High LDH may signal mortality risk in immune-mediated TTP

Cardiac, neurological symptoms not necessarily predictors, study finds

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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High levels of lactate dehydrogenase (LDH) in the blood — a sign that tissues and organs may have been damaged — may also signal a higher risk of death from immune-mediated thrombotic thrombocytopenic purpura (TTP), a study suggests.

In contrast, levels of troponin T or I — proteins that increase in the blood when the heart is damaged — and other early clinical findings related to cardiac or neurological symptoms did not appear to be linked to a higher risk of death in these patients.

“These findings suggest that early cardiac and neurological symptoms may not be definitive predictors of [immune-mediated] TTP-related death,” the researchers wrote. “Instead, extremely high LDH levels indicated a worse prognosis, highlighting the need for targeted monitoring and interventions in high-risk cases.”

The study, “Prognostic Relevance of Early Clinical and Laboratory Findings in Immune-Mediated Thrombotic Thrombocytopenic Purpura,” was published in Research and Practice in Thrombosis and Haemostasis by researchers in Japan.

Immune-mediated TTP, also known as acquired TTP, occurs when antibodies mistakenly attack an enzyme called ADAMTS13 and prevent it from working well. This enzyme normally prevents blood clots from forming when they aren’t needed. When ADAMTS13 is missing or is underactive, clots start to form in small blood vessels, blocking blood flow and leading to organ damage.

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TTP treatment usually involves plasma exchange — a procedure that helps remove disease-causing antibodies from the blood and supplies functional ADAMTS13 — along with medications that reduce the production of antibodies or prevent blood clots from forming. Despite treatment, some patients die early in the course of the disease, often due to heart or brain complications.

To identify early clinical findings that may help predict how the disease progresses, researchers drew on registry data from 125 patients, ages 8 to 88, who had been diagnosed with immune-mediated TTP. Between 2010 and 2023, 16 patients (13%) had relapses (a sudden worsening or reappearance of symptoms after a period of remission).

During that time, five patients (4%) died from immune-mediated TTP, four from sudden cardiac arrest (when the heart unexpectedly stops beating) and one from alveolar hemorrhage (bleeding into the air sacs in the lungs where gas exchanges take place). Ten (8%) died from causes unrelated to the disease.

Thirteen patients — all of whom survived — had cardiac symptoms at diagnosis, including shortness of breath with activity, chest pain, and chest discomfort. Of 112 patients with neurological data, almost all had symptoms such as impaired consciousness or confusion, headaches, and seizures. 

Results from an electrocardiogram (ECG) — a test that records the heart’s electrical activity — were available for 100 patients, and 49 showed abnormal findings. The most common was an irregular heartbeat in 21 patients, followed by T-wave abnormalities — a sign that the heart muscle may be stressed or damaged — in 10 patients. No signs of serious damage to the heart were found.

A transthoracic echocardiogram (TTE) — an ultrasound of the heart — was performed in 32 patients. Of these, 18 had abnormal findings, such as reduced blood pumping, leaky valves, or fluid buildup around the heart. One patient had a severely weakened heart muscle that later improved. However, neither ECG nor TTE findings were linked to death.

This suggests that it’s possible to recover at least some of the heart’s function “when diagnosis is made promptly and treatment is initiated without delay,” the researchers wrote. There’s a need for “early recognition and intensive management to maximize the likelihood of a favorable prognosis in TTP care,” they added.

Levels of troponin T or I were elevated in many patients, but these did not significantly differ between those who survived and those who didn’t. Similar findings were obtained in stored plasma samples from 80 other patients. Of the 10 patients with very high levels, eight survived and two died, suggesting that troponin T or I may not reliably predict prognosis in immune-related TTP.

None of the patients who died had received Cablivi (caplacizumab-yhdp), as these cases occurred before this medication, which prevents blood clots from forming, became available in Japan. In contrast, 15 survivors had been treated with it, suggesting that medications like Cablivi may extend survival, yet “more data and longer follow-up periods are required,” the researchers wrote.

Patients who died from immune-mediated TTP were older than survivors (median age 66 vs. 51) as were those who died from other causes (median age 77). However, patients who died from immune-mediated TTP had higher levels of LDH compared with both those who died from other causes (median of 2,560 units/mL vs. 1,166 units/mL) and survivors (median of 968 units/mL).

“Cardiac and neurological findings and troponin [levels] did not differ significantly among the groups,” the researchers wrote, suggesting that, contrary to earlier studies, “clinical findings did not predict disease mortality.”