Polycythemia is a l aboratory finding characterised b y an increased number of RBCs and an accompanying elevation in haematocrit and haemoglobin concentration in the peripheral blood. It is commonly an incidental finding.
Definition of terms
Term Definition Relative polycythemia An isolated decrease in plasma volume that elevates haemoglobin, haematocrit, and RBC count without increasing red cell mass. Absolute polycythemia A true increase in red cell mass. Primary absolute polycythemia Due to acquired or inherited mutations, e.g., Polycythemia Vera Secondary absolute polycythemia Due to circulating factors, e.g., EPO, hypoxia, EPO-secreting tumors Combined polycythemia A combined increased red cell mass and reduced plasma volume. This is seen in smokers Inapparent absolute polycythemia An equally increased red cell mass and plasma volume, which results in a normal haemoglobin, haematocrit, and RBC count.
Factors that stimulate the release of erythropoietin (EPO)
Anemia Hypoxemia
Decreased O2 release from Hb
Reduced oxygen delivery to the kidneys (Vaso-occlusion)
EPO-independent and EPO-driven erythrocytosis
EPO-independent erythrocytosis (e.g., Polycythemia Vera ) suppresses renal EPO production, resulting in low serum EPO concentrations
EPO-driven erythrocytosis, e.g., hypoxia or EPO-secreting tumors, is associated with high or normal serum EPO
Causes of polycythemia
Germline and somatic mutational causes of polycythemia (Primary Polycythemia)
JAK2 (PV), EPOR mutation, VHL gene mutation (Chuvash polycythemia), congenital methemoglobinemia, idiopathic familial polycythemia, high oxygen affinity hemoglobins, 2,3-BPG mutase deficiency, PHD2 , HIF2-alpha
Autonomous (Inappropriate) increase of EPO
EPO-producing neoplasms (RCC, HCC, Cerebellar hemangioblastoma, Phaeochromocytoma , Uterine fibroids)EPO-producing renal lesions (cysts, hydronephrosis, renal artery stenosis, and rarely distal tubular necrosis)
Appropriate increase in EPO
Hypoxemia: secondary to chronic pulmonary disease, R→L cardiac shunts, sleep apnea, Massive obesity aka Pickwickian syndrome, High altitude)Red cell defects : some cases of congenital methemoglobinemia, chronic CO poisoning, including Heavy smoking, Cobalt)
Miscellaneous causes
Use of androgens and anabolic steroids , diuretics (relative polycythemia), Blood doping in athletes (autologous blood transfusion ), Self-injection of EP , POEMS syndrome (autoimmune disease with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin lesions)
Differentials
Thalassemia minor
Polycythemia Vera Renal Cell Carcinoma
Functional endocrine tumors
Hepatocellular carcinoma
Carbon monoxide poisoning
Biochemistry
ACTH P: <80 ng/L ALT P: 5–35 U/L Albumin P: 35–50 g/L Aldosterone P: 100–500 pmol/L Alk. phosphatase P: 30–130 U/L α-Amylase P: 0–180 IU/dL α-Fetoprotein S: <10 kU/L Angiotensin II P: 5–35 pmol/L ADH P: 0.9–4.6 pmol/L AST P: 5–35 U/L Bicarbonate P: 24–30 mmol/L Bilirubin P: 3–17 μmol/L BNP P: <50 ng/L CRP P: <10 mg/L Calcitonin P: <0.1 mcg/L Calcium (ionized) P: 1.0–1.25 mmol/L Calcium (total) P: 2.12–2.60 mmol/L Chloride P: 95–105 mmol/L Cholesterol P: <5.0 mmol/L VLDL P: 0.128–0.645 mmol/L LDL P: <2.0 mmol/L HDL P: 0.9–1.93 mmol/L Cortisol AM P: 450–700 nmol/L Cortisol Midnight P: 80–280 nmol/L CK ♂ P: 25–195 U/L CK ♀ P: 25–170 U/L Creatinine P: 70–100 μmol/L Ferritin P: 12–200 mcg/L Folate S: 2.1 mcg/L FSH P: 2–8 U/L ♂; >25 menopause GGT ♂ P: 11–51 U/L GGT ♀ P: 7–33 U/L Glucose (fasting) P: 3.5–5.5 mmol/L Growth hormone P: <20 mu/L HbA1C (DCCT) B: 4–6% HbA1C (IFCC) B: 20–42 mmol/mol Iron ♂ S: 14–31 μmol/L Iron ♀ S: 11–30 μmol/L Lactate (venous) P: 0.6–2.4 mmol/L Lactate (arterial) P: 0.6–1.8 mmol/L LDH P: 70–250 U/L LH P: 3–16 U/L Magnesium P: 0.75–1.05 mmol/L Osmolality P: 278–305 mosmol/kg PTH P: 0.8–8.5 pmol/L Potassium P: 3.5–5.3 mmol/L Prolactin ♂ P: <450 U/L Prolactin ♀ P: <600 U/L PSA P: 0–4 mcg/mL Protein (total) P: 60–80 g/L Red cell folate B: 0.36–1.44 μmol/L Renin (erect) P: 2.8–4.5 pmol/mL/h Renin (recumbent) P: 1.1–2.7 pmol/mL/h Sodium P: 135–145 mmol/L TBG P: 7–17 mg/L TSH P: 0.5–4.2 mU/L T4 P: 70–140 nmol/L Free T4 P: 9–22 pmol/L TIBC S: 54–75 μmol/L Triglycerides P: 0.50–2.3 mmol/L T3 P: 1.2–3.0 nmol/L Troponin T P: <0.1 mcg/L Urate ♂ P: 210–480 μmol/L Urate ♀ P: 150–390 μmol/L Urea P: 2.5–6.7 mmol/L Vitamin B12 S: 0.13–0.68 nmol/L Vitamin D S: 50 nmol/L
Arterial Blood Gases
pH 7.35–7.45 PaCO₂ 4.7–6.0 kPa PaO₂ >10.6 kPa Base excess ±2 mmol/L
Urine
Cortisol (free) <280 nmol/24h Hydroxyindole acetic acid 16–73 μmol/24h Hydroxymethylmandelic acid 16–48 μmol/24h Metanephrines 0.03–0.69 μmol/mmol cr. Osmolality 350–1000 mosmol/kg 17-Oxogenic steroids ♂ 28–30 μmol/24h 17-Oxogenic steroids ♀ 21–66 μmol/24h 17-Oxosteroids ♂ 17–76 μmol/24h 17-Oxosteroids ♀ 14–59 μmol/24h Phosphate (inorganic) 15–50 mmol/24h Potassium 14–120 mmol/24h Protein <150 mg/24h Protein/creatinine ratio <3 mg/mmol Sodium 100–250 mmol/24h
Haematology
WCC 4.0–11.0 ×10⁹/L RBC ♂ 4.5–6.5 ×10¹²/L RBC ♀ 3.9–5.6 ×10¹²/L Hb ♂ 130–180 g/L Hb ♀ 115–160 g/L PCV ♂ 0.4–0.54 L/L PCV ♀ 0.37–0.47 L/L MCV 76–96 fL MCH 27–32 pg MCHC 300–360 g/L RDW 11.6–14.6% Neutrophils 2.0–7.5 ×10⁹/L (40–75%) Lymphocytes 1.0–4.5 ×10⁹/L (20–45%) Eosinophils 0.04–0.44 ×10⁹/L (1–6%) Basophils 0–0.10 ×10⁹/L (0–1%) Monocytes 0.2–0.8 ×10⁹/L (2–10%) Platelets 150–400 ×10⁹/L Reticulocytes 0.8–2.0% / 25–100 ×10⁹/L Prothrombin time 10–14 s APTT 35–45 s
Paediatric
Pulse Rate (bpm) Neonate 140–160 Infant <1yr 120–140 1–5 years 110–130 5–12 years 80–120 >12 years 70–100 Respiratory Rate (tachypnoea) 0–2 months ≥60/min 2–12 months ≥50/min 1–5 years ≥40/min >5 years ≥30/min Blood Pressure (mmHg) Term 65/45 1 year 75/50 4 years 85/60 8 years 95/65 10 years 100/70 Weight Formulas 3–12 months (a + 9)/2 kg 1–6 years 2a + 8 kg >6 years (7a − 5)/2 kg Haemoglobin (g/dL) Term newborn 13–20 1 month 11–18 2 months 10–15 1–2 years 10–13 >2 years 11–14 MUAC (6 months–5 years) Obese >17.5 cm Normal 13.5–17.4 cm At risk 12.5–13.4 cm Moderate malnutrition 11.5–12.4 cm Severe malnutrition <11.5 cm Developmental Milestones Social smile 1.5 months Head control 4 months Sits unsupported 7 months Crawls 10 months Stands unsupported 10–12 months Walks 12–13 months Talks 18 months CSF WBC (/mm³) Term newborn 0–25 >2 weeks 0–5
