Revised outcome definitions for iTTP and their clinical implications
| Category . | Outcome . | Definition . | Management implications . |
|---|---|---|---|
| Response | Clinical response | Sustained platelet count ≥150 × 109/L and LDH <1.5 times ULN and no clinical evidence of new or progressive ischemic organ injury. | Preremission implications |
| Exacerbation | Clinical exacerbation | After a clinical response and before a clinical remission, platelet count decreases to <150 × 109/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 d of stopping TPE or anti-VWF therapy | In general, TPE may be discontinued and patients may be discharged from the hospital soon after they achieve a clinical response. |
| Persistent severe ADAMTS13 deficiency after a clinical response is associated with an increased risk of clinical exacerbation. | |||
| Immunosuppression (e.g., corticosteroids, rituximab) may be used to induce an ADAMTS13 remission. | |||
| Use of anti-VWF therapy (e.g., caplacizumab) until attainment of ADAMTS13 remission is protective against clinical exacerbation. | |||
| Remission | Clinical remission | Sustained clinical response with either no TPE and no anti-VWF therapy for ≥30 d or with attainment of ADAMTS13 remission (partial or complete), whichever occurs first. | Postremission implications |
| Partial ADAMTS13 remission | ADAMTS13 activity ≥20% to <LLN.*,† | ADAMTS13 remission (partial or complete) is always accompanied by clinical remission. | |
| Complete ADAMTS13 remission | ADAMTS13 activity ≥LLN. | However, clinical remission may occur with or without an ADAMTS13 remission. | |
| Relapse | Clinical relapse | After a clinical remission, platelet count decreases to <150 × 109/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury. A clinical relapse must be confirmed by documentation of severe ADAMTS13 deficiency. | Patients in clinical remission who do not achieve an ADAMTS13 remission or who experience an ADAMTS13 relapse are at increased risk of clinical relapse. |
| ADAMTS13 relapse | After an ADAMTS13 remission (partial or complete), the ADAMTS13 level decreases to <20%.*,† | In such patients, preemptive immunosuppression (e.g., rituximab) may be used to attain an ADAMTS13 remission, thereby reducing the risk of clinical relapse. |
| Category . | Outcome . | Definition . | Management implications . |
|---|---|---|---|
| Response | Clinical response | Sustained platelet count ≥150 × 109/L and LDH <1.5 times ULN and no clinical evidence of new or progressive ischemic organ injury. | Preremission implications |
| Exacerbation | Clinical exacerbation | After a clinical response and before a clinical remission, platelet count decreases to <150 × 109/L (with other causes of thrombocytopenia excluded), with or without clinical evidence of new or progressive ischemic organ injury, within 30 d of stopping TPE or anti-VWF therapy | In general, TPE may be discontinued and patients may be discharged from the hospital soon after they achieve a clinical response. |
| Persistent severe ADAMTS13 deficiency after a clinical response is associated with an increased risk of clinical exacerbation. | |||
| Immunosuppression (e.g., corticosteroids, rituximab) may be used to induce an ADAMTS13 remission. | |||
| Use of anti-VWF therapy (e.g., caplacizumab) until attainment of ADAMTS13 remission is protective against clinical exacerbation. | |||
| Remission | Clinical remission | Sustained clinical response with either no TPE and no anti-VWF therapy for ≥30 d or with attainment of ADAMTS13 remission (partial or complete), whichever occurs first. | Postremission implications |
| Partial ADAMTS13 remission | ADAMTS13 activity ≥20% to <LLN.*,† | ADAMTS13 remission (partial or complete) is always accompanied by clinical remission. | |
| Complete ADAMTS13 remission | ADAMTS13 activity ≥LLN. | However, clinical remission may occur with or without an ADAMTS13 remission. | |
| Relapse | Clinical relapse | After a clinical remission, platelet count decreases to <150 × 109/L (with other causes of thrombocytopenia ruled out), with or without clinical evidence of new ischemic organ injury. A clinical relapse must be confirmed by documentation of severe ADAMTS13 deficiency. | Patients in clinical remission who do not achieve an ADAMTS13 remission or who experience an ADAMTS13 relapse are at increased risk of clinical relapse. |
| ADAMTS13 relapse | After an ADAMTS13 remission (partial or complete), the ADAMTS13 level decreases to <20%.*,† | In such patients, preemptive immunosuppression (e.g., rituximab) may be used to attain an ADAMTS13 remission, thereby reducing the risk of clinical relapse. |
ADAMTS13 level of 20% was selected as the threshold for defining partial ADAMTS13 remission and ADAMTS13 relapse based on limited evidence that an ADAMTS13 level at or above this threshold is protective against clinical relapse.15-18 We acknowledge that the minimum ADAMTS13 level above which patients are protected from clinical relapse is uncertain and requires further study.
Because there is biological variability in ADAMTS13 level, as well as variability in its laboratory measurement, it may be advisable to repeat the test for ADAMTS13 level to confirm an ADAMTS13 remission or ADAMTS13 relapse.