Handout # 5

Myeloproliferative Disorders (MPD)

Definition
Polycythemia Rubra Vera (PVR)

Pathogenesis
Neoplastic proliferation of trilineage myeloid stem cell causing primary increase in RBC mass and plasma volume. Increase in granulocytes and platelets also occurs but to a lesser extent. PRV is the only MPD with increase in RBC mass. RBC mass not same as RBC count.

Clinical
Median age: 60 years Hypervolemia: Increase in plasma volume, causing hypertension Hyperviscosity: Increased RBC mass predisposes to thrombotic episodes (MC COD). Acute myocardial infarction Stroke; Bowel infarction Hepatic vein thrombosis (MCC of Budd Chiari Syndrome) Hyperuricemia: Increased breakdown of nucleated cells --> increased purine metabolism Histaminemia: Increased release of histamine from basophils and mast cells. vasodilation --> plethoric appearing face pruritis after warm bath peptic ulcer disease from histamine stimulation of gastric acid

Laboratory findings
Hematocrit increased: >52% in men and >48% in women Increased RBC mass and plasma volume Leukocytosis and thrombocytosis Decreased EPO

Essential thrombocythemia (ET)

Neoplastic proliferation of trilineage myeloid stem cell causing primary increase in Megakaryocytes in BM leading to increase in number of platelets in peripheral blood.

Bleeding : usually GI with concomitant iron deficiency Throombosis: due to increased platelet number Erythromelalgia: throbbing and burning of hands and feet due to blood vessel occlusion. Splenomegaly

Agnogenic Myeloid Metaplasia (AMM) Synonyms: Myelofibrosis Key findings: tear drop RBCs

Chronic Myelogenous lekemia (CML)

Sequence of events: Proliferation of neoplastic stem cells begings in BM Marrow replaced by fibrous tissue Neoplastic cells relocate in the spleen. Extramedullar hematopoiesis occurs in spleen causing splenomegaly. Fibrosis of the bone marrow is due to benign reactive fibroblast proliferation as a result of PDGF from megakaryocytes. Review notes on CML

Splenomegaly with portal hypertension Splenic infarcts

Platelets: count >600,000 cells/mm3 and often in millions. Platelets have abnormal morphology and abnormal function causing prolonged bleeding time. WBC findings: increased WBC count (granulocytosis), basophilia and eosinophilia present. Bone marrow: increased megakaryocytes , abnormal morphology Normocytic normochromic anemia with tear drop RBCs WBCs: count 10,000 - 50,000 cells/mm3 Leukoerythroblastic smear Basophilia and eosinophilia present Platelets: thrombocytosis in 50% cases Bone marrow: marrow fibrosis Chromosome studies: Absent Philadelphia chromosome. Review notes on CML

Review notes on CML

Handout # 6

Myelodysplastic syndrome (MDS)

Definoition Myelodysplastic syndrome (MDS) Stem cell disease Frequently progresses to leukemia = Preleukemia Pathogenesis Neoplastic Stem cells proliferate in BM causing hypercellularity. The noplastic cells retain the capacity to mature and form mature cells but maturation is defective casuing ineffective hematopoiesis. This results in peripheral blood cytopenia. Pancytopenia in the PB is the rule Clinical Two types: Primary: occurs in older people Therapy related (tMDS): occurs in people undergoing chemotherapy. Typical Profile: Elederly person with severe cytopenias. Severe anemia with constant transfusion requirement. 10-40% patients with MDS end up developing acute myelogenous leukemia Laboratory findings Anemia Leukopenia Thrombocytopenia = Pancytopenia Myeloblast < 30% (may have Auer rods). Abnormal morphology of blood cells: Ringed siderblasts Dyspoietic erythroid cells Pseudo Pelger Huet cells Multilobated megakaryocytes