HEMA

• Functional disorders of neutrophils

  • Chronic granulomatous disease (CGD)
  • Both sex-linked and autosomal recessive inheritance with the ratio of affected males to females being 6:1
  • Morphologically normal, but functionally abnormal because of enzyme deficiency (NADPH Oxidase) that results in an inability to degranulate, which causes inhibited bactericidal function
  • Fatal early in life
• Tests for CGD

  Nitro blue tetrazolium

  • Normal WBC: able to reduce yellow water soluble tetrazolium to a blue insoluble formazan
  • CGD: remains yellow/colorless
• Chediak higashi granules (picture)

  Chediak higashi syndrome

  • Autosomal Recessive
  • Both morphologically andfunctionally abnormal leukocytes
  • Gene Affected: LYST Gene/ Chediak-Higashi Syndrome Chromosome 1 (CHS1 gene)
  • Pathophysiology: Neutrophil with large dark lysosomal granules; Monocyte with large azure granules; Lymphocyte with one large azure granules
  • Platelets:
  • Deficiency of dense granules
  • impaired/ abnormal platelet aggregation

  
• Clinical manifestations of Chediak higashi

  ● Hypopigmentation (Oculocutaneous albinism)

  ○ Since melanocytes are affected the formation of melanosomes are also affected

  ● Enlarged lymph nodes and mild splenomegaly:

  ● Immunodeficiency, infection, bleeding tendencies and albinism

  ● In severe cases, organ system affected are:

  ○ Liver, spleen, bone marrow

  ○ Neurologic manifestations: neuropathies, tremors, stroke

  ● PROGNOSIS

  ○ Death: First decade of their life due to septic shock or recurrent infections.

  ○ Accelerated Phase: Hepatosplenomegaly (due lymphoproliferation) and pancytopenia
• LAB TEST (Chediak higashi)

  ● Significant finding: Large granules

  ● WBC & PLT count - decreased

  TREATMENT

  ● Successful treatment: Bone marrow transplant Preventive measures: manage bleeding and infection by giving antibiotics

  ● For albinism: Avoid too much sun exposure
• Nuclear abnormalities: Pelger Huet anomaly

  • Decreased segmentation usually bilobed or unilobed
  • Function of the cell is considered normal despite morphologically abnormal
  • Characterized by coarse chromatin clumping pattern potentially affecting all leukocytes, although morphologic changes are most obvious in mature neutrophils
  • The disorder is a result of a mutation in the lamin Beta-receptor gene

  Nuclear

  • round, oval, dumbbell, peanut shape, "pince nez"
• Pelger huet anomaly/True or Congenital PHA

  • Autosomal dominant, can be homozygous or heterozygous
  • In true PHA, the number of affected cells is much higher than in pseudo-PHA

  ACQUIRED PSEUDO PELGER HUET ANOMALY

  • Found on myeloproliferative disorders such as CML, Myelodysplastic syndrome, HIV infection, TB, Mycoplasma pneumoniae infection, and other bacterial infections
  • Drugs are known to induce pseudo-PHA
• nuclear abnormalities

  A) undritz anomaly

  B) megaloblastic anemia

  C) neutrophils

  
• Cytoplasmic abnormalities: Alder-Reilly Granules

  • Transmitted as a recessive trait and is characterized by granulocytes with large, darkly staining metachromatic cytoplasmic granules composed primarily of partially digested mucopolysaccharides
  • Large purple black coarse cytoplasmic granules
  • Accumulation of degraded mucopolysaccharides
  • Can be found on all types of leukocytes
  • Associated with Mucopolysaccharidosis disorder such as Hunter’s and Hurler’s disease
  • The granules’ morphology may resemble heavy toxic granulation
  • Morphologically abnormal, but functionally normal
• Cytoplasmic abnormalities: May hegglin

  • is a rare, autosomal dominant platelet disorder characterized by thrombocytopenia, giant platelets, and large Dohle body-like inclusions in n,e,b,m
  • Large, crystalline, Dohle-like inclusions in the cytoplasm of neutrophils on Wright’s stain; gray blue and spindle-shaped
  • Morphologically abnormal but functionally normal
  • There are mutations in the MYH9 gene for production of myosin heavy chain type IIA
  • Presence of giant platelets, thrombocytopenia, and clinical bleeding are also associated with this anomaly
• monocyte/macropage function

  A) immune responsse

  B) antigenic information

  C) t-helper

  D) phagocytic

  E) igg

  F) scavenger cells

  G) antigen-antibody

  H) clotting factors

  I) old

  J) fibrin degradation

  K) cytokiness

  L) interleukins

  M) tumor necrosis

  
• MONOCYTES:

  • NUCLEUS • Round • Kidney-bean shaped • May show slight lobulation or may be folded
  • CYTOPLAS M • Abundant • Blue-gray • Ground glass appearance (slate-gray color)
  • Lifespan: 12 hrs
  • Functions
  • Phagocytosis
  • They counter attack different microorganisms by phagocytosis
  • FC of IgG & C3 complement
  • Both monocytes and the macrophage which is the tissue counter part of monoctyte carries the receptors of the FC portion of the immunoglobulin G (IgG) and C3 complement. They contain FC region of immunoglobulin and C3 complement
  • Responsible for the cellular and humoral activities in the blood