The Influence of Race and ADAMTS13 Status On Outcomes in Thrombotic Thrombocytopenic Purpura

Abstract 4638

Thrombotic thrombocytopenic purpura (TTP), a syndrome characterized by thrombocytopenia and microangiopathic hemolytic anemia due to deficiency of the von Willebrand factor cleaving protease ADAMTS13, was once a highly fatal condition, but therapeutic plasma exchange (PEX) has dramatically improved outcomes. We report the results of a retrospective chart review of TTP patients treated with PEX at our institution from September 2006 through December 2011. Complete demographic, clinical, laboratory, treatment, and response data were collected to examine the influence of race on clinical outcomes.

A total of 49 patients were treated for TTP. This cohort was predominantly female (71%) and African American (61%). Three patients were of Hispanic ethnicity. The median age was 50 years (14–81), and the median number of comorbidities at presentation was 4 (range 0–14). Assays for ADAMTS13 activity with reflex to ADAMTS13 inhibitor were performed by the Blood Center of Wisconsin. All patients were treated with PEX (1–1.5 plasma volume using fresh frozen plasma as replacement fluid) once daily until plateau in the platelet count, and then PEX frequency was tapered over 2 weeks in remitting patients.

The median number of PEX procedures for the first episode was 8 (1–22). The median total PEX for all episodes was 9 (1–56). The majority of patients, 37 (75.5%), received corticosteroids, and rituximab was administered to 19 (38.8%) of patients at some point during their treatment, usually for slow response or relapse.

An initial response to PEX, defined by normalization of platelet count (above 140×10⁹/L) and resolution of signs of hemolysis, was achieved in 36/49 (73.5%) patients. The response rate was not significantly different between African Americans (73.3%) and Caucasians (68.8%, p=0.742), and all 3 Hispanic patients responded to initial treatment. Pre-treatment ADAMTS13 activity was severely deficient (<10% of normal) in 20/39 (51.3%) patients. An inhibitor of ADAMTS 13 was detected (>0.4 Inhibitor Units) in 19/23 (82.6%) patients tested. African Americans were more likely to have severely deficient ADAMTS13 activity (16/25, 64%) than Caucasians (2/13, 15.4%; p=0.004).

The initial response rate was higher in patients with severely deficient ADAMTS 13 activity (90.0%) in comparison to those with >10% activity (68.4%), however the difference did not reach statistical significance (p=0.067). Of the patients with severely deficient ADAMTS 13 activity and detectable inhibitor levels, 89.5% had an initial response to PEX. All four patients with severely deficient ADAMTS 13 activity but undetectable inhibitor levels also responded to PEX.

The total number of relapse events was 16 (32.7%), and the median time to relapse was 19.4 months. All three Hispanic patients, 4 (25%) Caucasians, and 9 (30%) African Americans relapsed. One-year relapse free survival was similar among Caucasians and African Americans at 72% and 75% respectively (p=0.852). All three Hispanic patients relapsed within the first year. One-year overall survival was similar for Caucasians and African Americans at 81.3% and 83.3% respectively (p=0.968). A total of 10 deaths were documented. The causes of death were relapse of TTP (3/10), sepsis (4/10), GI bleeding (2/10), and unknown etiology (1/10).

In this unusual TTP cohort with 61% African Americans, we found that African Americans were more likely to have severely deficient ADAMTS13 activity than Caucasians, but response to PEX, relapse, and survival for Caucasian and African Americans were very similar. This study also supports pre-treatment assays for ADAMTS13 activity and its inhibitor, not only for the diagnosis of TTP, but also for predicting response to PEX therapy.