1) | 0.1 (0.0, 0.7) | 0.2 (0.0, 1.6) |
| IT37 | 2; 448 | Fixed effects‡ | 97.9 (94.6, 100.0) | 93.1 (90.4, 95.8) | 13.5 (9.5-18.9) | 0.0 (0.0-0.1) | 12.0 (8.8, 16.0) | 50.4 (41.7, 58.7) | 70.4 (62.6, 76.9) | 0.0 (0.0, 0.1) | 0.0 (0.0, 0.7) | 0.0 (0.0, 1.7) |
| HT37,61,62,77 | 5; 755 | Unified† | 98.3 (69.5, 99.9) | 97.5 (94.4, 98.9) | 39.5 (17.5-89.2) | 0.0 (0.0-0.40) | 28.5 (15.0, 47.6) | 74.8 (56.8, 87.1) | 87.5 (75.5, 94.1) | 0.0 (0.0, 0.4) | 0.1 (0.0, 2.9) | 0.2 (0.0, 6.6) |
| IgG-specific CLIA | ||||||||||||
| LT37,57,61,77 | 5; 741 | Unified† | 98.8 (69.2, 100.0) | 94.6 (90.7, 96.9) | 18.3 (10.6-31.5) | 0.01 (0.00- 0.40) | 15.6 (9.7, 24.1) | 57.9 (44.4, 70.3) | 76.3 (65.2, 84.8) | 0.0 (0.0, 0.4) | 0.1 (0.0, 3.2) | 0.2 (0.0, 7.2) |
| IT37 | 2; 448 | Fixed effects‡ | 78.6 (75.9, 81.2) | 98.7 (94.6, 100) | 42.3 (20.1-88.7) | 0.2 (0.1-0.3) | 29.9 (16.9, 47.3) | 76.1 (60.2, 87.0) | 88.2 (78.0, 94.0) | 0.2 (0.1, 0.3) | 1.5 (0.7, 2.2) | 3.4 (1.7, 5.0) |
| HT37,61 | 3; 552 | Fixed effects‡ | 74.2 (71.9, 76.5) | 99.1 (95.4, 100) | 47.8 (23.2-98.7) | 0.2 (0.1-0.4) | 32.6 (19.0, 49.9) | 78.3 (63.6, 88.1) | 89.4 (80.4, 94.6) | 0.2 (0.1, 0.4) | 1.5 (0.7, 2.9) | 3.4 (1.7, 6.6) |
| High-dose heparin confirmation step | ||||||||||||
| Polyspecific ELISA, LT21,40 | 2; 116 | Fixed effects‡ | 99.4 (94.7, 100)|| | 85.8 (83.1, 88.5) | 2.7 (1.6-4.7) | 0.3 (0.1-1.3) | 2.7 (1.6, 4.5) | 16.9 (10.7, 26.1) | 32.3 (22.0, 45.3) | 0.3 (0.1, 1.3) | 2.2 (0.7, 8.9) | 5.0 (1.7, 18.7) |
| IgG-specific ELISA, LT21 | 3; 1459 | Fixed effects‡ | 88.3 (87.0, 89.8) | 90.7 (89.2, 92.1) | 9.3 (7.8-11.1) | 0.1 (0.1-0.2) | 8.6 (7.3, 10.1) | 41.2 (37.0, 45.5) | 62.2 (57.9, 66.2) | 0.1 (0.1, 0.2) | 0.7 (0.7, 1.5) | 1.7 (1.7, 3.4) |
| IgG-specific ELISA, IT21 | 2; 1000 | Fixed effects‡ | 69.7 (68.2, 71.3) | 96.2 (94.7, 97.8) | 18.2 (12.8-25.8) | 0.3 (0.2-0.4) | 15.5 (11.4, 20.7) | 57.8 (49.1, 66.0) | 76.3 (69.3, 82.0) | 0.3 (0.2, 0.4) | 2.2 (1.5, 2.9) | 5.0 (3.4, 6.6) |
HT, high threshold; IT, intermediate threshold; LR, likelihood ratio; LT, low threshold; neg., negative; pos., positive; prev., prevalence; sens., sensitivity; spec., specificity.
Studies conducted in the same study population were included only once to maintain independency of observations.
Unified model,31 comprising a bivariate random-effects model32 and an HSROC model.33
In tests with <4 studies available, summary estimates were calculated using a fixed-effects model (Mantel-Haenszel method); however, the results of this analysis must be interpreted with caution because it is not accepted as a valid statistical technique in this situation.
Only 1 study available.
Result of fixed-effects model appears invalid because the favorable sensitivity depends on 1 study in which the only 1 HIT case was detected.67