What are the symptoms and treatment options for polycythemia?

Symptoms of Polycythemia

Polycythemia presents with symptoms related to hyperviscosity, microvascular disturbances, and thrombotic complications, with many patients experiencing pruritus (33%), headaches, visual changes (14%), erythromelalgia (5.3%), and splenomegaly with abdominal discomfort (36%). 1

Microvascular and Hyperviscosity Symptoms

• Pruritus (itching) occurs in approximately one-third of patients with polycythemia vera, often triggered or worsened by warm water exposure (aquagenic pruritus) 1, 2
• Erythromelalgia manifests as burning pain, redness, and warmth in the extremities (particularly hands and feet), affecting about 5% of patients 1, 3
• Visual disturbances including transient blurred vision, scotomas, or amaurosis fugax occur in 14% of patients due to microvascular occlusion 1
• Headaches and dizziness result from increased blood viscosity and impaired cerebral blood flow 2
• Tinnitus and vertigo may occur secondary to hyperviscosity affecting inner ear circulation 2

Thrombotic Manifestations

• Arterial thrombosis occurs in 16% of patients prior to or at diagnosis, presenting as stroke, myocardial infarction, or peripheral arterial occlusion 1
• Venous thrombosis affects 7% of patients and may involve unusual sites such as splanchnic veins (hepatic, portal, mesenteric), presenting with abdominal pain 1
• Cerebral ischemic attacks can be atypical in presentation due to microvascular rather than large vessel involvement 3

Physical Examination Findings

• Splenomegaly is present in 36% of patients and may cause left upper quadrant fullness or early satiety 1
• Plethora (ruddy, reddish complexion) particularly of the face and palms results from increased red cell mass 2
• Conjunctival injection and retinal vein engorgement may be visible on examination 2

Hemorrhagic Complications

• Bleeding risk is paradoxically increased despite thrombotic tendency, especially with extreme thrombocytosis (platelet count ≥1000 × 10⁹/L) due to acquired von Willebrand disease 1
• Bleeding manifestations include epistaxis, easy bruising, and gastrointestinal hemorrhage 2

Hematologic Findings at Presentation

• Thrombocytosis (platelet count >400 × 10⁹/L) occurs in 53% of patients 1
• Leukocytosis is present in 49% of patients 1
• Erythrocytosis is the defining feature, with hemoglobin >16.5 g/dL in men or >16.0 g/dL in women required for diagnosis 1

Secondary Polycythemia Symptoms

In secondary polycythemia, symptoms depend on the underlying cause:

• Hypoxia-driven causes (chronic lung disease, sleep apnea, high altitude) present with symptoms of the primary condition plus hyperviscosity symptoms 2, 4
• Smoker's polycythemia from chronic carbon monoxide exposure may be asymptomatic or present with cardiovascular symptoms, resolving with smoking cessation 4, 5
• Tumor-related polycythemia (renal cell carcinoma, hepatocellular carcinoma) may present with symptoms of the underlying malignancy 2, 4

Critical Clinical Pitfalls

• Asymptomatic presentation occurs in many patients, with polycythemia discovered incidentally on routine blood work 2
• Microvascular symptoms (erythromelalgia, visual changes) are often dismissed or misattributed to other conditions, delaying diagnosis 3
• Normal oxygen saturation on pulse oximetry does not exclude smoker's polycythemia, as standard pulse oximeters cannot differentiate carboxyhemoglobin from oxyhemoglobin 5
• Thrombosis may be the presenting manifestation in 16-23% of patients, occurring before polycythemia is recognized 1, 2

Treatment Options

Universal Management for All Polycythemia Vera Patients

• Therapeutic phlebotomy to maintain hematocrit <45% is mandatory for all patients to reduce thrombotic risk 1, 2
• Low-dose aspirin (50-100 mg daily) should be given to all patients unless contraindicated, to prevent microvascular disturbances and thrombosis 1, 2, 3

Risk-Stratified Cytoreductive Therapy

• High-risk patients (age ≥60 years or prior thrombosis) require cytoreductive therapy with hydroxyurea or interferon-alpha in addition to phlebotomy and aspirin 1
• Hydroxyurea is first-line cytoreductive therapy to lower platelet counts and reduce thrombotic risk 1, 2
• Interferon-alpha is an alternative cytoreductive agent, particularly in younger patients or those intolerant of hydroxyurea 2, 1
• Ruxolitinib (JAK inhibitor) is reserved for patients intolerant of or resistant to hydroxyurea, particularly effective for controlling pruritus and splenomegaly 1

Secondary Polycythemia Management

• Treat the underlying cause - this is the primary approach for secondary polycythemia 2, 4
• Judicious phlebotomy to hematocrit 55-60% may be considered in symptomatic patients with chronic hypoxic conditions (COPD, cyanotic heart disease), but aggressive phlebotomy should be avoided as it may worsen oxygen delivery 2
• ACE inhibitors or angiotensin II receptor blockers are effective for post-renal transplant erythrocytosis, which carries increased thrombotic risk 2
• Smoking cessation is the definitive treatment for smoker's polycythemia, with risk reduction beginning within 1 year 4, 5
• Theophylline has been shown to lower hematocrit in both COPD-associated polycythemia and post-renal transplant erythrocytosis 2

Symptom-Specific Management

• Aquagenic pruritus responds to selective serotonin reuptake inhibitors (SSRIs) 2
• Erythromelalgia is controlled with low-dose aspirin or by reducing platelet count to <400 × 10⁹/L 3