iTTP Marked by Reversible Skin Microvascular Hyporeactivity, Study Finds

People with immune-mediated thrombotic thrombocytopenic purpura (iTTP) have significantly impaired skin endothelial-mediated microvascular reactivity, according to a new study, but the situation appears to reverse during plasma exchange (PE) therapy.

The study, published in Critical Care, could broaden scientists’ understanding of organ injury pathophysiology in the disease.

Thrombotic thrombocytopenic purpura is a rare disease that can come in acquired or immune-mediated forms and is marked by thrombocytopenia and hemolytic anemia. In its immune-mediated form, neutralizing anti–ADAMTS-13 autoantibodies impair cleavage of von Willebrand factor (VWF) mega-multimers, ultimately leading to inadequate microvascular blood flow, tissue ischemia, and multiorgan failure, explained the study authors.

“Therefore, the iTTP pattern combines hemolytic anemia, thrombocytopenia, often with neurologic, cardiac, or renal abnormalities, still associated with a 10%-20% death rate,” they wrote.

Patients are typically treated with PE, immunosuppression, and the VWF-directed antibody therapy caplacizumab (Cablivi).

Although the effects of the disease on the heart and the brain have been well documented, the study authors said the disease’s impact on the endothelium has been less well explored. They therefore decided to look at endothelial-mediated vasoreactivity in patients with iTTP compared with controls and at any changes in that reactivity following therapy.

The authors prospectively tracked 18 adult patients admitted to the intensive care unit with confirmed iTTP cases. Seventy-two percent of the participants in the iTTP group were women, and the mean age of iTTP participants was 43 years. The authors compared those patients with a control cohort of 34 patients with diabetes after correction of ketoacidosis who were included in a previously published study.

“Such a control cohort was relevant because patients were young with rare comorbidities and no severe organ failure,” the investigators explained.

Neurological and cardiac issues at admission were common in the iTTP group (55% and 50%, respectively), and more than one-quarter of the patients (27.8%) had acute kidney injury. Upon admission, patients in the iTTP group had 2-fold lower skin microvascular blood flow compared with the control group, and “marked impaired endothelial-mediated microvascular reactivity,” the authors reported (mean [SD] area under the curve, 9627 [8122] vs 16,475 [11,738]; P = .03).

“This profoundly impaired microvascular vasoreactivity is similar to what our group previously observed in other critical conditions characterized by patent endothelial dysfunction such as critically ill COVID-19 septic shock or severe ketoacidosis,” the authors wrote.

However, reactivity improved after the first PE session, and improved yet again following the second PE session, they added.

The authors said their findings suggest that the impairment of microvascular reactivity in patients with iTTP could participate in organ injury, aside from the thrombotic process of the disease.

Although reactivity improved following plasma therapy, the investigators said that improvement cannot be directly linked to PE because almost all of the patients in the study were also being treated with steroids and caplacizumab at the time.

“Currently, there are no experimental data about the effect of caplacizumab on endothelial microvascular reactivity,” they noted.

They conceded that their study was a small, single-center study, which may limit the generalizability of their results. However, they said their findings offer important new insights into one aspect of iTTP that has historically been poorly understood.

Reference

Joffre J, Raia L, Urbina T, et al. Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura. Crit Care. Published online March 21, 2023. doi:10.1186/s13054-023-04405-w