Heme Onc Flashcards
Microcytic anemia
MCV<80
- iron deficiency
- thalassemia
- anemia of chronic disease
Normocytic anemia
MCV 80-100
retics high (>2%): hemorrhagic, hemolytic anemias retics <2%: leukemias, aplastic anemia, red cell aplasia, bone marrow failure syndromes
Macrocytic anemia
MCV>100
if megaloblasts and segmented neutrophils = megaloblastic: vitamin B12 def, folate deficiency, drug-induced
Non-megaloblastic: alcohol abuse, myelodysplastic, liver disease, congenital bone marrow failure syndromes
Mentzer index
MCV/RBC
>13 = iron deficiency
< 13 = thalassemia
Labs for hemolysis
increased retics, LDH, unconjugated bili,
decreased haptoglobin
Warm AIHA
vs. cold
Warm = IgG Cold = IgM
Pure red cell aplasia
- definition
- causes
= isolated anemia with very low reticulocytes
- post-viral: parvo B19,
- transient erythroblastopenia of childhood (TEC) - recovery in 1-2 months
- congenital pure red cell aplasia = Diamond Blackfan Anemia
Normal hemoglobins on electrophoresis
Hgb A: 95-98%
Hgb A2: 2-3%
Hgb F: 0.8-2%
HPLC for hemoglobin SS
- mostly Hgb S
- no hemoglobin A
- increased HgF
- increased Hg A2
Beta thalassemia major
diagnosis
hemoglobin analysis (No A)
- all A2 and F)
Features: skeletal findings, face, hepatosplenomegaly, para-aortic masses, Asian, African, Mediterranean
Complications of sickle cell
Infants: sepsis, dactylitis, sequestration
Older kids: sepsis, pain crisis, chest crisis, stroke, priapism
Management sickle cell disease and fever
- admit
- blood culture and then antibiotics e.g. CTX
- hydration (2x maintenance)
- incentive spirometry, O2 as needed
- simple transfusion only if indicated
Acute chest syndrome in sickle cell
- definition
- management
definition: fever, resp sx, new infiltrate on CXR
Mgmt:
- IV CTX, oral macrolide, supplemental O2
- simple transfusion if hemoglobin is >10 below baseline
- urgent exchange transfusion If rapid progression of ACS , decline in Hgb despite simple transfusion, progressing respiraotyr symptoms
Sickle cell disease surveillance
- pen prophylaxis to 5 yo
- vaccination (asplenic)
- folic acid
- transcranial dopplers (monitor for stroke risk)
- echo, PFTs, sleep studies
- silent strokes and neurocognitive issues
- pulmoanry HTN
- gallstones
- sleep apnea
- iron overload
Hydroxyurea in sickle cell disease
- decrease frequency of pain episodes/acute complication
- prevents life-threatening neurologic events in those at risk of stroke
watch for myelosuppression/ neutropenia
Hereditary spherocytosis
diagnosis
EMA testing by flow cytometry (osmotic fragility)
Complications of HS (3)
- hemolytic anemia
- aplastic crisis e.g. parvo
- increased gall stones
Tx: symptomatic transfusion, folate for some pts, splenectomy for some
General indications for a splenectomy (4+)
- traumatic splenic rupture
- congenital hemolytic anemia if require ongoing transfusions
- sickle cell anemia with recurrent splenic sequestration
- severe, symptomatic chronic ITP with failure to respond to medical management (last resort)
- more rare: splenic vein thrombosis, echinocccal cyst, splenic abscess, select leukemias, lymphomas, myeloproliferative d/os (very rare)
ITP red flags (7)
- age < 12 months
- family history of “ITP”
- congenital anomalies
- consanguinity
- constitutional symptoms
- significant lympahdenopathy+/- hepatosplenomegaly
- lack of response to first line tx
When to treat ITP
- if bleeding/high risk
1st line: IVIG, steroids, Anti-D
IVIG = response in 24-48hr (steroids 48-72hr), no worry about masking leukemia
inpts vs. outpatient
NAIT
- management
- transfuse if bleeding and/or platelets < 30
- random platelets = fastest
- then HPA-1 negative/matched platelets or washed mat platelets
- IVIG = increased response to transfusion, decreased duration of thrombocytopenia
Neonatal autoimmune thrombocytopenia
management
- generally less severe
- treatment: IVIG, transfusion if bleeding
Transfusing neonates platelets
- stable pts, plts < 20
- unstable, plts <30
- infant bleeding or invasive procedure, plts < 50
Red flags in neutropenia
- infections
- growth issues/ FTT
- mouth ulcers esp if cyclic
- other congenital anomalies
- consanguinity
- family hx of neutropenia/MDS/cancer
- other cytopenia
- no neutrophil response in time of fever/infection
First level investigations for neutropenia
- liver and renal function
- electrolytes
- CRP
- DAT
- immunoglobulins
- ANA
- Hgb analysis
(rpt CBC monthly to see if persists)
Aplastic anemia definition
- pancytopenia with a hypocellular bone marrow in absence of abN infiltrate or marrow fibrosis
at least 2 of the following: hgb<100, plt<50, ANC <1.5
Fanconi anemia
- screening test
- features
- chromosome fragility test
Features: congenital abN, short stature, digits, facies, cardiac/renal etc. cancer risk
Von Willebrand disease
- genetics
- screening test
- mostly AD
- screen: VWAg, Ristocetin cofactor (VWF activity), factor VIII
platelets should be normal in VWD
VWD types and treatment
Type 1 = most common, mild quantitative defect often treat with DDAVP
Type 2= rare d/o of VWF function; DDAVP with caution (sometimes make it worse)
Type 3 = severe, AR, very little/no VWF
- needs VWF replacement
Coag cascade
- Intrinsic pathway
Intrinsic pathway affects PTT
- 12, 11, 9, 8
Coag cascade
- extrinsic pathway
- what does it affect?
Extrinsic pathway affects PT/INR
- 7
Coag cascade
- common pathway
Affects PTT and PT/INR
10, 5, 2 (prothrombin), 1 (fibrinogen)
- think DIC, vitamin K deficiency
Hemophilia
- genetics
- factors
X-linked
Hemophilia A: Vactor VIII
Hemophilia B: Factor IX
Treatment: factor replacement e.g. prophylaxis or on demand bleeds
sx: circ bleeding, delayed surgical bleeds, muscle bleeds, jt bleeds
Classic hemorrhagic disease of newborn
from 24hrs to week
- up to 2% of infants who have not received Vit K prophylaxis
Diagnosis of DIC
Coagulopathy = increased INR, PT, PTT
- hypofibrinogen
- thrombocytopenia
- elevation in D-dimers/ fibrinogen degradation products
Transfusions
- frozen plasma
- cryoprecipitate
FP: for emergency reversal of warfarin, for active bleeding or surgery and coags >1.5x normal
Cryopreciptiate (factor 8, fibrinogen, VWF)
- for bleeding in pt with fibrinogen <1
- for bleeding with VWD or hemophilia ONLY if factor or DDAVP unavailable
pulmonary embolism investigations
CT angio is preferable to V/Q scan
Red flags for malignancy in lymphadenopathy
- firm, fixed, matted, non-mobile
- non-tender
- rapidly growing
- persistent > 6 weeks
- presence of constitutional sx or pruritis
- size > 2cm
- supraclavicular
osteosarcoma vs. Ewing
Osteo: metaphyses of long bones, sclerotic destruction, sunburst pattern, mets to lungs and bones
ES: diaphyses of long bones, flat bones, lytic, periosteal reaction, onion-skinning, mets to lungs and bones
Infratentorial tumors
- triad of sx
headache, nausea + emesis, papilledema
Other sx: disorders of equilibrium, gait, coordination, torticollis, blurred vision, diplopia, nystagmus
Supratentorial tumors
- presentation
Lateralized defects e.g. focal motor weakness, focal sensory changes, language disorders, focal seizures, reflex asymmetry, language disorders,
premature hand preference
3 acute chemo side effects
- myelosuppression
- nausea/vomiting/mucositis
- alopecia
Acute and late effects:
- asparaginase
Asparaginase: acute: pancreatitis, anaphylaxis, coagulopathy, hyperglycemia;
Acute and late effects:
- cisplatin
Acute: nausea, low Mg, renal, tinnitus,
Late: SNHL
Acute and late effects
- cytarabine
acute: fever, rashes, conjunctivities, nausea
NO late
Acute and late effects
- cyclophosphamide
Acute: hemorrhagic cystitis, SIADH, nausea
Late: infertility, secondary malignancies
Acute and late effects
- doxorubicin
Acute: red secretions, acute arrhtyhmia/heart failure, mucositis
Late: decreased cardiac function/heart failure
Acute and late effects
- etoposide
Acute: hypotension, allergy/anaphylaxis
Late: 2nd malignancy
Acute and late effects
- vincristine
Acute: constipation, foot drop, sensory neuropathy, vocal cord dsfxn, ptosis, jaw pain, SIADH
Late: incomplete recovery from severe neuropathy
Acute and late effects
- radiation therapy
Acute: skin redness, irritation, burn, mucositis, N+V, myelosuppression, tiredness, alopecia
Late: 2nd malignancies, pit dysfunction, low thryoid, pulmonary fibrosis, metabolic syndrome, poor growth, infertility, learning difficulties
Bleomycin and busulfan late side effect
pulmonary fibrosis
Cancer predisosition:
- Beckwith wiedemann
- NF-1
BW: Wilms tumor, hepatoblastoma, neuroblastoma
NF1: optic glioma, GIST, JMML, MPNST, pheo,
Wilms tumor
- syndromes predisposed
- WAGR
- Denys-Drash
- Beckwith-Wiedemann
- Sotos
- NF 1
Other: Simpson-Golabi-Behmel, Perlman
Leukemia
- syndromes predisposed
- T21, NF-1, Noonan, Li-fraumeni, Bloom syndrome
- Bone marrow failure syndromes
- Immunodeficiencies: WAS, X-linked agammaglobulinemia
CNS tumors
- syndromes predisposed
NF1, NF2, Tuberous sclerosis, von hippel-Lindau, Gorlin and turcot syndromes
G6PD blood smear
- RBC inclusions
- Heinz bodies
- bite taken from RBCs
- polychromasia representing reticulocytosis
Hemophilia lab findings
- PT is normal
- PTT is abnormal 2-3x ULN if severe
Iron deficiency anemia
treatment
3-6 mg/kg/day elemental iron
- limiting milk intake
Response to iron therapy
- 12-24hrs
- 48-72hrs
- 4-30 days
- 1-3 months
12-24hrs: clinical sx improve
48-72hrs: reticulocytosis peaking at 5-7 days
4-30 days: increase in hemoglobin level
1-3 months: repletion of stores
Indications for IRRADIATED RBCs
- reduces risk of post-transfusion GVHD use it in: - intrauterine or exchange transfusion, - SCID and DiGeorge requiring heart surgery - HSCT controversial: - prem infants - T-cell antibody therapy - organ allografts - immunosuppressive drugs -HIV
Fanconi anemia
- defining features
- diagnosis
- thumb, radius abnormalities, CALMs, squamous cell cancer, short stature
- chromosomal breakage test and gene sequencing
Schwackman diamond
- defining features
- diagnosis
- pancreatic insufficiency, short stature, abnormal thorax
- gene testing, evidence of pancreatic insufficiency, imaging showing fatty infilatration of pancreas
Dyskeratosis congenita
- defining features
- diagnosis
- nail findings, mucosal findings, hyperpigmented skin, squamous cell cancer
- quantitative analysis of telomere length (flow FISH), gene sequencing
Diamond Blackfan Anemia
Elevated adenosine deaminase levels! (differentiates it from TEC)
- > 90% in first year of life
- anemia - normochromic and macrocystic and reticulocytopenia
- absent RBC precursors
- Autosomal dominant
- other anomalies: craniofacial, upper limb and hand abnomrlaities (thumb), GU, cardiac, ophtho, MSK, short stature is common
High risk factors in ALL
- Age < 1 or > 10 years
- WBC > 50,000
- Present CNS disease
- DNA index <1.16
- cytogenetics (t4:11), t(9;22)
- slow response to therapy
Auer rods
AML
Reed-Sternberg cells
Hodgkin Lymphoma
Lymph node biopsy to be considered if
- persistent or unexplained fever
- weight loss
- night sweats
- supraclavicular location
- mediastinal mass
- hard nodes
- fixation to surrounding tissue
- increase in size over baseline in 2 weeks, no decrease in size in 4-6 weeks and no regression to normal in 8-12 weeks or if new signs and sx develop
Treatment neonatal alloimmune thrombocytopenia
- transfusion of compatible platelets (maternal washed, HPA1a- negative)
- IVIG
if known pre-natal maternal IVIG
Treatment neonatal autoimmune thrombocytopenia
- platelets if emergency
- IVIG to infant (sometimes steroids to infant after delivery)
If known, prenatal maternal steroids
Neuroblastoma tumor markers
urine homovanillic acid and vanillylmandelic acid
(catecholamine metabolites)
- elevated in 95%
Neuroblastoma
N-Myc amplifcation
N-Myc amplification is bad
Neuroblastoma stage 4s features
infants < 12 months with localized disease (aka can have skin, liver and small amount of BM involvement)
- spontaneously regresses in most cases
- chemo if unfavourable histology or sx from mass effect
Opsoclonus myoclonus (ataxia) syndrome
- rapid, dancing eyes
- myoclonus and ataxia (dancing feet)
DDX: acute cerebellar ataxia, neuroblastoma, para-infectious
Tumour lysis syndrome lab findings
- hyperkalemia
- hyperphosphatemia
- secondary hypocalcemia
- hyperuricemia
- AKI
Risk factors for TLS
- first 72 hrs after chemo/rads
- larger tumor burden, masses and higher WBC (blast counts)
- tumor type (Burkitt, TALL, AML, other NHL)
- pts with renal or cardiac dysfunction
Prevention of TLS
- IV hydration e.g. 2x maintenance
- use of hypouricemic agents e.g. allopurinol and rasburicase (not for G6PD)
- manage and monitor electrolyte disturbances
Presentation of pheochromocytoma
- paroxysmal hypertension (attacks eventually give way to continuous HTN), HA palpitations, AP, dizziness, V, sweating
- hypermetabolic so become cachectic
Preop management pheochromocytoma
- alpha blockage
- beta blockage
- fluid loading
Reversal agent for:
- warfarin
- heparin
- Warfarin: vitamin K plus either prothrombin complex concentrate or FFP
- Heparin: protamine
Treatment for polycythermia/ hyperviscosity
- partial exchange transfusion with normal saline
- consider if Hct > 70-75% or lower if signs of hyperviscosity are present
Transient myeloproliferative disorder
- high leukocyte counts, blast cells, associated anemia, thrombocytopenia, hepatosplenomegaly
- usually resolve within first 3 months of life
- require follow up because 20-30% will develop typical leukemia by 3 yrs
Sickle cell infectious organisms
- strep pneumonia
- haemophilus influenzae
- neisseria meningitidis
- salmonella
Hydroxyurea benefits
- decrease painful episodes, dactylitis
- decrease rate of acute chest syndrome
- decrease blood transfusions
- some evidence for prevention of recurrent priapism
Management sickle cell acute focal neuro deficit
- O2 to keep sats >96%
- blood transfusion within 1hr of presentation
- consider exchange transfusion (associated with decreased risk of second stroke vs. simple transfusion)
- neuroimaging
Prevention of stroke in Sickle Cell
- chronic blood transfusion therapy to keep maximum HbS concentration <30%
Sickle cell acute chest syndrome features
New density on CXR PLUS 2+ of:
- fever
- resp distress
- cough
- chest pain
Management acute chest syndrome in sickle
- 3rd gen cephalosporin and macrolide
- +/- asthma management
- oxygen
- pain control
- blood transfusion = only method to abort ACS; given if 1 of: decreasing O2 sat, increasing work of breathing, rapid change in resp effort, drop in Hgb 2g/dL below baseline, hx of ACS requiring ICU admission
Splenic sequestration
features and tx
- most often 6mo-2 yrs,
- rapid spleen enlargement and a decline in Hgb by 2g/dL from baseline
Tx: blood transfusion (generally 5mL/kg because spleen may release blood)
prevention = splenectomy
Hereditary spherocytosis
genetics/ epi
Autosomal dominant (mostly) Northern European
Hereditary spherocytosis
Diagnosis
- flow cytometry EMA binding test
- can be diagnosed with positive family history, and clinical/lab features e.g. splenomegaly, spherocytes, reticulocytosis, elevated mean corpuscular hemoglobin concentration
Hereditary spherocytosis indications for splenectomy
- Pts with severe HS (e.g. Hgb <60-80, reticulocytes>10%, regular transfusions)
- pts with moderate HS with frequent hypoplastic or aplastic crises, poor growth, cardiomegaly
Beta-thal major
- presentation
- treatment
- homozygous Beta gene defect
- progressive hemolytic anemia with profound weakness and cardiac decompensation
- Tx with transfusions for anemia but also growth failure, bone deformities, hepatosplenomegaly
Beta-thal major on Hb analysis
- increased HbF and HbA2,
TEC features
- children between 6 mo and 3 yrs (most >12mo)
- reticulocytopenia and mod-severe normocytic anemia (+/- mild neutropenia)
- NORMAL RBC adenosine deaminase levels
recover within 1-2 months
Monitoring anticoagulants
- LMWH
- warfarin
- UFH
- rTPA
- LMWH: anti-Xa level
- warfarin: INR
- UFH: PTT
- rTPA: fibrinogen/D-dimer
Absolute contraindications to tPA (thrombolytic therapy)
- major surgery within 7 days
- hx of significant bleeding - intracranial, pulmonary, GI
- peripartum asphyxia with brain damage
- uncontrolled HTN
- severe thrombocytopenia
if serious bleeding occurs, stop thrombolysis, start cryoprecipitate to replace fibrinogen
What is in cryoprecipitate?
- fibrinogen
- factor VIII
- Factor XIII
- von willebrand factor
