Question | Answer |
Hematopoiesis location;
First 2-4 weeks of gestation | Yolk Sac |
Hematopoiesis location;
5-8 weeks of gestation | Liver |
Hematopoiesis location;
5 months of gestation and beyond | Bone Marrow |
RBC lifespan in adult and newborn | 120 days;
45-60 days |
Microcytic Hypochromic anemia;
low MCV, low Fe, High TIBC, low Transferrin, low ferritin | Iron deficiency |
Anemia - normocytic to microcytic;
low FE, Low TIBC, Low to normal Tranferrin, normal to high ferritin;
Low EPO | Anemia of Chronic disease |
Anemia;
Low MCV, High RDW;
Chinese Toys;
Mexican Candy;
Neuropathy, dementia, abdominal pain, nausea, anorexia | Lead Toxicity |
Anemia;
All Hgb F at birth;
Transfusion dependant; | B thalassemia major
(Cooleys anemia) |
Impaired heme synthesis;
Ringed Sideroblast;
Pappenheimer bodies;
15-20% develop leukemia | Sideroblastic Anemia |
Goats Milk;
Watery diarrhea, flatulence, failure to thrive | Folate Deficiency |
Megaloblastic anemia;
Strict Vegan or Lack of intrinsic factor;
Neurologic: decreased proprioception, paresthesia, spastic ataxia, dementia | B12 deficiency |
Hypersegmented neutrophils | B12 deficiency |
Defect in Ankyrin, spectrin, band 3 or protein 4.2;
MCHC increased | Spherocytosis |
Decreased glutathione;
Fava beans, sulfonamides, anti-malarials, moth balls;
X-linked Autosomal Recessive; | Glucose-6-Phosphate Dehydrogenase Deficiency |
Reduced glycolysis;
Very High Hemolysis;
RBC enzyme deficiency;
Autosomal recessive | Pyruvate Kinase Deficiencies |
Acquired stem cell defect;
PIG-A defect;
CD 59: HRF - homologous restrictive factor;
CD 55: DAF - decay acceleration factor;
Symptoms: hematuria, thrombocytopenia, venous thrombosis, aplastic anemia at night | Paroxysmal Nocturnal Hemoglobinuria |
Treatment for PNH | Glucocorticoids;
Monoclonal anti-C5;
Stem-cell Transplant |
Chromosome 11 - point mutation resulting in substitution of adenine for thymine resulting in valine instead of glutamic acid | Sickle Cell Mechanism |
Upregulation of surface adhesion molecules results in adherence to endothelium | Pathophysiology of Sickle Cell diease |
Organism that causes aplastic crisis in sickle cell disease | Parvovirus B19 |
Therapy of choice for acute CVA from sickle cell crisis | exchange transfusion |
Mutation in ELA2 gene;
Cycles at 14 to 28 days;
repeated fever, aphthous ulcers, adenopathy, skin infections, pneumonia;
Nadir of peripheral neutrophils is <200 | Cyclic Neutropenia |
Inheritance pattern of cyclic neutropenia | Autosomal Dominant |
<10% neutrophils - chronically;
Risk of MDS/AML <20%;
Maturation arrest at promyelocyte stage;
Autosomal recessive | Severe Congenital Neutropenia
(Kostmann's Syndrome) |
SBDS gene;
Neutropenia, exocrine pancreatic failure, short stature, metaphyseal dysostoses;
Recurrent skin and sinopulmonary infections;
SCT is curative;
Autosomal Recessive | Shwachman-Diamond Syndrome |
Short limb dysostsis;
Defect in cell-mediated immunity associated with severe VZV infections;
Autosomal recessive inheritance, primarily amish | Cartilage Hair Hypoplasia |
Self limited isoimmuizations with foreign paternal neutrophil antigens;
Wears off in 6-12 weeks | Neonatal Isoimmune Neutropenia |
Diagnosis of exclusion;
asymptomatic neutropenia | Benign Neutropenia of Childhood |
Delayed umbilical Cord seperation 4-6 weeks;
Defect CD18 locus on Chromosome 21;
Elevated WBC >20K;
Autosomal Recessive | Leukocyte Adherence Deficiency |
Defective superoxide burst;
2/3 X linked;
1/3 autosomal recessive;
Recurrent skin, osteomyelitisi, perirectal, pneumonia from catalase producers | Chronic Granulomatous Disease |
Genetic defects: p22-phox, p47-phox, p67-phox, gp-91phox
NBT test | Chronic Granulomatous Disease |
Oculocutaneuous albinism, neutropenia, prolonged bleeding time, NK cell dysfunction, frequent infections;
Large graunules in neutrophils and eosinophils;
Autosomal Recessive | Chediak-Higashi Syndrome |
Elevated IgE >1,000;
Recurrent infections;
Eczema and allergies with boils | Hyperimmunoglobulin E syndrome
(Job Syndrome) |
MAHA, neurologic manifestations, renal dysfunction, thrombocytopenia, fever | TTP
Thrombotic Thrombocytopenia Purpura |
Acquired autoantibody in TTP | ADAMSTS13 |
Treatment for ITP | IVIG, Anti-D, Corticosteroids
Splenectomy |
Maternal IgG crosses the placenta and attaches to fetal platlets
PLA1 | Neonatal Alloimmune Thrombocytopenia |
Megakaryocytic bone marrow- thrombocytopenia;
Absent radii with normal thumbs;
Milk protein allergy;
Autosomal recessive | Thrombocytopenia absent radii syndrome (TAR) |
Small platelets;
Eczema and immunodeficiency;
SCT curative;
X-linked defect in WAS protein | Wiskott-Aldrich Syndrome |
Minor autosomal dominant defect on Chromosome 22;
Thrombocytopenia with uniformly large platelets;
Neutrophils have large blue Dohle-like bodies | May-Hegglin Anomaly |
Deficiency of glycoprotein Ib;
Giant platelets;
Abnormal platelet agglutination;
Autosomal Recessive | Bernard-Soulier Syndrome |
Abnormally formed GPIIb/IIIa;
mucocutaneous bleeding;
Autosomal recessive | Glanzmann's Thrombocytopenia |
Treatment for Glanzmanns thrombocytopenia | Platelet transfusion even if normal platelet count |
Decreased granules in platelets;
Oculocutaneous albinism;
Puerto Rican;
Autosomal recessive | Hermansky-Pudlak Syndrome |
Immune response to stem cells - idiopathic in majority; drugs, toxins, radiation, CMV, EBV, hepatitis, HIV, parvovirus
Anemia | Aplastic Anemia |
Treatments for Aplastic Anemia | Matched sibling SCT 80% cure
cyclosporin A + anti-thymocyte globulin |
defective DNA repair;
Short stature, abnormal thumbs and radii, microcephaly, cafe-au-lait spots, renal abnormalitiies | Fanconi Anemia |
Mutation sites in Fanconi Anemia | FANCA and FANCC |
Mortality from fanconi anemia | head and neck cancers, squamous cell carcinoma, and hepatic malignany
Risk of AML is 15% |
Hgb 6-8; Age 1-3 yo; insidious onset; normal MCV and Adenosine deaminase; self-limited | Transient Erythroblastopenia of Childhood (TEC) |
Anemia and reticulocytopenia;
Decreased RBC precursors;
<1 yo but may be diagnosed later in life;
Thumb abnormalities - bifid thumb, short stature, webbed neck, congenital heart disease, mental retardation | Diamond-Blackfan anemia |
Immune dysregulation;
Punched out lesion on plain radiography;
Usually >5 yo;
Treat with curettage, intralesional steroids, or focal radiation | Langerhans cell histiocytosis |
Bone disease plus skin, DI, exopthalmos, floating teeth, gingiva, chronic otitis externa | Mutifocal Histiocytosis |
Fever, HSM, lung, marrow, skin, and FTT; infantile presentation | Systemic Histiocytosis |
Fever, HSM, CNS symptoms, cytopenias, coagulopathy, hyperlipidemia, hyperferritinemia >1000K;
Acquired due to infection;
Familial due to perforin gene mutation | Hemophagocytic Lymphohistiocytosis
(HLH) |
Prolonged PTT, family history, normal PT, excluded vWD
X-linked recessive | Factor VIII deficiency |
Treatment of factor VIII def | Recombinant factor VIII;
DDAVP;
then consider FFP and cryo (discouraged) |
Inheritance pattern of factor IX def | X-linked;
Same therapy except using factor IX replacement |
Most common bleeding disorder;
Autosomal dominant;
Prolonged epistaxis, menorrhagia, mucosal bleeding, bruising, or post-surgical bleeding; prolonged PTT | von Willebrand disease |
Hageman Factor;
autosomal recessive;
Normal PT;
Markedly prolonged PTT;
No clinical bleeding | Factor XII deficiency |
Clot then start bleedin 12 - 24 hours later; Euglobulin lysis test - expose clot to 1M urea | Factor XIII deficiency |
Prolonged PT, PTT;
Thrombocytopenia;
MAHA;
Low fibrinogen;
D-Dimer increased;
Schistocytes | DIC
Disseminated intravascular coagulation |
Decreased production in factors II, VII, IX, X, protein C and S
Prolonged PT more than PTT | Vitamin K Deficiency |
Most common childhood cancer | Acute lymphoblastic leukemia |
Syndromes associated with ALL | Trisomy 21, ataxia telangiectasia, chromosomal breakage syndromes - Bloom and Fanconi |
In ALL:
intial WBC <50K;
age >1 but less than 10;
t(12,21), trisomy 4, 10, 17, t(4,11);
pre-B;
rapid early responder;
minimal residual disease (MRD) | Good prognosis in ALL |
In ALL:
Initial WBC > 50K;
Age <1 or >10;
T-cell or mature b-cell;
t(9,22);
Slow response or persistent MRD | Poor prognosis in ALL |
Induction therapy in ALL | vincristine, l-asparaginase, corticosteroids,(standard) +/- anthracyclines (high-risk) |
Maintenance therapy in ALL | Methotrexate, 6-mercaptopurine, corticosteroids, vincristine
IT MTX, cytarabine, steroids depending on protocol;
CNS irradiation only for high risk |
Associated syndromes with AML | Trisomy 21, fanconi, bloom, kostmann, NF-1, PNH, Etoposide( VP-16) exposure, ionizing radiation |
FAB classification:
M3 | Acute promyelocytic leukemia;
t(15,17);
DIC;
ATRA - all trans-retinoic acid;
90% survival |
FAB classification:
M2 | Acute myeloblastic leukemia with granulocyte maturation; t(8,21) |
FAB classification:
M7 | Acute megakayoblastic leukemia
Trisomy 21 |
FAB classification:
M 5 | Acute monocytic leukemia;
del 11q2, t(9,11), t(11,19);
CNS disease, gingival hyperplasia |
Induction therapy for AML | corticosteroids, cytarabine, anthracycline |
Triphasic: chronic, accelerated, blast crisis;
t(9,22) BCR/ABL gene fusion;
Massive leukocytosis with rare blasts | Chronic Myelogenous Leukemia |
Therapy for CML | tyrosine kinase inhibitor |
Splenomegaly, lymphadenopathy, cutaneous lesions, hemorrhagic symptoms; NF-1, ras gene mutation; monosomy 7 maybe present in 30% | Juvenile Myelomonocytic leukemia
(JMML) |
Therapy for Hodkins | Vincristine, bleomycin, cyclophosphamide, etoposide + XRT |
Associated with Non-hodgkin lymphoma | Ataxia-telangiectasia, HIV, imminodeficiencies |
mature b-cell tumor, often EBV related, often MALT-associated, fastest growing malignancy - doubling time of 18 hours; highest rate of tumor lysis | Burkitt's lymphoma
t(8,14) |
Most common non-CNS solid tumor in children; neural crest cells; elevated HVA/VMA; raccoon eyes; opsoclonus/myoclonus | Neuroblastoma |
Loss of function of tumor suppressor genes WT-1 and WT-2 from chromosome 11- | Wilms Tumor |
Associated with wilm's tumor | WAGR: aniridia, GU abnormalities, MR;
Beckwith-Wiedemann: organomegaly, omphalocele, hemihypertrophy; Denys-Drash: pseudohermaphroditism, nephropathy; Perlman syndrome: macrocephaly, macrosomia, organomegaly, abnormal facies |
Most common soft tissue tumor; associated with Li-fraumeni (p53) syndrome | Rhabdomyosarcoma |
Therapy for Rhabdomyosarcoma | vincristine, actinomycin-D, cyclophosphamide |
Associated with Osteosarcoma | Hereditary retinoblastoma; Li-Fraumeni syndrome, Rothmund-Thompson syndrome: short stature, telangiectasia, small hands/feet, hypoplastic thumbs; paget's disease, ionizing radiation, alkylating agents |
Bone or soft tissue tumor derived from neural crest cells; lytic onion skinning, diaphysis more commonly affected | Ewing's sarcoma |
Benign tumors of bone | Osteoblastoma;
Osteochondroma;
chondroblastoma;
Osteoid osteoma;
Enchondroma |
Most common posterior fossa tumor; low grade; presenationwith ataxia, headache, comiting | Cerebellar astrocytoma |
Vision changes, increased ICP, delayed puberty, neurobehavioral changes | Craniopharygioma |
Leukocoria, strabismus, eye pain, headache, heterochromia, spontaneous hyphema, acute closed-angle glaucoma | Retinoblastoma |
Endoderm, mesoderm, ectoderm | teratoma |
Most common malignant germ cell tumor; gonadal, sacrococcygeal, or midline, B-hcg absent; alpha-FP reliable | Endodermal sinus tumor (yolk sac tumor) |
Compnent of mixed germ cell tumor; B-HCG but no alpha-FP; aggressive | Choriocarcinoma |
Most common liver malignancy in children; elevated alpha fetal protein | Hepatoblastoma |