Polycythemia vera (PV) is a chronic blood cancer classified as a myeloproliferative neoplasm (MPN) that originates in the bone marrow. This condition is characterized by the overproduction of blood cells, primarily red blood cells, but often includes white blood cells and platelets. Thrombocytosis is the medical term for an excessive count of platelets, which are the cell fragments responsible for forming blood clots. The simultaneous occurrence of PV and thrombocytosis is frequent and requires careful management.
The Link Between Polycythemia Vera and Elevated Platelets
Polycythemia vera is a panmyelosis, meaning the disorder results in the uncontrolled proliferation of all three major blood cell lines in the bone marrow. This generalized overproduction is driven by an acquired genetic mutation that disrupts the normal signaling pathways that regulate blood cell growth. The cells in the bone marrow become hyper-responsive to growth factors, leading to autonomous and unregulated cell division.
The underlying issue is a defect in the hematopoietic stem cells, the precursors to all mature blood cells. These abnormal stem cells give rise to excessive megakaryocytes, which are the large bone marrow cells that produce platelets. Thrombocytosis is a common manifestation of this underlying bone marrow disorder, resulting from faulty signaling rather than a physiological need.
Symptoms and Diagnostic Markers
Patients with PV and elevated platelets may experience symptoms resulting from thickened blood and microvascular circulation issues. Common complaints include headaches, dizziness, and blurred vision. A specific symptom is erythromelalgia, which causes burning pain, redness, and warmth, typically in the hands or feet, due to small vessel occlusion. Other reported symptoms are fatigue, ringing in the ears (tinnitus), and severe itching (pruritus), often triggered by contact with warm water (aquagenic pruritus).
Diagnosis often begins with a routine Complete Blood Count (CBC) revealing an abnormally high platelet count (frequently exceeding 400 x 10⁹/L), alongside elevated hemoglobin and hematocrit levels. The presence of high counts in multiple cell lines suggests a myeloproliferative process. Further testing includes genetic analysis to identify specific mutations, a major criterion for confirmation. A low serum erythropoietin level also supports the PV diagnosis, as red cell production occurs independently of this hormone.
Understanding Vascular Risk
The primary danger associated with PV and thrombocytosis is a significantly increased risk of developing serious vascular events, collectively known as thrombosis. This risk stems from the hyperviscosity of the blood caused by the high red cell mass and the presence of abnormally activated platelets. These excessive platelets are numerous and often functionally hypersensitive, contributing to an unstable clotting environment.
Thrombotic events can occur in both arteries and veins, potentially leading to fatal outcomes. Arterial clots can cause a stroke or myocardial infarction (heart attack), while venous clots commonly manifest as deep vein thrombosis (DVT) or pulmonary embolism (PE). PV is also associated with thrombosis in unusual sites, such as the veins of the abdomen, which can lead to conditions like Budd-Chiari syndrome.
Paradoxically, some patients with very high platelet counts (often exceeding 1,000 x 10⁹/L) may experience a bleeding risk. This is due to acquired von Willebrand disease, where the large number of platelets absorbs and inactivates von Willebrand factor. This deficiency leads to an increased risk of hemorrhage despite the high cell count.
Managing Platelet Levels
The management of elevated platelet counts in PV focuses on mitigating the risk of thrombosis. A universal strategy involves the use of low-dose aspirin (typically 75 mg to 100 mg daily) to reduce platelet aggregation. This anti-platelet therapy helps prevent microvascular events and is generally safe, provided the patient does not have a high bleeding risk.
For high-risk patients, such as those over 60 or with a history of prior thrombosis, cytoreductive therapy is implemented to suppress the overproduction of blood cells. Hydroxyurea is a common first-line cytoreductive agent, working to lower the counts of red cells, white cells, and platelets. Other options include interferon-alpha, which is often considered for younger patients or those intolerant to hydroxyurea. The goal of this treatment is to manage thrombocytosis and maintain the hematocrit level below a target of 45%, which reduces the rate of major cardiovascular and thrombotic events.