Identification of Biomarkers in Patients with Thrombotic Thrombocytopenic Purpura Presenting with Large and Small Ischemic Stroke

Abstract

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder resulting in organ damage including ischemic strokes. We sought to characterize the neuroimaging patterns of stroke in a large cohort of patients with immune-mediated TTP (iTTP) and determined their associations with clinical and laboratory parameters and outcomes. Methods: We analyzed the Alabama TTP Registry who had laboratory confirmation of acute iTTP. We reviewed the neuroimaging patterns of those with ischemic stroke on MRI, clinical information, and laboratory results. Small ischemic strokes were ≤20 mm in their maximum diameter in the axial plane. Large ischemic strokes were >20 mm. Student t test, Mann-Whitney U test, and χ2 test were all used for data analysis. Results: Of 108 iTTP patients, 21 had ischemic stroke on neuroimaging. The median platelet count in these patients was 12 × 109/L (interquartile range, IQR, 8.8–21 × 109/L), plasma ADAMTS13 activity 1.8 U/dL (IQR 0–4.5 U/dL), and the mean plasma level of anti-ADAMTS13 IgG was 6,595.8 U/mL (SD 3,448.9 U/mL). Comparison between patients with large ischemic strokes (n = 10) and small ischemic strokes (n = 11) revealed that patients with small stroke were older (p = 0.043) and had higher plasma levels of citrullinated histone 3 (p = 0.006) and histone/DNA complex (p = 0.014) than those with large strokes. There were no significant differences between 2 stroke groups in mortality or exacerbation. Conclusions: iTTP patients can present with large ischemic strokes and are usually younger. Further research should be performed in assessing different etiologies of iTTP-associated stroke based on neutrophil extracellular trap formation biomarkers (e.g., histone markers) seen in small ischemic stroke.

Neurological manifestations in thrombotic microangiopathy: Imaging features, risk factors and clinical course

“…Despite the worse clinical presentation at diagnosis, the clinical course during hospitalization was similar to that observed in patients with mild or no neurological manifestations, since the number of TPE sessions needed for TMA remission, the duration of hospitalization and death did not substantially differ between the groups. Similar findings have been recently reported by other studies, in which neurological manifestations were not associated with disease exacerbation or mortality [29][30][31]. Neurological manifestations during an acute TMA event, however, seem to have an important impact on the development of cognitive disorders in the future, leading to depression, anxiety, and intellectual impairment [32].…”

“…The lack of ADAMTS13 tests is explained by the fact that, despite being necessary to confirm TTP diagnosis, the test is not easily available in the real world, particularly in low-and middle-income countries. For that reason, the PLASMIC score has been used to predict low ADAMTS13 activity [19][20][21][22][23][24][25][26][27][28][29][30][31][32]. The use of PLASMIC score in this study allowed us to suspect that most of our patients had TTP even though ADAMTS13 results were not available.…”

The standard of care for immune thrombotic thrombocytopenic purpura today

“…14,17,28 A computerized tomography (CT)/magnetic resonance imaging (MRI) scan may reveal large and/or small infarctions in the brain of patients with acute iTTP. 22,33,34 Based on these clinical and laboratory data, a presumptive diagnosis of iTTP can be made.…”

“…Approximately 50% of patients with acute iTTP may have elevated levels of serum or plasma troponins 14,30‐32 and mild to moderate elevation of serum creatine 14,17,28 . A computerized tomography (CT)/magnetic resonance imaging (MRI) scan may reveal large and/or small infarctions in the brain of patients with acute iTTP 22,33,34 . Based on these clinical and laboratory data, a presumptive diagnosis of iTTP can be made.…”

Systemic sclerosis complicated with renal thrombotic microangiopathy: a case report and literature review

“…The severe deficiency of ADAMTS13 appearing in TTP is defined as < 5–10% of normal protease activity. ADAMTS13 activity > 10% can help in the exclusion of TTP diagnosis [ 13 – 15 ]. Our case showed normal ADAMTS13 activity (74.2%) and negative ADAMTS13 antibody.…”