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 EDUWAY
Signs and Symptoms of Anemia
To Care For Patients

Central Nervous System

Fatigue
Headaches
Dizziness, vertigo
Depression
Retinal changes
Impaired cognitive function

Gastrointestinal System
Anorexia
Nausea
Vascular and Renal Systems
Low skin temperature
Pallid skin, mucous
membranes, and conjunctivae
Edema, swollen legs

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
Genital Tract
Menstrual problems
Loss of libido

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 !! 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 .

Hypoproliferative Anaemias
Nuclear
breakdown

Failure of cell
maturation

Cytoplasmic
breakdown

Folate or B12 deficiency

Haem defect

Globin defect

Defective DNA synthesis

Fe

Sickle cell A

Megaloblastic Anaemia
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Phorph

IDA, SA

Thalassemia

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
dalam tubuh
4 5 gr

Reaksi

redox enzimatik

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
Wegeners 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
No diagnosis
Single diagnosis
Anemia of chronic
disease
Malnutrition
Infection
Postoperative bleeding

Alcohol
deficiency
Modified fromIron
Principles
of Geriatric Medicine and Gerontology 4

53%
17%
30%
10%
9%
4%
3%
th

1%
ed. 1999 1%

Anemia in the Elderly

Diseases Associated with Anemia of Chronic
Disease
Acute infections
Chronic infections

Malignancy
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
(ug per L)

Sensitivity (%)

Specificity (%)

Likelihood
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
receptor

Increased

Normal

Transferrin receptor /
ferritin index

High

Low

Thank You ALL

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