Heme/Onc Flashcards
Sudden onset of fatigue, pallor, scleral icterus, and tachycardia with severe anemia and reticulocytosis in previously healthy patient would be
Autoimmune Hemolytic Anemia - EMERGENCY
- normocytic anemia
- reticulocytosis
Tx:
- DAT to confirm
- Steroids
- Tranfuse
Neonatal Thrombocytopenia:
Mom with ITP vs. Neonatal alloimmune thrombocytopenia.
Maternal ITP -> Neonatal thrombocytopenia
- bc maternal antibodies cross placenta and attack neonate’s
- Tx: IVIG
Neonatal alloimmune thrombocytopenia
- no maternal hx, maybe previous child with thrombocytopenia
- maternal antibody production to an antigen expressed on fetal platelets, which is not expressed on maternal platelets.
- Tx: If severe, it is treated with a transfusion of maternal platelets, because these do not express the offending antigen.
Signs of a posterior fossa brain tumor
Early morning vomiting
Headache
Gait imbalance
New head tilt or torticollis can also be seen!
Platelet function disorders
Glasmann Thrombasthenia (d/o platelet aggregation) Bernard Soulier (d/o platelet adhesion)
Normal platelet number but not function.
When is lymphadenopathy worrisome?
Persistent lymphadenopathy more than 1 cm in diameter, despite appropriate antimicrobial therapy for bacterial adenitis, should warrant an evaluation by a pediatric oncologist.
The presence of “B” symptoms (fever, weight loss > 5% body weight, night sweats) in the context of adenopathy should trigger a referral to a pediatric oncologist.
Evaluation by an oncologist should occur before a biopsy of enlarged lymph nodes.
Cancer associated with greatest risk of Breast cancer
Hodgkin’s Lymphoma
- chest irradiation to fields that include breast tissue
Risk of breast cancer is high and mortality is substantial.
Annual screening with mammogram, breast MRI, or both is recommended after age 25 or 8 years after completing treatment.
Diamond-Blackfan Anemia
Due to defect in maturation of RBCS
Babies - 2-6 months
Macrocytic anemia, low reticulocytes
Abnormal facies - light-colored hair, a small “snubbed” nose, hypertelorism, and a thick upper lip
Short, webbed neck
Limb abnl - thumbs (bifid, triphalangeal, subluxed, or hypoplastic), a flat, hypoplastic thenar eminence, and weak or absent radial pulses
cardiac, ophthalmologic, and urogenital anomalies
Tx:
- RBC transfusions, steroids, chronic transfusions, stem cell transplant
Iron deficient RBCS look like
small red blood cells
marked central pallor
small ring of hemoglobin on peripheral blood smear
Note: basophilic stippling is nonspecific - usually with Pb tox, thalassemia, or sideroblastic anemia
Fanconi Anemia
APLASTIC anemia - so you get hypocellular bone marrow with fatty infiltration
- hyperpigmentation of skin, cafe au lait
- growth retardation
- absent/hypoplastic thumb or radii
- RENAL abnormalities
- at risk for malignancy
Hemolytic anemia after a URI
Autoimmune Hemolytic Anemia - Direct Coombs test
Cyclic neutropenia would present with
Regular intervals of neutropenia (~21 +/- 3 days)
ANC < 1500 with BM hypoplastic with myelocyte arrest
You would get:
aphthous ulcers, stomatitis, pharyngitis, LAD
and then more serious infections like cellulitis, PNA, etc
At risk for sepsis caused by Clostridium
Cranial Radiation risk
For Children < 3 years old, cranial radiation will have profound neurocognitive effects and they will likely be incapable of independent living
Bleeding after circumcision is most likely due to? And what test would you order?
Hemophilia.
A = 8 B = 9 C = 11
A/B are X-linked. C is much less common and AR.
Sx: postcircumcision bleeding, epistaxis, soft-tissue bleeding, muscle hematoma, hemarthrosis, posttraumatic/surgical bleeding, or intracranial bleeding
Dx: Prolonged PTT and low factor levels.
Tx: Factor replacement, education
NOT vwD. That usually presents with mucosal bleeding from gums or nose
How to distinguish HbS/beta-thal vs. HbSS on labs?
HbSS
- not microcytic
- would not have increased A2 only F and S
- if on hydroxyurea, would increase F and cause macrocytosis
HbS/Beta-thal
- would have decreased or no A: no production of HbA (i.e. HbS/β0-thalassemia) or a reduced amount of HbA (i.e., HbS/β+-thalassemia).
- increased F, A2, S
- microcytic anemia
Most common presenting complications of sickle cell trait
Renal papillary necrosis with gross hematuria or hyposthenuria (inability to concentrate the urine)
Note: HbF is there until about 6months. Then electrophoresis pattern becomes A,S.
“Basophilic Stippling” is associated with?
Basophilic Stippling = blue granules (ribosomal precipitates ) of various sizes dispersed throughout the cytoplasm of the red blood cell
Associated with Lead Poisoning.
Which is associated with INCREASED Zinc protoporphyrin and Erythrocyte Protoporphyrin bc it disrupts pathway that incorporates iron into heme
Chronic benign neutropenia
Caused by autoantibodies to granulocytes
Usually 8-11 months, until 2 years
Benign condition
Persistently low as opposed to cyclic neutropenia
Factor 5 Leiden
Point mutation of Factor 5 = prevent cleavage of Factor 5 by activated protein C. ==> Thombosis!
G6PD Deficiency
- X-linked, Mediterranean origin
- reduced glutathione so rbcs cannot detoxify free oxygen radicals generated by drugs (dapsone, primaquine), foods (fava), or illness.
- hemoglobin precipitates into heinz bodies and rbc membrane is damaged leading to hemolysis and rbc destruction
Neuroblastoma - cutaneous findings
Neuroblastoma
- most common malig in infancy; usually dx’ed around 22 mo
- can arise at any site of the sympathetic nervous system but most common adrenal medulla or retroperitoneal sympathetic ganglion
- Bony mets are common and lead to significant pain and irritability
- SKIN: subcutaneous bluish nodules and periorbital ecchymoses associated with proptosis “raccoon eyes”
due to periorbital metastasis
- sometimes secrete VIP which causes diarrhea
- tumor makers: HVA and VMA are high
- CT shows calcifications (Unlike Wilms)
Langerhans cell histiocytosis
Langerhans Cell: antigen presenting cell of the skin
- Micro: Tennis racket–shaped Birbeck granules throughout the cytoplasm of the Langerhans cell
- BONE Lesions - osteolytic lesions, esp in SKULL, femur, humerus, vertebrae.
- EAR - Chronic ear drainage or chronic Mastoiditis
- Cutaneous - persistent SCALP or DIAPER seborrheic dermatitis
- EXCESSIVE URINE/DECREASED URINE OSMOLARITY - due to pituitary dysfunction and diabetes insipidus
Paroxysmal Nocturnal Hemoglobinuria
destruction of red blood cells by the complement system,
- hemolytic anemia
- pancytopenia
- arterial and venous thromboses
Gene: acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol leading to the absence of protective proteins on the membrane).
PIG-A gene on the X chromosome is messed up - enzyme that makes GPI
Liver tumor with high AFP
Hepatoblastoma
Osteosarcoma
Codman’s triangle
Sunburst pattern
Functional Platelet Disorders
Glanzmann thrombasthenia
- abnormality in the gene encoding the αIIb-β3 integrin fibrinogen receptor.
- platelets cant bind fibrinogen and aggregate
- mucocutaneous bleeding
- normal plt count*
Dx:
- poor aggregation to ADP, epinephrine, and collagen.
- do aggregate to ristocetin
Bernard-Soulier syndrome
- deficiency of glycoprotein Ib in the platelet membrane
- thrombocytopenia* giant platelets
Dx: opposite
- do aggregate in response to ADP, epinephrine, or collagen.
- do not aggregate in response to ristocetin
Osteoid Osteoma
- small radiolucent center with a sclerotic margin.
- PAINFUL as they secrete high levels of prostaglandin, and the pain is typically relieved by treatment with aspirin or other nonsteroidal antiinflammatory agents.
Surgical removal is generally recommended; minimally painful lesions may be followed and treated symptomatically because some lesions resolve with skeletal maturity.
B symptoms of Lymphoma
Weight Loss > 10%, Night Sweats, Fever
NOT bone pain or rash
Prolonged bleeding during 1st menstruation is usually due to
VWF disease. NOT hemophilia as it is in a girl and severe bleeding would have presented earlier age.
How does 6MP cause neutropenia?
Pts who have an underlying deficiency in thiopurine methyletransferase (TPMT)
TTP
FAT RN + elevated LDH/hyperbili
F is for fever, A is for anemia, and T is for thrombocytopenia. The R in RN is for renal dysfunction, while the N is for neurologic abnormalities.
thrombotic microangiopathic hemolytic anemia typically caused by antibodies against ADAMTS13, a protease that breaks down ultralarge von Willebrand Factor (vWF) multimers.
Characteristic lab findings include an elevated LDH, hyperbilirubinemia, and azotemia.
The condition is life-threatening because of the risk of thrombosis in small central nervous system or cardiac arteries. The treatment of TTP includes emergent plasmapheresis and corticosteroids.
HLH
Hemophagocytic Lymphohistiocytosis: 5 of the following
- fever
- splenomegaly
- cytopenias (at least 2 of the 3)
- hypofibrinogen
- hyperTAG, elevated ferritin, elevated IL2
- Low NK activity
- tissue showing HEMOPHAGOCYTOSIS (phagocytosis of rbcs or wbcs) wihtout evidence of malignancy
Can be inherited or secondary (due to infection)
=> immune dysregulation and life threatening illness
Ewing Sarcoma
- small, round, blue cell tumor of neural crest origin
- more common in caucasians
- may have fever, weight loss/systemic symptoms
- pain, swelling, and ONION skin appearance of lesion
- more commonly in DIAPHYSIS
Hodgkin’s Lymphoma
- can present as asymptomatic lymphadenopathy, usually cervical or supraclavicular
- 1/2 have “B” symptoms
Dx: lymph node biopsy/excision
Juvenile Xanthogranuloma
- benign, self limited form of non-langerhans cell histiocytosis -> spontaneous resolution is expected
- SKIN: solitary, erythematous, dome-shaped, nonumbilicated papules or plaques (often with mild surface scaling), older lesions take on a more intense yellowish-orange color
- HISTO: dense dermal infiltrates of histiocytes; giant cells with a central wreath of nuclei and peripheral rim of eosinophilic cytoplasm (“Touton giant cells”) are pathognomonic for the disorder.
MONITOR FOR CANCER
- increased risk fo juvenile myelomonocytic leukemia
- especially in those with café-au-lait macules or a family history of neurofibromatosis 1.
Retinoblastoma Genetic Inheritance
Requires inactivation of both copies of RB1.
And can be
Heritable = Autosomal dominant with 90% penetrance
- usually BOTH eyes affected
- if mom has it = one wildtype, one mutated then risk of child having it is 0.5 (allele) x 0.9 (penetrance) = 0.45% and reasonable to assume that father doesn’t carry germline mutation bc almost 80% of heritable cases arise from de novo mutations
Non-heritable
- usually unilateral
(If parent had it in only 1 eye = then risk of child affected is 1/20 or 5%)
Normal MCV calculation
MCV = 72 + age in years or 70-90
TEC vs. DBA
Both are anemias with LOW RETIC
TEC:
- Toddler
- transient
- NORMOCYTIC
DBA
- Dysmorphic facies
- Babies
- Anemia that is MACROCYTIC
- thumb abnormalities.
Neutropenia, Anemia, Pancreatic insufficiency, FTT, recurrent infections = what disease and what other features
Schwamann Diamond
Skeletal Abnormalities.
vWF vs. Hemophilia
vWD
- needed for plt aggregation and F8 fxn
- dental procedure or tonsillectomy
- epistaxis
- girl with menorrhagia
- abnormal PTT but can be normal too (with normal PT)
- vWF activity is low
Hemophila
- BOYS
- prolonged PTT
- deep joint bleeds, intracranial bleeding, bleeding after circ
ITP treatment
Treatment if
- active bleeding
- plt count < 10 even without bleeding (bc risk of spontaneous intracranial bleed is higher when plt < 10)
Tx: IVIG (or steroids or anti-Rh immune globulin)
NOT PLATELET TRANSFUSION - because transfused platelets will present antigens that continue to drive the autoimmune process.** THIS IS CONTRAINDICATED
ITP + headache = intracranial bleed!
Most pt with ITP will have resolution by 6 months.
Primary Ciliary Dyskinesia
Chronic sinusitis
Bronchiectasis
Heterotaxy
Male infertility
BUT MOST LIKELY to support diagnosis is homozygous mutation of DNAH11 mutation!
How to treat Priaprism in SCD
Aspiration of blood from the corpus cavernosum followed by irrigation with saline or adrenergic agonists alleviates the condition.
PREP Review
2017: 2. 3, 4, 10
Splenic Sequestration
Anemia, thrombocytopenia, palpable spleen
Tx: pRBC
Neuroblastoma in the chest
Posterior Thoracic Mass
Beckwith-Wiedemann screening
AFP q3mo until age 4 for hepatoblastoma
abd US q3mo until age 7-8 for nephroblastoma
