madman
Super Moderator
FIGURE 2 Management of erythrocytosis (Source: adapted from BSH guidelines 2019).6
Abstract
An absolute erythrocytosis is present when the red cell mass is greater than 125% of the predicted. This is suspected when the hemoglobin or hematocrit is above the normal range. An erythrocytosis can be classified as primary or secondary and congenital or acquired. The commonest primary acquired disorder is polycythemia vera. The diagnostic criteria for PV have evolved over time and this is the main diagnosis managed in hematology clinics. There are a variety of rare congenital causes both primary and secondary. In particular in young patients and/or those with a family history a congenital cause is suspected. There remains a larger cohort with acquired erythrocytosis mainly with non-hematological pathology. In order to explore for a cause of erythrocytosis, measurement of the erythropoietin level is a first step. A low erythropoietin level indicates a primary cause and a normal or elevated level indicates a secondary etiology. Further investigation is then dictated by initial findings and includes mutational testing with PCR and NGS for those in whom a congenital cause is suspected. Following this possibly bone marrow biopsy, scans, and further investigation as indicated by history and initial findings. Investigation is directed toward the identification of those with a hematological disorder which would be best managed following guidelines in hematology clinics and referral elsewhere in those for whom there are non-hematological reasons for the elevated hemoglobin.
1 | INTRODUCTION
Erythrocytosis refers to an elevation in hemoglobin (Hb) concentration and/or hematocrit (Hct) level above the established normal range for a specific population. It can be classified into two types: absolute erythrocytosis and relative erythrocytosis. Absolute erythrocytosis was traditionally confirmed by a red cell mass (RCM) exceeding 125% above the average predicted value based on gender and body mass.1 Relative erythrocytosis on the other hand refers to situations where there is a reduction in plasma volume, but the RCM remains within the normal range.2 Much of the literature and practice in this field concerns the criteria for diagnosis of polycythemia vera (PV). These have significantly evolved over time. We will discuss these below and then move to discuss the classification of different causes of erythrocytosis, diagnostic tools, and processes before finally discussing who should be referred and how referrals could be managed in terms of pre-screening and ongoing management.
2 | EVOLUTION OF DIAGNOSTIC CRITERIA FOR POLYCYTHEMIA VERA
2.1 | Classification of an erythrocytosis
3 | INVESTIGATIONS OF BENEFIT IN EXPLORATION OF AN ERYTHROCYTOSIS
3.1 | Erythropoietin
3.2 | Bone marrow biopsy
3.3 | Mutational testing/next-generation sequencing (NGS)-PV
3.4 | Mutational testing/next-generation sequencing-congenital erythrocytosis
3.5 | Workload management in hematology
4 | CONCLUSION
The investigation pathway for patients with a suspected erythrocytosis has evolved over the past two decades as a result of new findings improving our understanding of the pathogenesis of conditions such as PV—for example, the JAK2 mutations. In addition, there have been advances in technology. Examples of this would include improvements in EPO assays and the development of NGS approaches making other diagnostic tests such as p50 and EEC largely redundant. The pathway for investigating and indeed managing these patients is complex but can be navigated with a thorough and evidence-based approach with a high degree of accuracy. This is important as suspicion of erythrocytosis is a common cause for referral and finding on routine blood tests. Knowledge of the patient's history, lifestyle, medications and situation is vital to this process.
Abstract
An absolute erythrocytosis is present when the red cell mass is greater than 125% of the predicted. This is suspected when the hemoglobin or hematocrit is above the normal range. An erythrocytosis can be classified as primary or secondary and congenital or acquired. The commonest primary acquired disorder is polycythemia vera. The diagnostic criteria for PV have evolved over time and this is the main diagnosis managed in hematology clinics. There are a variety of rare congenital causes both primary and secondary. In particular in young patients and/or those with a family history a congenital cause is suspected. There remains a larger cohort with acquired erythrocytosis mainly with non-hematological pathology. In order to explore for a cause of erythrocytosis, measurement of the erythropoietin level is a first step. A low erythropoietin level indicates a primary cause and a normal or elevated level indicates a secondary etiology. Further investigation is then dictated by initial findings and includes mutational testing with PCR and NGS for those in whom a congenital cause is suspected. Following this possibly bone marrow biopsy, scans, and further investigation as indicated by history and initial findings. Investigation is directed toward the identification of those with a hematological disorder which would be best managed following guidelines in hematology clinics and referral elsewhere in those for whom there are non-hematological reasons for the elevated hemoglobin.
1 | INTRODUCTION
Erythrocytosis refers to an elevation in hemoglobin (Hb) concentration and/or hematocrit (Hct) level above the established normal range for a specific population. It can be classified into two types: absolute erythrocytosis and relative erythrocytosis. Absolute erythrocytosis was traditionally confirmed by a red cell mass (RCM) exceeding 125% above the average predicted value based on gender and body mass.1 Relative erythrocytosis on the other hand refers to situations where there is a reduction in plasma volume, but the RCM remains within the normal range.2 Much of the literature and practice in this field concerns the criteria for diagnosis of polycythemia vera (PV). These have significantly evolved over time. We will discuss these below and then move to discuss the classification of different causes of erythrocytosis, diagnostic tools, and processes before finally discussing who should be referred and how referrals could be managed in terms of pre-screening and ongoing management.
2 | EVOLUTION OF DIAGNOSTIC CRITERIA FOR POLYCYTHEMIA VERA
2.1 | Classification of an erythrocytosis
3 | INVESTIGATIONS OF BENEFIT IN EXPLORATION OF AN ERYTHROCYTOSIS
3.1 | Erythropoietin
3.2 | Bone marrow biopsy
3.3 | Mutational testing/next-generation sequencing (NGS)-PV
3.4 | Mutational testing/next-generation sequencing-congenital erythrocytosis
3.5 | Workload management in hematology
4 | CONCLUSION
The investigation pathway for patients with a suspected erythrocytosis has evolved over the past two decades as a result of new findings improving our understanding of the pathogenesis of conditions such as PV—for example, the JAK2 mutations. In addition, there have been advances in technology. Examples of this would include improvements in EPO assays and the development of NGS approaches making other diagnostic tests such as p50 and EEC largely redundant. The pathway for investigating and indeed managing these patients is complex but can be navigated with a thorough and evidence-based approach with a high degree of accuracy. This is important as suspicion of erythrocytosis is a common cause for referral and finding on routine blood tests. Knowledge of the patient's history, lifestyle, medications and situation is vital to this process.
