High-Risk Patient Groups

Patients with Coombs-negative hemolytic anemia are at high risk for PNH^2,4

• Patients with hemolytic anemia who are Coombs-negative or have concomitant iron deficiency are more likely to present with a PNH clone²
• Coombs-negative hemolytic anemia is the clinical hallmark of PNH⁴

Patients with hemoglobinuria are at high risk for PNH^2,4

Adapted from Morado M, et al. Cytometry B Clin Cytom. 2017;92(5):361-370.

Study description: A multicenter evaluation of the frequency of cases showing PNH clone cells in 3938 peripheral blood samples at diagnosis according to the medical indications that triggered screening for PNH by flow cytometry.¹

• Hemoglobinuria is a sign of intravascular hemolysis⁴
• Only 26% of patients with PNH report hemoglobinuria at presentation⁴
• According to the ICCS and IPIG Guidelines, any patient with unexplained hemoglobinuria should be tested for PNH^2,4

Early diagnosis is essential for improved patient management and prognosis^1,2

Patients with aplastic anemia (AA) are at high risk for PNH^2,4

Adapted from Morado M, et al. Cytometry B Clin Cytom. 2017;92(5):361-370.

Study description: A multicenter evaluation of the frequency of cases showing PNH clone cells in 3938 peripheral blood samples at diagnosis according to the medical indications that triggered screening for PNH by flow cytometry.¹

• In patients with AA, the bone marrow environment can promote expansion of a PNH clone^10-12

The number of PNH cells in patients with AA may increase rapidly and unpredictably over time^2,4,13,14

• In one study of 27 patients with AA, 48% (13/27) experienced an increase in PNH clone size¹⁴
  • 81% (22/27) received immunosuppressive therapy (IST)
• In another study of 83 patients with AA and a detectable PNH clone, who were treated with IST alone, 30% showed an increase in clone size¹³
  • 8% showed evidence of hemolysis and thrombosis

Patients with myelodysplastic syndromes (MDS) are at high-risk for PNH^2-4

Adapted from Morado M, et al. Cytometry B Clin Cytom. 2017;92(5):361-370.

Study description: A multicenter evaluation of the frequency of cases showing PNH clone cells in 3938 peripheral blood samples at diagnosis according to the medical indications that triggered screening for PNH by flow cytometry.¹

• The National Comprehensive Cancer Network (NCCN), the ICCS, and IPIG guidelines recommend testing all patients with MDS for PNH at diagnosis and routinely thereafter^4,7,15

Select MDS subgroups are more likely to present with a PNH granulocyte clone¹⁶

• MDS patients with a PNH clone often have one of the following characteristics:
  • hypocellular bone marrow
  • normal cytogenetics
  • high likelihood of response to immunosuppressive therapy
  • HLA-DR15 positivity, or moderate to severe thrombocytopenia¹⁷

Patients with unexplained cytopenias are at high risk for PNH^1,2

Adapted from Morado M, et al. Cytometry B Clin Cytom. 2017;92(5):361-370.

Study description: A multicenter evaluation of the frequency of cases showing PNH clone cells in 3938 peripheral blood samples at diagnosis according to the medical indications that triggered screening for PNH by flow cytometry.¹

Patients with unexplained thrombosis are at high risk for PNH^2,4

• Venous thromboembolism is 62x more likely in patients with PNH vs the general population²²

Complement-mediated hemolysis and platelet activation are the main contributors to morbidity and mortality in patients with PNH^5,26

• Platelet activation in PNH is due to⁶:
  • Loss of CD59 and assembly of C5b-9
  • Nitric oxide depletion
  • Direct effects of cell-free hemoglobin
  • Increased levels of reactive oxygen species
  • Endothelial dysfunction
  • Thrombin activation