ADAMTS13 activity measurements and final clinical diagnosis in patients with suspected TTP (n = 85)
| Patient . | ADAMTS13 . | Comment . | Functional inhibitor (BU/mL) . | |
|---|---|---|---|---|
| FRET (%) . | IB (%) . | |||
| Diagnosis of TTP by FRET and IB | ||||
| 1-60 | <10 | <10 | 20 (38%) of 52 survivors relapsed | |
| Diagnosis of TTP by FRET only | ||||
| 61 | <10 | 10 | No relapse | 0.5 |
| 62 | <10 | 12 | 1 relapse: both <10% | 1.2 |
| 63 | <10 | 12 | No relapse | 1.2 |
| 64 | <10 | 13 | No relapse | 0 |
| 65 | <10 | 13 | No relapse | 0.8 |
| 66 | <10 | 15 | No relapse | 0.6 |
| 67 | <10 | 18 | Died before PEX started | 0 |
| 68 | <10 | 20 | No relapse | 0.5 |
| 69 | <10 | 20 | 3 relapses: 2, both <10%; 1, IB 10% | 0 |
| 70 | <10 | 20 | No relapse | 0.5 |
| 71 | <10 | 25 | 2 relapses: 1, both <10%; 1, IB 18% | 0 |
| 72 | <10 | 30 | No relapse | 0.5 |
| 73 | <10 | 35 | 1 relapse: FRET <10%, IB 18 | 2 |
| 74 | <10 | 40 | 1 relapse: both <10% | >2 |
| 75 | <10 | 68 | 2 relapses, both <10% | >2 |
| Diagnosis of TTP by IB only | ||||
| 76 | 11 | <10 | No relapse | 1.3 |
| 77 | 16 | <10 | 2 relapses (no ADAMTS13 measurements) | >2 |
| 78 | 23 | <10 | Died with first episode | >2 |
| Diagnosis of TTP not supported by clinical features; alternative etiology established | ||||
| 79 | 6 | 13 | HIV, died; autopsy: systemic Kaposi sarcoma, no evidence of TTP | 0.9 |
| 80 | 9 | 20 | Bilirubin 24 mg/dL; died; autopsy: hepatic necrosis, no evidence of TTP | 1.3 |
| 81 | 9 | 25 | After unrelated donor HSCT, GVHD, systemic aspergillosis, bilirubin 64 mg/dL; died | >2 |
| 82 | 12 | 9 | Sepsis (Group A Streptococcus), hypotension, rhabdomyolysis, lactic acidosis; survived | 0 |
| 83 | 28 | 8 | Sepsis (Candida), hypotension, DIC, after liver transplant; died | 1.2 |
| Diagnosis of TTP supported by occurrence of relapses; neither FRET nor IB <10% | ||||
| 84 | 53 | 60 | 6 episodes: second, no measurements; third, FRET 15% with inhibitor, IB 50%; fourth through sixth: both measurements <10%, with inhibitors. | 0.8-1.4 |
| 85 | 100 | 16 | 4 episodes: PEX performed only for third episode; ADAMTS13 measured for episodes 3 and 4. | 1.9 |
| 100 | 29 | 1.3 | ||
| Patient . | ADAMTS13 . | Comment . | Functional inhibitor (BU/mL) . | |
|---|---|---|---|---|
| FRET (%) . | IB (%) . | |||
| Diagnosis of TTP by FRET and IB | ||||
| 1-60 | <10 | <10 | 20 (38%) of 52 survivors relapsed | |
| Diagnosis of TTP by FRET only | ||||
| 61 | <10 | 10 | No relapse | 0.5 |
| 62 | <10 | 12 | 1 relapse: both <10% | 1.2 |
| 63 | <10 | 12 | No relapse | 1.2 |
| 64 | <10 | 13 | No relapse | 0 |
| 65 | <10 | 13 | No relapse | 0.8 |
| 66 | <10 | 15 | No relapse | 0.6 |
| 67 | <10 | 18 | Died before PEX started | 0 |
| 68 | <10 | 20 | No relapse | 0.5 |
| 69 | <10 | 20 | 3 relapses: 2, both <10%; 1, IB 10% | 0 |
| 70 | <10 | 20 | No relapse | 0.5 |
| 71 | <10 | 25 | 2 relapses: 1, both <10%; 1, IB 18% | 0 |
| 72 | <10 | 30 | No relapse | 0.5 |
| 73 | <10 | 35 | 1 relapse: FRET <10%, IB 18 | 2 |
| 74 | <10 | 40 | 1 relapse: both <10% | >2 |
| 75 | <10 | 68 | 2 relapses, both <10% | >2 |
| Diagnosis of TTP by IB only | ||||
| 76 | 11 | <10 | No relapse | 1.3 |
| 77 | 16 | <10 | 2 relapses (no ADAMTS13 measurements) | >2 |
| 78 | 23 | <10 | Died with first episode | >2 |
| Diagnosis of TTP not supported by clinical features; alternative etiology established | ||||
| 79 | 6 | 13 | HIV, died; autopsy: systemic Kaposi sarcoma, no evidence of TTP | 0.9 |
| 80 | 9 | 20 | Bilirubin 24 mg/dL; died; autopsy: hepatic necrosis, no evidence of TTP | 1.3 |
| 81 | 9 | 25 | After unrelated donor HSCT, GVHD, systemic aspergillosis, bilirubin 64 mg/dL; died | >2 |
| 82 | 12 | 9 | Sepsis (Group A Streptococcus), hypotension, rhabdomyolysis, lactic acidosis; survived | 0 |
| 83 | 28 | 8 | Sepsis (Candida), hypotension, DIC, after liver transplant; died | 1.2 |
| Diagnosis of TTP supported by occurrence of relapses; neither FRET nor IB <10% | ||||
| 84 | 53 | 60 | 6 episodes: second, no measurements; third, FRET 15% with inhibitor, IB 50%; fourth through sixth: both measurements <10%, with inhibitors. | 0.8-1.4 |
| 85 | 100 | 16 | 4 episodes: PEX performed only for third episode; ADAMTS13 measured for episodes 3 and 4. | 1.9 |
| 100 | 29 | 1.3 | ||
The term “both” in the Comments column refers to measuring ADAMTS13 activity by both FRET and IB assays. The patients are presented in 5 categories. In patients 1-78, the diagnosis of TTP was supported by both ADAMTS13 activity <10% and clinical criteria (no alternative diagnosis was recognized as the cause of the clinical features). In patients 1-60, ADAMTS13 activity was <10% with both assays; in patients 61-75, the IB assay reported ADAMTS13 activity as 10%-68%; in patients 76-78, the FRETS assay reported ADAMTS13 activity as 11%-23%. These observations suggest that in vitro ADAMTS13 measurements may not always reflect in vivo ADAMTS13 activity. In patients 79-83, 1 of the 2 ADAMTS13 activity measurements was <10%, but another disorder was diagnosed as the cause of the clinical features. In patients 80 and 81, high bilirubin levels may have caused falsely low ADAMTS13 measurements by the FRET assay.13 In patients 84 and 85, TTP was suspected by clinical criteria but the diagnosis of TTP was not supported by measurements of ADAMTS13 <10%. Patients 79-85 are described individually in the text. Functional inhibitor measured at the time of the initial episode of TTP was expressed in Bethesda units (BU/mL). Titers of ≤0.4 BU/mL were considered to be within the normal range. Titers of ≥0.5 BU/mL are reported and are considered to be clinically important. Inhibitors were measured by the FRET assay unless noted. For patients enrolled from November 13, 1995, through August 1, 2005, functional inhibitor activity was also measured by the quantitative IB assay. IB inhibitor titers are described only if an inhibitor was not measured by the FRET assay. Five of the 60 patients in whom ADAMTS13 activity was <10% by both assays had no demonstrable inhibitor by the FRET assay; an IB inhibitor assay was not performed. In patients 69 and 71, the IB assay showed no inhibitor activity. In patient 67, a FRET inhibitor assay was not performed; no inhibitor was documented by IB. Patient 78 did not have a demonstrable inhibitor by the FRET assay; the IB inhibitor was >2. Patient 84 had demonstrable inhibitors at the time of episodes 3-6. In patient 85, inhibitor activity was not measured with the FRET assay but was documented by the IB assay.
DIC, disseminated intravascular coagulation; GVHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplant.