Doctors solve medical mystery to treat rare clotting disease with plasma
Regular infusions successfully managed atypical, late-onset hereditary TTP
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When a 55-year-old man developed sudden kidney failure, doctors discovered a rare blood-clotting disorder hiding behind a highly unusual genetic profile. A new case report reveals that regular infusions of fresh frozen plasma successfully managed his late-onset form of hereditary thrombotic thrombocytopenic purpura (TTP).
The case highlights the critical importance of testing for this rare disorder in patients who experience unexplained kidney failure and blood vessel damage.
Typically, hereditary TTP occurs when a person inherits mutations in both copies of the ADAMTS13 gene. However, this patient’s genetic profile was highly unusual, revealing a mutation in only one copy of the gene along with other genetic variants of unclear significance.
The case “illustrates the value and limitations of genetic testing,” researchers wrote in their case report “Adult-Onset Hereditary Thrombotic Thrombocytopenic Purpura Presenting as Kidney Failure: A Heterozygous ADAMTS13 Variant and Possible Modifying Polymorphisms,” which was published in Kidney 360.
Understanding how ADAMTS13 affects clotting
In hereditary TTP, mutations in the gene that instructs the body to make the ADAMTS13 enzyme lead to its absence or malfunction. Normally, ADAMTS13 helps prevent platelets from forming unnecessary clots. Without it, clots can block small blood vessels, causing symptoms.
The researchers detailed the man’s unusual case after he developed sudden kidney failure with no prior history or obvious triggers. He was admitted to the hospital with high blood pressure and rapidly declining kidney function on top of existing kidney disease from diabetes.
Urine tests showed large amounts of protein (albuminuria) and small amounts of blood (microscopic hematuria), signaling severe kidney damage. Blood tests revealed anemia and low platelet counts, along with signs of red blood cell destruction (hemolysis), although standard blood clotting times appeared normal.
These findings suggested thrombotic microangiopathy, a condition that damages organs, especially the kidneys, by blocking tiny blood vessels. Doctors started treatment with Soliris (eculizumab), an antibody that inhibits the complement system, a part of the immune system that can trigger some forms of thrombotic microangiopathy. However, his kidney function continued to decline after two doses.
The man developed high potassium levels and required dialysis, which filters waste and extra fluid from the blood when the kidneys can no longer do so. He also experienced confusion and temporary weakness in his right leg, though a brain scan showed no abnormalities.
A subsequent test revealed extremely low ADAMTS13 activity at 8 U/dL, below the normal range of 61 to 131 U/dL. Because no antibodies against the enzyme were present, doctors ruled out acquired TTP and diagnosed the hereditary form. They started infusions of fresh frozen plasma, which contains healthy ADAMTS13. This treatment eased hemolysis and cleared the patient’s confusion.
Long-term management and genetic questions
A kidney biopsy confirmed active blood vessel clotting on top of his pre-existing kidney disease. Because the damage was already too severe, his kidneys did not recover, and Soliris was stopped after three months because it was not providing benefit.
Genetic testing found one disease-causing mutation in the ADAMTS13 gene, called c.587C>T (p.Thr196Ile). While testing ruled out large missing pieces of DNA, it did find several other common genetic variants with unknown effects.
Even though the patient’s genetics were atypical, his response to fresh frozen plasma supported the diagnosis of hereditary TTP. His enzyme activity increased more than fourfold following treatment. He was placed on regular infusions every two weeks to maintain healthy ADAMTS13 levels, and his blood counts have remained stable, with no further episodes of anemia or low platelet counts.
“This case highlights a late-onset, atypical presentation of hereditary TTP and raises important questions,” the researchers wrote. “It underscores the need to consider ADAMTS13 deficiency in unexplained thrombotic microangiopathy and kidney failure, even in the absence of classic features.”
While the man remains on dialysis due to permanent kidney scarring, he was active on the kidney transplant waiting list at the time of the report’s publication.
