Heme/Onc Flashcards
Fanconi anemia
Pancytopenia!
- macrocytic RBC
- hypocellular bone marrow
Autosomal recessive
Aplastic anemia + bone marrow fail
Sx: Short Microcephaly Abnl thumbs Hearing loss Microphthalmia thrombocytopenia --> neutropenia --> anemia
Dx:
- Chromosomal breaks on genetic analysis in presence of diepoxybutane
Tx:
- transfusions
- abx
- steroids
- bone marrow transplant
Complication:
AML
1 RBC enzyme deficiency causing anemia
G6PD
Iron deficiency anemia
Microcytic hypochromic
Usually 6-24 mo old
#1 cause = inadequate intake of iron Usually on diet of milk
Iron deficiency anemia
- signs
- dx
- tx
Pale
Tachy
Koilonychia (spoon nails)
Dx
- retic count (minimal)
- CBC
- LOW serum iron and ferritin
- TIBC high
Tx
- ferrous sulfate (6 mg/kg/d)
- reticulocytosis should be seen within 72 h of start of ferrous sulfate
- get retic count 5d after starting iron
- Hg increase in 3-4 weeks
- continue iron for 4-5 months after Hb level returned to normal
- check Hct 1 mo after starting therapy
If iron therapy doesn’t work, consider Meckels
Hemolytic anemia
Premature destruction (eg spherocytosis) vs. enzymatic (G6PD)
Hereditary spherocytosis labs
Spherocytes
Increased
- retic count
- indirect bilirubin
- LDH
Decreased
- haptoglobin
Negative coombs
Osmotic fragility test +
G6PD labs
Blister cells
Reticulocytosis
Tx spherocytosis
Folate
Splenectomy for severe but only do > 5 yo
Remember to give vaccines for
- pneumo
- meningo
- Hib
Tx G6PD
Avoid triggers (sulfas, fava beans, high dose ASA, antimalarials)
Oral folic acid
Splenectomy w/ chronic disease
Sickle Cell disease
Valine –> glutamic acid @ 6th position of Beta chain
Sickling when oxygen low
NO features as newborn since HbF still there
Sx 2-4 months
Sickle cell sx
Dactylitis (swelling)
Autoinfarct of spleen –> encapsulated organism infection prone
Vasoocclusive episodes
Gallstones 2/2 increased bile production from chronic hemolysis
Prone to salmonella osteo
Aplastic crisis (2/2 parvovirus, etc)
Tx sickle cell
Maintenence:
- Immunize
- Ppx w/ PCN until 5 yo
- folic acid suppement
- hydroxyurea for pts w/ recurrent vascoocclusive events
Acute pain crises
- hydration
- analgesia
- transfusion
Fevers –> IV ceftriaxone
Aplastic crisis –> transfusion
Beta Thalassemia major
surplus of alpha globin chains
Sx after 6 months
PE:
- facial deformities 2/2 expansion of marrow
- splenomegaly
- heart failure 2/2 high urine output
- gallstones
Labs
- hypochromic microcytic anemia
- hemosiderosis
- increased unconj bilirubin
- dx w/ Hb electrophoresis
- high levels of HbF
Tx
- transfusion therapy
- chelation
- deferoxamine for hemochromatosis
Diamond Blackfan sydnrome
Congenital pure red blood cell anemia
Pale infants in first few days
Anemia 2-6 mo old
Macrocytic anemia
- but no hypersegmented neutrophils
Bone marrow - reduced red cell precursors
Elevated EPO
PE:
- short stature
- webbed neck
- cleft lip
- shielded chest
- triphalangeal thumbs
Tx
- transfusions
- steroids
Acquired Aplastic Anemia
Dec in RBC, WBC, platelet
Causes
- ionizing radiation
- chloramphenicol, sulfas, anticonvulsants
- parvovirus, mono
- idiopathic
High mortality rate!
Death 2/2 hemorrhage or infection
Idiopathic Thrombocytopenic Purpura (ITP) - etiology - features - dx - tx -
Immune mediated, can be preceded by viral infection
Signs:
- acute onset
- bruising and petechial rash
- joint bleeding rare
- NO splenomegaly
Dx
- bone marrow - normal or increased megakaryocytes; all other findings and cell lines normal
- varying degress of thrombocytopenia
Tx
- excellent even w/p Tx
- IVIG
Other causes of thrombocytopenia
Wiskott Aldrich (X linked)
Kasabach-Merritt
TAR syndrome
Kasabach Merritt
Rapidly enlarging cavernous hemangioma
+
Consumption coagulopathy –>
Thrombocytopenia
Usually cutaneous lesion
Low plt
Anemia
Tx:
- surgery to remove
- laser therapy
- high dose steroids
- interferon
- aminocaproic acid for coagulopahty
Thrombocytopenia + absent radius
TAR syndrome
Hemophilia A
- definition
- presentation
- PE
- dx
- tx
X linked recessive
Deficiency factor 8
Bleeding seen in neonatal period
Hemarthrosis can happen
Dx:
- family hx
- prolonged bleed after circumcision
- increased PTT
- decreased factor 8 activity, normal vWF
- plt normal
- PT normal
Tx
- tx bleeds w/ factor 8
- DDAVP to increase factor 8 levels in mild cases
Hemophilia B
- definition
- presentation
- PE
- dx
- tx
X linked recessive
Deficiency factor 9
Less common than A
Vit K dependent factor - not distinguishable clinically from A
Dx:
- low factor 9
Tx:
- replace factor 9
von Willebrand disease
- definition
- presentation
- PE
- dx
- tx
1 inherited bleeding tendency
Autosomal dominant
p/w nosebleeds, gum bleeds; spontaneous hemarthrosis rare
Dx:
- increased bleeding time
- mildly increased PTT
- normal platelets, PT
Tx
- FFP
- Cryoprecipitate
- DDAVP
Function of vWF
Adhesion platelets
Platelet to platelet aggregation
Carrier factor 8
Acute lymphocytic leukemia
- definition
- risks
- presentation
Lots of lymphoblasts in bone marrow
Peak @ 3-4 yo
Increased risk with:
- downs
- ataxia telangiectasia
- von Recklinhausen
- sideroblastic anemia
Presentation
- anorexia
- pallor
- bleeding
- bruising
- LAD
- splenomegaly
ALL
- dx
- tx
Dx:
- Blasts on periph smeark
- abnormal CBC
- maybe mediastinal mass on CXR
Tx:
- vincristine + prednisone + L asparagine
- ppx CNX radiation or intrathecal MTX
- maintenance therapy for 2-3 years
Bone marrow is most common site of relapse
Poor prognosis if < 2 yo, boy, black, CNS mets
Tumor lysis sydnrome
Hyperuricemia 2/2 chemo
Tx
- hydration
- alkalization of urine
- allopurinol
Be weary of Hyper K
Hyper PO4 can cause decrease in Ca resulting in tetany
Hodgkin disease
- risk factors
- what is it?
- presentation
Older kids
Risk factors:
- EBV???
- immunodeficiency?
Pathology:
- Reed sternberg cell
- 4 major histo types:
- lymphocyte predominant
- nodular sclerosing
- mixed cellularity
- lymphocytic depleted (worst prognosis)
Presentation
- localized adenopathy (firm, nontender enlarged cervical or supraclavicular LN)
- mediastinal mass
- night sweats
- fever, wt loss, anorexia
When do you do bone marrow bx for pts with HOdgkins?
Stage 3 or 4 disease
Pts w/ B symptoms
What are B symptoms
How often do they happen?
30% kids
Temp > 100.4
Night sweats
Wt loss more than 10% in 6 months
Tx Hodgkin’s disease
Determined by disease stage, age, presence or absence of B sx
Chemo:
- Mechlorethamine hydrochloride
- vincrisine sulfate
- procarbazine
- prednisone
OR
Doxyrubicin
Bleomycin
Vinblastine
Dacarbazine
Radiotherapy to LN
Prognosis good
Non-hodgkin lymphoma
- what is it
- risks
Neoplastic proliferation of immature lymphoid cells
vs ALL - accumulate outside of bone marrow
NHL kids younger than HL kids
Usually extranodal in presentation
Neoplasms of mature B cells
- Burkitts
- diffuse large B cell
- mantle cell
- follicular lymphoma
Neoplasms of mature T cells
- adult T cell
- mycosis fungoides/sezary syndrome
Burkitt’s lymphoma - genetics
t (8,14)
Mantle cell lymphoma - genetics
t (11,14)
translocation of cyclin D1 (11) and heavy chain Ig (14)
Follicular lymphoma - genetics
t(14,18)
translocation of heavy chain Ig (14) and bcl-2 (18)
Indolent course! difficult to cure. bcl2 —| apoptosis
What is Adult T cell lymphoma usually caused by?
HTLV-1
Tx nonhodgkins lymphoma
Surgical debulking
CHOP
- cyclophosphamide
- vincristine
- MTX
- prednisone
Brain tumors in kids
1 solid tumors in childhood
2/3 infratentorial
Cerebellar astrocytoma
1 tumor of kids and best prognosis
2 histo types of astrocytoma:
1) pilocytic (most common, benign)
2) diffuse or fibrillary
Kids 5-10 yo
MRI to see
Tx:
- resection
- chemo depending on type, age, and if tumor is recurrent
5 yr survival = 90%
Medulloblastoma
2 most common in kids
Primitive neuroectodermal tumor
Sometimes originate from roof of 4th ventricle
Aggressive, can mets extracranially
< 7 yo usually
Boys > girls
Usually in midline of cerebellum
Can cause hydrocephalus
Tx:
- surgical excision
- radiation
- chemo
Poor prognosis if < 4 yo
Brain stem fliomas
3 common posterior fossa tumor in kids
2 types:
1) anaplastic (poor prognosis)
2) low grade focal
Tx:
- limited radiotherapy
- chemo for palliative
- surgery
Poor prognosis in general
Ependymoma
Can be infra or supratentorial
4th ventricle is #1 site
Usually present as obstructive hydrocephalus
Tx:
- surgery usually doesn’t get it all
- radiotherapy
- cyclic chemo
Prognosis for 5 yr
- low grade (70%)
- high grade (20%)
Infratentorial tumors
Cerebellar astrocytoma
Medulloblastoma
Brainstem glioma
Ependymoma
Supratentorial tumors
Craniopharyngioma
Optic gliomas
Craniopharyngioma
Supratentorial
Cystic + solid areas that tend to calcify
Can present w/
- short stature
- periph vision loss
- hydrocephalus
Can see calcifications on Xray or CT
Tx:
- resect
- radiation maybe
Need to f/u closely b/c can get hypothyroidism, DI, adrenal insufficiency
Optic gliomas
Low grade astrocytomas
Cause decreased VA and pallor of the dics
More common in pts with:
- neurofibromatosis
- chiasmal tumors
Can present with asymmetric nystagmus if has chiasmatic tumor
Tx
- delayed until tumor progresses
- no tx if optic N tumor but normal vision - reeval q6 mo w/ CT
- chemo for pts w/ visual changes
- carboplatin + vincristine
Wilms Tumor
- what is it
- risk
- presentation
- ddx
Tumor of neoplastic embryonal renal cells of the metanephros
- blastema + epithelium + stroma
Histo
- spindle shaped cells
- anaplasia
- fibrillar inclusions
- w/ presence of striated muscle
Most renal tumors = Wilms tumors
Associations:
- WAGR (Wilms tumor, ANiridia, GU anomalies, MR)
- Beckwith-Wiedemann
- Denys Drash syndrome
Usually start ~3 yo
HTN in many presentations
Usually asymptomatic ab mass
- DOES NOT cross midline
Ddx - Neuroblastoma which is tumor of renal Origin
Wilms tumor
- dx
- tx
- prognosis
Dx
- UA = microscopic or gross hematuria
- US = see if intrarenal
- CT to see how much the tumor covers
- bx to stage
Tx
- surgical resection
- radiotherapy
- actinomycin D + vincristine
Prognosis - most are good
Neuroblastoma
- what is it
- risks
- presentation
1 solid malignancy in kids outside of CNS
Malignancy of neural crest cells - usually give rise to chromaffin and adrenal medulla
Usually in preschool kids, mostly < 5 yo
Boys > girls
Assoc w/ Beckwith Wiedemann syndrome
Presentation:
- ab mass
- HTN
- resp distress if in thoracic tumor
- horner syndrome
- opsoclonus myoclonus causing “dancing eyes and feet syndrome”
Mets common to bone, liver, skin
CROSSES the midline
Neuroblastoma
- dx
- tx
- complications
- prognosis
Dx
- CT scan
- VMA and HMA levels for dx and response to therapy
- bx
- should do bone marrow bx and bone scan for mets
- other markers: enolase, ferritin, LDH
Tx
- Stage I + II = surgery
- stage III + IV = chemo
- -vincristine + cyclophosphamide + doxorubicin + cis-platinum + etoposide + danorubicin
- high rate of spontaneous regression w/o therapy in stage IV-S (small tumors < 1 yo w/ mets but none to cortical bone)
Complications
- < 1 yo best prognosis
- > 2 yo worst prognosis
- N-myc amplification or 1p deletion poorer prognosis
Rhabdomyosarcoma
- what is it
- presentation
Striated muscle tumor #1 sarcoma in kids
Presentation
- # 1 = mass (nasopharynx, face, trunk, GU, etc)
- vaginal rhabdo –> vaginal grapelike mass (sarcoma botryoides)
- tumors can mets to lung or bone
Rhabdomyosarcoma
- dx
- tx
- complications
Dx
- CT or US
- bone marrow, bone scan, CXR, and chest CT before surgery
Tx
- dependent on primary tumor location
- rarely is it complete resectable
- will need combo of surgery or radiation or chemo
Primary site, extent of dz, and tx used determines best prognosis
Anemia of prematurity tx
with iron supp, hg checks, blood transfusion if needed
Iron is given not because iron deficiency but because it will be stored and reutilized during active phase if eruthropoiesis
Burr cells
- spiculated RBCs seen in uremia or as artifact of prep
Lab findings of sickle cell
Dec:
- hematocrit
Increased:
- retic
- serum LDL
- unconj bilirubin
Peripheral smear:
- sickled cells
- howell jolly bodies
Main dose limiting side effect of hydroxyurea
Myelosuppression
Wilms tumor vs neuroblastoma
Wilms tumor more common than neuroblastoma
WIlms does not cross midline
Neuroblastoma crosses midline
How do you dx paroxysmal noctunral hemoglobinuria?
sugar water test
The presence of Howell-Jolly bodies means…
splenectomy
1 cancer in kids
Acute lymphoblastic leukemia
Ages 2-5 yo
Iron deficiency in kids
Fe store usually run out by 6 mo so need to supplement then
DO NOT use cows milk –> will cause iron deficiency anemia
+ iron (oral) therapy in those with deficiency
- recheck Hg in 4 weeks
- con’t oral therapy until Hg normalizes
1 complication in sickle cell TRAIT is
painless hematuria
2/2 sickling in renal medulla
Kasabach Merritt phenomenon
Seen with large vascular anomalies
Platelet and RBC sequestration within vascular tumor causes peripheral thrombocytopenia, coagulopathy, and microangiopathic hemolytic anemia
Tx:
- steroids
- a-interferon
- vincristine
DIC lab values
Consumption of
- fibrinogen
- 2, 5, 8
Prolongation of:
- PT
- PTT
- TT
Decrease in
- factor 8
- platelet
Increase in:
- fibrin split production
