PB0350 - Deficiency of ultra-large von Willebrand factor multimers at diagnosis is associated with poor prognosis in acute immune-mediated thrombotic thrombocytopenic purpura.

Background: Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP) is a potentially fatal disease caused by failure cleaving von Willebrand factor (VWF) due to severe deficiency of plasma ADAMTS13. Although ADAMTS13 activity is useful for diagnosis, there are not yet sufficient markers to predict prognosis of acute iTTP. Ultra-large VWF multimers (UL-VWFM) usually appear in acute iTTP. However, UL-VWFM may not occur in severe iTTP with inflammation or DIC, as VWF can be degraded by factors other than ADAMTS13, such as neutrophil elastase.

Aims: To determine the relationship between UL-VWFM and prognosis of acute iTTP patients.

Methods: Using VWF multimers analysis and ADAMTS13-dependent VWF degradation product (VWF-DP) to evaluate the relationship between UL-VWFM and severity in acute iTTP patients in our hospital, and in deceased patients with iTTP in Nara Medical University TMA registry.

Results: In 13 patients with acute iTTP in our hospital, 4 patients had UL-VWFM at diagnosis (Group A), and 9 patients did not (Group B). Group B had significantly higher LDH and total-bilirubin at diagnosis, prolonged thrombocytopenia, significantly more plasma exchange and rituximab therapy, and higher mortality than Group A. UL-VWFM, not observed at diagnosis in Group B, appeared during the course of therapy. Next, in 17 deceased iTTP patients in the TMA registry, all cases did not have UL-VWFM at diagnosis (all cases were Group B). They could be further classified into two groups: those with loss of HMW-VWFM at diagnosis (Group B1) and the others (Group B2), and Group B1 had higher D-dimer level. There was a positive correlation between HMW-VWFM ratio and VWF-DP/VWF:Ag ratio (that is, VWF-DP was low in loss of HMW-VWFM), suggesting that VWF degradation or consumption was not dependent on ADAMTS13 in Group B1.

Conclusion(s): Acute iTTP without UL-VWFM at diagnosis have poor prognosis. Factors other than AMDATS13 may contribute to VWF degradation or consumption in severe iTTP.