Abstract
Abstract 2328
Congenital thrombotic thrombocytopenic purpura (TTP) is caused by genetic mutations in ADAMTS13, a metalloproteinase that cleaves ultra-large VWF multimers to generate normal sized multimers present in circulation. However, acquired deficiency of ADAMTS13 due to auto-antibodies is not universally accepted as diagnostic of idiopathic TTP. Distinguishing idiopathic TTP from other thrombotic microangiopatheis (TMA) is important in guiding treatment as plasma exchange (PE) is only beneficial in TTP and select cases of other microangiopathies such as atypical HUS. Since January 2006 we routinely obtain ADAMTS13 activity performed by FRET assay from The Blood Center of Wisconsin in all patients with TMA. We report the diagnostic utility of ADAMTS13 to distinguish TTP from other forms of TMAs.
A retrospective analysis was performed on consecutive patients with TMA who had ADAMTS13 assayed from January 2006 to October 2010. Demographics, presenting clinical and laboratory features are given in the Table. Responses to therapeutic plasma exchange (TPE), diagnoses at discharge, and other underlying clinical conditions were also recorded. Relevant statistical analysis was performed using unpaired t-test to compare means and Fisher's exact method for contingency tables.
We divided our cases based on severe ADAMTS13 deficiency (<10%) as TTP and non-severe deficiency (>20%) as TMA. TMA causes included quinine induced HUS (1), gemcitabine related HUS (1), malignant hypertension/pre-eclampsia/HEELP (3), sepsis (2), MCTD (5), malignancy (3), ITP (1), HIV/opportunistic infection (5), drugs (1), and multiple (5).
| . | TTP . | TMA . | p-value . |
|---|---|---|---|
| Total patients | 26 (31 episodes) | 27 | |
| Median Age | 39 | 47 | |
| Sex (females %) | 71% | 56% | |
| ADAMTS13 activity <10% (normal >67%) | 100% | 0% | |
| Mean ADAMTS13 activity | <10% | 55 ± 21% | |
| ADAMTS13 Inhibitor >0.4 units | 81% | 0% | |
| Admission platelet count x109/L (mean ± SD) | 25 ± 28 | 64 ± 41 | 0.0001 |
| Admission LD units/L (mean ± SD) | 1005 ± 634 | 1337 ± 1430 | 0.25 |
| Admission hematocrit % (mean ± SD) | 26.4 ± 7.7 | 26.8 ± 4.9 | 0.82 |
| Fever | 26% | 19% | 0.55 |
| Neurological symptoms | 58% | 44% | 0.43 |
| Creatinine mg/dL (mean ± SD) | 1.35 ± .93 | 2.49 ± 2.14 | 0.0094 |
| Schistocytes | 97% | 81% | .0913 |
| Low haptoglobin (<16 mg/dL) | 92% | 60% | .0087 |
| D-dimer elevated (>3.0 mg/L) | 57% | 57% | 1.0 |
| PLEX performed | 901 | 50% | |
| Post treatment Platelet count x109/L (mean ± SD) | 212 ± 79 | 122 ± 126 | 0.0024 |
| Post treatment LD units/L (mean ± SD) | 266±91 | 701±1101 | 0.042 |
| Mortality1-2 | 7% | 4% | 1.0 |
| . | TTP . | TMA . | p-value . |
|---|---|---|---|
| Total patients | 26 (31 episodes) | 27 | |
| Median Age | 39 | 47 | |
| Sex (females %) | 71% | 56% | |
| ADAMTS13 activity <10% (normal >67%) | 100% | 0% | |
| Mean ADAMTS13 activity | <10% | 55 ± 21% | |
| ADAMTS13 Inhibitor >0.4 units | 81% | 0% | |
| Admission platelet count x109/L (mean ± SD) | 25 ± 28 | 64 ± 41 | 0.0001 |
| Admission LD units/L (mean ± SD) | 1005 ± 634 | 1337 ± 1430 | 0.25 |
| Admission hematocrit % (mean ± SD) | 26.4 ± 7.7 | 26.8 ± 4.9 | 0.82 |
| Fever | 26% | 19% | 0.55 |
| Neurological symptoms | 58% | 44% | 0.43 |
| Creatinine mg/dL (mean ± SD) | 1.35 ± .93 | 2.49 ± 2.14 | 0.0094 |
| Schistocytes | 97% | 81% | .0913 |
| Low haptoglobin (<16 mg/dL) | 92% | 60% | .0087 |
| D-dimer elevated (>3.0 mg/L) | 57% | 57% | 1.0 |
| PLEX performed | 901 | 50% | |
| Post treatment Platelet count x109/L (mean ± SD) | 212 ± 79 | 122 ± 126 | 0.0024 |
| Post treatment LD units/L (mean ± SD) | 266±91 | 701±1101 | 0.042 |
| Mortality1-2 | 7% | 4% | 1.0 |
3 patients did not receive PLEX in TTP: 1 patient died during first PLEX, another patient (Jehovah's witness) refused FFP, and the third patient was started on steroids instead of PLEX
Mortality: TTP: 1-sepsis, 1-bronchiolitis obliterans, 2-did not receive standard PLEX (see notes in [1]), TMA: 1-respiratory failure
In our experience severe ADAMTS13 deficiency appears to distinguish TTP from TMA. TMA had better mortality despite either not initiating or discontinuing PE based on ADAMTS13 levels. However, if we had continued PE in TMA then these patients would have been considered as NON-ADAMTS13 deficient TTP who responded well to PE.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
