HEREDITARY thrombotic thrombocytopenic purpura (hTTP) is a rare and life-threatening disorder caused by a severe deficiency of the ADAMTS13 enzyme. A new study, led by Omid Seidizadeh, University of Milan, Italy, aimed to determine the prevalence of the condition to see if current estimations are accurate.
Historically, hTTP prevalence estimates have varied widely. A 2011 Japanese study suggested a prevalence of 1.1 cases per million while, in contrast, a 2015 study from Central Norway reported a higher prevalence of 16.7 cases per million, linked to the high frequency of specific ADAMTS13 mutations in the region.
This study utilised data for in exome and genome sequencing, identifying 6321 distinct ADAMTS13. Of these, 758 were determined to be pathogenic, of which 82% had not previously been found. Following analysis, the prevalence all 758 pathogenic variants, was predicted to be 40 cases per 106 and, of only the 140 previously reported variants, was estimated to be 23 per 106.
These findings suggest that hTTP prevalence is substantially higher than the currently estimated prevalence based on diagnosed patients suggesting that many patients with hTTP may not be diagnosed. The study also revealed significant variability in hTTP prevalence across different ethnic groups. East Asians had the highest estimated prevalence at 42 cases per 106, followed by Finnish and non-Finnish Europeans, while Middle Eastern and Ashkenazi Jewish populations showed much lower rates.
These results underscore the likelihood that hTTP is underdiagnosed, particularly in newborns and pregnant women, where symptoms may be mistaken for other conditions. Future early recognition of hTTP for patients with microangiopathic haemolysis and thrombocytopenia could prove beneficial for improving diagnosis and treatment outcomes
Katie Wright, EMJ
Reference
Seidizadeh O et al. Global prevalence of hereditary thrombotic thrombocytopenic purpura determined by genetic analysis. Blood Adv. 2024;8(16):4386-96.
