Table I.
Haematological response to complement inhibitors in paroxysmal nocturnal haemoglobinuria.
| Response category | Red blood cell transfusions | Haemoglobin level | Residual haemolysis and breakthrough episodes* , ** |
|---|---|---|---|
| Complete response | None |
≥130 g/l (males) or ≥120 g/l (females) |
LDH ≤1.5 × ULN and ARC ≤150 000/µl,§ no breakthrough episodes |
| Major response | None |
≥130 g/l (males) or ≥120 g/l (females) |
LDH >1.5 × ULN and/or ARC >150 000/µl,§ only subclinical breakthrough episodes |
| Good response | None |
≥10 and <130 g/l (males) or ≥10 and <120 g/l (females) |
Any LDH and ARC value, only subclinical breakthrough episodes (rule out bone marrow failure)† |
| Partial response | None or occasional (≤2 every 6 months) | ≥8 and <100 g/l | |
| Minor response# | None or occasional (≤2 every 6 months) | <80 g/l | |
| Regular (3–6 every 6 months) | <100 g/l | ||
| Reduction by ≥50%^ | <100 g/l | ||
| No response# | Regular (>6 every 6 months) | <100 g/l |
ARC, absolute reticulocyte count; LDH, lactate dehydrogenase; ULN, upper limit of the normal.
The presence of clinically meaningful episodes of breakthrough haemolysis downgrades the response category by one degree.
To rule out increased erythropoietic response to compensate ongoing haemolysis; the value of 150 000/µl is a tentative index based on 1.5 × ULN (which in most laboratories is set at 100 000/µl).
To assess the relative contribution of the degree of bone marrow failure to any response less than complete: a value of ARC below 60 000/µl could be a tentative index to establish such a contribution.
For patients with previous transfusion history (with a pre‐treatment follow‐up of at least six months).
For patients who do not accept red blood cell transfusions, minor response can be defined based on haemoglobin level ≥60 and <80 g/l, and no response based on haemoglobin <60 g/l. All haemoglobin, LDH and ARC values should be assessed based on the median value over a period of six months.
These response categories apply to patients with adequate control of intravascular haemolysis; patients with clinically meaningful haemolysis (e.g., recurrent symptoms or LDH stably >2 × ULN) are considered as non‐responders according to this classification.