What are the symptoms of erythrocytosis, particularly in patients with polycythemia vera?

Symptoms of Erythrocytosis and Polycythemia Vera

Patients with polycythemia vera commonly present with microvascular disturbances (headache, light-headedness, transient neurologic or ocular disturbances, tinnitus, atypical chest discomfort, paresthesias), pruritus (33-48% of patients), and erythromelalgia (3-5.3% of patients), along with splenomegaly (36%) and constitutional symptoms. 1, 2, 3

Microvascular and Neurologic Symptoms

The most frequent symptom category involves microvascular disturbances resulting from platelet-endothelial interactions in arterioles:

• Headache and light-headedness are among the most common presenting complaints 4, 1, 2
• Transient neurologic disturbances occur in approximately 14% of patients, including visual changes and focal neurologic symptoms 3, 2
• Tinnitus (ringing in the ears) is a characteristic microvascular symptom 4, 1
• Atypical chest discomfort that doesn't follow typical anginal patterns 4, 2
• Paresthesias (abnormal sensations like tingling or numbness) 4, 1, 2

These symptoms arise from transient inflammation-based occlusive phenomena in small vessels and represent a baseline prothrombotic state in PV. 4

Erythromelalgia

Erythromelalgia manifests as painful, burning sensations in the feet or hands associated with erythema and warmth, affecting 3-5.3% of PV patients. 4, 2, 3

• This condition is often associated with thrombocythemia and results from platelet-mediated endothelial cell injury causing inflammation and transient thrombotic occlusion by platelet aggregates 4
• Low-dose aspirin (81 mg/day) produces prompt relief within hours in most patients 4, 2
• Normalization of platelet count with cytoreductive therapy may be necessary in aspirin-refractory cases 4

Pruritus (Itching)

Generalized pruritus is documented in 33-48% of patients and is often exacerbated by hot baths or showers, making it one of the most agonizing symptoms. 4, 1, 2, 3

• Pruritus may cause sleep deprivation and interfere with social and physical activities 4
• The pathogenesis involves platelets and their contents, including prostaglandins and serotonin 4
• Selective serotonin reuptake inhibitors (SSRIs) show response rates higher than 80% 4, 2
• Low mean corpuscular volume (suggesting iron deficiency) correlates with active pruritus 4

Physical Examination Findings

Splenomegaly is present in approximately 36% of patients and may cause abdominal discomfort. 2, 3

• Splenomegaly is a key physical finding that helps distinguish PV from secondary erythrocytosis 5
• Leukocytosis (49%) and thrombocytosis (53%) are common laboratory findings 3

Thrombotic and Hemorrhagic Manifestations

Prior to or at diagnosis, arterial thrombosis occurs in 16% of patients and venous thrombotic events in 7%, including unusual sites like splanchnic veins. 3

• Myocardial infarction, stroke, and peripheral ischemic events represent the most common arterial complications 6
• Suboptimal cerebral blood flow occurs with hematocrit values between 46-52% 6
• Acquired von Willebrand disease occurs in more than one-third of PV patients, particularly with extreme thrombocytosis (platelet count ≥1000 × 10⁹/L), increasing bleeding risk 6, 3

Constitutional Symptoms

Non-specific constitutional symptoms are common and can significantly impact quality of life, potentially warranting cytoreductive therapy even in lower-risk patients. 2

Critical Diagnostic Distinction

Cyanosis (blueish discoloration) is NOT a feature of polycythemia vera—this distinguishes it from secondary erythrocytosis due to right-to-left shunting. 4

• Secondary erythrocytosis from hypoxemia may present with visible cyanosis when at least 5 g/L of unsaturated hemoglobin is present in tissue 4
• PV is a neoplastic proliferation fundamentally different from physiological secondary erythrocytosis 4
• JAK2 mutation is present in >95% of PV cases and is crucial for distinguishing it from secondary causes 1, 2, 3

Important Clinical Pitfall

Iron deficiency is frequently encountered in cyanotic individuals and PV patients undergoing phlebotomy, causing symptoms that mimic hyperviscosity (headache, fatigue, dizziness) and may lead to stroke or myocardial ischemia. 4, 2

• Iron deficiency reduces hemoglobin without proportionally changing hematocrit, compromising oxygen transport without lowering viscosity 4
• Serum iron, ferritin, and transferrin levels are required for diagnosis, as mean corpuscular volume is unreliable 4