INTRODUCTION

• A raised white blood cell count is often due to elevation of a single lineage
• There is a variation of neutrophil counts among different ethnic groups with people of African origin generally having slightly lower counts compared to Caucasians

VARIATIONS IN THE LEVELS OF CIRCULATING LEUKOCYTES

NEUTROPHILIA

• The cause of neutrophilia is often obvious from careful history and examination  Reactive neutrophilia is associated with;
  • A left shift
  • Toxic granulation
  • Döhle bodies and
  • High neutrophil alkaline phosphatase score (Normal NAP Score = 20-100)
• An increase in circulating neutrophils to a level greater than 7.5 × 10⁹/L is one of the most frequently observed blood count changes

Leukaemoid Reaction

• Occasionally, the white cell count is very high
• This is referred to as a Leukaemoid reaction
• It is a reactive and excessive leukocytosis usually characterized by the presence of immature cells (myeloblast, promyelocyte, myelocyte, metamyelocyte and band form) in the peripheral blood

Causes of Leukaemoid Reaction

• Severe and chronic infections
• Severe haemolysis
• Metastatic cancer

Leukoerythroblastic Reaction

• Acute and chronic myeloid leukaemia
• Myeloma
• Lymphoma
• Severe megaloblastic anaemia
• Severe haemolysis
• Osteoporosis

Leucoerythroblastic Blood picture

CAUSES OF NEUTROPHILIA

• Bacterial infections especially pyogenic bacteria  Inflammation and tissue necrosis e.g.
  • Myositis
  • Vasculitis
  • Cardiac infarction
  • Trauma
• Metabolic disorders e.g. ü Uraemia
  • Eclampsia
  • Acidosis
  • Gout
• Neoplasms – myeloproliferative disorders such as ;
  • Chronic myeloid leukaemia
  • Polycythaemia vera
  • Melanoma
  • Essential thrombocytaemia
  • Carcinomas
  • Lymphomas
  • Myelofibrosis
• Acute haemorrhage or haemolysis
• Corticosteroid therapy (inhibits margination)
• Treatment with myeloid growth factors e.g. G-CSF, GM-CSF

CAUSES OF NEUTROPAENIA

Neutropaenia can result from impaired production in the marrow or peripheral destruction.

Causes can be;

• Congenital e.g.
  • Kostmann’s syndrome
• Acquired - drug induced
  • Anti-inflammatory drugs Aminopyrine

 Phenylbutazone

• Antibacterial

 Chloramphenicol

 Co-trimoxazole

 Sulfasalazine

• Anticonvulsants

 Phenytoin

 Carbamazepine

• Immune
  • Systemic Lupus Erythematosus (SLE)
  • Felty’s syndrome
• Large granular lymphocytic leukaemia
• Infections
  • Hepatitis
  • Influenza
  • HIV
  • Typhoid fever
  • Miliary tuberculosis
• Bone marrow failure
• Splenomegaly

CAUSES OF EOSINOPHILIA

• Allergic diseases such as;
  • Bronchial asthma
  • Hay fever
  • Urticarial
• Parasitic disease
  • Amoebiasis
  • Hookworm
  • Filariasis
• Skin disease
  • Psoriasis
  • Pemphigus
  • Dermatitis herpetiformis
• Hypereosinophilic syndrome
• Pulmonary eosinophilia
• Hodgkin’s disease and other tumours
• Metastatic malignancy with tumour necrosis
• Eosinophilic leukaemia  Treatment with GM-CSF CAUSES OF BASOPHILIA
• Infection
  • Pox viruses
• Inflammatory conditions
• Metabolic conditions
  • Myxedema
• Myeloproliferative disorders

CAUSES OF MONOCYTOSIS

• Chronic infections
• Recovery from acute infections
• Neoplasia
• Myelodysplasia
• CMML^[1]

VARIATIONS IN PHAGOCYTE MORPHOLOGY

A number of hereditary conditions may give rise to changes in granulocyte morphology

Barr Bodies

• A ‘drumstick’ appendage present on the nucleus of neutrophils in normal females due to the presence of 2 X chromosomes

Pelger-Huet Anomaly

• It is an autosomal recessive disorder characterized by bilobed and occasional unsegmented neutrophils in the peripheral blood
• Are seen in cases of;
  • Mylodysplasia and
  • Acute myeloid leukaemia

Neutrophil Hypersegmentation

• It’s a rare autosomal dominant condition
• Neutrophil function is essentially normal
• Seen in cases of;
  • Megaloblastic anaemia
  • Renal failure
  • Cytotoxic drugs

May-Hegglin Anomaly (MHA)

• Is an autosomal dominant disorder characterized by various degrees of thrombocytopaenia that may be associated with;
  • Purpura and bleeding
  • Giant platelets containing few granules; and
  • Large, well-defined, basophilic, cytoplasmic inclusion bodies in granulocytes that resemble Döhle bodies

Alder Anomaly

• Is a rare autosomal recessive disorder in which the basic defect involves proteincarbohydrate complexes called mucopolysaccharides
• The accumulation of partially degraded (broken down) protein-carbohydrate complexes within the lysosomes account for the larger than normal purple-staining inclusions seen in all types of mature white blood cells and sometimes in earlier cells
• The granules may occur in clusters, rather than diffusely, throughout the cytoplasm as in toxic granulation
• These inclusions may be seen in the bone marrow more frequently than in the peripheral blood
• The physical characteristics associated with this disorder include gargoylism^[2] and dwarfism
• The function of the cells involved is not affected

Cheidak-Higashi Syndrome

• A rare autosomal recessive disorder, characterized by;
  • Occulocutaneous albinism
  • Recurrent and severe bacterial infections
  • Presence of giant blue-gray granules in WBCs
  • Mild bleeding diathesis^[3]
  • Progressive peripheral neuropathy and ü Cranial nerve abnormalities

Acquired conditions

• Toxic granulation and Döhle bodies
• These abnormality occurs in infection

ABNORMALITIES OF PHAGOCYTE FUNCTION

Abnormalities in Chemotaxis

• ‘Lazy leukocyte syndrome’ which is found in acute and chronic leukaemia
• Myelodysplasia and
• In patients on steroid therapy

Abnormalities in Phagocytosis

• Due to lack of opsonization as in;
  • Hypogammaglobulinaemia or
  • Lack of complement components

Abnormalities in Killing

• Abnormal leukocyte oxidative metabolism. Seen in;
  • Chronic granulomatous disease – a rare X-linked or autosomal recessive disorder
• Defect in bacterial killing. Seen in;
  • Myeloperoxidase deficiency
  • Cheidak-Higashi syndrome
• Defective killing of ingested microorganisms. Seen in;
  • Acute or chronic leukaemia and
  • MDS^[4]

DISORDERS OF DENDRITIC CELLS

Langerhan’s Cell Histiocytosis

 Formerly called histiocytosis X, Letterer-Siwe disease and eosinophilic granuloma  It affects children and presents with;

• Hepatosplenomegally
• Lymphadenopathy and
• Eczematous skin rash

DISORDERS OF MACROPHAGES

Haemophagocytic Lymphohistiocytosis

• A rare autosomal recessive disorder
• A disease of children between first 3 years of life
• There are increased number of histiocytes in the bone marrow which ingest red cells, WBCs and platelets
• A secondary form also exists especially post infections (viral, bacterial, protozoan and fungal)

Clinical Features

• Fever
• Splenomegaly
• Hepatomegaly
• Lymphadenopathy
• Signs and Symptoms of CNS Disease
• Pancytopaenia
• Liver dysfunction
• Coagulopathy

Haemophagocytosis in the bone marrow, liver, spleen and lymph nodes

[1] CMML – Chronic Monomyelocytic Leukaemia

[2] Dysmorphic facial features characterized by thickened gingiva (gums) and upturned nose

[3] Diathesis – a hereditary or constitutional predisposition to a disease or other disorder

[4] Myelodysplastic Syndrome