Risk of Venous Thrombosis in Secondary Erythrocytosis
The severity of secondary erythrocytosis per se is NOT a risk factor for venous thrombosis in otherwise healthy patients, and routine anticoagulation or prophylactic phlebotomy to prevent thrombosis is not indicated. 1
Key Evidence from Cyanotic Heart Disease
The most direct evidence addressing this question comes from patients with cyanotic congenital heart disease (CCHD), who represent a well-studied population with secondary erythrocytosis:
Cerebrovascular accidents in CCHD patients are NOT caused by the severity of erythrocytosis itself, but rather by microcytosis from iron deficiency due to inappropriate phlebotomies 1
Iron deficiency with microcytosis was the strongest independent predictor for cerebrovascular events in this population, not the hematocrit level 1
Thrombosis in CCHD is caused by multiple factors including coagulation abnormalities, blood stasis in dilated chambers, atherosclerosis, endothelial dysfunction, and arrhythmias—not the erythrocytosis itself 1
Clinical Implications for Management
When Symptoms Occur
Hyperviscosity symptoms are unlikely in iron-replete patients with hematocrit <65% 1
Symptomatic patients should be treated with IV hydration and iron supplementation (if deficient), NOT phlebotomy 2
Therapeutic phlebotomy should ONLY be performed when there are moderate/severe hyperviscosity symptoms, hematocrit >65%, AND the patient is not dehydrated or iron deficient 1
What NOT to Do
Currently available data do not support routine anticoagulation or aspirin in patients with secondary erythrocytosis to prevent thromboembolic complications 1
There is an increased risk of bleeding with anticoagulation in these patients 1
Repeated phlebotomy causes iron deficiency with microcytic erythrocytes, which increases whole blood viscosity and can potentially INCREASE rather than decrease cerebrovascular accident risk 2
Contrast with Primary Erythrocytosis
This stands in stark contrast to polycythemia vera (PV), where:
An association between elevated hematocrit and thrombosis HAS been established in PV patients 2, 3
PV patients have arterial thrombosis in 16% and venous thrombosis in 7% prior to or at diagnosis 3
All PV patients should receive therapeutic phlebotomy (goal hematocrit <45%) and low-dose aspirin 3
The incidence rate of thrombosis in PV is 4.51 cases per 100 person-years 4
Important Caveats
Secondary Causes with Increased Risk
Chronic lung disease (CLD) with erythrocytosis may have comparable thrombosis risk to PV, with an incidence rate of 6.24 cases per 100 person-years 4
This is significantly higher than obstructive sleep apnea with erythrocytosis (1.46 cases per 100 person-years) 4
The mechanism appears related to the underlying disease process rather than the erythrocytosis itself 4
Risk Factors to Address
Focus prevention efforts on modifiable risk factors rather than the erythrocytosis:
- Avoid dehydration 1, 2
- Prevent and treat iron deficiency 1, 2
- Manage underlying conditions (sleep apnea, lung disease) 4
- Address traditional cardiovascular risk factors 1
Bottom Line for Clinical Practice
In healthy patients with secondary erythrocytosis from conditions like high altitude exposure or sleep apnea, the erythrocytosis itself does not increase thrombosis risk and should not be treated with phlebotomy or anticoagulation. 1 The pathophysiology differs fundamentally from primary erythrocytosis (PV), where the malignant clone creates a prothrombotic state independent of hematocrit level. 3, 5