Polycythemia vera (PV) is a chronic blood disorder where the bone marrow produces too many red blood cells. This overproduction can lead to blood that is thicker than usual, increasing the risk of serious complications such as blood clots, heart attack, or stroke. Individuals with PV may also experience symptoms like persistent itching or an enlarged spleen. For many people diagnosed with high-risk PV, hydroxyurea is a common medication used to help manage the condition.
How Hydroxyurea Works for Polycythemia Vera
Hydroxyurea functions as a cytoreductive agent, meaning it reduces the number of blood cells produced in the bone marrow. The medication achieves this by interfering with DNA synthesis within rapidly dividing cells. Specifically, hydroxyurea inhibits an enzyme called ribonucleotide reductase, which is necessary for creating the building blocks of DNA.
By disrupting DNA production, hydroxyurea slows down the overactive bone marrow. This action leads to a decrease in the excessive formation of red blood cells, the primary concern in PV. The medication also reduces the production of other blood cells, including platelets and white blood cells.
The main goal of this cellular reduction is to decrease the overall thickness of the blood, often measured by hematocrit, aiming to keep it below 45%. Reducing blood viscosity lowers the risk of blood clots, a primary concern for individuals with PV. Additionally, this therapy helps alleviate common symptoms such as itching (pruritus) and discomfort from an enlarged spleen (splenomegaly).
Potential Side Effects of Hydroxyurea
Hydroxyurea can cause various side effects. Common and generally manageable effects include fatigue, mild nausea, vomiting, and a reduced appetite. Some individuals may also experience mouth sores (stomatitis), diarrhea, constipation, headaches, dizziness, or hair thinning.
A less common risk is bone marrow suppression, also known as myelosuppression. This occurs when hydroxyurea reduces blood cell production too much, leading to low levels of white blood cells (leukopenia or neutropenia), low platelets (thrombocytopenia), or anemia. This effect is closely monitored and is reversible if the medication dose is adjusted or temporarily stopped.
Long-term use of hydroxyurea is also associated with certain skin issues. These can include painful leg ulcers, as well as an increased risk of non-melanoma skin cancers, such as squamous cell carcinoma, basal cell carcinoma, and actinic keratoses. Individuals taking hydroxyurea should practice sun protection, including wearing protective clothing and sunscreen. Other skin changes, like hyperpigmentation, dry skin, and nail alterations, may develop over time.
There is a small, long-term risk of PV transforming into other blood disorders, such as myelofibrosis or acute leukemia. Hydroxyurea’s contribution to this transformation risk is considered lower compared to some older chemotherapy agents. The incidence of transformation to acute myeloid leukemia is low, while myelofibrosis transformation rates can be higher over time. This progression is also an inherent risk of the underlying polycythemia vera itself, regardless of treatment.
The Treatment and Monitoring Process
The dosage of hydroxyurea for polycythemia vera is individualized. Treatment starts with a low dose, such as 500 mg or 1000 mg daily, and is gradually adjusted. The doctor modifies the dose based on regular blood test results and how well the patient tolerates the medication.
Regular monitoring is an important part of therapy with hydroxyurea. Patients undergo frequent complete blood count (CBC) tests to track levels of red blood cells, white blood cells, and platelets. The aim is to keep the hematocrit, a measure of red blood cell concentration, below 45% and platelet counts below 400,000 per microliter, while ensuring white blood cell counts remain within a healthy range. Initially, blood tests may be performed every one to two weeks, becoming less frequent (such as every one to three months) once blood counts stabilize.
Consistent adherence to the prescribed dose and attending all scheduled follow-up appointments are important for effective management. These regular visits allow the healthcare team to assess the medication’s effectiveness, monitor for any potential side effects, and make timely dosage adjustments. Individuals should communicate any new or worsening symptoms to their healthcare team promptly.
Alternative and Supportive Treatments
Hydroxyurea is often part of a broader treatment strategy for polycythemia vera. Supportive treatments are commonly used, sometimes before or alongside cytoreductive agents. Phlebotomy, a procedure similar to blood donation where blood is removed from the body, is a common approach to reduce red blood cells and blood thickness. This procedure helps achieve the target hematocrit level and also induces a mild iron deficiency, which can limit new red blood cell production.
Low-dose aspirin, 81 mg daily, is also frequently prescribed for patients, unless contraindicated. Aspirin helps prevent blood clots by making platelets less sticky and can also help alleviate some PV-related symptoms, such as burning pain in the hands and feet or itching.
Should hydroxyurea not be tolerated or fail to adequately control the disease, other cytoreductive therapies are available. Interferon-alpha, including pegylated forms, is an injectable medication that reduces blood cell production. It may be considered for younger patients, those with specific symptoms, or if hydroxyurea proves ineffective.
Ruxolitinib (Jakafi) is another medication that inhibits specific enzymes (JAK1 and JAK2) and is used for patients who are resistant or intolerant to hydroxyurea. Ruxolitinib can effectively manage symptoms such as an enlarged spleen and itching. Other agents, such as busulfan, or newer therapies like rusfertide, which regulates iron metabolism, are also part of the evolving treatment landscape for polycythemia vera.