PS1098 ADULT ONSET HEREDITARY THROMBOTIC THROMBOCYTOPENIC PURPURA WITH A NOVEL ADAMTS13 MUTATION
Authors: Freue J. , Ostriz B. Rosales , Martin M. , Campestri R. 
Published: June 2019

Background:

Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and thrombocytopenia, often accompanied by fever, renal failure and neurological deficits. It is caused by severe deficiency of the Von Willebrand factor cleaving protease ADAMTS13. Most cases of TTP are acquired, caused by autoantibodies against ADAMTS13. Hereditary TTP is an autosomal recessive condition associated with a congenital ADAMTS13 deficiency.

It is a very rare disease, usually with an onset in newborns or early childhood. Although not a very common cause of TTP in adults, in some cases it can develop in adulthood. We described a case of acquired TTP on an adult patient.

Aims:

To describe a case of an adult patient with hereditary TTP and a new ADAMTS13 mutation

Methods:

Case: a 24 years old girl was admitted for urosepsis. She has previous history of a thrombocytopenia episode as a child which was interpreted as immune thrombocytopenia and did not required treatment. Her brother also had one similar episode but neither of them have ever been studied.

Laboratory findings were as follow: hg 12 g/dl, WBC 14000/mm3 (N 78 % L9 % M10 %) platelets 55000/mm3. Tp 100% kptt 32 sec. INR 1,1. Ferritin 120ng/ml, Transferrin Saturation 9%, reticulocytes 1%. Blood smear: microcytosis, without schistocytes. Coombs test was negative. Haptoglobin was low but LDH mildly elevated. Blood cultures were positives por E. coli.

As she had no symptoms of microangiopathic anemia, cytopenia was interpreted as autoimmune which had worsened in the context of sepsis. She initiated treatment with meprednisone 1 mg/kg/day. Rapid improvement of platelet count was confirmed and she was discharged.

Antinuclear antibodies, lupic anticoagulant, anticardiolipin igg and igm, antibeta2glicoprotein igg and igm, protein electrophoresis, complement, antitiroperoxidase, hepatitis B, C and hiv, glucose 6 phosphodehydrogenase (G6PD) were normal.

Bone marrow biopsy was done, flow cytometry and pathology were normal

She consulted two weeks later for left hemianopsia. Laboratory: hg 9 g/dl WBC 5600/mm3 platelet 48000/mm3. Ldh 550 U/L (100–200) haptoglobin <8 mg/dl. Normal renal function.

Blood smear: schistocytes 10 %

Brain MRI confirmed occipital ischemia

With diagnosis of TTP (SCORE PLASMIC 7) plasmapheresis was initiated. After 10 sessions platelet count and ldh normalized and she was discharged after 2 weeks.

At subsequent clinic follow‐ups she developed again thrombocytopenia and progressive ldh increase so she was re admitted for plasma exchange. The patient was found to have ADAMST13 activity of <5%; antibodies against ADAMTS13 were negative.

As a probable case of hereditary TTP she continued treatment with plasma infusions only.

Results:

Analysis of adamt13 mutations by NGS (illumina Hiseq ©) showed 2 variants in heterocigosis in the gene of ADAMTS13:

9, 136289599, c. DNAc.330+ 1G>A (variant described in the literature)

9, 136307563, c. DNAc.2012C>A s375415632, p. P671Q (a new mutation not previously described yet)

Summary/Conclusion:

We present this case because it is an unusual pathology which rarely presents in adulthood. It is interesting the finding of a mutation in the ADAMTS13 gene that up to the date has not been described in the literature.