WBC, plt Flashcards
Chronic ITP definition, epi, RF
plt <100 12+mo from dx
1/3 of ITP
RF: autoimm, teenager, F, DAT+, plt>20 at presentation
PETIT trial ITP (outcome, a/e)
eltrombopag for chronic ITP
phase 2
62% vs 32% had plt >50 at 6w
A/E: diarrhea, ALT/AST elevation
eltrombopag response rate and time to effect
60-80% response rate
most by 2w
only effective while drug is being admitted
eltrombopag dosing
50 mg daily, titrate to plt>50 max 75mg
East Asian and 1-5yo start at 50% dosing
WAS clinical features
eczema/atopy
FTT
immunodeficiency
microthrombocytopenia
malignancy risk
WAS HSCT indications
<5yo with MSD
neutrophil giant inclusions
Chediak Higashi
Chediak Higashi features and etiol
oculocutaneous albanism
giant lysosomal granules
neutropenia
plt storage pool deficiency
SCN DDx
Cyclic neutropenia
primary immune disorders
drug
nutritional (folate, B12, copper)
infectious suppression
SCN BM finding
promyelocyte maturational arrest
SCN and Kostmann mutations
ELANE (AD)
HAX1 (AR)
SCN tx
GCSF
2nd line: HSCT
SCN malignancy risk
MDS/AML
cumulative incidence 22% - 2%/y
Bernard Soulier pathophys, plt agg
GpIb-IX-V = CD42
plt-VWF adhesion defect
macrothrombocytopenia
agg: absent response to ristocetin only
Glanzmann’s Thrombasthenia pathophys, plt agg
GpIIb-IIIa = CD41
plt-VWF/fibrinogen aggregation defect
normal plt
agg: absent response to all except ristocetin
ITP tx
observation
CS
IVIG
acute: TXA, ENT, Niastase, plt transfusion
PlaNet2 study
<34w transfusion treshold <50 had increased death or major bleeding compared to <25
NAIT antibodies
HPA-1
Asian: HPA-4 and -5
NAIT tx
self limited, resolution in 1-4w as maternal Ab disappear
HUS
plt >30 or if bleeding
- maternal washed > HPA-1 neg > pooled
IVIG
fxn of
- neutrophil
- CD4 T
- CD8 T
- B
- monocyte
- NK
- eosinophil
- neutrophil: degranulation, NETosis, phagocytosis
- CD4 T: helper; class switching
- CD8 T: cytotoxic
- B: Ab production
- monocyte: Ag presentation
- NK: innate immunity
- eosinophil: allergy, Ag presentation
neutrophil production
proliferation 1w (myeloblast - promyelocyte, myelocyte)
maturation 1w (metamyelocyte - band - neutrophil)
intravascular 1d
tissues 1d
neutropenia grading
mild 1-1.5
mod 0.5-1
sev <0.5
neutrophil fxn steps
rolling/adherence
Chemotaxis (lipids, GMCSF, GCSF, IL-8)
Diapedesis (crossing endothelium)
Phagocytosis (CD11b, 18)
Degranulation
Neutropenia DDx
acquired
- post infectiou
- drug
- nutritional: B12, folate, Cu
- autoimmune: chronic benign neutropenia, Evans, ALPS, SLE
- hypersplenism
Congenital
- primary immune disorders
- SDS
- Chediak Higashi,
- SCN
- Cyclic
drug induced neutropenia
atb: cephalosporin, penicillin, sulfa
anti-thyroid: carbimazole, methimazole
anticonvulsant: carbamazepine, VPA, clozapine
alloimmune neonatal neutropenia pathophys, timeline, features
maternal IgG against fetal neutrophils
present at birth, resolves week-6mo
delayed cord separation, skin infection
Primary autoimmune neutropenia pathophys, epi, mgt
acquired anti-neutrophil Ab
<3yo
sometimes associated monocytosis
usually self-limited
Cyclic neutropenia features
21d cycles
reciprocal monocytosis
fever, pharyngitis, aphthous ulcers, peridontitis
Schwachman Diamond Syndrome features and pathophys
neutropenia, macrocytic anemia
exocrine pancreas dysfxn
Skeletal anomalies
SBDS mutations, aut rec
ribosomopathy
reticular dysgenesis define and tx
T-B-NK- SCID with agranulocytosis
HSCT
WHIM define and tx
Warts
hypogamm
infection
myelokathexis: BM sequestration of mature neutrophils
CXCR4 GOF mutation
supportive, GCSF, IVIG
leukocytosis DDx
1o neutrophilia: CSF3R mutation (GCSF receptor)
infection
malignancy
Drugs: CS (demargination)
autoimm/infl: KD, JIA
preg
smoking
T21
physiologic: altitude, vigorous exercise, heat stroke, sx, trauma
Eosinophilia definition and ix
> 500 cells/uL over 1 mo period and/or tissue confirmation
Mild 500-1500
Mod 1500-5000
Sev >5000
CBCD, smear
strongyloides and toxocara serology
B12
tryptase
Ig, T/B cell subsets
BMA/B
Hypereosinophilic Syndrome definition, etiol, tx
eosinophilia + end organ damage
1o: clonal expansion
2o: polyclonal expansion, cytokine driven
CS
2nd line: HU, interferon alpha, CSA
lymphopenia DDx
SCID
viral suppression
sepsis
drugs (chemo)
trauma, hemorrhage
malig
acute infectious lymphocytosis - etiol, mgt
enterovirus, pertussis
self-resolving
Thrombocytopenia DDx
Production: infiltrative, BMFS, TAR, CAMT, Bernard-Soulier, Gray Plt, infectious, drugs, toxins, malnutrition
Destruction: ITP, NAIT, drugs, consumption, thrombosis, vascular anomaly
Sequestration
Inherited macrothrombocytopenia DDx
May-Hegglin anomaly
Bernard Soulier
Gray Plt
Paris-Trousseau
DiGeorge
X linked macrothrombocytopenia (GATA-1 mutation)
ITP tx efficacy
CS
- response 72h
- 70-80% response rate
IVIG
- response 24-48h
- 90% response rate
IVIG S/E
neutropenia
allergic reaction - aseptic meningitis
bleeding
h/a
hemolysis
ITP BMA indications
chronic
other CBC anomalies
systemic symptoms
HIT type I vs II
I: direct heparin effect on plt, 2d, mild, self-limited
I: autoAb against heparin:plt factor 4 complex; 5d; more severe
Kasabach-Merritt heme features
consumptive coagulopathy
- hypofibrinogenemia
- severe thrombocytopenia
- prolonged INR/PTT
- elevated D-dimer
TTP pentad
MAHA
thrombocytopenia
fever
renal dysfunction
neuro changes
oculocutaneous albanism heme DDx
Chediak Higashi
- immunodeficiency, HLH
- giant lysosomal granules
Hermansky Pudlack
- plt dysfxn
- plt EM absense of plt dense granules
Gray Plat syndrome pathophys and genetics
macrothrombocytopenia
absent alpha granules
NBEAL2 mutations
TAR pathophys, presentation, tx
RBM8A mutation
thrombocytopenia
bilataral absence of radii (normal thumbs)
supportive
- most transfusion independent >1y
HSCT if ongoing cytopenias (rare)
CAMT pathophys, presentation, tx
c-MPL mutation (thrombopoietin receptor)
isolated thrombocytopenia in infancy with absent BM megakaryocytes
supportive
HSCT prior to severe pancytopenia
RUSAT
radioulnar synostosis with amegakaryocytic thrombocytopenia
HOXA11, MECOM mutations
alloimmune vs autoimmune neutropenia of infancy
alloimmune; maternal Ab; sick (delayed cord separation, omphalitis, infection, fever); lasts w-mo
autoimmune: acquired Ab; well; self-limited 2-4w
Cu deficiency heme consequence
neutropenia
smear: myeloid lineage vacuolization
Plt function disorders - which have normal plt vs thrombocytopenia
Macrothrombocytopenia: Bernard Soulier and Gray Plt
Normal plt: Glanzmann and Hermansky Pudlack
alpha vs dense granules
alpha: large proteins
- VWF
- fibrinogen
- PF4
- growth factors
- Factor V
- P-selectin
dense: small molecules
- ADP/ATP
- serotonin
- Ca
Plt dense granule conditions
Hermansky Pudlack
Chediak-Higashi
Plt alpha granule conditions
grey plt syndrome
ARC syndrome
Quebec plt disorder
Paris-Trousseau
gray play syndrome plt agg
absent second wave to epinephrine
