Hematology of White cell disorders - Stillwell Flashcards
bandemia
elevated number of band forms in the blood
neutropenia (aka agranulocytosis)
-decreased number of neutrophils in the blood
pancytopenia
-decreased WBCs, platelets, and RBCs
left shift**
- increase # of immature neutrophils** (including band cells (horseshoe), metamyelocytes, myelocytes, promyelocytes)
- stimulated by cytokines (TNF-alpha, IL-1)
- myeloblasts not seen –> think leukemia if present**
- see in inflammation/infection - bone marrow in overdrive
leukemoid rxn
-extreme leukocytosis, may see immature neutrophils present (but no blasts)
leukemia
-cancer of blood forming tissue (bone marrow and lymphatic system)
neutrophils aka granulocyte or PMN
- # 1 WBC on a differential (40-60% of Total leukocytes)
- 3-5 lobes common (>5 abnormal)
- band cell (bilobe nucleus) - 0-5% of WBCs (>5% during left shift inflammatory response)
lymphocyte
- 20-40% of all WBCs (2nd most common on differential)
- increased in viral infections
smudge cells**
-fragile B lymphocytes (atypical lymphocyte) –> seen in CLL (chronic lymphocytic leukemia)***
monocytes
- 4-8% of all WBCs
- larger, more cytoplasm than lymphocytes
- can differentiate into macrophages and dendritic cells
basophil and eosinophil
- basophil - darker granules (0-1% of WBCs)
2. eosinophil - eosinophilic granules; peroxidases (1-3% of WBCs)
Wright’s stain blood smear
- 1 WBC for every 500 RBCs or 40 platelets
- count # of platelets and multiply by 10k to estimate
differential count
- not included in a CBC**
- has to be specifically ordered**
- info. about the types and amount of WBCs in blood sample
- 2 types: manual and automated
manual differential
- lab tech looks at 100 WBCs on Wright stain –> gives you specifics about WBC toxic granulations, immature WBCs (left shift and band cells), RBCs, and platelets**
- howell jolly bodies (DNA fragments) if spleen isn’t working
- start with this with hematologic and septic issues**
automated differential
- machine evaluates thousands of cells, but can’t detect specifics like manual** (won’t see left shift cells)
- typical point of care diffs –> give you % of neutrophils, lymphocytes, and mid cells (mono+eos+baso+bands)
- auto diffs –> can differentiate b/w cells above
colony stimulating factors (CSFs)
- glycoproteins that help with cells viability, proliferation, differentiation, maturation, function, and regeneration
- stimulate WBC production and function –> help fight off infection
types of CSFs
- CSF-1 (macrophage-CSF or M-CSF)
- CSF-2 (granulocyte/macrophage-CSF or GM-CSF)
- CSF-3 (granulocyte-CSF or G-CSF)
- Multipotential-CSF (multiple-CSF)…..thought to be Interleukin-3 (IL-3)
CSFs - commercial preparations (recombinant, made in E. coli)***
- G-CSF (Filgrastim/tradename-Neupogen), short half-life
- G-CSF/polyethylene glycol (PEG-Filgrastim/trade name-Neulasta), longer half-life
- GM-CSF is (Sargramostim/tradename-Leukine)
-used to increase bone marrow recovery in chemo patients** (increased risk of sepsis with low WBCs)
no commercial preps for M-CSF or multiple-CSF
neutrophilia causes
- increased production - due to CML, inflammation, drugs, necrosis
- increased bone marrow production - due to corticosteroids, inflammation/infection/endotoxin
- demargination - due to EPI, corticosteroids, NSAIDs, stress
- decreased WBC removal - someone with splenectomy** (always have a higher white count)**
neutrophilia with leukemoid rxn**
- nonmalignant; high white count due to infection, necrosis, or severe bleeding
- elevated WBCs with neutrophilia and left shift (no dysplastic changes or blasts)
- diagnosis: no malignancy or blasts with left shift; leukocyte alkaline phosphatase (LAP) elevated in normal inflammatory response (LAP not found in CML or AML patients)*
- cause: C. difficile colitis and ischemic bowel/bowel infarction***
lymphocytosis causes
- count greater than 4k
1. increased production due to lymphomas or leukemias
2. increase bone marrow release due to many viral/bacterial/parasite infections, autoimmunity, thyrotoxicosis**
eosinophilia causes
- count >500
- western world –> allergic/atopic dermatitis most common cause**
- developing world –> parasite infections most common cause**
1. allergic disorders, nephritis, drug rxns (IgE mediated induced by basophils and mast cells)
2. parasitic infections (ex. trichinosis)
3. malignancies (Hodgkins lymphoma)
4. autoimmune - SLE, eosinophilic granulomatosis** with polyangitis (churg-strauss syndrome), sarcoidosis**
5. Hyper IgE syndrome (Job syndrome)
6. coccidioidomycosis, HIV
monocytosis causes
- count >950
- occur with chronic inflammation
1. increased production
2. increased bone marrow release - in a febrile person, TB always stimulates monocytosis***
basophilia causes
- count >200
- associated with neoplastic conditions and myeloproliferative neoplasms like CML
leukopenia causes
- low total WBC count
1. acute viral infections** (can also be bacterial)
2. pseudo-leukopenia** - sudden onset of severe infection –> WBCs migrate to site and bone marrow hasn’t had time to respond
neutropenia causes
- count <100 –> high risk for severe infection
1. acute viral syndromes** - ex. CMV, EBV
2. chronic viral syndromes* - ex. HIV, hepatitis B/C
3. rickettsial diseases
4. disseminated fungal and mycobacterial infections - wipe out bone marrow
5. autoimmunity - ex. SLE, RA, Felty’s syndrome** (large spleen) with pancytopenia, chron’s disease
6. folate/B12 deficiency*
7. EtOH* - toxic to bone marrow
8. hepatosplenomegaly*
9. congenital neutropenia*
10. primary bone marrow issues*
11. chemo and radiation
12. drugs* - ex. methotrexate, azathioprine, cyclophosphamide
13. toxins* - ex. arsenic**
neutropenic fever
- usually after chemo
- medical emergency**
- neutrophils <1k –> risk of severe sepsis**
- bacteria gram neg. rods bad**
- less sever by giving G-CSF prophylaxis
- evaluation: STAT urine/blood culture**
- treat: immediate broad spectrum antibiotics
- give G-CSF** (monocytes come back 1st then neutrophils)
- persistent fever for 5 days –> think fungi/virus and give anti fungal therapy**
lymphopenia causes
- count <1500
- poor nutrition
- T cell lymphopenia with AIDS/HIV, Idiopathic CD4 deficiency
- B cell lymphopenia leads to humoral deficiencies (immunosuppressed patients)
atypical lymphocytosis**
- reactive CD8 cytotoxic T lymphocytes** that are activated after antigen stimulation
- RBCs indent the cytoplasm**
- seen in EBV/CMV mono** (downey cell)**
toxic granulations
- toxic granules containing peroxidases/hydrolases of neutrophils
- seen in inflammatory conditions like sepsis
hypersegmented granulocytes**
- neutrophil will have 6 or more nuclear lobes (3-5 normal)***
- B12/folate deficiency is cause***
- sometimes Fe deficiency
Pelger-huet anomaly
- inherited (autosomal dominant) - heterozygote asymptomatic, homozygote is abnormal
- nuclei of neutrophils/eosinophils are bilobed “dumbbell”**
- acquired through AML/CML/myelodysplasia
Chediak-Higashi syndrome
- mutation of lysosome regulatory protein –> decreased phagocytic ability and WBCs lose migration ability**
- large granules** in cytoplasm containing peroxidase
- recurrent pyogenic infections and photosensitivity
Auer rods
- fused lysosomes with neutrophilic granules
- in myeloblasts with multiple auer rods –> AML**
- multiple auer rods in thick bundles(faggot cells) –> promyelocytic leukemia**
Dohl body
- light blue/grey inclusions in neutrophil cytoplasm**
- remnants of RER and ribosomes
- associated with left shifts and toxic granulations
dohl body compared to morulae**
- dohl body –> light blue/grey**
- morulae (in anaplasmosis or ehrlichiosis) –> dark purple**
hyper IgE syndrome (Job’s syndrome)
- abnormal neutrophil chemotaxis due to decreased production of interferon gamma by T cells
- recurrent staph aureus and candida infections, pulmonary problems, scoliosis**, retention of baby teeth, broad nose, hyper extensible joints
- very high IgE**
Sezary syndrome
- advanced stage cutaneous fungal infection with lymphadenopathy/leukemia
- associated with HTLV-1 virus
- sezary cells with cerebriform nuclei (convolutions)**
- flower cells**
smudge cells (aka basket cells)
- remnants of fragile B lymphocytes –> think CLL with multiple smudge cells***
- indented by RBCs
hairy cell leukemia
- B cell leukemia (subtype of CLL)
- accumulate in bone marrow plus splenomegaly –> cause bone marrow failure and pancytopenia**
- jagged edges/hairs around WBCs**
morulae in a granulocyte**
human granulocytic ehrlichiosis/anaplasmosis (HGE/HGA)**
morulae in a monocyte**
human monocyte ehrlichiosis (HME)**
N. gonorrhea**
disseminated gram neg. diplococci**
-sexually active women
