STUDY OF MICROVASCULAR DAMAGE IN PATIENTS WITH THROMBOTIC THROMBOCYTOPENIC PURPURA (MITHO)

The goal of this interventional, non-pharmacological clinical study is to assess microcirculatory dysfunction in patients with thrombotic thrombocytopenic purpura (TTP), both during the acute phase and in remission, compared with the general population.

Microcirculatory damage will be defined as the presence of at least one abnormal instrumental finding among brain magnetic resonance imaging (MRI), optical coherence tomography angiography (OCT-A), and nailfold videocapillaroscopy.

This is a monocentric, national study including two patient cohorts:

Cohort 1: patients enrolled during the acute phase Cohort 2: patients enrolled during remission Participants will be followed for three years with a total of five study visits.

Researchers will not test any drug but will perform detailed clinical, laboratory, and instrumental assessments to evaluate microvascular involvement over time.

Participants will:

• Undergo clinical evaluation, including internal medicine and neurological assessments
• Provide blood and urine samples for laboratory analyses
• Undergo instrumental examinations such as brain MRI, OCT-A, and nailfold videocapillaroscopy
• Receive psychological/neuropsychological evaluations
• Attend follow-up visits over a 3-year period (at baseline, 3 months [cohort 1 only], 12, 24, and 36 months)

Study Overview

• Status: Active, not recruiting
• Conditions: TTP - Thrombotic Thrombocytopenic Purpura
• Intervention / Treatment: Diagnostic test: Factor VIII (FVIII); Diagnostic test: Von Willebrand factor (VWF) antigen; Diagnostic test: VWF:RCo; Diagnostic test: VWF-propeptide; Diagnostic test: VWF multimers; Diagnostic test: sP-selectin; Diagnostic test: sCD40L; Diagnostic test: F1+2; Diagnostic test: VEGF-A; Diagnostic test: VCAM; Diagnostic test: ICAM; Diagnostic test: IL-1β; Diagnostic test: IL-6; Diagnostic test: PTX3; Diagnostic test: BlyS; Diagnostic test: Neutrophil elastase and myeloperoxidase (NETs) markers; Diagnostic test: soluble C5b-9; Diagnostic test: C5a; Diagnostic test: NFL; Diagnostic test: GFAP; Genetic: Whole exome sequencing - WES; Diagnostic test: Proteomic Analysis; Diagnostic test: evaluation of thrombus formation with Total Thrombus formation Analysis System (T-TAS); Diagnostic test: Microfluidic Flow Chamber

• Study Type: Interventional
• Enrollment (Estimated): 79
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milano
    • Milan, Milano, Italy, 20122
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• aged ≥18 years
• with a confirmed diagnosis of TTP (either congenital or acquired immune-mediated TTP)
• referred at our hospital (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico) in acute phase of a first or recurrent episode (cohort 1) or referred at our outpatient clinic (S.C. Medicina - Emostasi e Trombosi) during clinical remission at more than 3 months from the clinical response of the previous episode (cohort 2). In any case, patient enrolment will always take place in the S.C. Medicina - Emostasi e Trombosi
• providing a signed informed consent

Exclusion Criteria:

- Patients who do not possess the above inclusion criteria or have known contraindications to the instrumental exam included in the study (MRI).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Acute TTP; Patients enrolled during acute phase (cohort 1), T0= within 15 days from hospital admission.	Diagnostic test: Factor VIII (FVIII); The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: Von Willebrand factor (VWF) antigen; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VWF:RCo; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VWF-propeptide; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VWF multimers; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: sP-selectin; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: sCD40L; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: F1+2; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VEGF-A; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VCAM; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: ICAM; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: IL-1β; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: IL-6; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: PTX3; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: BlyS; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: Neutrophil elastase and myeloperoxidase (NETs) markers; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: soluble C5b-9; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: C5a; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: NFL; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: GFAP; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Genetic: Whole exome sequencing - WES; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: Proteomic Analysis; The study is defined as interventional because it includes assessments that are not part of routine clinical practice
Other: Remission TTP; Patients enrolled during clinical remission (cohort 2), T0= check-up visit performed at more than 3 months from clinical response of the previous episode	Diagnostic test: Factor VIII (FVIII); The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: Von Willebrand factor (VWF) antigen; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VWF:RCo; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VWF-propeptide; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VWF multimers; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: sP-selectin; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: sCD40L; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: F1+2; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VEGF-A; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: VCAM; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: ICAM; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: IL-1β; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: IL-6; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: PTX3; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: Neutrophil elastase and myeloperoxidase (NETs) markers; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: soluble C5b-9; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: C5a; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: NFL; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: GFAP; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Genetic: Whole exome sequencing - WES; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: Proteomic Analysis; The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: evaluation of thrombus formation with Total Thrombus formation Analysis System (T-TAS); The study is defined as interventional because it includes assessments that are not part of routine clinical practice; Diagnostic test: Microfluidic Flow Chamber; The study is defined as interventional because it includes assessments that are not part of routine clinical practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence	Prevalence of microcirculation damage in iTTP patients compared to general population	From enrollment to the last visit (after 36 months from T0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral microcirculation lesions	Evaluate cerebral microcirculation lesions (via brain MRI) in both acute and remission phases of TTP to monitor organ damage progression over time	From enrollment to the last visit (after 36 months from T0)
Retinal microcirculation changes	Assess retinal microcirculation changes (using OCT and OCT-A) during acute and remission phases of TTP to track organ damage evolution	From enrollment to the last visit (after 36 months from T0)
Peripheral microcirculation	Analyze peripheral microcirculation (with nailfold videocapillaroscopy) in acute and remission phases to evaluate progression of organ involvement in TTP	From enrollment to the last visit (after 36 months from T0)
Association between cerebral MRI lesions and cognitive or psychological symptoms	Explore the relationship between cerebral MRI lesions and cognitive or psychological symptoms during TTP remission, assessing symptom progression	From enrollment to the last visit (36 months from T0)
Modification of preclinical biomarkers	Explore the modification of preclinical biomarkers over time at different stage of the disease	From enrollment to the last visit (36 months from T0)
Associations between preclinical biomarkers and microcirculatory damage	Identify associations between preclinical biomarkers and microcirculatory damage in both acute and remission phases of TTP to predict risk and progression	From enrollment to the last visit (36 months from T0)

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Collaborators: Istituto Auxologico Italiano; Politecnico di Milano; Centro Cardiologico Monzino

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2026
• Primary Completion (Estimated): January 31, 2031
• Study Completion (Estimated): January 31, 2032

Study Registration Dates

• First Submitted: May 22, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Thrombophilia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombotic Thrombocytopenic; Investigative Techniques; Genetic Techniques; Sequence Analysis; Sequence Analysis, DNA; Whole Genome Sequencing; Exome Sequencing
• Other Study ID Numbers: IRCCSMaggioreH (IRCCSMaggioreH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No