Correlation between ADAMTS13 activity and neurological impairment in acute thrombotic microangiopathy patients

Abstract

Differential diagnosis between thrombotic thrombocytopenic purpura (TTP) and other thrombotic microangiopathies (TMA) is usually difficult because of frequently overlapping clinical presentations. Severely depressed ADAMTS13 activity (<10 %) seems distinctive for TTP because of its pathogenetic role. However a long debate exists in the literature about its sensibility and specificity. Our aim was to search for clinical differences between TMA patients referred to our laboratory, comparing them for protease activity <10 versus ≥10 %. ADAMTS13 activity ≥10 % patients (n = 73) showed a higher prevalence of drug- (p = 0.005) and cancer-associated (p < 0.001) TMA. Mean platelet count and renal dysfunction prevalence was lower (p < 0.001), while neurological impairment was more frequent (p = 0.001) in the <10 % ADAMTS13 activity group (n = 109), confirming previous literature findings. When taken neurological manifestations singularly, epilepsy (p = 0.04), focal motor deficit (p < 0.001) and cranial nerve palsy (p = 0.007) were more frequent in the <10 % activity group. In our case series, a <10 % ADAMTS13 activity depicts a group of patients with clinical features similar to TTP patients. Focal motor impairment or epileptic manifestations could further address toward a TTP diagnosis. Studies about treatment efficacy and follow-up are advised to determine whether laboratory findings can guide therapeutic decisions.

Clinical presentation in thrombotic thrombocytopenic purpura: Real‐world data from two Mexican institutions

“…35 In our study, ADAMTS13 activity was measured in only 12 patients; an activity of 0% was found in 10 patients, all of whom had an ADAMTS13 inhibitor. Furthermore, the predominance of neurological symptoms over kidney failure in patients with severe reduction of ADAMTS13 activity (<10%) has been reported, 28 an observation that was confirmed in our study.…”

“…However, fevers were more frequent in Chinese and Korean patients, with a prevalence higher than 50% . Additionally, more than half of the patients included in our analysis (60%) had some form of hemorrhagic manifestation, and in concordance with other studies, the appearance of cutaneous purpura was the most common . The prevalence of digestive symptoms was higher in our study than described elsewhere; they were present in 45% of patients, all of whom presented with nausea or vomiting.…”

“…24,27 Additionally, more than half of the patients included in our analysis (60%) had some form of hemorrhagic manifestation, and in concordance with other studies, the appearance of cutaneous purpura was the most common. 28 The prevalence of digestive symptoms was higher in our study than described elsewhere 10,[30][31][32] ; they were present in 45% of patients, all of whom presented with nausea or vomiting. Cardiorespiratory symptoms, such as dyspnea or chest pain, may suggest myocardial involvement.…”

“…10 An Italian study showed that neurological manifestations are more frequent in patients with severe ADAMTS13 deficiency, especially focal motor deficits and seizures. 28 Remarkably, 85% of our patients had systemic, nonspecific symptoms, with generalized malaise being the most frequent. Similar to other studies, initial appearance of a fever was not common; it was present in less than a third of cases.…”

“…In a British study including patients with congenital, idiopathic, and secondary TTP, more than 80% of patients had neurological symptoms at presentation; confusion was the most common in idiopathic TTP with a prevalence of 21%, followed by transient ischemic attack (15%), and coma (10%) . An Italian study showed that neurological manifestations are more frequent in patients with severe ADAMTS13 deficiency, especially focal motor deficits and seizures …”