JAK2 Negatif Eritrositoz Tanısal Algoritması JAK2 Unmutated Erythrocytosis – Tanı AlgoritmasıTanı Algoritması – JAK2 Negatif EritrositozDiagnostic algorithm for JAK2 unmutated erythrocytosis Önce görünür / yalancı polisitemiyi dışla ✔ Normal outlier ✔ Relative polycythemia (volume contraction) Long-standing duration / Family history Epo subnormal Epo receptor (EPOR) mutations If no HOAV but P50 < 25 mmHg - 2,3-bisphosphoglycerate deficiency (BPGM mutations)
- PIEZO1 mutations (iron overload, splenomegaly, hemolysis)
- Methemoglobinemia
Epo normal or increased Start with tests for high-oxygen affinity hemoglobin (HOAV) - Capillary electrophoresis
- HPLC
- Mass spectrometry
- HBB, HBA1, HBA2 sequencing
- Venous P50 determination (if available)
If no HOAV and P50 > 25 mmHg or unknown Germline oxygen sensing pathway mutations - VHL (von Hippel–Lindau): Chuvash polycythemia; Epo↑
- HIF2A (EPAS1): Epo↑
- PHD2 (EGLN1): Epo often normal
- EPO mutations: Epo↑ or normal
Other considerations - HFE mutations (ferritin↑)
- SLC30A10 mutations: hypermanganesemia, parkinsonism, cirrhosis
- ANKRD26 mutations: thrombocytopenia
Acquired or unknown duration “Compensated normal” or increased Epo Cardiopulmonary disease - Obstructive sleep apnea
- High altitude habitat
- Renal artery stenosis
- CO poisoning
- Smoking
- Cushing’s disease
Drug-induced - Testosterone / anabolic steroids
- Epo doping
- SGLT-2 inhibitors (gliflozins)
- Tyrosine kinase inhibitors
- Anti-angiogenic agents
- Anti-tuberculous agents
Epo increased Epo-producing tumors - Carcinomas (renal cell, hepatocellular)
- Cerebellar hemangioblastoma
- Meningioma
- Pheochromocytoma
- Uterine leiomyoma
- Parathyroid adenoma or carcinoma
Renal causes - Renal cysts (polycystic kidney disease)
- Post-renal transplant
- IgA nephropathy
Other considerations - TEMPI syndrome: telangiectasias, erythrocytosis with Epo↑, MGUS, perinephric-fluid collections, intrapulmonary shunting
- POEMS syndrome: polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes
In cases of otherwise unexplained erythrocytosis, consider hereditary erythrocytosis next-generation sequencing panel: ACO1, BHLHE41, CYB5A, CYB5R3, EGLN2, EGLN3, EPO, GFI1B, HIF1A, HIF1AN, HIF3A, HFE, KDM6A, PFKM, PKLR, SOCS3 … |
