Hydroxyurea (HU) is an oral medication widely prescribed as a disease-modifying therapy for chronic blood disorders, most notably Sickle Cell Disease (SCD) and specific myeloproliferative neoplasms (MPNs) like Polycythemia Vera (PV) and Essential Thrombocythemia (ET). HU works by inhibiting DNA synthesis, slowing the overproduction of abnormal blood cells in the bone marrow. Because this medication is intended for long-term use, abruptly stopping Hydroxyurea without medical supervision can lead to a rapid deterioration of the underlying illness, as its protective effects diminish quickly once treatment is interrupted.
Immediate Effects of Discontinuation
Stopping Hydroxyurea leads to a swift loss of therapeutic benefits, causing an acute worsening of the underlying blood disorder within weeks or months.
In patients with Sickle Cell Disease (SCD), the most immediate consequence is the rapid decline in fetal hemoglobin (HbF), which HU stimulates the body to produce. HbF interferes with the sickling of red blood cells; its reduction allows abnormal hemoglobin to polymerize, causing red blood cells to revert to their crescent shape. This loss of protection increases the frequency and severity of acute complications, such as vaso-occlusive crises (pain crises) and acute chest syndrome. The drug’s other benefits, including the reduction of white blood cell and platelet counts, which contribute to inflammation and blood vessel blockage, also reverse quickly.
For patients with myeloproliferative neoplasms (MPNs) like Polycythemia Vera or Essential Thrombocythemia, stopping HU can trigger a “rebound” effect in blood cell counts. HU acts as a cytoreductive agent, controlling the overproduction of red blood cells, white blood cells, and platelets. The abrupt cessation removes this suppressive effect, potentially causing a rapid surge in platelet count (thrombocytosis) and white blood cell count. This sharp increase significantly elevates the immediate risk of severe clotting events (thrombosis), such as deep vein thrombosis, stroke, or heart attack.
Loss of Long-Term Disease Protection
Stopping Hydroxyurea removes the ongoing preventative maintenance that protects major organs from chronic damage. Sickle cell disease (SCD) is characterized by persistent blood vessel damage and chronic inflammation that slowly leads to irreversible organ failure. HU therapy is associated with a sustained reduction in long-term complications, including stroke, pulmonary hypertension, and chronic kidney disease.
When HU is discontinued, the continuous damage to organs accelerates because the underlying disease process is no longer suppressed. Long-term follow-up studies suggest that mortality is significantly reduced in individuals with prolonged exposure to HU. Patients who never took HU or took it for less than five years had a higher rate of death from complications compared to those with long-term use.
In MPNs, the long-term benefit of HU is preventing the transformation of the disease into more aggressive forms, such as myelofibrosis or acute myeloid leukemia. Discontinuing the therapy allows the unchecked proliferation of abnormal blood cells to continue, increasing the risk of disease progression. The loss of control over blood counts, particularly in Polycythemia Vera, leads to chronic hyperviscosity of the blood, which contributes to long-term microvascular damage and organ dysfunction.
Common Reasons for Stopping Treatment
Patients often stop taking Hydroxyurea for various reasons related to managing a chronic condition and its treatment.
One frequently cited reason is the experience of side effects, which can include fatigue, hair loss, gastrointestinal issues, or painful leg ulcers. The myelosuppressive nature of the drug may also require temporary or permanent discontinuation under a doctor’s direction if it causes low white blood cell or platelet counts.
Other patients discontinue the medication because they perceive it to be ineffective, especially since the full benefits of HU can take several months to become apparent. Some stop because they feel their symptoms are significantly reduced, leading them to believe the medication is no longer necessary. Non-adherence due to simply forgetting to take the daily pill is a common unintentional barrier.
A medically valid reason for a planned pause is for reproductive health, such as a woman planning a pregnancy or a male partner attempting conception. However, discontinuation must be part of a detailed plan with a hematologist to manage the underlying disease during the break. Financial issues, difficulty accessing the medication, or poor communication with the healthcare provider also contribute to discontinuation rates.
Safe Discontinuation and Restarting Protocols
Hydroxyurea should never be stopped abruptly without first consulting the prescribing hematologist or specialist. Any decision to discontinue, even temporarily, requires a detailed, medically supervised plan to mitigate the risks of acute disease rebound. A planned pause involves comprehensive monitoring, with frequent complete blood counts (CBCs) to track the recovery of the bone marrow and the potential for a rapid increase in disease markers.
If discontinuation is medically necessary, such as due to severe drug toxicity or a planned pregnancy, the physician will determine an alternative treatment strategy to maintain disease control. For women who conceive while on HU, the drug is typically stopped in the first trimester. A specialist will often transition the patient to a non-drug therapy, such as blood transfusions, to manage the sickle cell disease during the pregnancy. Close monitoring of the patient’s blood work and clinical status is mandatory during this period.
When restarting HU after a temporary stop, the medication is usually initiated at a lower dose than the patient was previously taking. This cautious approach is necessary because the bone marrow’s sensitivity to the drug may have changed, and restarting at the full dose could cause severe myelosuppression (dangerously low blood counts). The dosage is then gradually increased, or titrated, over several weeks or months, with ongoing blood count monitoring until the patient reaches their maximum tolerated dose (MTD).