What are the complications of erythrocytosis?

Complications of Erythrocytosis

Erythrocytosis causes serious thrombotic and hemorrhagic complications through increased blood viscosity, with the most critical being cerebrovascular accidents, coronary events, and paradoxical bleeding diathesis—particularly when complicated by iron deficiency from inappropriate phlebotomy. 1

Cardiovascular and Thrombotic Complications

Vascular Occlusive Events

• Increased blood viscosity from elevated hematocrit aggravates vascular disease in coronary, cerebrovascular, and peripheral circulation, with particularly grave consequences in elderly patients 1
• Thrombotic events occur at significantly elevated rates, with incidence rates of 4.51-6.24 cases per 100 person-years in polycythemia vera and chronic lung disease with erythrocytosis 2
• Laminated thrombi develop in large, partially calcified and aneurysmal pulmonary arteries in up to 30% of patients with cyanotic heart disease and erythrocytosis 1

Cerebrovascular Complications

• Cerebrovascular accidents represent the most devastating complication, caused by thrombo-embolic events, rheological factors (particularly microcytosis), and endothelial dysfunction 1
• Iron deficiency-induced microcytosis is the strongest independent predictor for cerebrovascular events—not the severity of erythrocytosis itself 1
• Microcytic erythrocytes from iron deficiency induce higher viscosity than normocytic cells, paradoxically increasing stroke risk despite lower hematocrit 3

Mortality Risk

• Mortality rates are significantly elevated at 2.43-2.72 cases per 100 person-years in patients with chronic lung disease and polycythemia vera with erythrocytosis, compared to 0.17 in obstructive sleep apnea 2
• Erythrocytosis, when undiagnosed and untreated, leads to serious thrombotic events and higher mortality 4

Hemorrhagic Complications

Bleeding Diathesis

• Both bleeding and thrombotic diathesis occur simultaneously, creating a therapeutic dilemma as patients face dual risks 1
• Spontaneous bleeding is usually minor and self-limiting (dental bleeding, epistaxis, easy bruising, menorrhagia) 1
• Hemoptysis is the most common major bleeding event, reported in up to 100% of Eisenmenger patients, representing external manifestation of intrapulmonary hemorrhage 1

Hemostatic Abnormalities

• Coagulation abnormalities occur in up to 20% of patients with cyanotic congenital heart disease and erythrocytosis 5
• Abnormalities result from multiple factors including stasis in dilated chambers, atherosclerosis, endothelial dysfunction, and presence of thrombogenic materials 1

Hyperviscosity Syndrome

Clinical Manifestations

• Hyperviscosity symptoms include headache, faintness, dizziness, fatigue, tinnitus, blurred vision, paresthesia of fingers/toes/lips, muscle pain, and weakness 1
• Symptoms are classified as moderate when interfering with some activities and severe when interfering with most activities 1
• Hyperviscosity symptoms are unlikely in iron-replete patients with hematocrit <65% 1

Pathophysiology

• Compensatory erythrocytosis becomes pathologic by increasing blood viscosity, thereby decreasing perfusion and resulting in decreased total oxygen delivery 3
• Risk of venoocclusive/hyperviscosity syndrome increases with rising hematocrit, particularly above 65% 3

Iron Deficiency-Related Complications

Paradoxical Worsening

• Repeated inappropriate phlebotomies cause iron deficiency, which paradoxically worsens symptoms by reducing oxygen-carrying capacity and red cell deformability 1, 5
• Iron-deficient red blood cells with less oxygen-carrying capacity and reduced potential for deformation lead to increased stroke incidence 1
• Iron deficiency creates microcytic erythrocytes that induce higher viscosity than normocytic cells, increasing venoocclusive event risk 3

Clinical Impact

• Iron deficiency anemia should be avoided given the increased risk of strokes and vascular complications 1
• Creating iron deficiency through excessive phlebotomy can paradoxically worsen symptoms despite lower hematocrit 5, 6

Risk Factors for Thrombosis

Patient-Specific Factors

• Female gender, low oxygen saturation, older age, biventricular dysfunction, and dilated pulmonary arteries are identified risk factors for thrombotic complications 1
• Pre-existing conditions like chronic obstructive pulmonary disease increase hemoconcentration risk 1
• High BMI increases odds of erythrocytosis by 3.7-fold 7

Etiology-Specific Risks

• The risk of thrombosis in chronic lung disease with erythrocytosis is comparable to polycythemia vera 2
• Secondary erythrocytosis from various etiologies carries significant thrombotic risk, not just primary polycythemia vera 2, 8

Common Pitfalls in Management

Inappropriate Phlebotomy

• Routine phlebotomies without meeting established criteria (hemoglobin >20 g/dL, hematocrit >65%) should be avoided 1, 5, 6
• Repeated phlebotomy quickly leads to iron deficiency, creating higher-risk microcytic erythrocytes 3
• Therapeutic phlebotomy has very limited role and should only be performed with specific criteria met and no dehydration present 1

Anticoagulation Risks

• Currently available data do not support routine anticoagulation or aspirin to prevent thrombo-embolic complications in cyanotic patients 1
• There is increased bleeding risk with anticoagulation despite thrombotic risk 1