Downloaded 56 times
More Related Content
Similar to Hematological changes in systemic diseases
Hematological changes in systemic diseases
- 1. HEMATOLOGICAL CHANGES IN SYSTEMICDISEASES (NON-INFECTIOUS)
- 2. • Haematological changesin systemic diseases • Infectious • Non- Infectious
- 3. OVERVIEW • Anaemia ofchronic disease • Malignancy • Connective tissue disorder • Renal disease • Endocrine disease • Liver disease
- 4.
- 6. PATHOGENESIS • Cytokine inhibitionof erythropoiesis • Block in release of iron from macrophages • Shortened erythrocyte survival
- 7. 1) Cytokine inhibitionof erythropoiesis Cytokines, interleukin-1, TGF-beta, TNF Inhibits EPO production anaemia IFN IL-1 Inhibits EPO effect on erythroid progenitor cells Anaemia
- 8. 2) Block inrelease of iron from macrophages TNF Block in mobilization of iron from macrophages Aggregates of iron in marrow macrophages Low serum iron, TIBC Normal / increased iron stores
- 9. 3) Shortened RBCsurvival Extra corpuscular factors Eg.- Non-specific macrophage activation, hemolytic factors elaborated from tumors, vascular factors, bacterial toxins Reduced livespan of RBCs
- 10.
- 11. Differentiating ACD fromIDA S.No Parameter Normal value ACD IDA 1 Serum iron 10-70 micro g/dL Reduced Reduced 2 TIBC 100-300 micro g/dL Decreased/normal Reduced 3 Transferrin saturation 10-25% Decreased/normal Reduced 4 Serum ferritin 220-250 microg/dL Normal/Increased Low 5 ZPP Male 1-27 microg/dL Female 11-45 microg/dL Increased Increased 6 sTfR 1.15 – 2.75 mg/L Normal High
- 12. • Management: EPO correction(more important than iron metabolism)
- 13.
- 14. CELLS / SYSTEMINVOLVED CHANGES RBC Anaemia Polycythemia WBC Granulocytosis Granulocytopenia platelets Thrombocytopenia Thrombocytosis Platelet function abnormality Coagulation DIC
- 15. Causes of anaemiain cancer patients: • Pre-existing nutritional deficiency, • hemolysis, • blood loss, • infiltration of the bone marrow by tumor cells and • myelosuppression due to therapy (chemo and radiation therapy) • Cancer per se The CRA of chronic disease is characterized by anaemia being proportional to the tumor burden and a relatively late manifestation of the malignancy. This is due to functional iron deficiency, shortened RBC lifespan and reduced production of EPO (mediated by inflammatory cytokines).
- 16.
- 17. Hemolysis • Warm antibodyis associated with CLL, Hodgkin’s disease, Non- Hodgkin’s disease • Cold antibody is associated with chronic cold agglutinin disease, Waldernstrom’s macroglobulinemia, myeloma
- 18.
- 19. Distinguishing warm Vscold antibodies S.No Parameters Warm antibodies Cold antibodies 1 Immunoglobulin class IgG (predominantly) IgM IgA IgM (predominantly) IgG 2 Optimal reactivity 37 degree C <30 degree C @4 degree C 3 Mechanism of hemolysis Attachment of membrane bound Ig or C3b to macrophage receptors (extravascular) Complement lysis (intravascular), Attachment of membrane bound to C3b to macrophage receptors (extravascular) 4 Specificity Usually anti-Rh Usually anti-I PCH anti-P 5 Peripheral blood smear Spherocytes Red cell agglutinates 6 Site Extravascular Intravascular
- 20. Drug induced hemolysis •Mitomycin • Cyclosporin • Cisplatinum
- 21. NATIONAL CANCER INSTITUTE- ANAEMIA SCALE
- 22. Megaloblastic anaemia Uncontrolled malignantcell proliferation Excessive utilization of folic acid Deficiency of folic acid Megaloblastic anaemia
- 23. Red cell aplasia •Associated with thymoma in 50% cases Production of antibodies to erythroid precursors Treatment: • surgical removal • Immunosuppressive treatment with cyclophosphamide, cyclosporine, steroids, plasma exchange are more prone to lead to relapse.
- 24. Leucoerythroblastic anaemia • Erythroblasts+ granulocyte precursors (myelocyte & myeloblast) identified in peripheral smear
- 25. Pathogenesis Ca breast, prostate,lung , thyroid, kidney, GIT, melanoma Primary myelofibrosis and marrow infiltration by tumors Disturbance in marrow micro-vasculature Early release of precursors Leukoerythroblastic picture
- 26. • Peripheral smearfindings nucleated RBCs Band forms metamyelocytes myelocytes promyelocytes
- 29. Polycythaemia • Rare complicationof non-hematological malignancy • Cause Elaboration of tumour cells by EPO and EPO like peptides
- 30. RCC, Hepatoma, uterinemyoma, androgen secreting ovarian tumors, pheochromocytoma, cerebellar hemangioblastoma Production of EPO and EPO like peptides Polycythemia
- 33. Granulocytosis Inflammation by tumorcells Interaction between cancer cell and host T lymphocytes with mononuclear phagocytic cells Production of cytokines Induces WBC differentiation and proliferation
- 34. Granulocytopenia • Secondary tochemotherapy/ radiotherapy • Marrow infiltration (lymphoma)
- 35. Platelets • THROMBOCYTOPENIA (<1,00,000/mm.cu) reduced production (marrow infiltration, secondary to chemo/radio) increased destruction (DIC) hypersplenism (splenic infiltration by lymphoma/CLL)
- 36. • THROMBOCYTOSIS reactive phenomenonin cancer patients < 1000 x 109/L
- 37. • PLATELET FUNCTIONABNORMALITY Impaired function excessive bleeding Causes: IgM in Waldenstrom’s macroglobulinemia IgG in Myeloma Cancer cells
- 38. Pathogenesis IgM & IgG Platelet aggregation Platelet adhesion Cacells ADP, Prostaglandin, thrombin release Platelet aggregation
- 39. Coagulation DIC underdiagnosed in cancerpatients manifests as migratory thrombophlebitis (trousseau’s sign) non-bacterial thrombotic endocarditis
- 40. Pathogenesis of DICin malignancy Commonly encountered in adenocarcinoma (git, pancrease, lung, breast, prostate Occasionaly glioblastoma or other brain tumors Production of tissue factors by tumor cells Or increased tissue factor generated on the surface of monocytes or macrophages Tissue factor binds to factor VII Activates factors IX and X Rarely – cysteine protease, which directly activates factor X
- 41.
- 42. CELLS / SYSTEMINVOLVED FEATURES RBC Anaemia WBC Neutropenia Lymphopenia Eosinophilia PLT Thrombocytopenia COAGULATION DIC
- 43. Anaemia • Associated Fedeficiency (NSAIDS intake) • Folate deficiency • Warm AIHA with IgG and complement – SLE, RA, mixed CTD • Sideroblastic anaemia – SLE, RA
- 44. WBC • Felty’s syndrome neutropenia+ splenomegaly in RA
- 45. Pathogenesis Increased margination &sequestration of neutrophils in enlarged spleen Immune complex and humoral mediated inhibition of granulopoiesis in marrow Antibody production to mature neutrophils
- 46.
- 47. EOSINOPHILIA • SLE • RA •PAN • Churg Strauss syndrome (released of cytokines by T cells)
- 48. Platelet • Thrombocytosis (non-specific)- generally CTD • SLE, Mixed CTD, Scleroderma, RA, Dermatomyositis – IMMUNE TCP • SLE - TTP
- 49. COAGULATION SLE Lupus anti-coagulant Thrombotic tendencies,TCP, recurrent miscarrages, pulmonary HTN
- 50.
- 51.
- 53. CELLS/SYSTEM INVOLVED FINDINGS RBCANEMIA POLYCYTHAEMIA PLATELETS THROMBOCYTOPENIA Part of HUS HEMOSTATIC ABNORMALITIES
- 54. Pathogenesis 1) Decreased EPOproduction 2) Role of toxic metabolites 3) Inflammatory cell mediators
- 55. 2) Role oftoxic metabolites Reduced ability to excrete potentially toxic metabolites Shortens RBC lifespan, marrow suppression Anaemia Eg- HUS
- 56. HEMOLYTIC UREMIC SYNDROME hemolyticanemia (anemia caused by destruction of red blood cells) acute kidney failure (uremia) low platelet count (thrombocyto penia).
- 57. Pathogenesis E.Coli produces VEROTOXIN Damageto endothelium of glomerular capillaries & renal arterioles Localised platelet deposition Intravascular coagulation Ischemic renal cortical necrosis
- 58. Investigations • Peripheral smear: •Fragmented RBCs • Reticulocytosis • Occasional nucleated RBCs • Increased EPO • Increased S. Creatinine • Thrombocytopenia • Bone Marrow: increased megakaryocytes (compensatory)
- 59. D/D for HUS •TTP ( HUS + FEVER + NEUROLOGICAL SYMPTOMS) normal cleaving of Von Willibrand multimer is impaired. a) congenital absence of ADAMTS-13 cleaving protease b) immunologic inactivation of protease
- 60. 3) Inflammatory cellmediators Chronic inflammatory conditions Hepcidin production INHIBITS: iron absorption in enterocytes INHIBITS: iron release through ferroportin Anaemia
- 61. ANAEMIA • Normocytic normochromicanaemia + ecchinocytes (burr cells) • Retic count – normal/ slightly low • Bone marrow – Normoblastic erythropoiesis without erythroid hyperplasia • Management : r EPO in renal failure – iv, sc, ip. Chronic ambulatory peritoneal dialysis
- 62. Peritoneal dialysis Circulating inhibitorsare removed Folic acid deficiency and blood loss leads to secondary IDA
- 63. POLYCYTHAEMIA Renal tumors (PNS) Regionalrenal hypoxia Ectopic EPO production polycythaemia
- 66. Main Haemostatic abnormalitiesin patients with Chronic Kidney Disease 1. Increased tissue factor 2. Increased Von Willebrand factor 3. Increased factor VII a 4. Increased factor XII a 5. Increased activated protein C 6. Increased fibrinogen 7. Reduced tissue plasminogen activator 8. Inreased plasminogen activator inhibitor 1
- 67.
- 68. • THYROID GLAND •ADRENAL GLAND • TESTOSTERONE • PITUITARY GLAND
- 69. THYROID HORMONE • Stimulateserythropoiesis • Involved in tissue O2 demands
- 70. HYPOTHYROIDISM WOMEN Menorrhagia Iron deficiency anaemia Microcyticanaemia MEN T3 T4 required for iron augmentation With associated achlorhydria Microcytic Anaemia
- 71. • WBC ANDPLATELET – unaffected • MYXEDEMA COMA – pancytopenia + marrow hypoplasia
- 72. HYPERTHYROIDISM MACROCYTIC ANAEMIA INTHYROID IS DUE TO Plasma dilution folate deficiency Commonly encountered in thyrotoxicosis.
- 73. ADRENAL GLAND Glucocorticoids Interacts witherythropoietin Enhances erythroid colony proliferation Stimulates erythropoiesis
- 74. • Addison’s disease(primary adrenal insufficiency / hypocortisolism): - normocytic normochromic anaemia • Cushing’s syndrome • Primary aldosteronism polycythemia
- 75. TESTOSTERONE stimulates EPO secretionDirect effect on marrow Androgen receptors in marrow Stromal cell, endothelial cell, macrophages, myeloid precursor cells Not erythroid cells
- 76. PITUITARY INSUFFICIENCY Hypothalamic tumors Pituitarytumors, failure, hemorrhage/ infarct Anterior lobe of pituitary involvement Defective production of ACTH, TSH, FSH, LH, GH, Prolactin Deficiency of thyroxine, adrenal hormones, androgens ANAEMIA
- 77.
- 78. Cells Findings Conditions REDCELLS ANAEMIA Anaemia of chronic disease Folate deficiency Iron deficiency (blood loss) Hypersplenism Disseminated intravascular coagulation (DIC) (rare) POLYCYTHAEMIA Hepatocellular carcinoma (rare) Infectious hepatitis (rare) WHITE CELLS NEUTROPHILIA Infection Malignancy Haemolysis NEUTROPENIA Hypersplenism PLATELETS THROMBOCYTOPENIA Hypersplenism DIC Auto-immune THROMBOCYTOSIS Hepatoma IMPAIRED FUNCTIONS Inhibitory factors
- 79.
- 80. • Macrocytosis seen inalcoholic liver disease
- 81. Target cells increased membranelipid content increased surface area of RBCs
- 82. • ACANTHOCYTES (SPURCELLS)
- 83. • Wilson’s disease: copperion toxicity to rbc membrane hemolysis
- 84. PORTAL HTN Congestivesplenomegaly Plt sequestration in spleen REDUCED TPO PRODUCTION AUTO-ANTIBODIES PRODUCTION TCP
- 85. PLATELET FUNCTION DEFECTS Excessiveplasmin formation Increased production of endothelial derived platelet inhibitors, NO, prostaglandin PLATELET MEMBRANE PROTEOLYSIS
- 86. COAGULATION DEFECTS 1-Increased bleedingrisk : • Decreased production of non-endothelial cell-derived coagulation factors (eg, factors II, V, VII, IX, X, XI, XIII) • Thrombocytopenia • altered platelet function • abnormalities of fibrinogen • decreased thrombin activatable fibrinolysis inhibitor (TAFI)
- 87. 2-Increased thrombotic risk: Decreased level of the liver-synthesized natural anticoagulant: - proteins C and S - antithrombin levels -Plasminogen Elevated levels of endothelial cell-derived factor VIII and von Willebrand factor (Vwf) So ….. • In liver disorders especially cirrhosis we have disruption of these opposing pathways lead to different and potentially changing hemostasis
- 88. HYPER COAGULABILITY • Decreasedlevels of liver synthesized procoagulant factors •Abnormalities of platelet number • Abnormalities of platelet function • Hyperfibrinolysis HYPOCOAGULABILITY • Several endothelium- derived procoagulant factors are increased in cirrhosis, including factor VIII & von Willebrand factor
- 89. Hypercoagulability in cirrhosiscan lead to: Macro and micro-thrombi production resulting in various complications
- 90. Macro-thrombotic Complications • Portalvein thrombosis • Deep vein thrombosis • Pulmonary embolism Micro-thrombotic complication • subtle complications • Intra-hepatic microthrombi → localized ischemia • →scarring and accelerated development of cirrhosis in a process known as parenchymal extinction → liver atrophy
- 91. Non-alcoholic fatty liverdisease (NAFLD)and hypercoagulopathy obesity insulin resistance diabetes dyslipidemia
- 92. Reduced sensitivity toinsulin Increased fatty acid levels forming thromboxane A2, and lowdensity lipoprotein (LDL) levels increased platelet aggregation.
- 93. REFERENCES: • Prabhash K,Nag S, Patil S, Parikh P M. Optimising management of cancer related anemia. Indian J Cancer 2011;48:1-10 • Hoffbrand Postgraduate Haematology, Sixth edition, pp.940 - 955 • Kaushansky, K., & Williams, W. J. (2010). Williams hematology. New York: McGraw-Hill Medical. • Clinical Laboratory Hematology, 3rd Edition, Shirlyn B. McKenzie
- 94.