K6 Klasifikasi Anemi(PK)

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    DASAR2 TERJADINYA

    ANEMI .

    Prof. Adi Koesoema Aman SpPK(KH).

    Dr. Tapisari Tambunan SpPK(K)

    Divisi Hematologi Departement PatologiKlinik FK USU / RSUP H.A.Malik , Medan

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    Definition of Anaemia

    Decrease in the number of circulating red

    blood cell mass and there by O2carrying

    capacity

    Most common hematological disorder by far

    Almost always a secondary disorder

    As such, critical for all practitioners to knowhow to evaluate / determine its cause / treat

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    Central Nervous System

    Fatigue

    Headaches

    Dizziness, vertigo

    Depression

    Retinal changes Impaired cognitive function

    Immune System

    Impaired T-cell and

    macrophage function

    Cardiorespiratory System

    Exertional dyspnea

    Tachycardia, palpitations

    Cardiac enlargement, hypertrophy

    Increased pulse pressure,

    systolic ejection murmur

    Risk of life-threatening cardiac

    failure

    Gastrointestinal System

    Anorexia

    Nausea

    Genital Tract Menstrual problems

    Loss of libido

    Vascular and Renal Systems

    Low skin temperature

    Pallid skin, mucous

    membranes, and conjunctivae

    Edema, swollen legs

    Adapted from Ludwig H, Fritz E. Semin Oncol.1998;25:2-6; Ludwig H, Strasser K. Semin Oncol.2001;28:7-14.

    Signs and Symptoms of Anemia

    TheMEDUWAYTo Care For Patients

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    What is Anemia

    Important to remember

    Anemia is a clinical sign of disease

    It is not a single disease by itself

    Need to look for the underlying cause !

    Will we ignore a fever with out investigation ?

    Its diagnosis is not that simple!! Well make it

    Its very common and imp. in our practice

    Drug Rx. depends on the cause

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    Causes of Anaemia

    1. Decreased production of Red Cells

    - Hypo proliferative, marrow failure

    2.Increased destruction of Red Cells- Hemolysis (decreased survival of

    RBC)

    3. Loss of Red Cells due to bleeding

    - Acute / chronic blood loss

    (hemorrhagic) .

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    ADA 3 PENYEBAB UTAMA ANEMI

    1. KEHILANGAN DARAH YG BERLEBIHAN

    2. GANGGUAN PEMBENTUKAN ERITROSIT

    3. DESTRUKSI ERITROSIT MENINGKAT .

    4. BERKURANGNYA FAKTOR YANG MEMBENTUK

    ERITROSIT .

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    Hypoproliferative Anaemias

    Failure of cellmaturation

    Nuclear

    breakdown

    Cytoplasmic

    breakdown

    Megaloblastic Anaemia

    Defective DNA synthesis

    Folate or B12deficiency Haem defect Globin defect

    Thalassemia

    Sickle cell AFe Phorph

    IDA, SA

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    BESI IRON)

    HEME IRONHEMOGLOBINMYOGLOBIN

    ENZIM : SITOKROM, KATALASE, PEROKSIDASE

    NON HEME IRONFerritin

    Hemosiderin

    Transferrin

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    ZAT BESI DALAM TUBUH

    Hemoglobin

    Myoglobin

    Reaksi redox enzimatik

    FerritinTansferin

    Hemosiderin

    Total Besi

    dalam tubuh

    4 5 gr

    PERAN FISIOLOGIS

    CADANGAN

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    HEMOLYTIC ANEMIACauses

    INTRACORPUSCULAR HEMOLYSIS

    Membrane Abnormalities

    Metabolic Abnormalities

    Hemoglobinopathies

    EXTRACORPUSCULAR HEMOLYSIS

    Nonimmune

    Immune

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    HEMOLYTIC ANEMIAMembrane Defects

    Microskeletal defects

    Hereditary spherocytosis

    Membrane permeability defects

    Hereditary stomatocytosis

    Increased sensitivity to complement

    Paroxysmal nocturnal hemoglobinuria

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    HEMOLYTIC ANEMIACauses

    INTRACORPUSCULAR HEMOLYSIS

    Membrane Abnormalities

    Metabolic Abnormalities

    Hemoglobinopathies

    EXTRACORPUSCULAR HEMOLYSIS

    Nonimmune

    Immune

    Mi i thi H l ti

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    Microangiopathic Hemolytic

    Anemia

    Causes

    Vascular abnormalities

    Thrombotic thrombocytopenic purpura Renal lesionsMalignant hypertension

    Glomerulonephritis

    Preeclampsia

    Transplant rejection

    VasculitisPolyarteritis nodosa

    Rocky mountain spotted fever

    Wegeners granulomatosis

    Microangiopathic Hemolytic

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    Microangiopathic Hemolytic

    Anemia

    Causes - #2

    Vascular abnormalities

    AV FistulaCavernous hemangioma

    Intravascular coagulation predominant

    Abruptio placentae

    Disseminated intravascular coagulation

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    IMMUNE HEMOLYTIC ANEMIAGeneral Principles

    All require antigen-antibody reactions

    Types of reactions dependent on: Class of Antibody

    Number & Spacing of antigenic sites on cell Availability of complement

    Environmental Temperature

    Functional status of reticuloendothelial system

    Manifestations Intravascular hemolysis

    Extravascular hemolysis

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    Aplastic Anemia

    Failure of the bone marrow percursors to produce maturecells. Characterized by hypocellular marrow and pancytopenia.

    Etiology:

    Acquired: More commonInherited: Fanconi anemia

    Acquired:1. Drugs

    - Cytotoxic drugs - Antibiotics- Chloramphenicol - Anti-inflammatory

    - Anti-convulsant - Sulphonamides

    - 2-3 months usually between exposure and the development of aplasticanemia.

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    Aplastic Anemia: (Cont.)Acquired:

    RadiationsChemicals e.g., Benzene and pesticides

    Viruses: Hepatitis A, Non-A and Non-B

    Herpes simplex

    E-B virus

    Parvovirus: Transient

    Important clinically in patients with hemolytic anemias

    5-10% of cases of AA in the West and 10-20% in the Far East.

    2-3 months between exposure to the virus and the development

    of AA.Immune: SLE, RA (rheumatoid arthritis)

    Pregnancy

    Idiopathic: 75%

    PNH

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    Pathogenesis

    Potential mechanisms:

    Absent or defective stem cells (stem cell failure). Abnormal marrow micro-environment. Inhibition by an abnormal clone of hemopoietic cells.

    Abnormal regulatory cells or factors. Immune mediated suppression of hematopoiesis.

    It is believed that genetic factors play a role. Thereis a higher incidence with HLA (11) histo comp.

    Antigen. Immune mechanism is involved.

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    Pathogenesis (Cont)The latest theory is: there is an intrinsic derangement

    of hemopoietic proliferative capacity, which is consistentwith life. The immune mechanism attempt to destroythe abnormal cells (self cure) and the clinical course andcomplications depend on the balance. If the immunemechanism is strong, there will be severe pancytopenia.

    If not, there will be myelodysplasia.

    Forms of disease:Inevitable: dose related e.g. cytotoxic drugs, ionizing radiation.The timing, duration of aplasia and recovery depend on thedose. Recovery is usual except with whole body irradiation.

    Idiosyncratic: unpredictable to drugs e.g., anti-inflammatoryantibiotics, anti-epileptic, these agents usually do not producemarrow failure in the majority of persons exposed to theseagents.

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    Anemia in the Elderly

    Anemia of Chronic Disease

    Most common cause of anemia in hospitalized patients.

    Anemia correlates with severity of underlying disease.

    Serum erythropoietin levels may be inappropriately low.

    Response to erythropoietin administration variable.

    In selected diseases (e.g. Myeloma, RA, CRF) responses to

    erythropoietin possible with serum levels < 200 U/L (N, 12 52).

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    Anemia in the Elderly

    Anemia of Chronic Disease

    Pathogenesis

    Impairment of iron utilization

    Inhibition of erythropoeisis

    Blunted response to erythropoietin

    Reduced RBC survival

    Possible functional adaptation of innate immune system

    Iron sequestration as a microbicidal strategy

    Altered macrophage responses

    Cytokine mediated

    Th1 - IFNg, TNFa, IL-1

    Th2 IL-4, IL-10, IL-6

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    Anemia in the Elderly

    Special Considerations

    Multifactorial often with multiple medical problems& polypharmacy.

    Onset of symptoms is usually insidious & frequentlynonspecific.

    Anemia in the elderly has increased consequences.

    RBC indices often unreliable.

    Myelosuppression more common & severe.

    Quality of life issues may be more pronounced.

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    Anemia in the Elderly

    Time of Diagnosis

    Annual medical examination 7%

    Onset of acute medical problem 8%Follow up of a chronic medical problem 9%

    Following admission to hospital 75%

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    Anemia in the Elderly

    Multiple diagnoses 53%No diagnosis 17%

    Single diagnosis 30%

    Anemia of chronicdisease

    10%

    Malnutrition 9%

    Infection 4%Postoperative bleeding 3%

    Alcohol 1%

    Iron deficiency 1%Modif ied from Principles of Geri atri c Medicine and Gerontology 4thed. 1999

    Anemia in the Elderly

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    Anemia in the Elderly

    Diseases Associated with Anemia of Chronic

    DiseaseAcute infections Malignancy

    Chronic infections Metastatic carcinoma

    Tuberculosis Hematologic malignancies

    Infective endocarditis Leukemia

    Chronic urinary tract infection Lymphoma

    Chronic fungal infection Myeloma

    Chronic inflammatory disorders Chronic renal insufficiency

    Rheumatoid disease HypothyroidismCollagen vascular disease Protein-energy malnutrition

    Polymyalgia rheumatica

    Acute and chronic hepatitis

    Decubitus ulcer

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    Anemia in the Elderly

    Sensitivity & Specificity of Serum Ferritin in Iron DeficiencyAnemia

    Serum ferritin

    (ug per L) Sensitivity (%) Specificity (%)

    Likelihood

    ratio*

    < 200 94 71 3.2

    < 45 85 92 11.1

    < 15 59 99 54.5

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    Anemia in the Elderly

    Iron Def. ACD

    Serum iron Reduced Reduced

    TIBC Increased Reduced

    Transferrin saturation Reduced Normal

    Serum ferritin Reduced Normal or

    Increased

    Plasma transferrinreceptor Increased Normal

    Transferrin receptor /

    ferritin index

    High Low

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    Thank You ALL