1 / 46

Leukocyte Disorders

Leukocyte Disorders. Quantitative Disorders of the Neutrophil. Neutrophil function in the immune system Age specific WBC & differential counts Neutropenia & ANC Neutropenias with etiologies extrinsic to the bone marrow Intrinsic disorders of proliferation & maturation

cade
Télécharger la présentation

Leukocyte Disorders

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Leukocyte Disorders Quantitative Disorders of the Neutrophil

  2. Neutrophil function in the immune system • Age specific WBC & differential counts • Neutropenia & ANC • Neutropenias with etiologies extrinsic to the bone marrow • Intrinsic disorders of proliferation & maturation • Neutropenias associated with phenotypic abnormalities • Evaluation of children with neutropenia • Principles of neutropenia therapy

  3. Neutrophil Functions In the Immune system • Inflammation • Phagocytosis • Bactericidal effect • Immune regulation

  4. Age Specific Leukocyte Differential

  5. Neutropenia & ANC • Neutropenia:A decrease in the absolute number of circulating segmented neutrophils and bands in the blood {CBC & differential count} • ANC: Total WBC * segmented & band % • ANC for the general population ranges between 1500-8000 cells /mm3 for Caucasian children> 6yrs. • ANC = 1000-1500/mm3 :mild neutropenia • ANC = 500-1000/mm3 : moderate neutropenia • ANC <500 : sever neutropenia

  6. Neutropenia…..cont. • Neutropenic pts are mostly infected with endogenous flora, but colonization with nosocomial organisms is observed. • Susceptibility to bacterial infections, even with sever neutropenia, varies. • Some pts with chronic neutropenia do not have serious infections even with ANC<200 , because other parts of the IS are intact. • With immunosuppressive drugs, esp. with malignancy , serious bacterial infections occur.

  7. Neutropenia….cont. • Most frequent pyogenic infection : cutaneous cellulitis,abscesses or furunculosis,pneumonia, septicemia,stomatitis,gingivitis,perirectal infections & otitis media. • Susceptibility to parasitic , viral or fungal infections or bacterial meningitis is not increased. • The most common pathogens are Staph.aureus & G –ve organisms. • Signs & symptoms of local infection & inflammation : exudate , abscess formation & regional LN enlargement are less evident. • Erythema , pain , tenderness , warmth & fever are present

  8. Neutropenias : Extrinsic vs. Intrinsic. • Pathophysiologic classification of neutropenias : • Intrinsic disorders of bone marrow affecting production , proliferation & maturation of myeloid cells. • Factors extrinsic to bone marrow : redistribution between marginating and circulating neut`s ,shortened survival . • Extrinsic are more common than intrinsic.

  9. Neutropenias with extrinsic etiologies: Infection • Among the most common causes. • Multifactorial: • Direct marrow suppression • Depletion of marrow reserves of neut`s and bands • Redistribution due to endothelial activation( TNF, IL-1 , ICAM 1-2 ) • Aggregation &sequestration ( Complement activation ) • Direct destruction of neut`s ( Pathogens) • Indirect destruction ( antibodies )

  10. Infection….cont. • Viral infections: the commonest ( RSV, varicella, influenza A&B,measles & rubella . • Develops in 1st 24-48 hrs , may persist 3-8 days. • Correlates with acute viremia • Common viral infxns may cause sever neutropenia , short lived , rare 2ndary bact infection. • Rarely requires specific management.

  11. Infections ….cont. • IM, hepatitis , HIV may cause sever , protracted neutropenia & cytopenia, due to infxn of precursor cells , or neut sequestration. • Neutropenia occurs in bact, protozoal ,rickettsial & sever fungal infxns. • Chronic infxns : TB , brucella ,typhoid , malaria . • Sepsis .

  12. Drug Induced Neutropenia • Toxic vs. hypersensitivity. • Immune mediated • Withdraw all unessential drugs. • Withdraw the offending drug. • If no response : consider rhG-CSF (5-10 mcg/kg subcut.)

  13. Immune neutropenia • Associated with anti –neutrophil antibodies. • Complement mediated lysis & splenic phagocytosis of opsonized neutrophils. • Antibodies are detected by a combination of immunofluorescence & microcapilary agglutination assays.

  14. Alloimmune Neonatal Neutropenia: • Transplacental passage of maternal IgG against fetal neutrophils. • Presents in the 1st 2 weeks : delayed separation of umbilical cord , skin infxn , fever & pneumonia . • Sever neutropenia which corrects by ~ 7 wks • Treatment : supportive care and appropriate antibiotics.

  15. Autoimmune neutropenia of Infancy: • Primary autoimmune neutropenia (AIN): granulocyte specific autoantibodies. • Infants : 5-15 months , F:M =6:4. • In 90% no risk of sever pyogenic infxn , even if neutropenia is severe. • 95% undergo spontaneous remission within 7-24 months. • Patients with severe infections , or surgical candidates can be treated with rhG-CSF .

  16. Reticuloendothelial Sequestration • Splenic enlargement : portal HTN ,splenic disease or hyperplasia . • Moderate neutropenia , thrombocytopenia & anemia. • Bone marrow compensation. • Treatment of the underlying cause. • Splenectomy.

  17. Replacement of the Bone Marrow: • Bone Marrow infiltration : • Malignancies: Leukemias, lymphomas,Neuroblastoma, rhabdomyosarcoma& Ewing sarcoma. • Peripheral cytopenias

  18. Ineffective Myelopoiesis: • Deficiencies: B12, Folic acid. • Starvation:Anorexia nervosa, marasmas. • Prolonged parenteral feeding.

  19. Cytotoxic Chemotherapy & Radiation Therapy: • Drop of WBC count occurs at 7-10 days , may persist for 3-7 weeks. • Pts are predisposed to serious infections.

  20. Intrensic Disorders of Proliferation and Maturation: • Cyclic Neutropenia : • Rare cytopoietic disorder (1/1000,000) • Autosomal dominant. • Regular periodic oscillations of neutrophilic count • Period 21-+4 days • Variable infxns • 10% used to develop fatal Clostridium perfringensinfxn • Cyclic hematopoiesis

  21. Cyclic Neutropenia • Dx • Obtain 3 bld counts / wk , for 2 months. • Genetic studies : mutation in elastase gene. • Rx: • RhG-CSF: cycle will change from 21 to 9 –11 days. • Fatal infxns and extensive antibiotic use have diminished.

  22. Intrensic disorders ….cont. • Severe Congenital Neutropenia : Kostmann • Arrest in maturation at the promyelocytic stage. • Sporadic disorder, occurs in early childhood. • ANC less than 200/mm3 • Pts present with variable infxns. • Gingivitis is the most frequent finding. • Mild hepatosplenomegaly is common • S areus , Streptococcus are the most frequent organisms.

  23. SCN… • Anemia , eosinophilia , monocytosis , mid plt elevation. • Bone marrow shows maturation arrest. • 10% of patients convert to MDS/ AML, associated with monosomy 7 , trisomy 21. • In 80% of MDS/AML , point mutations in G-CSF receptor gene occur. • More than 90% of patients respond to CSF, the other 10 % are candidates for stem cell transplantation.

  24. Intrensic Disorders….cont. • Severe Chronic Idiopathic Neutropenia: • Children beyond 2 yrs. • ANC below 500.recurrent pyogenic infxns( skin , mucous membranes , lungs , LN ) • Occasionally associated with disorders of immunoglobulin production. • The onset of mucous membrane involvement helps distinguish it from other entities.

  25. Intrensic Disorders …cont. • Chronic Benign Neutropenia of Childhood: • Neutropenia in an otherwise normal child. • Mild to moderate neutropenia, not associated with severe infxns. • Spontaneous remissions ? • Patients should not be subjected to prolonged corticosteroid therapy , cytotoxic drugs,or splenectomy.

  26. Netropenias Associated with Phenotypic Abnormalities • Shwachman-Diamond Syndrome • Familial Disorder, AR trait. • Chronic moderate neutropenia & pancreatic insufficiency. • Malabsorption and growth failure. • Different from CF : normal sweat chloride , no pulmonary involvement. • Occasionally anemia , thrombocytopenia., hypocellular bone marrow.

  27. Shwachman-Diamond Syndrome ..cont. • Metaphyseal Dysostosis in toddlers. • Recurrent bacterial infections. • Aplastic anemia develops in 25% of patients. • Leukemic transformation.

  28. Cartilage-Hair Hypoplasia: • AR, in Amish populations. • Dwarfism , fine hair,moderate neutropenia. • Impaired cellular immunity. • Life threatening VZV infections. • Rx: Allogenic, HLA identical BMT.

  29. Dyskeratosis Congenita: • X-linked recessive. • Nail dystrophy, leukoplakia, skin hyperpigmentation. • Marrow hypoplasia. • 1/3 have neutropenia. • No severe infections and pts survive to adulthood.

  30. Evaluation of Children With Neutropenia: • Obtain a thorough history: • Onset , frequency,severity of infxns. • Drug history for toxic exposure. • Family history of recurrent infxns, or unexplained infant death. • Physical examination: • Growth and development . • Phenotypic abnormalities. • Sites of bacterial infxns • Lymphadenopathy, hepatosplenomegaly. • Pallor, ecchymosis , petechiae. • Fever (not rectally)

  31. Evaluation of Neutropenic Patient: • Laboratory tests: • Confirm neutropenia, according to age. • Further evaluation depends on clinical setting , duration and severity of neutropenia. • CBC • Bone marrow aspirate & Bone marrow cyto genetics. • Antineutrophil antibodies • Serum folate , B12 • Antinuclear antibodies • Pancreatic enzymes, skeletal evaluation. • Immunological evaluation.

  32. Principles of Therapy for Neutropenia: • Approach varies according to type of neutropenia. • The significance of fever. • Septicemia is a major risk. • Acute septicemia is more common in the acute neutropenias .

  33. Acute Onset Neutropenia: • Management of infection: • Early recognition & treatment. • Pattern of fever & blood cultures. • Other investigations. • Withdraw ongoing chemotherapy.

  34. Management….cont. • Antibiotic regimens: • IV broad spectrum antibiotics. • Combination therapy. • Duration of treatment: • Persistence of fever , neutropenia. • Identification of pathogen. • Repeat cultures with spikes of fever.

  35. Management of Neutropenia …cont. • Acute neutropenia: • Possibility of fungal infection. • rhG-CSF • Chronic neutropenia: • Management depends on pts history. • Antibiotics. • rhG-CSF, complications ? • Corticosteroids for autoimmune neutropenia

  36. QUIZ: • In a 2-year old Caucasian child , neutropenia is defined as an absolute neutrophil count less than : • 500 • 1500 • 2500 • 3500 • 4500

  37. QUIZ: • Which one of the following is the most common cause of neutropenia in a 4-year old child: • Acute lymphoblastic leukemia • Cyclic neutropenia • Intercurrent viral infection • Kostmann syndrome • Nutritional deficiency

  38. QUIZ: • Cyclic neutropenia is characterized by regularly recurring episodes of neutropenia that last for 3-6 days. The interval between the neutropenic phases is most likely to be: • 1 week • 3 weeks • 6 weeks • 12 weeks • 16 weeks

  39. QUIZ: • A 4-year old boy has a culture positive staph skin infection.Absence of which of the following signs would be most consistent with a neutropenia ? • Erythema • Exudate • Pain • Warmth • Tenderness

  40. QUIZ: • You have diagnosed primary autoimmune neutropenia in a 9-month old girl. You are most likely to tell the parents that: • Periodic examination of the bone marrow is required . • Repeated gynogenic infection will occur throughout life. • Severe neutropenia is not an associated finding. • Spontaneous remission occurs in 95% of patients. • Treatment with rhG-CSF is recommended for any infection

  41. THANK YOU !!

More Related