POLYCYTHAEMIA

MBBS 2022-2023
Year 3

Associate Professor Dr. Wint Wint Thu Nyunt

Department of Medicine
MAHSA University
 LECTURE: POLYCYTHAEMIA
LEARNING OUTCOMES
1. Polycythaemia/ erythrocytosis: terminology, causes, approach to
polycythaemia
2. Polycythaemia vera (PV):
• Pathogenesis
• Clinical features
• Diagnostic criteria
• Investigations
• Risk stratification
• Outline of management
• Prognosis
 ERYTHROCYTOSIS
• Patients with a persistently raised haematocrit (Hct) (> 0.52 males, > 0.48 females) for more than
2 months should be investigated.
• ‘True’ polycythaemia (or absolute erythrocytosis) indicates an excess of red cells.
• ‘Relative’, ‘apparent’ or ‘low-volume’ polycythaemia is due to a decreased plasma volume.
 APPROACH TO POLYCYTHAEMIA
• History
• Physical examination
• Investigation
HAEMATOPOIESIS
Haematopoiesis describes the
formation of blood cells.
• Haematopoietic stem cell (HPSC)
differentiates into common
myeloid progenitor (CMP) or
common lymphoid progenitor
(CLP) cells.
• Megakaryocyte-erythroid
progenitors (MEPs) produce
megakaryocytic/erythroid lineage
cells.
• Granulocyte-monocyte
progenitors (GMPs) produce
myeloid/monocytic lineage cells.
• Common lymphoid progenitors
(CLPs) produce B and T
lymphocytes and NK cells.
 MYELOPROLIFERATIVE NEOPLASMS
• Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell disorders characterized
by proliferation of one or more myeloid lineages, peripheral blood cytosis with effective
maturation, bone marrow hypercellularity/fibrosis, and splenomegaly.
 POLYCYTHEMIA VERA
• BCR::ABL1-negative myeloproliferative neoplasm which is characterized by panmyelosis,
particularly increased red blood cell proliferation.
• Virtually all patients carry JAK2 V617F, a somatic gain-of-function mutation.
JAK2 (Janus kinase 2) mutation
• a gene found on the short arm of chromosome 9 (9p)
• account for hypersensitivity of hematopoietic progenitor cells in MPNs to growth factors and
other cytokines.

• Most cases present in a polycythemic phase with elevated hemoglobin/hematocrit.

• Some patients present in a spent phase, with cytopenias (including anaemia) in association with
post-polycythemic myelofibrosis, ineffective haematopoiesis, and increasing splenomegaly.
 POLYCYTHEMIA VERA
CLINICAL FEATURES
• Mainly in patients over the age of 40 years
• Incidental finding of a high haemoglobin
• Symptoms of hyperviscosity
lassitude, loss of concentration, headache, dizziness, blackouts, pruritus, epistaxis
• Aquagenic pruritus (itching after exposure to water)
• Increased risk of arterial thrombosis, particularly stroke, & venous thromboembolism
• Peptic ulceration is common, sometimes complicated by bleeding.
• Often plethoric
• Hepatosplenomegaly
• Gout (due to high red cell turnover)
 POLYCYTHEMIA VERA
INVESTIGATION
• Full blood count: increased Hb, increased Hct, neutrophil and platelet
counts are frequently raised.
• Peripheral blood smear/ full blood picture: increased red cells
• Serum erythropoietin level: subnormal
• Blood for JAK2 mutation study: JAK2 mutation
• Bone marrow aspirate and trephine biopsy examination: panmyelosis
• In the occasional JAK-2-negative cases, a raised red cell mass and
absence of causes of a secondary erythrocytosis must be established.
• Investigations for cardiovascular risk factors
Bone marrow aspirate.
E Stained macroscopic
appearance of marrow
aspirate: smear (left) and
squash (right).
F Microscopic appearance
of stained marrow particles
and trails of
haematopoietic cells.
Bone marrow trephine.
B Macroscopic appearance of
a trephine biopsy.
C Microscopic
appearance of stained section
of trephine.
MIPSS-PV: Mutation-Enhanced
International Prognostic System
for Polycythemia Vera
 POLYCYTHEMIA VERA
MANAGEMENT
• Aspirin reduces the risk of thrombosis.
• Venesection gives prompt relief of hyperviscosity symptoms.
• Between 400 and 500 mL of blood (less if the patient is elderly) are removed.
• Venesection is repeated every 5–7 days until the haematocrit is reduced to below 45%.
• Less frequent but regular venesection will maintain this level until haemoglobin remains reduced because of iron deficiency.
• Evaluate for indications of cytoreductive therapy
Treatment options
Hydroxycarbamide or interferon-alfa
• Suppression of marrow proliferation may reduce the risk of vascular occlusion, control spleen size and reduce transformation to
myelofibrosis.
Ropeginterferon alfa-2b-njft
Peginterferon alfa-2a
Ruxolitinib
• Manage cardiovascular risk factors
• Monitor for new thrombosis or bleeding
• Monitor signs/ symptoms of disease progression
• Clinical trial
 POLYCYTHEMIA VERA
PROGNOSIS
• Median survival after diagnosis in treated patients exceeds 10 years.
• Some patients survive more than 20 years; however, cerebrovascular or coronary events occur in up to 60%
of patients.
• The disease may convert to another myeloproliferative disorder, with about 15% developing acute leukaemia
or myelofibrosis.
 REFERENCES
 Penman, I.D., Ralston, S.H., Strachan, M.W., Hobson, R. eds., 2022. Davidson's Principles and
Practice of Medicine. 24th edition. Elsevier Health Sciences.
 uptodate.com
 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. Revised 4th edition
 NCCN guideline MPN 3.2022