Qualitative Leukocyte Abnormalities

Lazy Leukocyte Syndrome

- rare, inherited
- presents in children
- NO response to chemotactic factors

Chemotactic factors

direct the migration of neutrophils to a localized area of inflammation

Chronic Granulomatous Disease

- defective NADPH oxidase (resp. burst)
- cells can ingest/can't kill
- harder time w/ cat + organisms

Nitro blue tetrazolium (NBT)

test for respiratory burst. In presence of CGD, granules don't turn blue (NBT negative)

What are the clinical presentations associated with CGD?

frequent infection, enlarged spleen and liver, lymphadenitis, granulomas in many organs

dihydrorhodamine 123 (DHR 123)

incubate granulocytes w/ bacteria and dye, measures oxidative burst (CGD: dec % of phagocytic activity)

Myeloperoxidase (MPO) Deficiency

- Grignaschi anomaly
- benign, autosomal recessive
- MPO mediates oxidative destruction by H2O2

Why is MPO deficiency usually benign, and what can make it severe?

- usu. benign bc there are other peroxidation pathways
- if diabetic, prone to Candida albicans infections

Chediak-Higashi Syndrome

- autosomal recessive (CHS1/LYST gene)
- 1 + 2 granules fuse
- defective leukocyte granules

What would the leukocytes in a pt with Chediak-Higashi look like/stain like?

- large, course, irregular lysosome granules
- stain positive for MPO and acid phosphatase

Chediak-Higashi is commonly presents with...........

albinism, bleeding, delayed killing of bacteria (frequent infection)

Toxic Granulation

- tiny azurophilic cytoplasmic granules (metas, bands, segs)
- peroxidase positive (primary granules)
- cytoplasmic vacuoles

How would you determine if toxic granulation and vacuoles are due to condition or artifacts?

High WBC w/ left shift and compare with other smears (could be a dye issue)

Dohle Bodies

- small oval inclusions in PERIPHERAL cytoplasm
- remnants of RNA and free ribosomes
- positive w/ periodic acid-Schiff (PAS)

What are Dohle Bodies associated with?

Scarlet fever, burns, infection, aplastic anemia, toxic chemical exposure

May-Hegglin Anomaly

- rare, autosomal dominant (MYH9 gene)
- precipitation of non-muscle myosin heavy chains (adhesion)
- normal functioning neutrophils large plts

What would a pt with May-Hegglin Anomaly present with?

- things that look like Dohle bodies
- PAS negative
- 50%: thrombocytopenia, poorly granulated, bleeding tendencies

Alder-Reilly Anomaly

- azurophilic granules in ALL WBCs
- mucopolysaccharides incompletely degraded and accumulate in lysosomes

Ehrlichia

- E. chaffeensis or ewingii
- divide to form vacuole bound colonies on WBCs (morulae)

What does Ehrlichia present with?

fever, leukopenia, thrombocytopenia, elevated liver enzymes

Pelger-Huet anomaly

- autosomal dominant
- can't segment normally
- cells function normally

How could you tell if a patient is homo or heterozygous for Pelger-Huet anomaly?

- hetero: peanut shape/ glasses
- homo: no segmentation at all

Pseudo-Pelger-Huet

- weird neu >30% (inherited is > 50%)
- neutrophils may be hypogranular
- COVID-19, leukemia, drugs, infection

Hereditary Hypersegmentation

- autosomal dominant
- asymptomatic
- majority of neu have 5 or more lobes

What causes pyknotic nuclei in white cells?

dying neutrophils (apoptotic)

Gaucher's Disease

- faulty glucocerebrosidase gene (GBA)
- build up of glucocerebroside in ALL macrophages
- glycosphingolipid accumulation in cytoplasm

In Gaucher's Disease, where can you find affected macrophages?

liver, spleen, and bone marrow

What do the macrophages look like in Gaucher's? stain?

pale, wrinkled or striated, stain PAS positive

Niemann-Pick Disease

- can't cleave phosporyl-choline from sphingmyelin
- build up of spingomyelin

What doe monocytes/macrophages look like in Niemann-Pick disease? stain?

foamy appearance, PAS negative