Notifications
Clear all

GRANULOCYTE ABNORMALITIES WITH CLINICAL CORRELATIONS


ug
Posts: 33
 ug
Admin
Topic starter
(@mr-right)
Reporter
Joined: 4 months ago

 

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