Schematic view of the architecture of red bone marrow

Indication of bone marrow study

 Diagnose a disease or condition involving the bone

marrow or blood cells
 Determine the stage or progression of a disease
 Determine whether iron levels are adequate
 Monitor treatment of a disease
 Investigate a fever of unknown origin
 Anaemia

Anaemia is defined as a reduction in the

concentration of circulating haemoglobin of blood
below the level that is expected for healthy persons
of same age and sex in the same environment.

The tests used for this purpose are estimation of haemoglobin

concentration and packed cell volume.
There are two methods for determining PCV—
macromethod (Wintrobe method) and micromethod
(microhaematocrit method).
Red cell indices: Red cell indices are helpful in the
morphological classification of anaemias. They are
derived from the values of red cell count, haemoglobin
(Hb) concentration, and packed cell volume (PCV).

The normal ranges of red cell indices in adults are as

follows:
MCV = 80–100 fl
MCH = 27–32 pg
MCHC= 32–36 g/dl
Anaemias are classified as normocytic, microcytic, and
macrocytic on the basis of MCV. Since MCV measures
average cell volume, it may be normal even though there
is marked variation in size of red cells (anisocytosis).
Low MCH is found in microcytic hypochromic
anaemia, while high MCH in macrocytic anaemia.
Low MCHC occurs in microcytic hypochromic
anaemia. An increase in MCHC occurs in
hereditary spherocytosis.
Red cell distribution width (RDW): RDW is the degree of
variation of red cell size and can be determined on some
blood cell analysers. This parameter may sometimes be
helpful for distinguishing iron deficiency anaemia from
βthalassaemia minor (low MCV with high RDW: iron
deficiency anaemia; low MCV with normal RDW:
βthalassaemia minor).
Morphological classification of anaemias
 ESR
The ESR is the measurement of the sedimentation of red
cells in diluted blood after standing for 1 h in an open-ended
glass tube of 30 cm length mounted vertically on a stand.

Inflammatory response to tissue injury (i.e. the acute phase

response
Increases fibrinogen, haptoglobin, caeruloplasmin,
immunoglobulins (Ig) & C-reactive protein (CRP),
Decreases- albumin.
The rate of sedimentation is mainly dependent on the
plasma concentration of large proteins (e.g. fibrinogen
and immunoglobulins).
The normal range in
Men is 1–5 mm/hour
Women 5–15 mm/hour,
There is a progressive increase with age.
The ESR is raised in a wide variety of systemic
inflammatory and neoplastic diseases and in pregnancy.
Lower than expected readings occur in polycythaemia
vera because of the high red cell concentration.
Higher than expected values may occur in severe anaemia
because of the low red cell concentration.
An extremely high ESR value (>100 mm/hr)
 Infection- Kala azar, TB
 Multiple myeloma,
 Lymphoplasmacytic lymphoma (Waldenström
macroglobulinemia),
 Giant cell (temporal) arteritis,
 Polymyalgia rheumatica, hypersensitivity
vasculitis.
 Aplastic anaemia
 Leukaemia
 Basic pathophysiological categories of anaemia

 Blood loss
 Impaired red cell production
Inadequate supply of nutrients essential for eythropoiesis,
such as:
iron deficiency
vitamin B12 deficiency
folic acid deficiency
protein-calorie malnutrition
other less common deficiencies
 Depression of erythropoietic activity
Anaemia associated with chronic disorders, such as:
infection
connective tissue disorders
inflammatory disorders:
disseminated malignancy
Anaemia associated with renal failure
 Aplastic anaemia
 Anaemia due to replacement of normal bone marrow by:
leukaemia
lymphoma
myeloproliferative disorders
myeloma
myelodysplastic disorders
 Anaemia due to inherited disorders, such as
thalassaemia
 Excessive red cell destruction
Due to intrinsic defects in red cells
Due to extrinsic effects on red cells
 Recognition and investigation of the anaemic patient

The basic questions to be considered are:

1. Is the patient anaemic?
2. If this is the case, what is the type of anaemia indicated
by examination ot the blood?
3. What is the cause of the anaemia?
 Is the patient anaemic?

Symptoms
 Common: Fatigue, tiredness, effort intolerance,
effort dyspnoea, palpitations
 Less common: Faintness, giddiness, pounding in the
ears, effort angina
Signs
 Common: Pallor
 Less common: High cardiac output state, congestive
cardiac failure*
*More likely in elderly subjects.
What is the type of anaemia?
 Microcytic, hypochromic anaemia

MCV <80 fL
MCH <27 pg

D/D
Iron deficiency
Anaemia of chronic disease
Thalassaemia
Sideroblastic anaemia
 Iron deficiency anaemia

The amount of iron in the adult human body is normally

about 50 mg/kg in males and 40 mg/kg in females.
 Causes of iron deficiency.
Chronic blood loss
Uterine
Gastrointestinal, e.g. peptic ulcer, oesophageal
varices, aspirin (or other non‐steroidal anti‐
inflammatory drugs) ingestion, gastrectomy,
carcinoma of the stomach, caecum, colon or
rectum, hookworm, schistosomiasis, angiodysplasia,
inflammatory bowel disease, piles, diverticulosis
Rarely, haematuria, haemoglobinuria, pulmonary
haemosiderosis, self‐inflicted blood loss.
Increased demands
Prematurity
Growth
Pregnancy
Erythropoietin therapy
Malabsorption
Gluten‐induced enteropathy, gastrectomy, autoimmune
gastritis
Poor diet
A major factor in many developing countries but rarely the
sole cause in developed countries
Pathophysiology
 Diagnosis
There are two steps in diagnosis
To establish that the anaemia is due to iron
deficiency,
To determine the cause of the iron deficiency

History : particularly chronic haemorrhage, pica etc.

Clinical features: Pallor, Koilonychia, when present,

strongly suggests the diagnosis, There may be
glossitis, angular stomatitis etc.
Blood examination shows:
In CBC: Hb-decreased, [Link]. MCHC- decreased
Blood Film: Typical hypochromic, microcytic
elongated pencil shaped cells are characteristic.
Biochemical tests: serum iron is reduced to
2.5 to 10 umol/L.
The total iron binding capacity is increased up to
100 umol/L or even more,
Percentage saturation of the iron-binding protein is
decreased to below 16 per cent.
Serum ferritin is less than 12 ug/1 in uncomplicated
cases,
• Most sensitive and specific test for diagnosis of iron
deficiency anaemia is S. ferritin. Serum ferritin decreases
even before the appearance of anaemia
• Serum ferritin correlates with body iron stores (1 μg/L
serum ferritin ≈10 mg storage iron)
• Serum ferritin < 12 μg/L is highly specific for diagnosis of
iron deficiency anaemia
• Not suitable for diagnosing iron deficiency in patients
with concomitant inflammatory, neoplastic, or liver
disorder.
 To find out the cause of iron deficiency
History
Females in the reproductive period of life
 Menstrual history especially menorrhagia
 Pregnancies number and frequency
 Miscarriages
 Diet
 Alimentary blood loss
 Haematuria, epistaxis, haemoptysis
 Gastrointestinal surgery
 Chronic aspirin ingestion
Males and post-menopausal females
Alimentary blood loss
(a) symptoms suggestive of gastrointestinal disorder
dyspepsia, weight loss, anorexia, abdominal pain,
diarrhoea,
constipation, alteration of bowel habits, dysphagia, acid
regurgitation
(b) haemorrhoids
(c) haematemesis or melaena
Epistaxis, haematuria, haemoptysis
Gastrointestinal surgery
Diet
Chronic aspirin ingestion
Infants and children
Detailed dietary history, especially of supplemental
feeding
Prematurity, multiple births or iron deficiency in
mother
Gastrointestinal disturbance
Blood loss
Physical examination
 Abdomen abdominal mass, tenderness, features of
liver disease
 Rectal examination and proctoscopy
 Pelvic examination
 Telangiectasia of face and mouth
Investigations commonly required
 Examination of faeces for occult blood. Repeat several
times if necessary

 Upper gastrointestinal tract endoscopy or barium

swallow, meal and follow-through (peptic ulcer, hiatus
hernia, carcinoma of stomach, oesophageal varices,
Meckel's diverticulum)

 Colonoscopy or barium enema (carcinoma of colon and

caecum, ulcerative colitis, diverticula, angiodysplasia)

 Sigmoidoscopy (carcinoma of rectum, ulcerative colitis)

 Microscopic examination of urine (haematuria)

 Sideroblastic anaemia

This is a refractory anaemia defined by the presence

of many pathological ring sideroblasts in the bone
marrow. These are abnormal erythroblasts
containing numerous iron granules arranged in a
ring or collar around the nucleus instead of the few
randomly distributed iron granules seen when
normal erythroblasts are stained for iron.
Sideroblastic anaemia is diagnosed when 15% or
more of marrow erythroblasts are ring sideroblasts.
Types
[Link]
[Link]