What are the indications of low and high hematocrit?

Indications of Low and High Hematocrit

Low Hematocrit: Clinical Significance and Indications

Low hematocrit indicates anemia and requires evaluation for iron deficiency, blood loss, hemolysis, or bone marrow dysfunction, with specific thresholds varying by sex (men <42%, women <38%). 1

Diagnostic Thresholds and Evaluation

• Hematocrit below 30% is associated with significantly increased mortality risk (12-33% higher all-cause mortality) in hemodialysis patients, even after adjusting for comorbid conditions 2
• Low hematocrit with low mean cell volume (MCV) indicates microcytic anemia, most commonly iron-deficiency anemia when lead poisoning, infection, chronic inflammation, and thalassemia are excluded 1
• A high red blood cell distribution width (RDW >14.0%) combined with low MCV specifically indicates iron-deficiency anemia, whereas low MCV with RDW ≤14.0% suggests thalassemia minor 1

Physiological Impact

• Low hematocrit prolongs bleeding time by reducing the physical dispersion of platelets toward the subendothelial surface in small vessels and decreasing platelet activation from red blood cell-released ADP 3
• Transfusion of red blood cells can correct the prolonged bleeding time observed in anemic patients, making hematocrit clinically important in managing bleeding tendencies 3

Laboratory Workup for Low Hematocrit

• Complete blood count with red cell indices, reticulocyte count, differential blood cell count, serum ferritin, transferrin saturation, and C-reactive protein (CRP) should be obtained 4
• Erythrocyte protoporphyrin concentration >80 μg/dL in children aged 1-2 years or >70 μg/dL in adults indicates iron deficiency 1
• Serum ferritin concentration directly correlates with iron stores (1 μg/L = approximately 10 mg stored iron) and serves as an early indicator of low iron stores 1

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High Hematocrit: Clinical Significance and Indications

High hematocrit (>55% in men, >49.5% in women) indicates erythrocytosis and requires differentiation between primary polycythemia vera, secondary causes (hypoxia, malignancy, testosterone), and relative polycythemia from dehydration. 4

Diagnostic Thresholds and Risk Assessment

• Hematocrit >45% significantly increases thrombotic risk, with the CYTO-PV trial demonstrating that maintaining hematocrit 45-50% versus <45% resulted in 9.8% versus 2.7% cardiovascular events (HR 3.91; 95% CI 1.45-10.53) 1
• Hemoglobin >18.5 g/dL in men or >16.5 g/dL in women, or hematocrit >55% in men or >49.5% in women, defines true polycythemia requiring evaluation 4
• Therapeutic phlebotomy is indicated only when hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with symptoms of hyperviscosity, after excluding dehydration 4

Primary Erythrocytosis (Polycythemia Vera)

• JAK2 mutation testing (exon 14 and exon 12) is essential, as up to 97% of polycythemia vera cases carry this mutation 4
• WHO diagnostic criteria require either both major criteria (elevated hemoglobin/hematocrit AND JAK2 mutation) plus one minor criterion, OR first major criterion plus two minor criteria 4
• All polycythemia vera patients must maintain hematocrit strictly below 45% through phlebotomy (300-450 mL weekly or twice weekly initially, then as needed) combined with daily low-dose aspirin (81-100 mg) 1

Secondary Erythrocytosis Causes

• Hypoxia-driven causes: chronic obstructive pulmonary disease, obstructive sleep apnea (producing nocturnal hypoxemia), cyanotic congenital heart disease with right-to-left shunting, high-altitude adaptation, and smoking ("smoker's polycythemia" from carbon monoxide-induced tissue hypoxia) 4
• Hypoxia-independent causes: renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma, uterine leiomyoma, meningioma (all producing erythropoietin), testosterone therapy, and exogenous erythropoietin administration 4
• Relative polycythemia: dehydration, diuretic use, burns, and stress polycythemia (Gaisböck syndrome) cause plasma volume depletion without true red cell mass increase 4

Management Approach for High Hematocrit

• For polycythemia vera: phlebotomy to maintain hematocrit <45%, low-dose aspirin daily, and cytoreductive therapy (hydroxyurea or interferon-alpha) for high-risk patients (age >60 years or prior thrombosis) 1
• For secondary erythrocytosis: treat the underlying condition—smoking cessation for smoker's polycythemia, CPAP for obstructive sleep apnea, dose reduction or discontinuation of testosterone, management of chronic lung disease 4
• Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 4

Critical Pitfalls to Avoid

• Never perform aggressive phlebotomy without volume replacement, as this causes further hemoconcentration and increases thrombotic risk 4
• Do not overlook coexisting iron deficiency in erythrocytosis, particularly in cyanotic heart disease or polycythemia vera, which causes microcytic polycythemia with elevated RBC count but reduced hemoglobin 4
• Mean corpuscular volume (MCV) is unreliable for screening iron deficiency in erythrocytosis; serum ferritin, transferrin saturation, and iron levels are required 4
• If iron deficiency is confirmed despite erythrocytosis, cautious oral iron supplementation with close hemoglobin monitoring is necessary, as rapid increases in red cell mass can occur 4

Special Populations

• In cyanotic congenital heart disease, erythrocytosis is compensatory to optimize oxygen transport; evaluate for intercurrent issues (dehydration, iron deficiency, infection) rather than performing phlebotomy unless hematocrit >65% with hyperviscosity symptoms 4
• In patients on erythropoietin therapy, avoid rapid hematocrit increases (>8 percentage points per month) and reduce dose by 25% if this occurs 4
• Normal hematocrit varies by sex: adult males/post-menopausal females 47±6%, menstruating females 41±5%, with differences emerging at puberty due to testosterone and estrogen effects 4