Abstract
The Oklahoma TTP-HUS Registry enrolled 360 consecutive patients, 1989–2006, who had a clinical or renal biopsy diagnosis of an initial episode of TTP-HUS and a request for plasma exchange treatment (PEX). 47 (13%) appeared to have a drug-associated etiology determined by the use of a drug previously reported to be associated with TTP or HUS.
| Patient Characteristics . | Quinine (n=23) . | Ticlopidine (n=2) . | Clopidogrel (n=1) . | Calcineurin inhibitors (n=5) . | Chemotherapy (n=16) . |
|---|---|---|---|---|---|
| *median; ‡seizure, stroke, coma, focal abnormalities anytime during the course; †most abnormal values at diagnosis ± 7 days, median; **defined by ↑ Cr ≥0.5 mg/dL x 2 days or Cr ≥4.0 and dialysis; §only for patients who received PEX | |||||
| Age* (years) | 61 | 68 | 17 | 52 | 57 |
| Female (%) | 96% | 50% | 100% | 60% | 69% |
| Race (% white) | 96% | 50% | 100% | 100% | 94% |
| Time from last dose* | 3 days | 3 days | 0 days | 1 day | 105 days |
| Severe neurologic abnormalities (%)‡ | 30% | 50% | 0% | 40% | 6% |
| Platelet count†(/μL ) | 26 | 6 | 81 | 35 | 38 |
| Hematocrit†(%) | 23 | 23 | 13 | 21 | 22 |
| LDH†(U/L) | 2143 | 2120 | 581 | 1346 | 805 |
| Creatinine†(mg/dL) | 7.0 | 4.0 | 1.6 | 7.0 | 4.5 |
| Acute renal failure (%)** | 91% | 0% | 0% | 40% | 38% |
| Response to PEX§ | 95% (21/22) | NA | 100% (1/1) | 25% (1/4) | 47% (7/15) |
| Death (30 days) | 13% | 50% | 0% | 20% | 13% |
| Death (1 year) | 13% | 50% | 0% | 20% | 69% |
| Patient Characteristics . | Quinine (n=23) . | Ticlopidine (n=2) . | Clopidogrel (n=1) . | Calcineurin inhibitors (n=5) . | Chemotherapy (n=16) . |
|---|---|---|---|---|---|
| *median; ‡seizure, stroke, coma, focal abnormalities anytime during the course; †most abnormal values at diagnosis ± 7 days, median; **defined by ↑ Cr ≥0.5 mg/dL x 2 days or Cr ≥4.0 and dialysis; §only for patients who received PEX | |||||
| Age* (years) | 61 | 68 | 17 | 52 | 57 |
| Female (%) | 96% | 50% | 100% | 60% | 69% |
| Race (% white) | 96% | 50% | 100% | 100% | 94% |
| Time from last dose* | 3 days | 3 days | 0 days | 1 day | 105 days |
| Severe neurologic abnormalities (%)‡ | 30% | 50% | 0% | 40% | 6% |
| Platelet count†(/μL ) | 26 | 6 | 81 | 35 | 38 |
| Hematocrit†(%) | 23 | 23 | 13 | 21 | 22 |
| LDH†(U/L) | 2143 | 2120 | 581 | 1346 | 805 |
| Creatinine†(mg/dL) | 7.0 | 4.0 | 1.6 | 7.0 | 4.5 |
| Acute renal failure (%)** | 91% | 0% | 0% | 40% | 38% |
| Response to PEX§ | 95% (21/22) | NA | 100% (1/1) | 25% (1/4) | 47% (7/15) |
| Death (30 days) | 13% | 50% | 0% | 20% | 13% |
| Death (1 year) | 13% | 50% | 0% | 20% | 69% |
Calcineurin inhibitors were cyclosporine (3) and tacrolimus (2); chemotherapy agents were mitomycin C (11), gemcitabine (2), gemcitabine/taxotere (1), pentostatin (1), and BCNU (1). 32 patients, including patients in all 5 drugs categories, had ADAMTS13 activity measured; all were ≥ 25%. Patients were predominantly women (81%), similar to patients with severe ADAMTS13 deficiency, and almost all white (94%), distinct from patients with severe ADAMTS13 deficiency (
Conclusions:
Quinine was the most common drug associated with TTP-HUS.
Drug-associated TTP-HUS appears to have 2 distinct etiologic mechanisms:
acute and potentially immune-mediated reactions (quinine, ticlopidine, clopidogrel) and
cumulative, dose-dependent toxicity (calcineurin inhibitors, chemotherapy agents).
Although the role of PEX in the recovery of patients with drug-associated TTP-HUS is unclear, PEX may be appropriate initial treatment since some patients appear to respond and since a drug-associated etiology cannot be certain when patients initially present.
Author notes
Disclosure: No relevant conflicts of interest to declare.
