In rare late onset case, woman’s congenital TTP starts in adulthood
Severe kidney impairment also marked diagnosis for 23-year-old: Report
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Congenital thrombotic thrombocytopenic purpura (TTP) typically develops in infancy or early childhood, but clinicians have now reported a rare case involving a young woman in Germany for whom the first signs of the bleeding disorder appeared in early adulthood.
The 23-year-old woman had received hospital treatment for a knee injury but then developed nausea and vomiting the following day. She was transferred to a second hospital after a reevaluation at the first treatment center found low levels of platelets, which help the blood clot, as well as severe acute kidney injury — a finding that, the researchers noted, is not usually seen in TTP.
She was ultimately diagnosed with congenital TTP (cTTP) after genetic testing showed disease-causing mutations in both copies of the ADAMTS13 gene.
“The present case is notable for its atypically late onset, with pronounced renal [kidney] impairment at first presentation — an uncommon feature in cTTP,” the researchers wrote.
A report detailing the woman’s diagnosis, titled “Late Onset of Congenital TTP: Case Presentation and Review of the Literature,” was published in the journal Clinical Medicine Insights: Case Reports.
TTP is a blood disorder in which small blood clots form in blood vessels, leading to organ damage. It is caused by a deficiency of the ADAMTS13 enzyme, which is normally needed to prevent platelets — small cell fragments that help form blood clots — from developing clots when they aren’t needed.
When this enzyme is deficient or absent, small clots can form in blood vessels throughout the body, a process known as thrombotic microangiopathy. It can lead to low platelet counts, red blood cell destruction, and organ damage.
The condition is most commonly acquired and develops when patients begin producing antibodies that target ADAMTS13, preventing the enzyme from functioning properly. But about 3%-5% of all TTP cases are congenital, meaning that inherited mutations in the ADAMTS13 gene cause the enzyme to be abnormal or missing.
Congenital TTP usually first seen early in life
The vast majority of cTTP cases manifest early in life, with patients experiencing repeated episodes of red blood cell destruction in damaged blood vessels and low platelet levels. These episodes are often triggered by infections or other physical stressors.
There have been reports of cTTP manifesting in adulthood, often triggered by pregnancy, but some of these patients had received transfusions shortly after giving birth. Thus, it is possible that the adult-onset presentations for these patients were simply a reactivation of the disease, according to the researchers.
The team noted that individuals with cTTP often have mild reductions in platelet levels and normal kidney function. Now, however, a trio of German researchers reported the case of young woman who was diagnosed with cTTP and showed both severely low platelet counts and severe kidney impairment.
The woman had sought follow-up medical care after developing persistent nausea, vomiting, and abdominal and back pain following a knee injury treated at the first hospital. She then was transferred to the second hospital.
Laboratory tests revealed low platelet levels, signs of red blood cell destruction, and impaired kidney function, consistent with thrombotic microangiopathy, according to the report. A pregnancy test came back negative.
Further analyses showed that her ADAMTS13 activity was severely reduced, leading clinicians to initially suspect acquired TTP. She was given therapies commonly used for the acquired form, but blood tests did not detect anti-ADAMTS13 antibodies, and her enzyme activity remained very low, raising suspicion for an inherited form of the disease.
Given the rarity of TTP, early recognition requires a high degree of clinical suspicion, particularly in the presence of [red blood cell destruction in small blood vessels] and [low platelet levels]. … Rapid diagnostic confirmation and timely initiation of treatment are critical.
Genetic analysis ultimately confirmed the diagnosis of cTTP. Following this, her treatment was adjusted to regular plasma infusions to replace the missing enzyme.
After one year, the patient remained clinically stable, her kidney function returned to normal, and there was no disease recurrence, per the researchers.
“Given the rarity of TTP, early recognition requires a high degree of clinical suspicion, particularly in the presence of [red blood cell destruction in small blood vessels] and [low platelet levels],” the researchers concluded, noting that “rapid diagnostic confirmation and timely initiation of treatment are critical.”
