Patient characteristics
| Patient . | History . | Initial laboratory results . | ADAMTS13 . | Initial treatment . | Outcome . |
|---|---|---|---|---|---|
| P1 | 54-yo woman with TTP diagnosed 21 y ago and frequent relapses presented with unexplained bruising on right arm. Previous treatments included TPEx, steroids, rituximab, and vincristine. Her last relapse was 8 y prior to this presentation. | Platelets: 11 × 109/L Hgb: 8.4 g/d L Cr: 1.8 mg/dL Tbili: 0.6 mg/dL LDH: 465 U/L Haptoglobin: <6 mg/dL ARC: 100 000/μL PB smear: numerous schistocytes per high power field | Activity: 5% Inhibitor: yes (>8 IU) | (1) Prednisone 1 mg/kg/d × 10 d followed by slow taper. (2) TPEx × 12 sessions: daily until day 10 followed by taper completed on day 15. (3) Rituximab: given weekly at 375 mg/m2 × 2 doses in hospital, starting day 5. | Platelet count normalized on day 8 and remained stable until discharge on day 15. |
| P2 | 57-yo woman with metastatic melanoma being treated with ipilimumab and nivolumab (4 cycles of nivolumab and ipilimumab given every 3 weeks, last cycle being 41 d prior to admission) presented to the ED with complaints of dizziness and weakness for 4 d, and leg bruises for 3 wk. She denies fevers or neurologic symptoms. | Platelets: 8 × 109/L Hgb: 7.2 g/d L Cr: 0.85 mg/dL Tbili: 3.6 mg/dL (indirect 2.95 mg/dL) LDH: 1562 U/L Haptoglobin: <6 mg/dL ARC: 250 000/μL PB smear: numerous schistocytes per high power field | Activity: <5% Inhibitor: yes (ADAMTS13 IgG Ab titer of 68 and inhibitor titer 0.7 IU) Repeat activity (inhibitor titer): 11% (0.8) on day 17, 11% (<0.4) on day 28, <5% on days 70 (<0.4) and 120 (0.4) | (1) Pulse steroids (methylprednisolone). (2) Daily TPEx started on day 2 of admission. The frequency of TPEx was increased to twice daily on day 8 and then switched to daily at 1.5 exchange volume on day 10 until discharge on day 25. She received a total of 24 TPEx sessions during her hospital stay. (3) Rituximab: Given weekly at 375 mg/m2 × 4 doses were given, starting day 3. | Platelet count normalized to 163 × 109/L on day 6 for 1 d, before trending down again. Patient’s platelet counts fluctuated significantly before stabilizing within the normal range starting day 22. Patient expired 154 d from TTP diagnosis due to progression of metastatic melanoma and iTTP (see supplemental Figures 2-5). |
| P3 | 25-yo woman with history of metastatic anaplastic ependymoma diagnosed 6 y ago, treated with multiple rounds of radiation therapy and chemotherapy in the past who presented with low-grade fever and bruising for 3 d. Current treatment included temozolomide for the preceding 12 mo. | Platelets: 6 × 109/L Hgb: 6.3 g/dL Cr: 1.14 mg/dL Tbili: 5.6 mg/dL (indirect 4.88 mg/dL) LDH: 1132 U/L Haptoglobin: <6 mg/dL ARC: 120 000/μL PB smear: numerous schistocytes per high power field | Activity: <5% Inhibitor: yes (2.4 IU) Repeat activity (inhibitor titer): <5% on day 12, 93% on day 15, and 87% (<0.4) on day 32 | (1) Prednisone 1 mg/kg × 3 wk before a taper was initiated. (2) TPEx started on day 2 of admission, increased to twice daily on days 13-19 due to poor response, and then continued daily until day 36 (total 42 sessions). (3) Rituximab: given weekly; 375 mg/m2 × 4 doses starting day 3. (4) Bortezomib: given days 13, 16, and 20 at 1 mg/m2. | Platelet count was 6 × 109/L on the day of discharge (day 40), but with no other corroboratory evidence of ongoing TTP activity, the impression was that the low count was because of underlying malignancy and/or nutritional deficiencies. Bone marrow biopsy performed day 39 was unremarkable (see supplemental Figures 2-5). |
| Patient . | History . | Initial laboratory results . | ADAMTS13 . | Initial treatment . | Outcome . |
|---|---|---|---|---|---|
| P1 | 54-yo woman with TTP diagnosed 21 y ago and frequent relapses presented with unexplained bruising on right arm. Previous treatments included TPEx, steroids, rituximab, and vincristine. Her last relapse was 8 y prior to this presentation. | Platelets: 11 × 109/L Hgb: 8.4 g/d L Cr: 1.8 mg/dL Tbili: 0.6 mg/dL LDH: 465 U/L Haptoglobin: <6 mg/dL ARC: 100 000/μL PB smear: numerous schistocytes per high power field | Activity: 5% Inhibitor: yes (>8 IU) | (1) Prednisone 1 mg/kg/d × 10 d followed by slow taper. (2) TPEx × 12 sessions: daily until day 10 followed by taper completed on day 15. (3) Rituximab: given weekly at 375 mg/m2 × 2 doses in hospital, starting day 5. | Platelet count normalized on day 8 and remained stable until discharge on day 15. |
| P2 | 57-yo woman with metastatic melanoma being treated with ipilimumab and nivolumab (4 cycles of nivolumab and ipilimumab given every 3 weeks, last cycle being 41 d prior to admission) presented to the ED with complaints of dizziness and weakness for 4 d, and leg bruises for 3 wk. She denies fevers or neurologic symptoms. | Platelets: 8 × 109/L Hgb: 7.2 g/d L Cr: 0.85 mg/dL Tbili: 3.6 mg/dL (indirect 2.95 mg/dL) LDH: 1562 U/L Haptoglobin: <6 mg/dL ARC: 250 000/μL PB smear: numerous schistocytes per high power field | Activity: <5% Inhibitor: yes (ADAMTS13 IgG Ab titer of 68 and inhibitor titer 0.7 IU) Repeat activity (inhibitor titer): 11% (0.8) on day 17, 11% (<0.4) on day 28, <5% on days 70 (<0.4) and 120 (0.4) | (1) Pulse steroids (methylprednisolone). (2) Daily TPEx started on day 2 of admission. The frequency of TPEx was increased to twice daily on day 8 and then switched to daily at 1.5 exchange volume on day 10 until discharge on day 25. She received a total of 24 TPEx sessions during her hospital stay. (3) Rituximab: Given weekly at 375 mg/m2 × 4 doses were given, starting day 3. | Platelet count normalized to 163 × 109/L on day 6 for 1 d, before trending down again. Patient’s platelet counts fluctuated significantly before stabilizing within the normal range starting day 22. Patient expired 154 d from TTP diagnosis due to progression of metastatic melanoma and iTTP (see supplemental Figures 2-5). |
| P3 | 25-yo woman with history of metastatic anaplastic ependymoma diagnosed 6 y ago, treated with multiple rounds of radiation therapy and chemotherapy in the past who presented with low-grade fever and bruising for 3 d. Current treatment included temozolomide for the preceding 12 mo. | Platelets: 6 × 109/L Hgb: 6.3 g/dL Cr: 1.14 mg/dL Tbili: 5.6 mg/dL (indirect 4.88 mg/dL) LDH: 1132 U/L Haptoglobin: <6 mg/dL ARC: 120 000/μL PB smear: numerous schistocytes per high power field | Activity: <5% Inhibitor: yes (2.4 IU) Repeat activity (inhibitor titer): <5% on day 12, 93% on day 15, and 87% (<0.4) on day 32 | (1) Prednisone 1 mg/kg × 3 wk before a taper was initiated. (2) TPEx started on day 2 of admission, increased to twice daily on days 13-19 due to poor response, and then continued daily until day 36 (total 42 sessions). (3) Rituximab: given weekly; 375 mg/m2 × 4 doses starting day 3. (4) Bortezomib: given days 13, 16, and 20 at 1 mg/m2. | Platelet count was 6 × 109/L on the day of discharge (day 40), but with no other corroboratory evidence of ongoing TTP activity, the impression was that the low count was because of underlying malignancy and/or nutritional deficiencies. Bone marrow biopsy performed day 39 was unremarkable (see supplemental Figures 2-5). |
Ab, antibody; ARC, absolute reticulocyte count; Cr, creatinine; ED, emergency department; Hgb, hemoglobin; LDH, lactate dehydrogenase; P1, patient 1; P2, patient 2; P3, patient 3; PB, peripheral blood; Tbili, total bilirubin; TTP, thrombotic thrombocytopenic purpura; yo, year old.