Table 3.
Risk factors for thrombotic complications in PNH
| Study | Year | Population | Study design | No. of patients | PNH testing method | Risk factor for thrombosis | Effect of PNH clone size |
|---|---|---|---|---|---|---|---|
| de Latour et al36 | 2008 | Patients treated in 58 hematologic centers in France | Retrospective | 460 | Ham test or flow cytometry (PNH clones >5%) | • Age >55 years: HR 1.8 • Transfusions: HR 1.7 • Thrombosis at diagnosis: HR 3.7 • Warfarin as primary prophylaxis: HR 5.2 |
>50% clones associated with higher risk of TE: HR 3.2 |
| Lee et al44 | 2013 | South Korean National PNH Registry | Retrospective | 301 | Ham test, sucrose-lysis test, and flow cytometry (no minimal cutoff) | • LDH ≥1.5 × ULN: OR 7.0 Higher predictive value in combination with symptoms: • LDH ≥1.5 × ULN plus abdominal pain: OR 17.8 • LDH ≥1.5 × ULN plus chest pain: OR 19.0 • LDH ≥1.5 × ULN plus dyspnea: OR 10.3 • LDH ≥1.5 × ULN plus hemoglobinuria: OR 10.3 |
No significant effect of clone size PNH clone <20%: 16% TE PNH clone 20%-50%: 19% TE PNH clone >50%: 20% TE |
| Schrezenmeier et al45 | 2014 | International PNH Registry | Retrospective | 900 | Clinical diagnosis and/or flow cytometry (no minimal cutoff) | • LDH ≥1.5 × ULN: 15.6% (vs 8.4% <1.5 × ULN) • PNH clone ≥50% |
PNH clone <10%: 5.3% TE PNH clone 10%-49%: 7.7% TE PNH clone ≥50%: 15.4% TE |
| Long et al46 | 2017 | Peking Union Medical College Hospital | Retrospective | 104 | Flow cytometry (PNH clones >1%) | • PNH clone ≥50%: OR 9.78 • ABO gene rs495828 GT+TT: OR 5.63 • ABO gene rs2519093 TC+TT: 5.95 |
PNH clone ≥50%: OR 9.78 |
| Griffin et al. 201947 | 2019 | Leeds UK PNH Database | Retrospective study of thrombosis in patients with PNH with PNH clone >10% and LDH <2 × ULN) | 25 of 429 patients had PNH clone >10% and LDH <2 × ULN | Flow cytometry (PNH clones >10%) | • Group 1: PNH white cells >30%, PNH red cells <10%, LDH <2 × ULN: 6 of 11 (54%) had TE • Group 2: PNH white cells >30%, PNH red cells >10% with higher proportion of type II red cells than type III red cells, LDH <2 × ULN: 2 of 11 (18%) had TE • Group 3: PNH white cells 10%-30%, PNH red cells <10%, LDH <2 × ULN (0 of 3 had thrombosis) |
In patients with TEs, PNH clone ranged from 49% to 100%; median clone sizes were 93% (group 1) and 89% (group 2) |
| Huang et al.48 | 2019 | Peking Union Medical College Hospital | Retrospective | 99 | Flow cytometry (PNH clones >1%) | • PNH clone ≥80%: OR 1.056 • Hemoglobin ≤7.5 g/dL: OR 4.202 • Platelets >100 × 109/L: OR 6.547 • ABO gene rs495828 = G: OR 5.243 |
Only evaluated cutoff of PNH clone ≥80%: OR 1.056 |
| Hoechsmann et al43 [abstract] | 2020 | International PNH Registry | Retrospective case control | 57 TE cases, 189 non-TE controls | NA | • Recent HDA: OR 2.65 • LDH ≥1.5 × ULN plus 2-3 HDA symptoms: OR 8.61 • LDH ≥1.5 × ULN plus ≥4 HDA symptoms: OR 14.5 • History of TE: OR 3.6 • History of MAVE: OR 2.17 • Recent prophylactic anticoagulation: OR 4.35 |
PNH clone ≥50% |
| Füreder et al49 | 2020 | Austrian PNH network | Retrospective | 59 | Flow cytometry | 14 of 59 patients had TE; 5 of 14 patients had clone size recorded, which ranged from 80% to 100% | Larger clone size in patients with TE |
HDA, recent high disease activity, defined as occurring within 6 months of TE event, LDH ≥1.5 × ULN, and hemoglobin <10 g/dL or at least 1 of the following symptoms: abdominal pain, dyspnea, dysphagia, fatigue, hemoglobinuria, and male erectile dysfunction; HR, hazard ratio; MAVE, major adverse vascular event; OR, odds ratio; TE, thromboembolic event.