Heme/Onc Flashcards
Acute Lymphoblastic Leukemia
Two main complications?
- -re: infection?
- -re: side effect of chemo?
Acute Lymphoblastic Leukemia
Features
–nonspecific onset: bone and joint pain in lower extremities; pallor, bruising, epistaxis, petechiae, lymphadenopathy
Labs
–anemia, thrombocytopenia
Bone Marrow Aspirate
- -lymphoblasts
- lymphoblasts are PAS, TdT positive
Complications
- infxn: pneumocystis pneumonia
- chemo sfx: tumor lysis syndrome –> hyperuricemia, hyperkalemia, hypophosphatemia
Presentation
- -painless, firm cervical or supraclavicular nodes, anterior mediastinal mass in 15-19 year old
- -night sweats, fever, weight loss
Histo
–Reed-Sternberg cell (large cell with multiple, multilobular nuclei)
Dx?
Hodgkin Lymphoma
Childhood Brain Tumors
Most common location?
–re: tentorium
Most common supratentorial tumors? (2)
Most common infratentorial tumor?
Childhood Brain Tumors
Supratentorial
- Cranipharyngioma
- -panhypopituatarism, growth failure, visual loss
- -calcification at sella turcica - Optic nerve glioma
- -unilateral visual loss, proptosis, eye deviation,
- -assoc w neurofibromatosis
Infratentorial
- -more common
- -Juvenile Pilocytic Astrocytoma
Wilms Tumor
–often an asymptomatic abdominal mass
Q: WAGR syndrome?
Rhabdomyosarcoma
–associated with neurofibromatosis
Q: Name of type that looks like grapes?
Wilms Tumor
WAGR: wilms tumor, aniridia, genitourinary anomalies, mental retardation
Rhabdomyosarcoma
–Botryoid
Presentation
- -episodic severe HTN; palpitations, diaphoresis, h/a, abdominal pain, vomiting
- -retinal papilledema, hemorrhages, exudate
Labs
–elevated catecholamines
Diagnosis
–use I-131 metaiodobenzylguanidine scan
Treament
–removal with pre-op alpha/beta blockade
Dx?
Mode of inheritance?
Association?
Pheocromocytoma
- -AD
- -associated with neurofibromatosis
*NB: also assoc w MEN-2A, MEN-2B, tuberous sclerosis, Sturge-Weber, ataxia-telangiectasia
Physiologic Anemia of Pregnancy
Why does EPO decrease at birth?
In a full-term infant, when does the physiologic nadir usually occur?
Physiologic Anemia of Infancy
(Physiologic Nadir)
Physiology
1. Intrauterine hypoxia –> increased EPO –> increased RBC production
- Birth –> increased FiO2 –> decreased EPO –> progressive drop in Hb, Hct over first 2-3m until tissue oxygen needs are greater than delivery
- -normochromic, normocytic
*Occurs earlier in preterm infants
Beta-Thalassemia
- Decreased synthesis of what chain?
- Why does it not present until 2-3m after birth?
- What is the uniting causal factor of expansion of face and skull; hepatosplenomegaly; “crewcut” on Xray; and “chipmunk facies”?
- What infection can cause aplastic crisis?
Beta-Thalassemia
1. decreased beta globin synthesis –> alpha tetramers; increased HbF at birth is temporarily protective
- after a few months of life –> anemia, hypersplenism, cardiac decompensation
- Extramedullary hematopoiesis –> expansion of face and skull; hepatosplenomegaly; “crewcut” on Xray; “chipmunk facies”
- Parvo B19 –> aplastic crisis
DDx: Congenital Anemia
- triad: macrocytic anemia, low reticulocytes, congenital anomalies (eg, short stature, craniofacial deformities, triphalangeal thumbs)
- pancytopenia; absent or hypoplastic thumbs
DDx: Congenital Anemia
1. Blackfan-Diamond Syndrome (Congenital Pure Red-Cell Anemia) --increased RBC programmed cell death --increased RBC adenosine deaminase --Triad *macrocytic anemia *low reticulocytes *congenital anomalies: short stature, craniofacial deformities, triphalangeal thumbs
- Fanconi Anemia
- -AR; chromosomal breaks
- -short stature; hyperpigmentation or cafe-au-lait spots; absent or hypoplastic thumbs; low set ears; middle ear abnormalities due to infection/hemorrhage
- -increased risk of leukemia and cancer
Sickle Cell Anemia
- First presentation? re: hands, feet
- Risk for what type of osteomyelitis?
- Altered splenic function leads to increased susceptibility to infection with encapsulated bacteria (3)
- Aplastic crisis after what infection?
- Sickled RBCs, target cells, and what other smear finding?
- What immunizations (2) and prophylactic antibiotic (1) are important?
Sickle Cell Anemia
- Hand-foot syndrome - acute distal dactylitis; symmetric painful swelling of hands and feet due to ischemic necrosis
- Salmonella osteomyelitis
- encapsulated bacteria: S. pneumococcus, H. influenzae, N. meningitidis
- Parvo B19 - aplastic crisis
- Sickled cells, target cells, Howell-Jolly bodies
- Immunization with pneumococcal, 23-valent meningococcal vaccines; daily penicillin prophylaxis age 2m-5y
G6PD Deficiency
–within 24-48 h after ingesting an oxidant (eg, acetasalicylic acid, sulfa drugs, anti-malarials, fava beans) or infection –> rapid drop in Hb, hemoglobinuria, and jaundice
- Mode of inheritance?
- Smear finding?
G6PD Deficiency
- -within 24-48h after ingesting oxidant or infection –> rapid drop in Hb, hemoglobinuria, jaundice
- -XLR
- -Heinz bodies
Iron Deficiency Anemia
- Histology? re: cell size, color
- Cow’s milk is a risk factor.
- -Do not initiate before what age? - To distinguish Fe Deficiency Anemia v thalassemia
- -re: RDW; serum Fe and ferritin
Iron Deficiency Anemia
- microcytic, hypochromic
- No cow’s milk until age 1 yr
* cow’s milk –> creates intestinal mucosa abnormalities –> occult blood loss
* no more than 24oz per day - Fe deficiency anemia
- -increased RDW
- -decreased serum Fe and ferritin
Lead Poisoning
–microcytic, hypochromic anemia
Presentation
- -behavioral changes
- -cognitive/development dysfxn
- -GI: constipation
- -CNS: h/a, lethargy (due to cerebral edema)
- -Oral: gingival lead lines
Screening at 12m, 24m
–5ug/dL is acceptable
- Chelation Therapy
- -at 45-70 ug/dL? (1)
- -at greater than 70: EDTA plus dimercaprol
Lead Poisoning
RFs: low SES; older housing
Presentation: hyperactivity; cognitive and developmental delay; constipation; gingival lead lines; cerebral edema and increased ICP
Screening: 12m, 24m
–5ug/dL is acceptable
Chelation Therapy
- 45-70: DMSA (succimer, oral)
- greater than 70: EDTA plus dimercaprol
DDx: Bone Tumors
- osteogenic sarcoma
- Ewing sarcoma
- osteoid osteoma
- Which one on Xray appears lytic with laminar periosteal elevation (onion skin)?
- Which one on Xray shows sclerotic destruction (sunburst)?
- Which one on Xray shows a small round central lucency with a sclerotic margin?
- Which one is relieved with NSAIDs?
- Which one has risk factors of retinoblastoma and radiation?
DDx: Bone Tumors
Osteogenic Sarcoma
- -sclerotic destruction (suburst)
- -RFs: retinoblastoma, radiation
- -elevated Alk Phos, LDH
Ewing Sarcoma
- -central lytic lesion
- -laminar periosteal elevation (onion skin)
- -“onion skin” appearance is followed by mottled “moth-eaten” appearance with extension into soft tissue
Osteoid Osteoma
- -small round central lucency with sclerotic margin
- -relieved with NSAIDs
- -pain worse at night, unrelated to physical activity
NB: systemic symptoms may be absent in OS, ES
Sickle Cell Anemia
MoI?
sickling –> inflexible and fragile RBC membrane –> (extra-, intra-vascular) hemolysis
Lab Findings
- LDH?
- What type of hyperbilirubinemia?
- Reticulocytes?
- Haptoglobin?
What rx can be used as prophylaxis for vaso-occlusive pain crisis?
Sickle Cell Anemia
MoI: AR
sickling –> inflexible, fragile RBC membrane –> hemolysis
Labs
- -increased LDH
- -unconjugated hyperbilirubinemia
- -reticulocytosis
- -decreased haptoglobin
*Haptoglobin - binds free Hgb from destroyed RBCs; transports Hgb to liver for heme catabolism
Vaso-occlusive pain crisis prophylaxis
- -Hydroxyurea
- stimulates production of fetal Hgb
- sfx: myelosuppression
NB: exchange transfusion can be used in acute crisis (eg, stroke)
Evaluation of Anemia
- decreased MCV (4 dx)
- -Fe deficiency
- -thalassemia
- -what other 2? - normal MCV, increased reticulocytes
- -hemorrhage
- -hemolysis - normal MCV, decreased reticulocytes
- -medication sfx
- -leukemia
- -what other 2? - increased MCV
- -B12 or folate deficiency
Evaluation of Anemia
- decreased MCV
- -Fe deficiency
- -thalassemia
- -lead poisoning
- -sideroblastic anemia - normal MCV, increased reticulocytes
- -hemorrhage
- -hemolysis - normal MCV, decreased reticulocytes
- -leukemia
- -medication sfx
- -aplastic anemia
- -infection - increased MCV
- -B12 or folate deficiency
What protein helps absorb Fe from duodenum into blood?
What protein is responsible for carrying Fe in the blood?
–how is this protein affected by inflammation?
What protein is responsible for storing Fe in cells?
–how is this protein affected by inflammation?
Ferroportin
- -helps absorb Fe from duodenum into blood
- inhibited by Hepcidin, which is increased during inflammation
Transferrin (TIBC)
- -transfers Fe in blood
- -decreased during inflammation
Ferritin
- -stores Fe in cells
- -increased during inflammation
Immune Thrombocytopenic Purpura
- sudden onset of petechiae and purpura 1-4w post-viral infection
- -decreased platelets; other cell lines normal
Pathogeneis: IgG autoAb against what platelet antigen?
Tx:
- NO transfusion!
- No tx if only cutaneous s/s; usually self-resolving
- IVIG or glucocorticoids if bleeding present
Immune Thrombocytopenic Purpura
- -IgG autoAb against GP2b3a platelet Ag
- -Ab-platelet complex destroyed in spleen
Peripheral Blood Smear Findings
- RBCs with single round blue inclusions
- -seen on Wright stain
- -presence indicates lack of splenic function
- -SCD, hereditary spherocytosis - Due to hemoglobin precipitation to form insoluble precipitants
- -visualized with dye such as Crystal Violet
- -G6PD deficiency
Peripheral Blood Smear Findings
- Howell-Jolly Bodies
- -RBCs with single round blue inclusions seen on Wright stain
- -SCD, hereditary spherocytosis - Heinz bodies
- -Hgb precipitants visualized with crystal violet dye
- -G6PD deficiency
Peripheral Blood Smear Findings
Associated pathologies?
- Basophilic stippling (2)
- Bite cell
- Target cell (2)
- Heinz bodies
* Hgb precipitants seen with crystal violet stain - Howell-Jolly bodies
* basophilic nuclear remnants - Helmet cells
Peripheral Blood Smear Findings
- Basophilic stippling
- -lead poisoning, thalassemia - Bite cell
- -G6PD deficiency - Target cell
- -thalassemia
- -asplenia - Heinz bodies
- -G6PD deficiency - Howell-Jolly bodies
- -asplenia - Helmet cells
- -DIC, HUS, TTP
Neonatal Polycythemia
Two uniting causal pathways?
Neonatal Polycythemia
- in-utero hypoxia –> increased erythropoiesis
- -maternal HTN, diabetes, smoking, IUGR - erythrocyte transfusion
- -TTTS, delayed cord clamping
*viscous blood impairs organ perfusion
S/S
- -plethoric skin
- -respiratory distress, cyanosis
- -hypoglycemia
- -irritability, jitteriness
Physiology of Coagulation
- Vitamin K is important for formation of which six proteins/factors?
- Which measure of bleeding is associated with the extrinsic pathway? Which factor is associated?
- Which measure of bleeding is associated with the intrinsic pathway? Which four factors are associated?
- Which factor is responsible for conversion of fibrinogen to fibrin? Which measure of bleeding is associated with this conversion?
Physiology of Coagulation
- Vit K –> formation of Factors II, VII, IX, X; proteins C and S
- Extrinsic pathway - PT
- -factor VII
- -prolonged by anticoagulants - Intrinsic pathway - PTT
- -factors VIII, IX, XI, XII - Factor IIa (thrombin) converts fibrinogen to fibrin
- -factor II (prothrombin)
- -thrombin time
Evaluation of Bleeding Disorders
Minor bleeds - von Willebrand Disease (vWD)
*petechiae, mucosal bleeding
Deep bleeds - clotting factor deficiency (hemophilia)
- -Which measure is increased in hemophilia?
- -Mode of inheritance for hemophilia?
- -Hemophilia A - deficiency of what factor?
- -Hemophilia B - deficiency of what factor?
Tx
- -replace specific factor (prophylaxis)
- -desmopressin/DDAVP
Evaluation of Bleeding Disorders
Hemophilia
- easy bruising; hemarthroses
- -increased PTT; all others normal
- -XLR
Hemophilia A
–factor VIII deficiency
Hemophilia B
–factor IX deficiency
- Complication: Hemophilic Arthropathy
- -recurrent hemarthroses –> Fe and hemosiderin deposition in joints –> joint synovitis, fibrosis –> chronic worsening joint pain and swelling
von Willebrand Disease
What are the two functions of vWF?
- -re: platelets
- -re: factors
Mode of inheritance for vWD?
S/S
- -mucocutaneous bleeding
- -what lab finding?
Name of diagnostic test?
Tx?
von Willebrand Diseae
vWF: two functions
- -platelet adhesion
- -carries factor VIII
vWF deficiency
- -AD
- -abnormal platelet adhesion –> mucocutaneous bleeding
- -decreased factor VIII –> increased PTT
Dx: ristocetin test
Tx: desmopressin
–induces vWF release from W-P bodies
DDx: pediatric malignant abdominal mass
- asymptomatic abdominal mass; age 2-5
- abdominal mass that cx midline; systemic s/s; 1st year of life
DDx: pediatric malignant abdominal mass
- Wilms Tumor
- -asymptomatic abdominal mass; age 2-5 - Neuroblastoma
- -abdominal mass that cx midline; 1st year of life; systemic s/s
DDx: leukemia and lymphoma
- age 2-5y; fever, URI s/s; bone and joint pain; hepatosplenomegaly; pallor; epistaxis; petechiae
* anemia, thrombocytopenia - 15-19y; fever, weight loss, night sweats, anorexia; painless, firm cervical or supraclavicular LNs; anterior mediastinal mass
* Reed-Sternberg cell (large cell with multiple nuclei) - fever, cough; progressive respiratory s/s due to anterior mediastinal mass; abdominal pain and mass
DDx: leukemia and lymphoma
- Acute Lymphoblastic Leukemia
* Dx: BM shows lymphoblasts - Hodgkin Lymphoma
* Dx: LN biopsy - Non-Hodgkin Lymphoma
* Dx: biopsy
Hemolytic Uremic Syndrome
Context and Presentation
- -recent diarrheal illness
- -bloody diarrhea
- -HTN
- -pallor, petechiae
- -oliguria
Etiologies
- -E. coli O157:H7
- -Shigella, Salmonella, Campylobacter
Two key findings on peripheral smear
–re: RBCs, platelets
Hemolytic Uremic Syndrome
Pathophysiology
- E coli verotoxin damages endothelial cells –> platelet microthrombi
- platelet microthrombi –> RBC shearing –> hemolytic anemia –> pallor
- platelet microthrombi –> thrombocytopenia –> petechiae
- platelet microthrombi –> intrarenal thrombi –> renal failure
Peripheral Smear
- -schistocytes
- -megakaryocytes (giant platelets)
Labs
- -decreased Hgb
- -elevated LDH
- -elevated indirect bilirubin
- -elevated reticulocytes
- -elevated BUN, creatinine
- -thrombocytopenia
Triad: impaired upward gaze, obstructive hydrocephalus, precocious pubery
Dx?
Pinealoma
- Parinaud Syndrome
- -impaired upward gaze
- -upper eyelid retraction
- -ptosis
- -pupillary abnormalities - Obstructive hydrocephalus
- -h/a, ataxia, vomiting, papilledema - Precocious puberty
- -due to secretion of beta-hCG
Hereditary Spherocytosis
MoI?
Pathophysiology
–defect of tethering proteins –> fragile spherocytes –> can’t pass thru spleen –> hemolytic anemia, splenomegaly
Name of two tethering proteins?
Features
–anemia, hyperbilirubinemia, biliary gallstones, susceptible to Parvo B19 aplastic crisis
Dx Tests
- -increased osmotic fragility on acidified glycerol lysis test
- -abnormal eosin-5-maleimide binding test
Hereditary Spherocytosis
MoI: AD
Pathophysiology
- -defect of tethering proteins –> fragile spherocytes –> can’t pass thru spleen –> hemolytic anemia, splenomegaly
- -tethering proteins: ankyrin, spectrin
- -loss of membrane blebs –> increased MCHC
Features
- -anemia
- -hyperbilirubinemia
- -biliary gallstones
- -susceptible to Parvo B19 aplastic crisis
Dx Tests
- -increased osmotic fragility on acidified glycerol lysis test
- -abnormal eosin-5-maleimide binding test
