Study rationale: Viral infections, such as CMV, are a risk factor for TA-TMA (transplantation-associated TMA). Viral infections increase interferon (IFN) levels and high IFN levels are associated with thrombotic microangiopathy (TMA). IFNs contribute to TMA pathogenesis through suppression of VEGF transcription. Disruption of the VEGF signalling pathway in the kidney is associated with TMA.

Primary objective: To determine the association between IFN levels and the development of biopsy-proven or clinically diagnosed TA-TMA.

Secondary objective(s): To explore the relationship between complement activation and IFN in patients with TMA.

To explore if high IFN levels are associated with low VEGF-A levels. Endpoint: The study aims to investigate the role of IFN in the pathogenesis of secondary thrombotic microangiopathy (focusing on patients with TA-TMA). It seeks to clarify whether IFN, next to complement dysregulation, is a driver of endothelial damage and TMA in these patients.

Inclusion Criteria:

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

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. 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):

1. Patients after allogeneic or autologous hematopoietic stem cell transplantation (HSCT) OR patients after solid organ transplantation OR patients with DITMA AND

2. Tissue diagnosis of TMA (pathological diagnosis) OR

3. 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):

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

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

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

Exclusion Criteria:

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

1. Participant has a personal or family history of aHUS
2. Participant has a history of malignant hypertension
3. Participant has a history of active cancer, excluding the haematological cancer for which the patient received the stem cell transplantation (if applicable)
4. The participant received prior complement inhibition
5. The participant received prior anti-interferon treatment
6. 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
7. Participation in an interventional study with an investigational medicinal product (IMP) or device