Eritrositozun Genetik İzleri: Tam Kan Sayımı Parametreleri ve/veya Serum Eritropoetin Düzeyi ile JAK2 Mutasyonunun Varlığını Belirleyebilir miyiz?

Abstract

Giriş: Bu çalışmada, yüksek rakımda yaşayan eritrositozlu hastalarda hemogram, biyokimyasal parametreler ve serum eritropoietin (EPO) düzeyleri kullanılarak JAK2V617F mutasyonunun varlığını öngörmeyi amaçladık. Yöntem: Bu retrospektif çalışmada, 2022–2025 yılları arasında eritrositoz nedeniyle başvuran ve en az bir yıldır yaklaşık 1800 metre rakımda yaşayan 186 hasta değerlendirildi. Eritrositoz varlığı, 2022 Dünya Sağlık Örgütü kriterlerine göre konuldu. Hastaların demografik özellikleri, hematolojik ve biyokimyasal parametreleri ile serum EPO düzeyleri, JAK2V617F mutasyonunun varlığına göre karşılaştırıldı. Ardından çok değişkenli lojistik regresyon ve ROC analizleri uygulandı. Bulgular: Çalışmaya dahil edilen 186 hastanın 151’i (%81.2) JAK2V617F negatif, 35’i (%18.8) pozitifti. Mutasyon pozitif hastalar anlamlı derecede daha yaşlıydı (p < 0.001). Tek değişkenli analizlerde; hemoglobin (p = 0.015), Ortalama Eritrosit Hacmi (MCV) (p = 0.029), Ortalama Eritrosit Hemoglobini (MCH) (p < 0.001), Ortalama Eritrosit Hemoglobin Konsantrasyonu (MCHC) (p < 0.001) ve EPO (p < 0.001) düzeylerinin düşük olduğu; buna karşılık Eritrosit Sayısı (RBC) (p = 0.001), Trombosit Sayısı (PLT) (p < 0.001), Eritrosit Dağılım Genişliği (RDW) (p < 0.001) ve Laktat Dehidrogenaz (LDH) (p < 0.001) düzeylerinin yüksek olduğu saptandı. Çok değişkenli lojistik regresyon analizinde RBC (p = 0.023) ve PLT (p = 0.006) mutasyon pozitifliği için bağımsız belirteçler olarak saptandı. EPO (p = 0.057) ve Ortalama Trombosit Hacmi (MPV) (p = 0.092) sınırda anlamlılık gösterirken, JAKPOT skoru modelde anlamlı bulunmadı (p = 0.176). ROC analizine göre PLT, JAK2V617F mutasyonunu ayırt etmede en güçlü parametreydi (AUC: 0.849); MPV düşük tanısal performans gösterdi. RBC ≥ 6.61 × 10¹²/L ve PLT ≥ 336.5 × 10⁹/L eşik değerleri, mutasyon öngörüsünde yüksek doğruluk sağladı. Sonuç: RBC ve PLT düzeyleri, JAK2V617F mutasyonunun varlığını öngörmede güçlü ve maliyet-etkin belirteçlerdir. EPO düzeylerinin katkısı sınırlı kalmış, JAKPOT skoru ise etkisiz bulunmuştur. Eritrositozun değerlendirilmesinde, özellikle yüksek rakım gibi çevresel faktörlerin tanısal parametrelerin yorumunu önemli ölçüde etkileyebileceği dikkate alınmalıdır.

Keywords

• Eritrositoz
• Trombosit Sayısı
• JAK2V617F mutasyonu
• eritrosit sayısı

Genetic Markers of Erythrocytosis: Can the Presence of JAK2 Mutation Be Determined via Complete Blood Count Parameters and/or Serum Erythropoietin Level?

Abstract

Introduction: In our study, we aimed to predict the presence of the JAK2V617F mutation using haemogram, biochemical parameters, and serum erythropoietin (EPO) levels in patients with erythrocytosis living at high altitudes. Methods: In this retrospective study, 186 patients who presented with erythrocytosis between 2022 and 2025 and had resided at an altitude of ~1800 metres for at least one year were examined. The presence of erythrocytosis was determined according to the 2022 World Health Organisation criteria. Demographic, haematological, and biochemical parameters, as well as serum EPO levels, of the patients were compared according to the presence of the JAK2V617F mutation. Multivariate logistic regression and ROC analysis were then applied. Results: The study included 186 patients; 151 (81.2%) were negative for the JAK2V617F mutation, and 35 (18.8%) were positive. Mutation-positive patients were significantly older ( p < 0.001). Univariate analyses revealed decreased levels of haemoglobin (p = 0.015), Mean Corpuscular Volume (MCV) (p = 0.029), Mean Corpuscular Hemoglobin (MCH) (p < 0.001), Mean Corpuscular Hemoglobin Concentration (MCHC) (p < 0.001), and EPO (p < 0.001). They significantly increased proliferative parameters, including Red Blood Cell Count (RBC) (p = 0.001), Platelet Count (PLT) (p < 0.001), Red Cell Distribution Width (RDW) (p <0.001), and Lactate Dehydrogenase (LDH) (p < 0.001). When these variables were analysed by multivariate logistic regression analysis, RBC (p = 0.023) and PLT (p = 0.006) were found to be independent predictors of mutation positivity. EPO (p = 0.057) and Mean Platelet Volume (MPV) (p = 0.092) showed borderline significance, whereas the JAKPOT score was not significant in the multivariate model (p = 0.176). According to ROC analysis, PLT was the most powerful parameter in differentiating JAK2V617F mutation (AUC: 0.849), whereas MPV had low diagnostic performance. RBC ≥6.61 × 10¹²/L and PLT ≥336.5 × 10⁹/L thresholds provided high accuracy in mutation prediction. Conclusion: RBC and PLT levels are robust and cost-effective markers for predicting the presence of JAK2V617F mutation. EPO levels made a limited contribution. Otherwise, the JAKPOT score was ineffective. Environmental factors, especially high altitude, should be considered when interpreting diagnostic markers in erythrocytosis.

Keywords

• Erythrocytosis
• Platelet Count
• JAK2V617F mutation
• red blood cell count

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