The three major myeloproliferative syndromes are:
1. Polycythemia Vera: It is the most common myleoproliferative disorder and is characterized by an increase in red blood cells (RBC) mass. massive splenomegaly and clinical manifestations related to increased blood viscosity. It also includes neurological manifestations like Vertigo, tinnitus, headache and visual disturbances. Increased RBC mass can also lead to thromboses that can causes complications like myocardial infarction, stroke and peripheral vascular disease.
Polycythemia vera must be distinguished from other causes of increased RBC mass, and this can be done by assaying serum erythropoietin levels. In polycythemia vera serum erythropoietin is low while in other causes erythropoietin levels are high.
Bone marrow biopsy showing hypercellularity with trilineage growth (panmyelosis) with prominent erythroid, granulocytic, and megakaryocytic proliferation
Management: Patients are effectively managed with phlebotomy. Some patients may require splenectomy, and those with pruritits may benefit from psoralens and UV light.
2. Idiopathic Myelofibrosis: This rare entity is characterized by marrow fibrosis, myeloid metaplasia with extramedullary hematopoiesis and splenomegaly. Evaluation of blood smear reveals tear drop shaped RBC, nucleated RBC and some early granulocytic forms, including promyelocytes.
However many entities may lead to marrow fibrosis and extramedullary hematopoiesis, so the diagnosis of primary idiopathic myelofibrosis is made only when other potential causes are ruled out.
The following diseases are to be included in differential diagnosis:
- Polycythemia vera
- Hodgin's disease
- Cancer metastases to marrow (especially from breast and prostate)
- Infection ( Particularly granulomatous infections)
- Hairy cell leukemia
Management: Supportive therapy is usually used. Inhibitors of JAk2 and telomerase have shown activity in reducing splenomegaly and marrow fibrosis in some cases. No study has yet shown a particular drug therapy to improve survival.
3, Essential Thrombocytosis: It is usually noticed incidentally upon routine platelet count done in asymptomatic patients. Many other conditions can also lead to increased platelet count and so the diagnosis is one of exclusion. Platelet count must be > 500,000/microliter, and other known causes of thromocytopenia must be ruled out including CML, iron deficiency anemia, splenectomy, malignancy, infection, hemorrhage, polycythemia vera, myelodysplasia and recovery from vitamin B 12 deficiency.
Although most patients are asymptomatic some may develop headaches, transient ischemic attacks, or other bleeding or thrombotic disease.
Hypercellularity with a large number of megakaryocytes
Management: Interferon alpha is an effective thearpy as are anagrelide and hydroxyurea. Treatment should not be given just the absolute platelet count is high in the absence of other symptoms .