A Prospective Study on the Long-Term Vascular Burden in Thrombotic Thrombocytopenic Purpura Patients

Study Overview
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Brief Summary
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A prospective cohort study of thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome patients who have presented with their acute episode and are in remission within the last 30 days. They will be followed for 12 months from the time of their initial scan, followed by a long-term follow up study.

Detailed Description
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The investigators will conduct a prospective cohort study at the London Health Sciences Centre, Ontario, Canada. The investigators will identify 15-30 idiopathic thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome patients who are in remission within the last 30 days. They will be followed for 12 months from the time of their remission. Study procedures include routine laboratory monitoring, biomarker assessments, cardiovascular and neurocognitive functional assessments, and non-invasive imaging studies. The long-term follow-up thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome study will help to assess the mechanisms of vascular injuries, evaluate cardiovascular and cerebrovascular monitoring tools, and generate novel ideas to prevent further vascular injuries.

Official Title
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A Prospective Study on the Long-Term Vascular Burden in Thrombotic Thrombocytopenic Purpura Patients

Conditions
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Thrombotic Thrombocytopenic Purpura

Intervention / Treatment
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* Diagnostic Test: CT Perfusion Study
* Diagnostic Test: Echocardiogram
* Diagnostic Test: neuro-cognitive assessment
* Diagnostic Test: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (=18 years) with a recent diagnosis of their first episode of idiopathic TTP, who have been treated with plasma exchange with or without other therapies, and who are in remission. Remission is defined as the normalization of platelet counts and lactate dehydrogenase levels with no clinical signs or symptoms of microvascular injury for more than 30 days. The patients will be included in the study within 30 days of remission of their symptoms. The patients will all meet the following diagnostic criteria for idiopathic TTP: (1) thrombocytopenia with platelet count <150 x 109 /L, (2) microangiopathic hemolytic anaemia (presence of red blood cell fragmentation by peripheral blood smear), (3) elevation of lactate dehydrogenase (LDH)> 1.25 X of the upper limit of normal, and (4) ADAMTS13 Activity < 10% Exclusion Criteria: Patients will be excluded if they have diagnoses of typical HUS (diarrhea-associated HUS), atypical HUS, and disseminated intravascular coagulation, have abnormal international normalized ratio at the time of presentation, have diagnoses of malignant hypertension at the time of presentation, are on the following drugs within 90 days prior to their presentation: ticlopidine, clopidogrel, mitomycin C, gemcitabine, cyclosporine, and quinine, have a history of hematopoietic stem cell transplantations prior to their presentation, have a history and/or diagnosis of vasculitis, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, antiphospholipid antibody syndrome, or HIV/AIDS, have a history of solid organ malignancy within 5 years prior to presentation, i.e. lung, breast, gastric, colon, pancreatic, prostate, or liver, are pregnant at the time of presentation, have severe bronchospasm, unstable angina, and severe ischemic heart disease, have advanced kidney failure (estimated Glomerular Filtration Rate < 30 mL/min/1.73m2), and have history of allergic reaction to contrast dye.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: CT Perfusion Study|Brain and cardiac CT perfusion scan|
|Diagnostic Test: Echocardiogram|Speckle tracking Echocardiography|
|Diagnostic Test: neuro-cognitive assessment|Cambridge Brain Sciences neuro-cognitive assessment|
|Diagnostic Test: MRI|MRI to assess white matter changes|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vascular events affecting the brain and heart | The investigators will report the proportion of patients who have functional and/or structural vascular events affecting the brain and heart, after the first acute idiopathic TTP events | 0-12 months |