Can a patient have Hereditary Hemorrhagic Telangiectasia (HHT) and Polycythemia Vera (PV) simultaneously?

Can a Patient Have HHT and Polycythemia Vera Simultaneously?

Yes, a patient can have both Hereditary Hemorrhagic Telangiectasia (HHT) and Polycythemia Vera (PV) simultaneously, though this represents a complex clinical scenario requiring careful management of competing bleeding and thrombotic risks. 1

Pathophysiologic Independence

These are two distinct disease entities with separate genetic mechanisms:

• HHT is an autosomal dominant vascular disorder caused by loss-of-function mutations in genes encoding proteins of the BMP signaling pathway (primarily ENG, ACVRL1, SMAD4, or GDF2), affecting vascular endothelium and causing abnormal blood vessel formation. 1, 2

• PV is a clonal myeloproliferative neoplasm caused by acquired somatic mutations (typically JAK2V617F) affecting hematopoietic stem cells and causing erythrocytosis, representing a fundamentally different pathophysiologic process. 1

• The European Heart Journal recognizes chronic myeloproliferative disorders, including polycythemia vera, as possible risk factors for pulmonary arterial hypertension in patients with HHT, indicating that clinical overlap between these conditions is recognized. 1

Critical Diagnostic Pitfall

The most dangerous clinical error is assuming anemia excludes PV in an HHT patient. 1

• Iron deficiency from chronic HHT bleeding (epistaxis, gastrointestinal telangiectases) can completely mask the elevated red cell mass of PV, resulting in a normal or even low hematocrit despite underlying PV. 1

• You must assess complete iron studies (ferritin, transferrin saturation, serum iron) and consider JAK2 mutation testing even with normal hematocrit if clinical suspicion exists (thrombotic events, splenomegaly, pruritus after bathing, erythromelalgia). 1

• The pro-hemorrhagic platelet defects in PV include acquired von Willebrand disease, which occurs in more than a third of PV patients and is associated with a bleeding diathesis—this compounds the bleeding risk already present from HHT. 3

Management Algorithm for Co-Occurring HHT and PV

1. Hematocrit Management (Highest Priority)

• Phlebotomy targeting hematocrit <45% is essential to reduce thrombotic events, which substantially reduces but does not abolish thrombosis risk in PV patients. 3, 1

• This target applies regardless of HHT bleeding manifestations, as the thrombotic risk from uncontrolled PV outweighs bleeding concerns in most scenarios. 1

• Monitor closely during phlebotomy as HHT patients may have baseline iron deficiency—adjust frequency based on iron studies and clinical bleeding severity. 1

2. Antiplatelet Therapy Decision

• Low-dose aspirin is standard for PV patients to reduce cardiovascular events, but its use must be carefully weighed against HHT bleeding risk. 1

• Consider aspirin if the patient has high thrombotic risk (prior thrombosis, cardiovascular risk factors, age >60 years) and relatively controlled HHT bleeding (minimal epistaxis, no active gastrointestinal bleeding). 1

• Withhold aspirin if the patient has severe recurrent epistaxis requiring frequent intervention, active gastrointestinal bleeding, or large untreated visceral AVMs. 1

3. Cytoreductive Therapy for High-Risk PV

• High-risk PV patients (age >60 years or prior thrombosis) require cytoreductive therapy, with hydroxyurea being the standard first-line agent for patients over 40 years, and interferon-α preferred for younger patients. 1

• Cytoreductive therapy may actually benefit HHT patients by reducing platelet counts and potentially decreasing bleeding from acquired von Willebrand disease associated with extreme thrombocytosis. 3, 1

4. Comprehensive HHT Screening (Mandatory)

• Perform Doppler ultrasonography for hepatic vascular malformations as first-line imaging, as hepatic AVMs create left-to-right shunts causing high cardiac output that could be catastrophically worsened by PV-related hyperviscosity. 1, 4

• Screen for pulmonary AVMs using contrast echocardiography or chest CT, as these create right-to-left shunts with risk of paradoxical emboli—a risk dramatically amplified by PV's prothrombotic state. 1, 4

• Obtain brain MRI to detect cerebral vascular malformations, as the combination of HHT cerebral AVMs and PV thrombotic tendency creates extreme stroke risk. 1, 4

5. Absolute Contraindications

• Liver biopsy is absolutely contraindicated in HHT patients due to catastrophic hemorrhage risk from hepatic vascular malformations, regardless of PV status or need for bone marrow evaluation. 1, 4

• If bone marrow biopsy is needed to confirm PV diagnosis, this can be performed safely as bone marrow vasculature is not affected by HHT. 1

Monitoring Strategy

• Check complete blood count, iron studies (ferritin, transferrin saturation), and hematocrit every 1-3 months to balance PV control against HHT-related iron deficiency. 1

• Assess bleeding severity using validated epistaxis scoring tools and monitor for new gastrointestinal bleeding, adjusting antiplatelet therapy accordingly. 1

• Screen for thrombotic events (arterial and venous) at each visit, as the baseline prothrombotic state in PV involves widespread activation of coagulation proteins, reduced levels of physiologic anticoagulants, and decreased fibrinolytic activity. 3

Treatment of HHT Bleeding in This Context

• Begin with nasal moisturization for epistaxis, escalating to oral tranexamic acid if inadequate, which reduces epistaxis duration by 17.3% and composite epistaxis endpoints by 54%. 1, 4

• Reserve systemic bevacizumab for refractory cases failing all other interventions, as it produces a 50% reduction in epistaxis severity score and may improve both HHT bleeding and potentially modulate the vascular complications. 1, 4

• Aggressive iron replacement (oral or intravenous) is essential to maintain adequate iron stores while managing both conditions. 1, 4