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Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
Haemopoiesis, blood malignancies, coagulation and platelet
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Haemopoiesis, blood malignancies, coagulation and platelet

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pathology haematology

pathology haematology

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  • 1. Haemopoiesis, blood malignancies, coagulation and platelet function defects Dr H.M.D.Moratuwagama Department of Pathology Faculty of Medicine-Ragama
  • 2. Haemopoiesis
  • 3. Sites of Haemopoiesis • Yolk sac • Liver and spleen • Bone marrow – Gradual replacement of active (red) marrow by inactive (fatty) tissue – Expansion can occur during increased need for cell production
  • 4. Sites of Haemopoiesis • Fetus- 2 months –Yolk sac 2-7 months-Liver/Spleen 5-9 months-BM • Infants-BM • Adult-Axial skeleton
  • 5. Components of Haemopoiesis • Cells • Bone marrow stroma • Growth factors
  • 6. Cells • Stem cells • Self renewal • Plasticity • Progenitor cells • Developmentally-restricted cells • Mature cells • Mature cell production takes place from the more developmentally-restricted progenitors
  • 7. Haemopoiesis Common myeloid progenitor cell Common lymphoid progenitor cell
  • 8. BM • Stromal cells -adipocytes,fibroblasts,osteoblasts,endothelial cells ,macrophages • Microvascular network
  • 9. Regulation of haemopoiesis • Transcription factors -CEBP-Myeloid -GATA 1-Erythroid • Growth factors
  • 10. Haemopoietic growth factors • Glycoprotein hormones • GM-CSF • Granulocyte-Macrophage colony stimulating factor • G-CSF Granulocyte colony stimulating factor • M-CSF • Macrophage colony stimulating factor • Erythropoietin(kidney) • Erythropoiesis stimulating hormone (These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation) • Thrombopoietin(liver) • Stimulates megakaryopoiesis
  • 11. Haemopoietic growth factors cont. • Cytokines • • • • • • • IL 1 (Interleukin 1) IL 3 IL 5 IL 6 TNF SCF (Stem cell factor, also known as kit-ligand) TGF-β/IFN-γ-Negative effect
  • 12. Role of growth factors in normal haemopoiesis
  • 13. Erythropoiesis and erythrocytes • Lifespan – 120 days • Non nucleated • Biconcave disc • Production regulated by Epo • Needs Fe, B12, folate & other elements for development
  • 14. Granulopoiesis • Granulocytes E – Neutrophils – Eosinophils – Basophils • Only mature cells are present in peripheral blood N B
  • 15. Granulopoiesis • Neutrophil – 2-5 lobe nucleus – Primary or secondary granules • Pink (azurophilic granules) • Grey-blue granules – Life 10 hours • Precursors – – – – – Myeloblast <4% Pro myelocytes Myelocytes Metamyelocytes Band form (stab form)
  • 16. Monocytes • Larger than lymphocyte • Oval or indented nucleus • Monocytes >>>>to macrophage • Specific function depends on the tissue type
  • 17. Lymphopoiesis
  • 18. Thrombopoiesis • Platelet play a major role in primary hemostasis • Life span 7-10 days • Production, fragmentati on of cytoplasm • Megakaryocytes undergoes endomitotic division
  • 19. Summary • Normal haemopoiesis is necessary for the survival • It is under the control of multiple factors • Normal bone marrow environment is necessary for normal haemopoiesis • Decreased production results in cytopenias
  • 20. Blood malignancies
  • 21. Blood malignancies LEUKAEMIA LYMPHOMA
  • 22. Blood malignancies Leukaemia Acute Chronic Myeloid Lymphoid Myeloid Lymphoid AML ALL CML CLL
  • 23. Aetiology of haemopoietic malignancies • Idiopathic • Inherited factors-Down’s syn.,Blooms syn.,Fanconi’s anaemia • Chemicals-ex:Benzene • Drugs-Alkylating agents • Radiation • Infections-viruses-HTLV-1/EBV/HHV8 Bacteria-H pylori-MALT Lymphoma
  • 24. Leukemia • Acute leukemias: rapid onset, rapid death if treatment is not successful • Chronic leukemias: natural history measured in years, even without initial treatment
  • 25. Two-hit model of leukemogenesis Loss of function of transcription factors needed for differentiation eg. FLT3, c-KIT mutations N- and K-RAS mutations BCR-ABL TEL-PDGF R eg. AML1-ETO CBF -SMMHC PML-RAR differentiation block Gain of function mutations of tyrosine kinases + enhanced proliferation Acute Leukemia
  • 26. ALL naïve B-lymphocytes Lymphoid progenitor Plasma cells T-lymphocytes AML Hematopoietic stem cell Myeloid progenitor Neutrophils Eosinophils Basophils Monocytes Platelets Red cells
  • 27. Myeloid maturation myeloblast promyelocyte myelocyte metamyelocyte band neutrophil MATURATION Adapted and modified from U Va website
  • 28. Acute Leukemia • accumulation of blasts in the PB/BM
  • 29. AML
  • 30. Auer rods in AML
  • 31. ALL
  • 32. Classification of acute leukemias ALL AML • mainly children • curable in 85% of children • curable in minority of adults • mainly adults • curable in minority of adults
  • 33. Clincal manifestations • symptoms due to: – marrow failure – tissue infiltration – leukostasis – constitutional symptoms – Others- DIC (acute promyelocytic leukaemia) • usually short duration of symptoms
  • 34. Marrow failure • Neutropenia: :infections, sepsis • Anaemia : fatigue, pallor • Thrombocytopenia: bleeding
  • 35. Infiltration of tissues/organs • enlargement of liver, spleen, lymph nodes • gum hypertrophy • bone pain • other organs: CNS, skin, testis, any organ
  • 36. Constitutional symptoms • • • • Fever sweats weight loss LOA
  • 37. Investigations • • • • • FBC+BP Bone marrow aspiration & trephine biopsy Special stains-Sudan black/PAS Flow cytometry Cytogenetics-t(15,17)-Acute promyelocytic leukaemia
  • 38. Principles of treatment • combination chemotherapy – first goal is complete remission – further Rx to prevent relapse • supportive medical care – transfusions, antibiotics, nutrition • psychosocial support – patient and family
  • 39. CML • • • • Clonal disorder of pluripotent stem cell Philadelphia chromasome t(9,22) Enhanced thyrosine kinase activity(TK) Clnical features: due to hypermetabolism, splenomegaly,BMF,leukosta sis Treatment-TKI
  • 40. CLL • Common in elderly/west
  • 41. Lymphoma Clonal proliferation of lymphoid cells Non Hodgkin B cell T cell Follicular Mantle DLBCL Hodgkin
  • 42. Clinical presentation • • • • Lymphadenopathy Bone marrow failure Organ involvement Constitutional symptoms(B symptoms)
  • 43. Investigations • • • • • • • FBC+BP ESR LDH Radiology Biopsy Flow cytometry Immunohistochemistry
  • 44. Management • • • • Aggressive/indolent Stage-early/advanced Patient factors Options-watch and wait Chemotherapy Radiotherapy Immunotherapy BMT
  • 45. Haemostasis
  • 46. HEMOSTASIS Definition • Hemostasis: drives from the Greek meaning “The stoppage of blood flow”. • Components involved in haemostasis *Blood vessel *Platelets *Coagulation factors *Coagulation inhibitors *Fibrinolysis
  • 47. Vessel wall, Blood flow & Coagulation Substances drmsaiem
  • 48. In Case if there is an Endothelial Injury (Bleeding must be prevented at site of injury) drmsaiem
  • 49. HEMOSTASIS Under normal conditions, the formation and dissolution of thrombi is maintained in a delicate balance.
  • 50. Clotting cascade
  • 51. Fibrinolysis
  • 52. Tests used in coagulation disorders Screening tests 1.FBC+BP 2.BT 3.PT 4.APTT 5.TT 6.Fibrinogen Others: Factor assays/VWF assays/platelet function tests/D-dimer/PFA 100/TEG ect.
  • 53. Abnormal bleeding • Vascular disorders • Platelet disorders-Thrombocytopenia Platelet function defects • Defective coagulation
  • 54. Platelet function disorders Congenital • Glanzmann’s disease /Thrombasthenia • Bernard- Soulier syndrome • Storage pool diseases Acquired • Anti platelet drugs • Hyperglobulinaemia • MPD/MDS • Uraemia
  • 55. Glanzmann’s disease /Thrombasthenia • Def. Gp 11b/111a • Platelet aggregation –only with ristocetin Bernard-Soulier syndrome • Gp 1b def. • Large platelet • Thrombocytopenia • Platelet aggregation-not with ristocetin
  • 56. Bernard-Soulier vs Glanzmann’s
  • 57. Coagulation disorders Congenital • Haemophilia A(F VIII) • Haemophilia B(F IX) • VWD • Fibrinogen,XI,X,V,II def Acquired • Liver disease • DIC • Vit K def
  • 58. THANK YOU

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