10.polycethemia hematology laboratory.pptx

HEMATOLOGYHematology

1. Polycythemia Polycythemia is an elevated red blood cell ( RBC ) count that is accompanied by an increased packed cell volume ( PCV ) and increased hemoglobin level. Polycythemia may be relative or absolute . In relative polycythemia , the RBC count is not truly increased , but the PCV is elevated because there is less fluid (plasma) in the blood, which makes the relative amount of RBCs appear to be high. Absolute polycythemia occurs when more RBCs are produced than normal and their count is truly elevated. Absolute polycythemia could be primary or secondary.

2. Absolute vs. Relative Erythrocytosis Absolute Relative

3. Oxygen delivery vs. Hematocrit

4. Causes of Increased Red Cell Mass ( Erythrocytosis ) Relative: Stress erythrocytosis - chronically reduced plasma volume. Disorders associated with decreased plasma volume ( dehydration e.g., diarrhea, emesis, renal diseases ). Primary: ( Polycythemia vera ) Unregulated neoplastic proliferation [gene mutations e.g PVera (JAK 2 )]. Secondary: Chronic pulmonary or cardiac disease ( ↓O 2 ) Decreased 2,3-diphosphoglycerate ( ↓2,3 DPG) High oxygen affinity hemoglobinopathy Increased carboxyhemoglobin (in smokers ) and methemoglobin Residence at high altitude (↓O2) Adrenal cortical hypersecretion Hydronephrosis Tumors producing erythropoietin or anabolic steroids

5. Primary: Polycythemia vera Names: Polycythemia vera , Polycythemia rubra vera , Primary polycythemia, Myeloproliferative disorder, Erythremia ,…etc. Definitions: PVera : Increase in RBC mass with/without increase in granulocytes and platelets in the absence of physiologic stimulus. Hb is > 16.5 (w) or >18.5  (m) HCT > 48 (w) or > 52 (m)

6. JAK2 mutation Janus Kinase 2 (JAK2) has tyrosine kinase activity and is involved in signal transduction from EPOR (erythropoietin receptor) to nucleus for gene expression Mutation occurs in pseudokinase (normally negative regulator of kinase activity) domain of JAK2 gene resulting in constitutively activated tyrosine kinase

7. Signs and Symptoms of Polycythemia Vera More Common Hematocrit level >52 percent (0.52) in white men, > 47 percent ( 0.47) in blacks and women Hemoglobin level >18 g per dL (180 g per L) in white men, >16 g per dL (160 g per L) in blacks and women) Plethora Pruritus after bathing Splenomegaly Weight loss Weakness Sweating Less Common Bruising/epistaxis Budd- Chiari syndrome Erythromelalgia Gout Hemorrhagic events Hepatomegaly Ischemic digits Thrombotic events (DVT, MI, stroke) Transient neurologic complaints (headache , tinnitus, dizziness, blurred vision, paresthesias ) due to h yperviscocity . Atypical chest pain ← Erythromelalgia

8. Diagnosis A diagnosis of polycythemia vera is made when a patent fulfills all three of the major criteria Or any two major and any two minor criteria Major Criteria - Total RBC vol Men > or = to 36 mL/kg Women > or = to 32 mL/kg - Arterial O2 saturation > or = to 92% - Splenomegaly Minor Criteria - Thrombocytosis with platelet count > 400,000/mL - Leukocytosis with WBC > 12,000/mL - Increased leukocyte alkaline phosphatase LAP > 100U/L (no infection) - ↑Serum B12 > 900 pg /mL or binding capacity UB12 BC > 2200 pg /mL

9. Diagnosis-Revised WHO Criteria Major criteria Hemoglobin >18.5 g/ dL in men, 16.5 g/ dL in women  Presence of JAK2 617V>F or other functionally similar mutation such as JAK2 exon 12 mutation Minor criteria Bone marrow biopsy showing hypercellularity for age with trilineage growth ( panmyelosis ) with prominent erythroid , granulocytic, and megakaryocytic proliferation Serum erythropoietin level below the reference range for normal Endogenous erythroid colony formation in vitro (2 major + 1 minor OR 1 st major + 2 minor) Workup: H/H EPO SaO2 JAK2 screen (95-100% pts with PV have JAK2 mutation 3 ) Bone marrow EEC: endogenous erythroid colony formation

10. Lab. diagnosis Peripheral blood findings Increased hemoglobin & hematocrit Normal red blood cell morphology ( normochromic normocytic ), unless iron deficient or spent phase Normoblasts may be present Mild to moderate leukocytosis Mild neutrophilia with a left shift and a few immature cells and/or basophilia . Thrombocytosis

11. This disease may also alter the results of the following tests: ↑Lactate dehydrogenase u/a ↑Serum uric acid ↑T- wbc (>12,000/µL) in 60 % of patients RBC count ↑ Platelets count (400,000-800,000/mL in approximately 50% of patients). ↓ Platelet aggregation test ↑Leukocyte alkaline phosphatase (>100 U/L) in 70% of patients. ↑Hemoglobin & PCV ↓ ESR Erythropoietin: ↓in PVera & ( ↑or ↕ in secondary Polycythemia) Iron stores are decreased or absent Cytogenetics : Chromosomal abnormalities (deletions or Trisomy) Lab. diagnosis

12. Bone marrow studies are not necessary to establish the diagnosis but the findings of: hypercellularity hyperplasia of the erythroid , granulocytic and megakaryocytic cell lines myelofibrosis support the diagnosis of a myeloproliferative process. Lab. diagnosis

13. Prognosis Prognosis: Untreated median survival: 6-18 months Treated median survival: 13 years Most common cause of death: thrombosis (29 percent ) hematologic malignancies (23 percent ) non-hematologic malignancies (16 percent ) hemorrhage (7 percent ) myelofibrosis ( 3 percent )

14. Treatment Phlebotomy : goal Hct <42%/45% Low dose aspirin in all Hydroxyurea if high risk of thrombosis (Age>60, prior thrombosis) Symptomatic (allopurinol, antihistamines)