DASAR2 TERJADINYA

ANEMI .

Prof. Adi Koesoema Aman SpPK(KH).

Dr. Tapisari Tambunan SpPK(K)

Divisi Hematologi Departement Patologi

Klinik FK USU / RSUP H.A.Malik , Medan
 Definition of Anaemia

Decrease in the number of circulating red

blood cell mass and there by O2 carrying
capacity
Most common hematological disorder by far
Almost always a secondary disorder
As such, critical for all practitioners to know
how to evaluate / determine its cause / treat

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The
M EDUWAY
To Care For Patients

Signs and Symptoms of Anemia

Central Nervous System Immune System
• Fatigue • Impaired T-cell and
• Headaches macrophage function
• Dizziness, vertigo
Cardiorespiratory System
• Depression
• Exertional dyspnea
• Retinal changes
• Tachycardia, palpitations
• Impaired cognitive function
• Cardiac enlargement, hypertrophy
Gastrointestinal System • Increased pulse pressure,
• Anorexia systolic ejection murmur
• Nausea • Risk of life-threatening cardiac
failure
Vascular and Renal Systems
• Low skin temperature Genital Tract
• Pallid skin, mucous • Menstrual problems
membranes, and conjunctivae • Loss of libido
• 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.
 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 !! We’ll 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 .
 Hypoproliferative Anaemias
Failure of cell
maturation
Nuclear Cytoplasmic
breakdown breakdown

Folate or B12 deficiency Haem defect Globin defect

Defective DNA synthesis Fe Phorph Sickle cell A

Megaloblastic Anaemia IDA, SA Thalassemia

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 HEME – IRON
HEMOGLOBIN
MYOGLOBIN
ENZIM : SITOKROM, KATALASE, PEROKSIDASE

BESI (IRON)

NON HEME – IRON

Ferritin
Hemosiderin
Transferrin
ZAT BESI DALAM TUBUH
PERAN FISIOLOGIS

Hemoglobin
Myoglobin

Total Besi Reaksi redox enzimatik

dalam tubuh
4 – 5 gr CADANGAN

Ferritin
Tansferin
Hemosiderin
 HEMOLYTIC ANEMIA
Causes
INTRACORPUSCULAR HEMOLYSIS
– Membrane Abnormalities
– Metabolic Abnormalities
– Hemoglobinopathies
EXTRACORPUSCULAR HEMOLYSIS
– Nonimmune
– Immune
 HEMOLYTIC ANEMIA
Membrane Defects
Microskeletal defects
– Hereditary spherocytosis
Membrane permeability defects
– Hereditary stomatocytosis
Increased sensitivity to complement
– Paroxysmal nocturnal hemoglobinuria
 HEMOLYTIC ANEMIA
Causes
INTRACORPUSCULAR HEMOLYSIS
– Membrane Abnormalities
– Metabolic Abnormalities
– Hemoglobinopathies
EXTRACORPUSCULAR HEMOLYSIS
– Nonimmune
– Immune
 Microangiopathic Hemolytic
Anemia
Causes

Vascular abnormalities
– Thrombotic thrombocytopenic purpura
– Renal lesions
Malignant hypertension
Glomerulonephritis
Preeclampsia
Transplant rejection
– Vasculitis
Polyarteritis nodosa
Rocky mountain spotted fever
Wegener’s granulomatosis
 Microangiopathic Hemolytic
Anemia
Causes - #2

– Vascular abnormalities
AV Fistula
Cavernous hemangioma
Intravascular coagulation predominant
– Abruptio placentae
– Disseminated intravascular coagulation
IMMUNE HEMOLYTIC ANEMIA
General 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
 Aplastic Anemia
Failure of the bone marrow percursors to produce mature
cells. Characterized by hypocellular marrow and pancytopenia.

Etiology:
Acquired: More common
Inherited: Fanconi anemia
Acquired:
1. Drugs
- Cytotoxic drugs - Antibiotics
- Chloramphenicol - Anti-inflammatory
- Anti-convulsant - Sulphonamides
- 2-3 months usually between exposure and the development of aplastic
anemia.
 Aplastic Anemia: (Cont.)
Acquired:
Radiations
Chemicals 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
 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. There

is a higher incidence with HLA (11) histo comp.
Antigen. Immune mechanism is involved.
 Pathogenesis (Cont…)
The latest theory is: there is an intrinsic derangement
of hemopoietic proliferative capacity, which is consistent
with life. The immune mechanism attempt to destroy
the abnormal cells (self cure) and the clinical course and
complications depend on the balance. If the immune
mechanism 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 the
dose. Recovery is usual except with whole body irradiation.

Idiosyncratic: unpredictable to drugs e.g., anti-inflammatory

antibiotics, anti-epileptic, these agents usually do not produce
marrow failure in the majority of persons exposed to these
agents.
 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).
 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
 Anemia in the Elderly

Special Considerations
• Multifactorial often with multiple medical problems
& polypharmacy.
• Onset of symptoms is usually insidious & frequently
nonspecific.
• Anemia in the elderly has increased consequences.
• RBC indices often unreliable.
• Myelosuppression more common & severe.
• Quality of life issues may be more pronounced.
 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%
 Anemia in the Elderly
Multiple diagnoses 53%
No diagnosis 17%
Single diagnosis 30%
Anemia of chronic 10%
disease
Malnutrition 9%
Infection 4%
Postoperative bleeding 3%
Alcohol 1%
Modified fromIron deficiency
Principles of Geriatric Medicine and Gerontology 4 th ed. 1999 1%
 Anemia in the Elderly
Diseases Associated with Anemia of Chronic
Disease
Acute 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 Hypothyroidism
Collagen vascular disease Protein-energy malnutrition
Polymyalgia rheumatica
Acute and chronic hepatitis
Decubitus ulcer
 Anemia in the Elderly
Sensitivity & Specificity of Serum Ferritin in Iron Deficiency
Anemia

Serum ferritin Likelihood

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

< 200 94 71 3.2

< 45 85 92 11.1

< 15 59 99 54.5
 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 transferrin Increased Normal
receptor

Transferrin receptor / High Low

ferritin index