The Role of interferOn and Complement in SecondAry thRombotic micrioangiOpathy

Inclusion criteria

Participants eligible for inclusion in this study must meet all of the following criteria:

• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
• At least 18 years of age at the time of signing the Informed Consent Form (ICF)

Specifically for the patients with TMA (G1 and G4):

• Patients after allogeneic or autologous hematopoietic stem cell transplantation (HSCT) OR patients after solid organ transplantation OR patients with DITMA AND
• Tissue diagnosis of TMA (pathological diagnosis) OR
• Clinical diagnosis of TMA based on the following criteria, with ≥4 out of 6 features fulfilled within 14 days (15,52,53):

• de novo Coombs negative hemolytic anemia OR (in case of HSCT)

• failure to achieve transfusion independence despite neutrophil engraftment
• hemoglobin decline by ≥ 1g/dL
• new onset transfusion dependence
• otherwise unexplained de novo thrombocytopenia (< 50 x 109/L) OR a 25% decrease in platelet count OR (in case of HSCT)

• failure to achieve platelet engraftment despite neutrophil engraftment
• higher than expected transfusion needs
• refractory to platelet transfusion *≥50% reduction in platelet count after full platelet engraftment
• lactate dehydrogenase (LDH) above the upper limit of normal
• schistocytes (=>2 / high power field (HPF)
• new onset hypertension OR worsening of existing hypertension requiring additional antihypertensive therapy
• proteinuria > 1g/g creatinine on a random urine protein-to-creatinine ratio Date of TMA diagnosis = first date when ≥4 out of the 6 features are fulfilled.

Specifically for the group of patients without TMA, with infection (G2):

• Patients after allogeneic or autologous hematopoietic stem cell transplantation (HSCT) OR patients after solid organ transplantation AND
• Symptomatic viral infection (evaluated by the treating physician).

Specifically for the group of patients without TMA, without infection (G3):

• Patients after allogeneic or autologous hematopoietic stem cell transplantation (HSCT) OR patients after solid organ transplantation AND
• No symptomatic viral infection (evaluated by the treating physician).

Exclusion criteria

Participants eligible for this study must not meet any of the following criteria:

• Participant has a personal or family history of aHUS
• Participant has a history of malignant hypertension
• Participant has a history of active cancer, excluding the haematological cancer for which the patient received the stem cell transplantation (if applicable)
• The participant received prior complement inhibition
• The participant received prior anti-interferon treatment
• If applicable: Female who is pregnant, breast-feeding or intends to become pregnant the following year or is of child-bearing potential and not using an adequate, highly effective contraceptive
• Participation in an interventional study with an investigational medicinal product (IMP) or device