From the Research
Upshaw-Schulman syndrome is a rare genetic disorder caused by mutations in the ADAMTS13 gene, leading to decreased or absent production of the plasma von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS13, resulting in circulating ultra-large multimers of VWF that can cause microthrombi, intravascular occlusion, and organ damage. This condition is also known as hereditary thrombotic thrombocytopenic purpura (hTTP) 1. The diagnosis of Upshaw-Schulman syndrome is typically made by ADAMTS13 gene analysis, and patients may present with a range of clinical manifestations, including thrombocytopenia, microangiopathic hemolytic anemia, and organ damage 2, 3, 4.
Key Characteristics
- Caused by mutations in the ADAMTS13 gene
- Leads to decreased or absent production of ADAMTS13
- Results in circulating ultra-large multimers of VWF
- Can cause microthrombi, intravascular occlusion, and organ damage
Clinical Manifestations
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Organ damage, including renal impairment, cerebral infarctions, and cardiac hypofunction 5
- Patients may have many overt or clinically silent manifestations, and a high index of suspicion is required for diagnosis 1
Treatment
- The primary treatment is prophylaxis with plasma infusions or plasma-derived factor VIII products, providing sufficient ADAMTS13 to prevent acute episodes 1
- Recombinant ADAMTS13, which is near to approval, will immediately be the most effective and also the most convenient treatment 1
- Current prophylactic plasma infusion protocols may not adequately prevent long-term cumulative organ damage, and a higher dosage of ADAMTS13 supply using recombinant ADAMTS13 agent may be needed in these patients 5