Patients with PV are at higher risk for developing venous and arterial blood clots, which may result in serious events including heart attack and stroke. To reduce this risk, controlling hematocrit levels to less than 45% and starting low-dose aspirin is extremely necessary.
CBC Monitoring/Phlebotomy Course
The patient was started on low dose aspirin and treated with phlebotomy. In the first month of treatment, the patient required 9 phlebotomies to achieve a Hct of less than 45%, but then was able to go a few months between procedures. BP readings normalized with phlebotomy. Unfortunately, frequency of procedures was increasing prior to transfer of care to our clinic, and the patient had been undergoing phlebotomy monthly for the last 3 months.
Laboratory test results on presentation to our clinic were WBC 22,000/µL; Hct 49%; platelets 774,000/µL; ferritin 9 ng/mL; and very low EPO level. Because of the patient’s elevated WBC count and need for frequent phlebotomy, we recommended initiating cytoreductive therapy with hydroxyurea; however, the patient declined the treatment.
Phlebotomy continued every 2 to 3 months to maintain a target Hct of less than 45%. Platelets started to increase further, and when they reached 1.2 million, von Willebrand factor (vWF) activity was checked, noted to be low, and low-dose aspirin was temporarily put on hold. Facing the risk of bleeding with extreme thrombocytosis, persistent need for phlebotomy, and leukocytosis, the patient was now amenable to starting hydroxyurea therapy. In addition, he had developed symptoms of disease including bone pain, headaches, and fatigue that were preventing him from working full time.
Treatment with Hydroxyurea
Hydroxyurea therapy was started at a dose of 1000 mg orally daily and was tolerated without adverse effects. WBC, RBC, and platelets all responded well. Within 1 month, WBC decreased from 23,900/µL to 10,600/µL, and platelets decreased from 884,000/µL to 204,000/µL. Hct increased from 43.3% to 46.1%, likely because of the length of time since his last phlebotomy. Repeat vWF activity showed this had normalized with the reduction in platelet count, and low-dose aspirin was resumed. The patient underwent phlebotomy and continued the hydroxyurea as dosed for the next 3 months.
Symptomatically, the patient felt better after starting hydroxyurea, presumably due to better disease control, and returned to work full-time. However, after 4 months of treatment at this dose, he still required phlebotomy every other month; therefore, the hydroxyurea dose was increased to 1500 mg orally daily.
The patient was monitored monthly and continued to require phlebotomy every other month. His platelets were well-controlled, but WBC started to drop to less than the lower limits of normal. In addition, the patient developed hypertension and was referred to a cardiologist for antihypertensive therapy, as optimal control of cardiovascular risk factors is necessary to reduce the risk of cardiovascular events in patients with PV.
After 5 months on the higher dose of hydroxyurea, the need for phlebotomy remained persistent. The hydroxyurea dose could not be increased any further due to a risk of neutropenia; therefore, alternative therapeutic options were discussed with the patient.
Pegylated interferon was previously discussed with the patient at treatment initiation; however, he did not want to risk the potential for flulike symptoms because of his frequent travel for work. He was still of this mindset, therefore, we did not pursue treatment with this biologic agent.
We discussed treatment with ruxolitinib, a JAK1/2 inhibitor that is FDA approved in the setting of uncontrolled blood counts despite treatment with hydroxyurea as well as intolerance of hydroxyurea. His disease fits into the refractory category, proving to be more advanced with the persistent need for phlebotomy despite receiving the maximally tolerated hydroxyurea dose.
How would you approach the transition from hydroxyurea to ruxolitinib?
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