New Guideline Released on Managing Complications in Polycythemia Vera

The British Society for Haematology has released a new updated guideline¹ that offers practical guidance for the management of specific situations and complications of polycythemia vera (PV) and outlines management of the diverse types of secondary erythrocytosis. The guideline was compiled using a process that evaluated levels of evidence and strength of recommendations in the medical literature from 1215 articles that were generated between 2005 and 2017.

Thrombosis in PV. Thrombotic events are the major cause of morbidity and mortality in PV, and their prevention is the main objective of treatment. Additionally, these events have a signiifcant economic impact. Approximately a third of patients present with a thrombotic event, and younger patients diagnosed with PV have an increased risk of early death from cardiovascular disease than the general population, accounting for 45% of all deaths in PV. Arterial thrombosis involving large arteries and peripheral vascular disease are more common than venous thromboembolism in PV.

• Cardiovascular risk factors should be assessed and controlled (especially hyperlipidemia, hypertension, smoking history, and diabetes).
• Long-term cardiovascular risk should be formally assessed at baseline and then annually using a validated score such as QRISK.
• Both primary and secondary prevention should include control of cardiovascular risk factors in accordance with current recommendations. Medication use is discussed.

The guideline recommends the following for acute thrombotic events:

• Treatment of acute arterial or venous thrombosis should follow specialty guidelines.
• Institute cytoreductive therapy to ensure control of blood counts to the therapeutic target and venesection to keep hematocrit below 0.45.
• Secondary prevention tactics such as indefinite anticoagulation, which should be initiated for unprovoked venous thromboembolism dependent on bleeding risk. Cytoreduction and venesection to keep hematocrit below 0.45.

Unusual sites of venous thrombosis are more common in patients with myeloproliferative neoplasms, including splanchnic vein thrombosis (SVT) and cerebral vein thrombosis. The splanchnic circulation is particularly vulnerable in patients with JAK2 and V617F mutations.

• Patients presenting with SVT not associated with local malignancy should be tested for the presence of JAK2 and V617F mutations and, if negative, CALR mutation.
• Patients with SVT should be treated with long-term anticoagulation; patients with CVT should be treated with long-term anticoagulation.
• Cytoreduction and control of blood counts should be undertaken in keeping with management of high-risk PV.
• Patients should be managed in a multidisciplinary setting in conjunction with interventional radiology and hepatology.

Hemorrhage. While less frequent and a less severe complication of PV than thrombosis, hemorrhage affects the skin, mucous membranes, and the gastrointestinal tract.

• Screen for acquired von Willebrand syndrome (aVWS) if a bleeding history is present. If negative, test for platelet function defect and consult a hemostasis expert.
• Exercise caution with use of antiplatelet drugs/anticoagulants in patients with extreme thrombocytosis but balance the thrombotic and bleeding history of the patient.
• Manage significant bleeding episodes with tranexamic acid and/or platelet transfusion; cease/reduce aspirin.
• Optimize cytoreductive treatment.

Patients with PV undergoing surgery are, paradoxically, at high-risk of both hemorrhage and thrombosis. It is therefore important that these patients are assessed preoperatively and abnormal counts are optimized, balancing the acute need for surgical procedure against the risk of bleeding and thrombosis. Recommendations for perioperative management include:

• Involvement of a hematologist to optimize count control and individualize perioperative plan.
• Use of standard protocols for managing antithrombotic prophylaxis.
• If the patient has a bleeding history, preoperative screening for coagulation tests, aVWS, and platelet function tests.

Pruritis. A common phenomenon in PV, pruritis occurs in up to 85% of patients and can be challenging to manage. It can have a significant negative impact on quality of life, affecting sleep and participation in social activities. Intensity varies but can be severe, causing emotional depression, anxiety, and even suicide ideation. Pruritis can persist even after blood counts are normalized. The guideline discusses medications and other therapies and cooperative consultation with dermatologists in refractory cases.

Pregnancy. PV is uncommon in females of reproductive age, but the guidance makes recommendations for pregnancy management in PV patients, which should be done in close cooperation between obstetricians and hematologists.

Secondary erythrocytosis. The guideline addresses secondary erythrocytosis, both idiopathic (IE) and congenital. There are no clinical studies on the use of aspirin or venesection in IE and thus evidence-based recommendations cannot be made. Thrombotic risk factors should be evaluated in each individual IE case. Genetic testing is recommended. Congenital erythrocytosis encompasses a wide range of defects and is rare, with little hard data available to help advise on its management. Low-dose aspirin and venesection should be considered.

Finally, the guidelines discuss recommendations for erythrocytosis in hypoxic pulmonary disease and posttransplant erythrocytosis.

Reference

1. McMullin MFF, Mead AJ, Ali S, et al; British Society for Haematology Guideline. A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis. A British Society for Haematology Guideline [published online November 13, 2018]. Br J Haematol. doi: 10.1111/bjh.15647.