Abstract: TH-PO610

Upshaw–Schulman Syndrome

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Afzal, Muhammad, OU Tulsa, Tulsa, Oklahoma, United States
  • Baradhi, Krishna M., None, TULSA, Oklahoma, United States
Background

Hereditary Thrombotic Thrombocytopenic Purpura (TTP) is an extremely rare life threatening disorder characterized by thrombotic microangiopathy caused by severely reduced activity of the von-Willebrand factor-cleaving protease ADAMTS13. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia and microangiopathic hemolytic anemia.

Methods

A male infant who was cyanotic at birth was found to have thrombocytopenia of 18000/microliter presumed to be from sepsis as it improved with platelet transfusion and antibiotics. This was followed by recurrent hospitalizations every few years either for diarrhea or anemia or renal failure in the context of severe thrombocytopenia. However, each time, he was misdiagnosed as Evan’s syndrome or Hemolytic uremic syndrome(HUS) until he succumbed to stroke at the age of 18 years. This time, as he had classical features of TTP in the form of stroke, anemia, renal failure and thrombocytopenia, an evaluation for TTP was initiated. His ADAMTS 13 activity came back as < 10% without the inhibitor. Genetic testing showed biallelic mutations in the ADAMTS13 gene. Both parents were carriers. He was diagnosed with Hereditary TTP and was started on monthly plasma infusions. His renal function eventually deteriorated by the age of 31 years requiring dialysis. He continues to have monthly plasma infusion and is relatively doing well.

Conclusion

Hereditary TTP also known as Upshaw–Schulman Syndrome is an autosomal recessive condition caused by biallelic mutations in ADAMTS13. It represents <5 percent of all TTP cases. Clinical features are similar to acquired TTP or other thrombotic microangiopathies often leading to patients being misdiagnosed as having ITP, HUS, HELLP, or Evan’s syndrome. Hereditary TTP should be considered in any one who presents with microangiopathic hemolytic anemia and thrombocytopenia in infancy, childhood or pregnancy. The diagnosis is made by demonstration of severe ADAMTS13 deficiency without an inhibitor and confirmed by demonstration of ADAMTS13 gene mutation(s). Without appropriate diagnosis and treatment, it can be life threatening. Treatment of an acute episode with plasma infusion should not be delayed while confirming the diagnosis. Plasma infusion is the treatment of choice rather plasma exchange. Recombinant ADAMTS13 is under development. All siblings of an individual with hereditary TTP should be tested.