What is polycythemia in a patient with a history of deep vein thrombosis (DVT)?

Polycythemia Definition

Polycythemia is an abnormal increase in red blood cell mass that causes elevated hematocrit and hemoglobin levels, creating a hypercoagulable state through increased blood viscosity, platelet dysfunction, and systemic prothrombotic mechanisms—particularly dangerous in patients with DVT history who face compounded thrombotic risk. 1, 2

Classification Framework

Polycythemia divides into two fundamental categories that determine both pathophysiology and management 1:

Apparent (Relative) Polycythemia

• Reduced plasma volume with normal red cell mass 1
• Hematocrit elevation without true increase in total red blood cells 1

True Polycythemia

True polycythemia represents actual increased red cell mass and subdivides into 1:

Primary Polycythemia (Polycythemia Vera)

• Clonal myeloproliferative disorder with autonomous red cell production 1, 3
• JAK2 V617F mutation present in >95% of cases 4
• Erythropoietin levels are suppressed below normal range 1, 4
• Characterized by erythropoietin-independent erythroid colony formation 3

Secondary Polycythemia

• Compensatory response to hypoxia or pathologic erythropoietin production 1
• Erythropoietin levels elevated or high-normal 1, 4
• JAK2 V617F mutation absent 4

Pathophysiologic Mechanisms Relevant to DVT Risk

Hyperviscosity and Flow Dynamics

• Increased hematocrit elevates blood viscosity, which paradoxically decreases oxygen delivery to tissues by reducing capillary flow 1
• Aortic oxygen saturations <75% represent the critical threshold where decompensated erythrocytosis occurs 1
• In low shear rate conditions (large veins), axial migration of red blood cells displaces platelets and leukocytes toward the endothelium, enhancing thrombogenic interactions and explaining venous thrombosis patterns 2

Platelet Abnormalities

• Thrombocytopenia occurs inversely related to hematocrit levels, with mild decreases (100,000-150,000/mm³) more common than severe (<50,000/mm³) 1
• Platelet aggregation studies demonstrate decreased function related to polycythemia severity (hemoglobin >19 g/dL, hematocrit >59%) 1
• Diminished platelet adenylate cyclase response to prostaglandin D2 (a physiological inhibitor) combined with increased baseline thromboxane A2 production creates a prothrombotic state 2
• Platelet survival decreases to <80 hours versus normal 80-130 hours 1

Systemic Prothrombotic State

• Widespread activation of coagulation proteins occurs alongside reduced levels of antithrombin III, proteins C and S 2
• Decreased fibrinolytic activity results partly from increased plasminogen activator inhibitor levels 2
• Increased d-dimer levels support the hypothesis of disseminated intravascular coagulation in severe cases 1
• These abnormalities persist even with hematocrit control, explaining residual thrombotic risk 2

Critical Diagnostic Distinctions

The distinction between primary and secondary polycythemia is essential 1, 4:

• Erythropoietin measurement: Suppressed in polycythemia vera, elevated/normal in secondary causes 1, 4
• JAK2 V617F testing: Present in >95% of polycythemia vera, absent in secondary polycythemia 4, 3
• Hemoglobin thresholds: Mild elevations (<18.5 g/dL in men) more typical of secondary causes 4
• Oxygen saturation: Normal in polycythemia vera, reduced in hypoxia-driven secondary polycythemia 1

Management Implications for DVT Patients

Hematocrit Control

• Target hematocrit <45% significantly reduces thrombotic events based on the CYTO-PV trial 2
• Aggressive phlebotomy improves median survival from <2 years to >10 years 2
• In patients requiring IVC filter placement, lowering hemoglobin and hematocrit as early as possible is critical to prevent filter thrombosis 5

Anticoagulation Considerations

• Standard anticoagulant volumes must be adjusted in polycythemia because reduced plasma volume in whole blood samples can falsely lower measured coagulation factor levels 1
• Phlebotomy substantially reduces but does not abolish thrombosis risk, indicating factors beyond hematocrit contribute to the prothrombotic state 2
• Case reports document thrombo-occlusion below IVC filters despite anticoagulation and therapeutic phlebotomy in polycythemia vera patients 5

Risk Stratification

• Age ≥60 years and history of thrombosis represent the most important risk factors 6
• Elevated hematocrit and leukocytosis associate with increased thrombosis risk 6
• Highest thrombosis rates occur shortly before or at diagnosis, decreasing over time with treatment 6

Common Pitfalls

• Do not assume adequate hematocrit control eliminates thrombotic risk—qualitative platelet defects and systemic prothrombotic abnormalities persist 2
• Pre-analytical variables significantly affect measurements; time between blood collection and analysis matters 4
• In high hematocrit samples, standard anticoagulant amounts with reduced plasma volume distort coagulation studies 1
• Iron deficiency in polycythemia creates microcytic hypochromic red cells that are rigid and less deformable, paradoxically worsening tissue oxygenation despite lower hemoglobin 1