GENERAL PATHOLOGY

1. HAEMATOLOGICAL
DISORDERS
Dr. MURALI B M
Professor of pathology

2. hematopoeisis

3. Introduction
• Blood consists of red blood cell, white cells
platelets, and plasma.
• Plasma is the liquid component of the blood
which contains soluble fibrinogen
• Haemopoiesis is the formation of the blood
cells
• The bone marrow is the only source of blood
cells during normal childhood and adult life
the growth factor erythropoietin controls the
production of red blood cells
• Reticulocytes are young red cells recently
released from the bone morrow.

4. • Reticulocytes normally represent <2% of total
circulation red blood cells
• Reticulocytes give a guide to the erythroid
activity in the bone marrow
• Increase with hemorrhage, haemolysis and
after treatment with specific haematinics in
deficiency states

5. Normal Red Blood Cells - Peripheral Blood Smear
Normal Red Blood Cells - Peripheral Blood Smear

6. Normal Values for Adult Peripheral Blood
Men Women
Hb (g/dL) 13 - 18 11.5 - 15.5
PCV (haematocrit, L/L) 0.42 - 0.53 0.36 - 0.45
RCC (1012/L) 4.5 - 6.0 3.9 - 5.1
MCV (fL) 80 - 96
MCH (pg) 27 - 33
MCHC (g/dL) 32 - 35
WCC (109/L) 4.0 - 11.0
Platelets (109/L) 150 - 400
ESR (mm/h) <20
Reticulocytes (%of total RCC) 0.2 - 2.0

7. Anaemia
• The principal physiological function of (Hb)
haemoglobin is to carry and deliver O2 to
the tissues from the lungs.
• Hb is a tetramer consisting of two pairs of
globin polypeptide chains
• Anaemia is present when there is decrease
in the level of Hb in the blood below the
reference range for the age and sex of the
individuals

8. Classification of the Anaemia
Microcytic Normocytic Macrocytic
Small red cells,
MCV <80fL
- Iron deficiency
- Anaemia of chronic
disease
- Thalassaemia
-Siderolbastic
anaemia
Normal-sized red
cells, normal MCV
- Acute blood loss
- Anaemia of chronic
disease
- Mixed deficiency of
vitamin B12 & iron
- Haemolytic anaemia
- hypothyroidism
Large red cells, MCV
>96fL
- Megaloblastic
- vitamin B12 deficiency
- folate deficiency
- myelodysplasia
-Haemolytic anaemias

9. Etiological classification

10. Symptoms of Anaemia
• Symptoms depend on the severity
and speed of onset
• Fatigue
• Dyspnaea (SOB)
• Palpitation
• Headache
• Tinitus
• Anorexia
• Bowel disturbance

11. Signs of Anaemia
• Paller (look at conjunctivae)
• Severe anaemia (hyperdynamic circulation
• Tachycardia, murmurs
• Cardiomegally
• Heart failure
• Oral discomfort
• Oral ulcerations
• Glossitis
• Angular cheilitis

12. Iron Deficiency Anaemia (IDA)
• Iron is necessary for the formation of
haemoglobin
• Iron deficiency is the most common
cause of anaemia worldwide
Causes
• The most common cause is the blood
loss from uterus or gastrointestinal tract,
peptic ulcer, carcinoma or hemorrhoids

13. Other Causes
• Increased demands e.g., during growth and
pregnancy
• Decreased absorption in small bowel
diseases-coeliac disease, malabsorption
• Poor dietary intake

14. Clinical Features
• Brittles hair & nails
• Atrophic glossitis
• Angular stomatitis
• Koilonychia (spoon shaped nail)
• Rarely, pharyngeal webs which may cause
dysphagia (Paterson-Brown –Kelly Syndrome)

15. Angular stomatitis

17. Investigations
• Blood count low Hb with a low MCV
• Blood film microcytic and hypochromic red
blood cells, anisocytosis, penicillocytes
• Low Serum ferritin (iron store)
• Low Serum iron and high TIBC
• Absence of iron in the Bone marrow examination

18. Hypochromic Microcytic
Hypochromic MicrocyticAnemia (iron deficiency)
Anemia (iron deficiency)

19. Fig. 1 Microcytosis in a
patient with β thalassaemia
trait; the MCV was 62 fl. The
blood film also shows mild
hypochromia, anisocytosis
and poikilocytosis.
Fig. 2. The blood film of a patient
with iron deficiency anaemia
showing anisocytosis, poikilocytosis
(including elliptocytes),
hypochromia and microcytosis.
The blood count (Coulter S Plus IV) was:
RBC 4.22 × 1012/l, Hb 7 g/dl, Hct
0.29, MCV 67 fl, MCH 16.6 pg,

20. Treatment
• Find and treat the underlying cause
• Oral iron ferrous sulphate 200mg TDS
• Parenteral iron –poor response to oral iron
• Blood transfusion when necessary

21. Blood Transfusion
• In patients with severe anemia or acute
bleeding blood transfusion may be
required.
• Donors and recipients need to be blood
group ‘matched’ for successful transfusion
the ABO system and rhesus (Rh) system
should be determined.
• Complications and side effects:
1. Anaphylaxis
2. Febrile reactions
3. Heart failure
4. Infection (e.g. HIV, cytomegalovirus
hepatitis B and C, syphilis)

22. Macrocytic Anaemia
The red cells are larger than normal
• Macrocytosis MCV >96 femtolitres (MCV >110FL)
• Common Causes include :
• vit B12 deficiency
• Folate deficiency
• Cytotoxic Drugs like azathioprine or cyclophosphamide
• Hypothyrodism
• Alcoholism
• Liver disease
• Pregnancy
• Bone marrow inflltrations

23. Investigation
• Hb, PCV & Blood Indices.
• Low platelet count.
• Blood film – shows macrocytic red cells,
Howel jolly bodies, remnants of nucleus,
Hypersegmented neutrophis,
• Bone marrow examination : Megaloblastic
erythropoiesis
• Vitamin B/12 and folate levels.
• Liver and thyroid function tests.
• Markers for haemolysis like – low
hemoglobin , increase reticulocytes count ,
increase LDH , decrease haptoglobin ,
positive coob's test.

24. Macroovalocytes
Macroovalocytesand
and Hypersegmented Neutrophil
Hypersegmented Neutrophil

26. Fig. 8.27 The blood film of an elderly
woman with both malabsorption of
vitamin B12 and dietary deficiency of
folic acid showing marked
anisocytosis, macrocytosis, several
oval macrocytes, a teardrop
poikilocyte and a hypersegmented
neutrophil. The blood count (Coulter
S Plus IV) was: WBC 4.2 × 109/l, RBC
0.76 × 1012/l, Hb 3.6 g/dl, Hct 0.10,
MCV 133 fl, MCH 47.4 pg, MCHC
35.6 g/dl, platelet count 50 × 109/l.
Fig. 8.28 The blood film of a
patient
with pernicious anaemia
showing
macrocytosis and a circulating
megaloblast

27. Pernicious Anaemia
• Is autoimmune condition
• Atrophy of gastric mucosa
• Failure of intrinsic factor production and
consequent vit B12 malabsorption

28. Epidemiology
• Low dietary intake
• Vegans
• Impaired absorption
• Stomach
• Pernicious anaemia
• Gastrectomy
• Small bowel
• Ileal disease or resection
• Coeliac disease
• Tropical sprue
• Bacterial overgrwoth
• Congenital transcobalamin II deficiency (rare)
Associations
• Thyroid disease – vitiligo
• Addison disease – carcinoma of the stomach

29. Common Features
• Tiredness and weakness (90%)
• Dyspnoea (70%)
• Paratheiae (40%)
• Sore red tongue (25%)
• Diarrhea
• Mild jaundice
• Mild spleenomegally
• Fever
• Neuropsychiatric (dementa)

30. Angular Stomatitis + smooth painful tongue

31. Investigations
• Blood count and film (mcv >110
FL/macrocytes)
• Serum vit B12 is low
• Parietal cell antibodies
Treatment
intramuscular hydroxycobalamin (vit B12)

32. Fig. 8.2 The blood film of a
patient
with the anaemia of chronic
disease
consequent on a lymphoma,
showing
mild anisocytosis, poikilocytosis
and hypochromia. The blood
count
(Coulter S Plus IV) was: RBC
3.10 × 1012/l, Hb 7.4 g/dl, Hct
0.23,
MCV 75.6 fl, MCH 23.8 pg, MCHC
31.5 g/dl.
Fig. 8.3 A dimorphic blood film
from a patient with congenital
sideroblastic anaemia. There is a
minor population of cells that are
hypochromic and microcytic with
a tendency to target cell
formation; there is also
poikilocytosis. The patient had
previously responded to
pyridoxine with a rise of Hb and
was
taking pyridoxine when this blood
specimen was obtained.

33. Haemolytic anaemia (HA)
 HA results from increased destruction of
red cells and reduction of red cell life span
(normally 120days)

34. Causes of Hemolytic Anaemia
Inherited Acquired
Red cell membrane defect
Hereditary spherocytosis
Hereditary elliptocytosis
Immune
Autoimmune hemolytic anaemia
Haemolytic transfusion reactions
Drug-induced
Hemoglobin abnormalities
Thalassaemia
Sickle cell disease
Non-immune
Paroxysmal nocturnal hemoglobinuria
Microangiopathic hemolytic anaemia
March hemoglobinuria
Red cell metabolic defects
Glucose-6-phosphate
dehydrogenase deficiency
Pyruvate kinase deficiency
Miscellaneous
Infections (e.g., malaria)
Drugs/chemicals
Hypersplenism

35. Hereditary spherocytosis Hereditary elliptocytosis
Hereditary Ovulocytosis Hereditary Stomatocytosis

36. Investigations
• FBC, reticulocytes, bilirubin
• LDH, hepatoglobin
• Direct coomb’s test
• Hb electrophoresis
• Osmotic fragility test

37. Sickle cell disease
• Sickling disorders due to abnormal
production of abnormal ß- peptide chains
• Hbs polymerizes when dexogenated
• Tests Hb 6-8g/dL, reticulocytes 10-20%

38. • Anaemia,
• jaundice,
• painful swelling of hands and feet,
• chronic ill health,
• bone necrosis
• osteomylitis,
• chronic leg ulcers
• short stature (secondary to chronic anaemia
Signs and symptoms

39. Complications of sickle cell
disease
1. Acute chest syndrome
2. Stroke
3. Aplastic Aneamia
4. Painful bone crises
5. Splenic sequestration

40. Treatment include
• Treatment of the pain with strong
pain killers
• Rehydration with intravenous fluid
• IV antibiotic if there is infection
• Folic acid
• Hydroxurea
• Bone marrow transplantation in
young people with severe disease

41. Glucose-6-phosphate Dehydrogenase
Deficiency (G6PD)
• Cause neonatal jaundice, chronic anaemia and acute
haemolysis
• Haemolysis precipitated by the following : fava
beans , infection, drugs such as quinire,
paramaquire,(antimalarial) sulphanamides drugs and
ciprofloxacin drug
• Treatment
• avoid precipitants
• blood transfusion
• Common in men
• Mild (African type)
• Severe (Mediterranean type)

42. Haematological Malignancy
• Lukemias
• Are neoplastic proliferation of white blood cells.
• Neoplastic proliferation of hemopoitic stem cells with
infiltration to tissues.
• Exposure to many chemical agents, viruses and
radiation is implicated in the causation of leukemia
• Non-lethal genetic mutation is the molecular basis of
leukemias

43. Leukemias
• Classified as Acute & Chronic leukemias based on
the onset and clinical features
• Also classified further on type of cells involved and
the level of maturation arrest in the bone marrow
• Acute lymphoblastic leukemia (ALL)  is
predominantly disease of childhood.
• Acute myeloid leukemia (AML)  seen in older
adults
• Chronic leukemias are commonly seen in middle
and old age

44. Classification of leukemias
Based on clinical onset
• Acute
• Chronic
Acute Leukemias further classified by FAB
group classification
• Acute myeloid leukemia ( M1 to M7)
• Acure lymphoid leukemia ( L1 to L3)

45. Clinical features of acute
leukemia
• Unwell , Fever , Paler. Weight loss
• Symptoms of anaemia
• Breathless (Difficulty in breathing).
• Repeated fever-abscess-infection
• Enlargement of Lymphnodes, spleen
and liver.
• Purpura- tiny bleeding spots .
• Bruising / bleeding specially oral
mucosa

46. • Unwell , Fever , Paler. Weight loss
• Symptoms of anaemia
• Breathless.
• Enlargement of spleen, liver and
lymphnodes
• Bleeding from gums
• All may present with gingival
hypertrophy
Clinical features of
Chronic leukemia

47. Common symptoms of leukemia

48. Gingival hypertrophy
Bleeding tendency

49. Gingival hypertrophy

50. Hemorrhagic blood disorder

51. Laboratory Diagnosis of leukemia
• CBC - Hb , TLC . Plt
• Blood Picture:
• Anemia,
• Luekocytosis with presence of immature cells
and blast cells,
• Thrombocytopenia.
• Bone marrow examination:
• Hyperplastic marrow,
• Maturation arrest.

52. • Biochemical changes: Increased uric acid,
Increased enzymes.
• Chromosomal abonormalities: Ph’ chromosome,
t(9;22) in CML – reciprocal translocation of long
arm of chromosome 9 to 22 (fusion gene – (bcr-
abl1)
• Cytochemistry: to differentiate different types of
immature cells
• Immunochemistry- to classify and type of cells
… helps deciding treatment and determining
prognosis
Laboratory Diagnosis of
leukemia

53. Acute leukemia

54. AML M1 AML M2 AML M3
AML M4 AML M5
AML M6
AML M7

55. ALL ALL L1
ALL L2 ALL L3

56. CML CML
CLL CLL

57. Treatement of leukaemia
• Blood and platelet transfusion.
• IV antibiotic.
• IV fluid + allopurinol to prevent tumor lysis
syndrome.
• Chemotherapy.
• +/- bone marrow transplant.