Congenital thrombotic thrombocytopenic purpura presenting in adulthood with recurrent cerebrovascular events

Abstract

Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, life-threatening disease, characterised by episodes of microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and small vessel thrombosis. We describe a case of cTTP first diagnosed at age 70 years in a female presenting with an acute ischaemic stroke and thrombocytopenia, in whom A Disintegrin And Metalloproteinase with a Thrombospondin type 1 Motif, member 13 (ADAMTS13) levels were <10%, suggestive of thrombotic thrombocytopaenic purpura (TTP). The patient underwent plasma exchange and started rituximab for presumed immune TTP; however, anti-ADAMTS13 antibody titres were negative on two occasions. This, together with a history of pregnancies complicated by presumed disseminated intravascular coagulation, and two previous episodes of sepsis with MAHA, prompted investigation for cTTP, which was confirmed by genetic testing. Despite treatment with infusions of solvent/detergent-treated, virus-inactivated fresh frozen plasma, she has re-presented with further neurological deficit, associated with new infarcts on imaging. cTTP has a varied phenotype which, as demonstrated in this case, can include large vessel occlusion.

Morbidities and mortality in patients with hereditary thrombotic thrombocytopenic purpura

“…Prophylactic treatment was reported for 110 (53%) of the 207 symptomatic patients who survived infancy. Prophylaxis began at a median age of 14 years (range, newborn 21 -70 23 years). Prophylaxis was almost always with plasma, commonly described as 1 to 3 units of plasma at 2- to 3-week intervals.…”

Two ischemic stroke events within 48 h: a case report of an unusual presentation of thrombotic thrombocytopenic purpura

“…Similar to the prolonged course of treatment in our patient, studies showed that high titers of inhibitors of ADAMTS-13 are associated with delayed response to therapy, high risk of complications, and higher rates of refractory disease and relapses [ 19 , 20 ]. Of note, while there are reports of patients with TTP who presented with IS as an atypical presentation [ 15 , 21 ], there are very few reports of new ischemic lesions during hospitalization following the first ischemic stroke event [ 14 , 15 ]. One was a 70-year-old female who presented with confusion, fever, and gastrointestinal symptoms who deteriorated neurologically during hospitalization, and the brain MRI revealed multiple acute and subacute infarcts in both cerebral hemispheres, midbrain, and right cerebellum.…”

“…One was a 70-year-old female who presented with confusion, fever, and gastrointestinal symptoms who deteriorated neurologically during hospitalization, and the brain MRI revealed multiple acute and subacute infarcts in both cerebral hemispheres, midbrain, and right cerebellum. The patient had a history of hypertension, diabetes, rheumatoid arthritis, two miscarriages complicated by disseminated intravascular coagulation, two transient ischemic attacks, and a left occipital infarct and she was diagnosed with congenital TTP [ 14 ]. Another one was a 43-year-old female who was admitted with left hemiparesis, homonymous hemianopia, and dysarthria.…”

“…There was no evidence of venous thrombosis or vascular lesions on magnetic resonance angiography (MRA) and magnetic resonance venography (MRV). Since malignant bone marrow infiltration is one of the main differential diagnoses in a patient with MAHA and thrombocytopenia [ 14 ], hematology was consulted. They asked for a bone marrow aspiration and biopsy (day 8), which showed normocellular marrow with increased erythroid series.…”

“…Second, stroke is considered to be an unusual inaugural presentation of TTP. Third, there are currently very few reports of new ischemic lesions during hospitalization in individuals with iTTP following the first ischemic stroke event [ 14 , 15 ]. Notably, some of these patients had the congenital type of the disease, making our patient even more intriguing.…”