Hematology: Non-Malignant Myeloid Disorders

What are the 6 stages of neutrophil maturation?

myeloblast

promyelocyte

neutrophilic myelocyte

neutrophilic metamyelocyte

neutrophilic band

segmented neutrophil

What are the lifespans of the following WBCs?

neutrophils

eosinophils

basophils

T-cell lymphs

B-cell lymphs

monocytes

neutrophils:

Where are WBCs found? (3 pools)

storage pool: bone marrow

marginal pool: walls of blood vessels, lungs, liver, spleen

circulating pool: peripheral blood

When do monocytes increase?

in the recovery phase of infection (clean up crew!)

What are the 3 possible mechanisms for granulocytopenia?

1) reduced granulopoiesis with myeloid hypoplasia (chemo)

2) increased ineffective granulopoiesis (quantity over quality)

3) reduced granulocyte survival (leukocyte antibody, increased splenic sequestration, leukotoxic substances)

What can cause *acute* granulocytosis? What two shifts does it cause?

can be from stress, exercise, epinephrine

*increased marrow storage shift

*increased marginal pool shift

What can cause *chronic* granulocytosis? What are the mechanisms?

recurrent or sustained physiologic stimulus (e.g. pregnancy, immunocompromised)

*increased proliferation and production from the bone marrow

*increased granulocytic survival

*decreased movement from the circulating pool

What causes eosinophilic granulocytosis? (NAACP)

Neoplasms (CML, Hodgkins, myelofibrosis, polycythemia vera)

Allergic reaction

Asthma

Connective tissue disorders

Parasites (pinworm)

What 5 conditions could cause basophilia?

1) allergic reactions

2) basophilic leukemia

3) polycythemia vera

4) chronic myelogenous leukemia (CML)

5) myelofibrosis

What lab tests can be done to evaluate granulocytosis?

bacterial, viral, Rickettsial, or parasite studies

CBC

Bone marrow (when suspecting neoplasms)

LAP

Chromosome studies

What is the LAP test? What is the range?

Determines true leukemia vs. leukmoid increase in neutrophils

hyposegmentation of neutrophils (in 90-95% of neutrophils); no hematological or physical S/S

Pelger-Huet

What do the neutrophils of Pelger-Huet look like? What is the term for this?

"Pence-Nez"

2 lobes with a filament connecting them (eyeglasses, noseplug)

an *acquired* form of Pelger-Huet induced by drugs or seen in leukemia; not true Pelger-Huet

pelgeroid

anomaly that presents with low WBC, low and deficient PLTs

May-Hegglin anomaly

What is the key inclusions of May-Hegglin anomaly?

(Dohle-oid) Dohle bodies

giant, bizzare PLTs

What are Dohle bodies made of?

ribosomal RNA

What are the S/S of May-Hegglin anomaly?

Most patients are in good health. 1/3 of cases have mild to severe hemorrhagic disease (e.g. nose bleeds)

What gene is mutated in Chediak-Higashi syndrome?

CHSI gene

the ineffective killing of bacteria due to impaired release of enzymes by enlarged granules

Chediak-Higashi syndrome

What is the prognosis of Chediak-Higashi syndrome?

death usually occurs before early teens from recurrent *pyogenic infections* (puss-y)

What is the visible sign of Chediak-Higashi syndrome?

partial ocularcutaneous albinism

What is the smear like in Chediak-Higashi syndrome?

abnormal granulation (large, dotty granules); occurs when primary and secondary granules fuse together

azuerophilic granules in NK cells

What are the WBC and PLT counts in Chediak-Higashi syndrome?

both decreased-- leukopenia and thrombocytopenia

What is the other name for Alder-Reilly anomaly?

Hurler's anomaly

caused by a metabolic disorder of mucopolysaccharides

Alder-Reilley anomaly

What are the characteristics of Alder-Reilley anomaly?

toxic gran

lysosomal storage disorder

giant granules in neutrophils, lymphs, monos

associated with gargoylism (wide head, nose points up, ears stick out, short stature)

condition where bacteria are ingested but not killed

Chronic Granulomatous Disease

What is the mechanism of Chronic Granulomatous Disease (why can't cells kill bacteria)?

cells can't produce hydrogen peroxide in conjunction with other oxygen metabolites which are necessary to kill organisms

What bacteria cause infections in Chronic Granulomatous Disease?

catalase positive organisms (staphs, some Enterobacteriaceae)

What is the common cause of death in Chronic Granulomatous Disease?

speticemia or chronic pulmonary disease in early childhood

What is the treatment for Chronic Granulomatous Disease?

gene therapy or stem cell transplant

What is the lab test for Chronic Granulomatous Disease? What is the principle?

Nitro Blue-Tetrazolium Test (NBT)

semi-quantitive assay that tests the phagocytic function of polymorphonuclear leukocytes (PMNLs)

cells SHOULD reduce a colorless NBT into a blue-black deposit within the cells, in CGD the PMNs do not produce this color