Laboratory characteristics of the 9 patients with VITT-like anti-PF4 antibodies without proximate exposure to heparin or vaccination
| . | Patient 1∗ . | Patient 2† . | Patient 3 . | Patient 4 . | Patient 5 . | Patient 6 . | Patient 7 . | Patient 8‡ . | Patient 9 . |
|---|---|---|---|---|---|---|---|---|---|
| Platelet count nadir, × 109/L | 81 | 49 | 22 | 41 | 43 | 50 | 55 | 24 | 49 |
| D-dimer level (FEU; < 0.5 mg/L) | 10.4 mg/L | >35 mg/L | >35 mg/L | n.d. | >30 mg/L | >10 mg/L | 124 mg/L | >20mg/L | >35 mg/L |
| Anti-PF4/heparin IgG EIA (OD) | Strongly positive (3.10) | Strongly positive (2.22) | Strongly positive (3.04) | Strongly positive (1.99) | Strongly positive (2.55) | Strongly positive (2.1) | Strongly positive (2.76) | Strongly positive (2.72) | Strongly positive (2.30) |
| HIPA | Negative | Negative | Negative | Weakly positive (inhibited by low-dose heparin§) | Negative | Negative or weakly positive over 13 years (inhibited by low-dose heparin§) | Weakly positive (inhibited by low-dose heparin§) | n.d. (SRA with 0.1 U/mL UFH strongly positive22) | Negative |
| PIPA | Strongly Positive (lag time ≤5 min) | Strongly Positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | n.d. (VITT-like profile in the fluid-phase EIA22) | Strongly positive (lag time ≤5 min) |
| HemosIL Acustar HIT IgG (PF4-H) (= rapid anti-PF4/heparin assay) | Negative | Negative | Negative | Positive | Positive | Positive | Negative | Negative | Negative |
| Prototype VITT IgG (PF4) assay (= new rapid anti-PF4 assay) | Positive | Positive | Positive | Positive | Positive | Positive | Positive | Positive | Positive |
| MS sequencing of the light-chain variable region subfamily | IGKV1-5∗01 | IGKV1-39∗01 | IGLV3-21∗02 | IGLV1-51∗01 | n.d. | IGLV3-21∗02; IGKV3-20∗01 | n.d. | n.d. | n.d. |
| . | Patient 1∗ . | Patient 2† . | Patient 3 . | Patient 4 . | Patient 5 . | Patient 6 . | Patient 7 . | Patient 8‡ . | Patient 9 . |
|---|---|---|---|---|---|---|---|---|---|
| Platelet count nadir, × 109/L | 81 | 49 | 22 | 41 | 43 | 50 | 55 | 24 | 49 |
| D-dimer level (FEU; < 0.5 mg/L) | 10.4 mg/L | >35 mg/L | >35 mg/L | n.d. | >30 mg/L | >10 mg/L | 124 mg/L | >20mg/L | >35 mg/L |
| Anti-PF4/heparin IgG EIA (OD) | Strongly positive (3.10) | Strongly positive (2.22) | Strongly positive (3.04) | Strongly positive (1.99) | Strongly positive (2.55) | Strongly positive (2.1) | Strongly positive (2.76) | Strongly positive (2.72) | Strongly positive (2.30) |
| HIPA | Negative | Negative | Negative | Weakly positive (inhibited by low-dose heparin§) | Negative | Negative or weakly positive over 13 years (inhibited by low-dose heparin§) | Weakly positive (inhibited by low-dose heparin§) | n.d. (SRA with 0.1 U/mL UFH strongly positive22) | Negative |
| PIPA | Strongly Positive (lag time ≤5 min) | Strongly Positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | Strongly positive (lag time ≤5 min) | n.d. (VITT-like profile in the fluid-phase EIA22) | Strongly positive (lag time ≤5 min) |
| HemosIL Acustar HIT IgG (PF4-H) (= rapid anti-PF4/heparin assay) | Negative | Negative | Negative | Positive | Positive | Positive | Negative | Negative | Negative |
| Prototype VITT IgG (PF4) assay (= new rapid anti-PF4 assay) | Positive | Positive | Positive | Positive | Positive | Positive | Positive | Positive | Positive |
| MS sequencing of the light-chain variable region subfamily | IGKV1-5∗01 | IGKV1-39∗01 | IGLV3-21∗02 | IGLV1-51∗01 | n.d. | IGLV3-21∗02; IGKV3-20∗01 | n.d. | n.d. | n.d. |
FEU, fibrinogen equivalent units; LMWH, low molecular weight heparin; MS, mass spectrometry; n.d., not done; PLT count, platelet count; SRA, serotonin release assay.
Detailed course described in Greinacher et al.20
Detailed course described in Greinacher et al.21
Detailed course described in Warkentin et al.22
Inhibition by low-dose heparin indicates increased lag time (vs buffer). Patient included because >95% serotonin-release was seen at both 0 and 0.1 U/mL heparin, and the fluid-phase EIA confirmed VITT rather than HIT reaction pattern.