Should a patient with polycythemia and superficial venous thrombosis be anticoagulated?

Anticoagulation for Superficial Venous Thrombosis in Upper Limb with Polycythemia Vera

Yes, this patient should receive anticoagulation therapy for 45 days with prophylactic-dose fondaparinux 2.5 mg daily or LMWH, combined with optimal management of the underlying polycythemia vera including hematocrit control to <45% and low-dose aspirin. 1

Primary Recommendation for Superficial Venous Thrombosis

The most recent CHEST guidelines (2021) specifically address superficial venous thrombosis (SVT) and recommend anticoagulation for patients at increased risk of clot progression to DVT or PE 1. While the guidelines focus on lower limb SVT, the principles apply to upper limb SVT, particularly in high-risk patients with underlying prothrombotic conditions like polycythemia vera.

Specific Anticoagulation Regimen

• First-line agent: Fondaparinux 2.5 mg subcutaneously daily for 45 days 1
• Alternative: Prophylactic-dose LMWH for 45 days if fondaparinux is unavailable or refused 1
• Oral alternative: Rivaroxaban 10 mg daily for 45 days if parenteral anticoagulation is refused or impractical 1

The 2012 CHEST guidelines established that SVT ≥5 cm in length warrants prophylactic-dose anticoagulation to prevent progression to DVT/PE 1. The 2021 update reinforced this recommendation with moderate-certainty evidence 1.

Polycythemia Vera-Specific Considerations

The presence of polycythemia vera significantly elevates thrombotic risk and strengthens the indication for anticoagulation. 1, 2

Thrombotic Risk in Polycythemia Vera

Polycythemia vera creates a prothrombotic state through multiple mechanisms 1:

• Elevated hematocrit increases blood viscosity and reduces flow rates
• Qualitative platelet defects with increased thromboxane A2 production
• Leukocyte activation and endothelial dysfunction
• Baseline activation of coagulation proteins
• Reduced levels of natural anticoagulants (antithrombin III, proteins C and S)

Essential Concurrent Management

Hematocrit control to <45% is mandatory to reduce cardiovascular death and major thrombosis risk 2. This is achieved through:

• Phlebotomy as needed to maintain target hematocrit
• Low-dose aspirin (unless contraindicated by bleeding risk) 2
• Cytoreductive therapy if patient is high-risk (age ≥60 or prior thrombosis) 2

Duration and Monitoring

The standard 45-day course of prophylactic anticoagulation for SVT should be completed 1. However, given the underlying polycythemia vera:

• After completing the 45-day course for acute SVT, consider extended anticoagulation if the patient has additional risk factors such as prior thrombotic events or inadequately controlled disease 3, 4
• A systematic review found that anticoagulation combined with cytoreduction provided the lowest recurrence risk (8% with DOACs plus cytoreduction) in MPN patients with VTE history 3
• Long-term vitamin K antagonist therapy reduced re-thrombosis risk 2.8-fold in PV/ET patients with prior thrombosis 4

Important Caveats

Bleeding Risk Assessment

While polycythemia vera increases thrombotic risk, it can also cause bleeding through 1:

• Acquired von Willebrand disease (occurs in >33% of PV patients, especially with extreme thrombocytosis)
• Qualitative platelet defects
• Poor platelet aggregation responses

Monitor for bleeding complications, particularly if platelet count is markedly elevated (>1,000/μL) 1. The bleeding risk does not negate anticoagulation indication but requires vigilance.

Anticoagulation Intensity Matters

Studies in PV patients show that subtherapeutic anticoagulation (INR <2.0) is associated with recurrent thrombotic events 5. When prophylactic dosing is used for SVT, ensure consistent administration and consider therapeutic dosing if thrombus extends or symptoms worsen.

Location-Specific Considerations

Although guidelines primarily address lower limb SVT, upper limb SVT in polycythemia vera warrants the same aggressive approach because 1:

• The prothrombotic state affects all vascular beds
• Risk of extension to deep veins remains significant
• The 2021 CHEST guidelines note that factors favoring anticoagulation include severe symptoms, history of VTE, and active cancer—all analogous to having an underlying MPN 1

Clinical Algorithm

1. Initiate anticoagulation immediately: Fondaparinux 2.5 mg SC daily (or prophylactic LMWH if unavailable) 1
2. Optimize PV management concurrently: Target hematocrit <45% via phlebotomy, add low-dose aspirin if not already prescribed 2
3. Continue anticoagulation for 45 days minimum 1
4. At 45 days, reassess: If PV is well-controlled with no prior thrombotic history, consider stopping anticoagulation but continue aspirin and hematocrit control 2
5. Consider extended anticoagulation if: prior thrombotic events, inadequate disease control, or recurrent/progressive symptoms 3, 4