hematology ppt.pptx. .

Renal pathalology

1. Myeloproliferative disorders

2. Definition MPD is a group of uncommon acquired conditions which are characterized by clonal proliferation of one or more haemopoieticelements . Excessive proliferation of erythroid cells, myeloid elements, or megakaryocytic elements in bone marrow and in many cases, in liver and spleen. This is a group of slow growing blood cancers in which large number of abnormal WBCs or RBCs or platelets grows and spread in the bone marrow and peripheral blood . There are three myeloproliferative disorders which are all related to one another, known as non-leukemic myeloproliferativedisorders : 1.Polycythemia Vera (PV) 2.Myelofibrosis 3.Essential thrombocythaemia

3. General features of Myeloproliferative disorders All three are connected to dysfunction and dysregulationof haemopoieticstem cells and all three have one or two shared features including: Overproduction of one or more blood elements. Hypercellular bone marrow or bone marrow fibrosis Cytogenetic or chromosomal abnormalities: 25% of all cases of myeloproliferative disorders Thrombotic and hemorrhagic problems Transformation to acute leukemia Myelofibrosis of bone marrow is typical. 20-30% of all patients with these disorders usually have chromosomal abnormalities. Most patients usually have splenomegaly and usually die within 1.5 –2.5 years without treatment

4. PolycythermiaVera Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by the overproduction of  RBCs ( erythrocytosis ), WBCs, and platelets This triad differentiates PV from erythrocytosis seen with chronic  hypoxia and other conditions . Classification Primary PV is due to a myeloproliferative disorder. Secondary polycythemia  is due to an increase in EPO caused by environmental circumstances or other conditions: Lung disease/chronic hypoxia Sleep  apnea Smoking High altitude EPO-secreting tumors, such as renal cell carcinoma

5. Etiology and Pathophysiology Etiology Not fully understood Most patients have a mutation of the Janus kinase-2 gene (JAK2) on chromosome 9, which encodes for a protein essential for RBC production. Pathophysiology The JAK2 gene is involved in signal transduction for EPO, thrombopoietin , and granulocyte colony-stimulating factor (G-CSF). A JAK2 mutation, found in 98% of patients with PV, results in enhanced cytokine signaling that results in the increased production of all hematopoietic stem cells. Other mutations lead to sustained activation of JAK2 kinase, which causes excess blood cell production independent of EPO: Calreticulin (CALR) mutations have been found in patients with PV without a JAK2 mutation. Lymphocytic adaptor protein (LNK) mutations have been found in patients with isolated erythrocytosis .

6. Clinical Presentation Result from hyperviscosityand hypermetabolism Headache, blurred vision and night sweats Splenomegaly (2/3 patients) –60 -70% Hemorrhage (GIT, uterine, cerebral) or venous (leg veins) are frequent Hypertension (1/3 patients) Gout due to raised uric acid level Peptic ulceration occurs in 5 –10% of patients

7. Lab findings RBCs count, Hemoglobin and Hematocritincrease Neutrophilleukocytosisseen in over 50 –60% of patients, some have increased circulating basophils Raised platelet count (50% of patients) > 400 ×109/L Increase in serum, vitamin B12 and vitamin B12 binding capacity Hypercellularbone marrow with prominent megakaryocytes Blood viscosity increases Plasma Urateoften increases

8. Management The therapeutic goal is to reduce the hematocrit to < 45%. Phlebotomy is the mainstay of therapy. Myelosuppressive therapies : Hydroxyurea  Ruxolitinib  ( JAK2  inhibitor) Interferon Low-dose aspirin is used to reduce the symptoms of microvascular events. Allopurinol is used for hyperuricemia. Antihistamines are used to relieve the sensation of pruritus In rare cases, stem cell transplantation can be performed