MODULE – 3

(ANAEMIA)

HAEMATOLOGY
 UNIT 3
LEARNING SCHEDULE – 18
(ANAEMIA-)
 Anaemia
LEARNING OBJECTIVES – (LS-18):
APLASTIC ANAEMIAS

1. To be able to define Aplastic Anaemias

2. To know the various causes and thus classes of Aplastic
Anaemia
3. For each cause to be able to explain the pathophysiology
4. To know the expected laboratory findings and symptoms
of Aplastic Anaemias
Introduction
• Is one of a group of hypoproliferative disorders in which
there is cellular depletion and a reduced production of all
blood cells, pancytopenia.
• It is usually idiopathic but thought to be a result of two
possible mechanisms:
➢ An antibody directed against an antigen on stem cells
or
➢ An immune mechanism that is at play, in which T
lymphocytes suppress stem cell proliferation
• Aplastic anaemia should not be confused with selective
suppression of Erythroid stem cells (pure red cell
aplasia), in which anaemia is the only manifestation
Causes of Aplastic Anaemia
Congenital
• Fanconi
• Dyskeratosis congenita
Acquired
• Idiopathic
Secondary
• Inevitable (cytotoxic drugs, radiation) Idiosyncratic -
chloramphenicol, sulfonamides, gold, chlorpromazine,
carbimazole
• Chemical agents/toxins - benzene
• Infection - viral hepatitis (non-A, non-B, non-C)
• Neoplasia - Acute Lymphoblastic Leukaemia
• Metabolic disorders
• Pregnancy
Clinical features of AA

• Aplastic anaemia affects persons of all ages and both

sexes.
• The slowly progressive anaemia causes the insidious
development of weakness, pallor, and dyspnea.
• Thrombocytopenia often presents with petechiae and
ecchymosis.
• Granulocytopenia may be manifested only by frequent
and persistent minor infections or by the sudden onset of
chills, fever, and prostration
• Splenomegaly is characteristically absent in aplastic
anaemia.
Clinical features of AA – Cont’d

• Typically, the red cells are normocytic and

normochromic, although slight macrocytosis is
occasionally present;
• Reticulocytes are reduced in number due to the decrease
in the rate of production of the red cells
• Treatment includes transfusion support and steroids,
with a few patients recovering spontaneously.
• Occasionally, stem cell transplantation is used to treat
severe aplastic anemia presentation
 Anaemia Of Chronic Disorders &
Inflammation And Other Causes Of BM
Failure
 Learning objectives

• To know:
• Anaemia of Chronic diseases
• The pathophysiology and diagnosis of ACD
• other causes of Bone marrow failure
 Introduction

• This is the anaemia that manifests in hospitalized patients

with chronic inflammatory and malignant diseases
• It superficially resembles the anaemia of iron deficiency
• It stems from inflammation-induced sequestration of iron
within the cells of the mononuclear phagocyte
(reticuloendothelial) system
 Epidemiology
• According to WHO Chronic diseases, such as heart disease,
stroke, cancer, chronic respiratory diseases and diabetes, are
by far the leading cause of mortality in the world,
representing 63% of all deaths.
• Anaemia of chronic disease is the second most prevalent
anaemia after anaemia caused by iron deficiency
Causes

• Infectious diseases
• Inflammatory diseases
• Neoplastic diseases
• Chronic heart failure
• Diabetes mellitus
• Obesity
• Chronic kidney disease
• Liver cirrhosis
Pathophysiology
Diversion of iron traffic
• Characterised by hypoferremia in the presence of
adequate iron stores
• IL-6 impairs iron utilisation by elevating Hepcidin levels
• Hepcidin suppresses dietary iron absorption and release
of iron from Hepatocytes and Macrophages
Inhibition of erythropoiesis
• Cytokines directly affect erythropoiesis by inhibiting the
growth of Erythroid progenitor cells
• TNFα and IFNs block BFU-e and CFU-e formation as
well as proliferation
• TNFα has also been shown to reduce the lifespan of
RBCs
Pathophysiology – Cont’d

Blunted EPO response

• TNFα and IFNγ inhibit the production of erythropoietin
in the kidney

➢ The limited availability of iron and the decreased biologic

activity of erythropoietin lead to inhibition of
erythropoiesis and the development of anaemia
Clinical features

• Hb levels do not usually go below 9.5 g/dL

• The serum iron levels are usually low
• The red cells can be normocytic and normochromic, or
may resemble anaemia of iron deficiency
• increased storage iron in the bone marrow
• High serum ferritin concentration and a reduced total
iron-binding capacity (TIBC), all of which readily rule
out iron deficiency or reduced transferrin saturation
levels
Other Causes Of Bone Marrow Failure
Introduction
• Bone marrow failure leads to peripheral blood cytopaenias
in all cell lines (pancytopaenia)
• The cytopaenias result because of a specific failure of bone
marrow precursor cells to produce mature cells.
• Lymphocytes are usually not affected
Pathophysiology
• A decrease in or damage to the hematopoietic stem cells and
their microenvironment, resulting in hypoplastic or aplastic
bone marrow
• Maturation defects, such as vitamin B-12 or folate deficiency
• Differentiation defects, such as myelodysplasia
Clinical features
• Related to pancytopaenia
➢ Bleeding disorders
• Thrombocytopaenic type dependent on platelet number
➢ Anaemia
• Gradual onset due to the long lifespan of RBCs
➢ Recurrent infection
• Related to neutropaenia and severity dependent on
neutrophil count
• Related to the underlying condition
Drugs

Several drugs have been implicated in bone marrow

suppression:
• Anti rheumatic drugs – Methotrexate, Sulphasalazine
and Hydroxychloroquin
• Anti thyroid medications – Carbimazole or Neo
Mercazole (CMZ) and Propylthiouracil
• Anti tuberculous drugs – Rifampicin, Ethambutol
• NSAIDs - phenylbutasone, indomethacin, gold
• Anti convulsants - Phenytoin and Carbamazepine
• Amino salicylates – Sulfasalazine
• Antibiotics – Ciprofloxacin, cefoxitin, Chloremphenical
 Drugs – Cont’d
The etiology of such BM failure due to drugs is thought to be
due to
• A direct cytotoxic effect
• Inevitably cause BM failure
• The timing, duration of aplasia and recovery is dose
dependent
• Recovery is usual except with whole body irradiation
• Immune-related idiosyncratic response
Drugs – Cont’d

• The type severity of the BM failure is variable from drug

to drug
• Chloramphenicol causes a dose dependent suppression
of haemopoiesis, particularly affecting erythropoiesis.
• Sulphonamides and Cotrimoxazole have been shown to
cause a pancytopaenia
• Aminosalicylates been associated with blood dyscrasias,
including BM failure.
Chemicals
• Industrial and domestic chemicals have also been
implicated.
• Benzene is a carcinogen and chronic exposure produces
pancytopenia associated with a hyperplastic or dysplastic
marrow.
• Benzene is a myelotoxin and exposure to sufficient levels
leads inevitably to marrow damage.
• Insecticides, in particular γ hexachlorocyclohexane,
pentachlorophenols and DDT, have each been implicated
in this regard.
• Self-reported house treatment for woodworm has
recently been strongly associated with risk of aplastic
anaemia, along with exposure to radiation in the
workplace
Viruses
• Hepatitis, presumably of viral origin, is a precursor of
aplastic anaemia in about 5–10% of cases in the West; it
is perhaps double in the Far East
• The association is based on clinical grounds and the
presence of abnormal liver Function tests.
• The delay between the clinical hepatitis and the onset of
pancytopenia is about 2– 3 months
• Parvovirus B19 infection in non-immune individuals may
lead to a transient pure red cell aplasia
• The virus specifically infects the erythroid burst-forming
units (BFU-E).
• Epstein–Barr virus infection is commonly accompanied
by neutropenia or thrombocytopenia, probably of an
immune origin
 Systemic Lupus Erythematosus (SLE)
• Aplastic anaemia may occasionally occur in association with
systemic autoimmune disorders such as Systemic Lupus
Erythematosus (SLE).
• SLE produces a hypocellular bone marrow,
• May also be associated with a truly autoimmune
pancytopenia with a cellular bone marrow.
Acquired pure red cell aplasia

• Granulocyte and megakaryocyte series are normal or

increased.
• Failure of erythropoiesis may occur as a primary
acquired event or may be associated with other
disorders.
• The condition presents as anaemia with
• Reticulocytopenia
• BM with a total lack of erythrocyte precursors or a
maturation arrest with a lack of late erythroid
precursors.
Myelophthisic Anaemia

• Is caused by the extensive replacement of the marrow by

tumors or other lesions.
• It is most commonly associated with metastatic breast,
lung, or prostate cancer, but other cancers, advanced
tuberculosis, lipid storage disorders, and osteosclerosis
can produce a similar clinical picture.
• The principal manifestations of marrow infiltration
include anaemia and thrombocytopenia; in general, the
white cell series is less affected