Heme-Onc Flashcards
What is leukodepletion used for for transfusions?
- Removes any additional neutrophils that happened to get into pRBC product
- Reduces risk of febrile transfusion reaction
What is irradiation used for in transfusions?
- Small lymphocytes are not removed with leukodepletion but irradiation damages the DNA of donor lymphocytes which makes unable to undergo replication
- Important for immunocompromised recipients
- Eliminates risk of GVHD
Hereditary spherocytosis genetics
- Autosomal dominant is most common (defect in gene encoding cell membrane protein ankyrin)
- Common in European ancestry
- Causes fragile red blood cell membranes and shortened life span
Hereditary spherocytosis complications
- Parvovirus B19 infection: aplastic crisis leading to bone marrow suppression (low retics on CBC)
- Gallstones
Barth syndrome
- Congenital neutropenia
- Cardiomyopathy
- Proximal skeletal myopathy
Cartilage-hair hypoplasia
- Congenital neutropenia
- Impaired immunity
- Short limbed dwarfism
- Fine hair
Chediak-Higashi syndrome
- Congenital neutropenia
- Albinism
Dyskeratosis congenita
- Congenital neutropenia
- Abnormal skin pigmentation
- Nail dystrophy
- Leukoplakia of oral mucosa
Schwachman Diamond syndrome
AUTOSOMAL RECESSIVE
- Congenital neutropenia
- Skeletal abnormalities (rib cage)
- FTT due to exocrine pancreatic dysfunction
- Recurrent bacterial infections
Langerhans cell histocytosis signs/symptoms
- Osteolytic painful bony lesions
- Pituitary lesions leading to DI
- Skin lesions in diaper and scalp that don’t respond to normal therapies
- Kid with rash and draining ears
- Coin shaped lesions in scalp
Langerhans cell histiocytosis workup
- Skeletal survey
- MRI brain to evaluate pituitary
- Bone marrow if any cytopenias
Von Willebrand disease labs
- Abnormal PTT that corrects in a mixing study suggest abnormal intrinsic cascade (von Willebrand factor)
- Need to check von willebrand factor and platelet function tests
Neonatal alloimmune thrombocytopenia cause
- Maternal alloantibody to an antigen on the father’s platelets and the newborn’s platelets
- Most commonly on chromosome 17
- Transient, requires no treatment
Osteosarcoma symptoms/epidemiology
- Most common in teenagers going through growth spurt
- Present with weeks of unilateral limb pain, waking up at night with pain, limping
- Mets to lungs (10-20% have mets at diagnosis)
- Distal femur and proximal tibia (THE KNEE!) are most common, next is the shoulder
Osteosarcoma lab/imaging and treatment
- Elevated LDH, ESR, and alkaline phosphatase
- Xray shows sunbursting (calcified blood vessels)
- Tx is surgery, chemo, radiation
Ewings sarcoma xray findings
- Onionskinning (layers of periosteal reaction)
- Often has soft tissue component
Osteoid osteoma symptoms and xray findings
- Tibia/femur pain, worse at night, relieved by ibuprofen
- Central radiolucent area surrounded by thick sclerotic bone
Conditions that increase risk for leukemia
- Down syndrome
- SCID
- Ataxia telangiectasia
- Fanconi anemia
- Bloom syndrome
- Klinefelter syndrome
- Noonan syndrome
- Neurofibromatosis
Symptoms of ALL
- Pallor, fatigue, bruising, lymphadenopathy, BONE PAIN, fevers
- PANCYTOPENIA
- Most common in ages 2-5
- More common in Caucasians and males
- MCC death is infection/sepsis
Most common sites for relapse in ALL
- CNS and testes
- Early relapse has a worse prognosis
Best test to get in a kid with unexplained lymphadenopathy
Chest xray to look for mediastinal mass –> lymphoma
Symptoms of Hodgkin’s lymphoma
- Teenager with non-tender enlarged cervical/SUPRACLAVICULAR lymph nodes
- Weight loss, fevers, night sweats
- HAVE to get a chest xray
Reed sternberg cells on lymph node biopsy
Hodgkin’s lymphoma
Symptoms of non-hodgkin lymphoma
- Younger child (not teen), rapid presentation and often have airway compression
- Can also be foudn in the abdomen (non-tender mass)
Most common solid tumor of infancy
Neuroblastoma
- Most common in kids less than 5
- Highest rate of spontaneous regression of any malignancy
- 95% survival if it occurs before 12 months of age –> most important prognostic factor
Presentation of neuroblastoma
- Persistent bone/joint pain
- Non-tender abdominal mass (2/3 of the time in the adrenal glands)
- Weight loss, night sweats, fevers
- UTI from obstructing abdominal mass
- Raccoon eyes and proptosis (due to mets)
- Horner syndrome (mediastinal tumor compressing the recurrent laryngeal nerve)
- Irritability, hypertension, diarrhea (catecholamine production)
- Opsoclonus-myoclonus paraneoplastic syndrome
Diagnostic tests for neuroblastoma
- Biopsy of tumor
- Elevated urine VMA and HMA along with neuroblasts in bone marrow
- MIBG scan
Cause of raccoon eyes
- Basal skull fractures (child abuse)
- But can also be associated with neuroblastoma
Symptoms of retinoblastoma
- Absence of red reflex or strabismus
- Present under age 5
Genetics of retinoblastoma
- If unilateral and unifocal –> sporadic
- If bilateral –> Autosomal dominant with incomplete penetrence
- RB1 gene on chromosome 13
- If parent has it in 2 eyes there’s 50% chance of child getting it, if in only 1 eye then only 5% chance
Diagnosis/treatment of retinoblastoma
- Diagnose with ultrasound or MRI (try to avoid CT)
- Tx with surgical excision, chemo, and radiation
Trilateral retinoblastoma
- Pineal gland tumors
- Bilateral retinoblastomas
- At risk for osteosarcoma, other sarcomas, malignant melanomas
Rhabdomyosarcoma symptoms
- MC soft tissue sarcoma
- Constipation, rectal exam with a visible/palpated mass
- Grape like mass protruding from the vagina
- Head/neck rhabdo in young kids, truncal/extremity rhabdo in teens
Risk factors for tumor lysis syndrome
- Initiation of chemo for large tumors, lymphomas, leukemias
- Can be triggered by systemic steroids
Labs in tumor lysis syndrome
Elevated:
- Phosphate
- Uric acid
- Potassium
- LDH
- Creatinine (leading to low UOP)
Tx with hydration, alkalinization, allopurinol
Epidemiology of childhood cancers
- Leukemia (ALL more common than AML)
- CNS tumors
- Neuroblastoma
- Lymphoma
- Wilm’s Tumor
- Hodgkins
- Rhabdomyosarcoma
- Retinoblastoma
Symptoms of spinal cord compression
- Bowel/bladder dysfunction
- Neurologic symptoms
- Tx with steroids and radiation
Complications of anterior mediastinal mass
- Respiratory distress when supine
- DO NOT INTUBATE! –> airway compression is below the cords so can’t oxygenate/ventilate if you give them anesthesia
Causes of anterior mediastinal mass
Thymoma
Teratoma
Thyroid carcinoma
Terrible lymphoma
Red face (plethora), facial swelling, cyanosis, distended neck veins in cancer patient
Superior vena cava syndrome due to compression of SVC by an anterior mediastinal mass (most commonly lymphoma)
B-cell ALL prognostic factors
- High risk:
< 1 year of age or > 10 years of age
WBC > 50K at presentation
B-cell ALL prognostic factors
- High risk:
< 1 year of age or > 10 years of age
WBC > 50K at presentation
Treatment of leukemia
- 95% achieve remission in induction phase
- Consolidation
- Interim maintenance
- Delayed intensification
- Maintenance
Auer rod in cells
- AML
- More common in congenital leukemias
- Only 50% survival
Aklylating agents (cytoxan) chemotoxicity
Gonadal dysfunction, infertility issues
Cyclophosphamide chemotoxicity
Hemorrhagic cystitis
Cisplatin chemotoxicity
Hearing loss and peripheral neuropathy
Bleomycin chemotoxicicty
Pulmonary fibrosis
Anthracyclines (doxorubicin, daunomycin) chemototxicity
Cardiac toxicity
Vincristine/vinblastine chemotoxicity
Neurotoxicity and SIADH
Methotrexate chemotoxicity
Oral/GI ulcers, bone loss
Chemo for hodgkins lymphoma
Cytoxan, doxorubicin, bleomycin, vincristine, etoposide, prednisone
Relationship between staging and prognosis of neuroblastoma
- Infant with stage III, favorable histology, unamplified N-MYC (3 year survival > 80%)
- Infant with stage III, unfavorable histology, amplified N-MYC (3 year survival < 30%)
Time for physiologic anemia of the newborn
Around 2-3 months of life (8-10 weeks) - Hgb 9 can be normal at this age
- Cause is low erythropoietin level
- Preemies can have this drop closer to 1-2 months
Three main causes of microcytic anemia
- Thalassemias
- Too little iron
- Too much lead
Normal hemoglobin chains
- Hgb F: 2 alpha and 2 gamma
- Hgb A: 2 alpha and 2 beta
- Hgb A2: 2 alpha and 2 delta
Alpha Always. Gamma Goes. Becomes Beta.
Causes of hemolytic anemia with G6PD deficiency
Fava beans, aspirin, nitrofurantoin, chloramphenicol, antimalarial drugs, vitamin K analogs
Bone with bone on xray disease correlation
Sickle cell disease
Two defective alpha alleles causes what
- Alpha thalassemia minor/trait
- Symptomatic or have a mild hypochromic anemia
- Dx via hemoglobin electrophoresis with a thalassemia panel (EP alone will be normal)
- Newborn screen may show hemoglobin Bart
Three defective alpha alleles causes what
- Alpha thalassemia intermedia –> hemolysis and hepatomegaly
- Hemoglobin Bart on newborn screen
- Tx with transfusions or splenectomy
Four defective alpha alleles causes what
- Hydrops fetalis
- Intrauterine infusions can help survival but patients will need life long transfusions until bone marrow transplant
Defect in one of the beta globin genes
- Beta thalassemia minor/trait
- Asymptomatic
- Hemoglobin electrophoresis has elevated A2
Defect in both beta globin gene alleles
- Beta thalassemia major
- Small for age Greek child with progressive microcytic hypochromic anemia, fatigue, enlarged liver/spleen
- Skull xray with hair on end (due to extramedullary hematopoiesis
- Newborn screen will have F only pattern
- Tx with chronic transfusions or transplantation
- Long term complications are cholelithiasis and hemochromatosis
Sickle cell anemia on hemoglobin electrophoresis
Hemoglobin F and hemoglobin S
Beta thalassemia on hemoglobin electrophoresis
Low/no hemoglobin A1, elevated hemoglobin A2, hemoglobin F
Causes of increased RDW in microcytic anemia
Iron deficiency and lead toxicity
Causes of normal RDW in microcytic anemia
Thalassemia
Complication of low iron
Even without anemia it can cause mild delays in cognitive development
Treatment for iron deficiency anemia
Ferrous sulfate until 2 months after hemoglobin normalizes (to replenish iron stores)
Gold standard test for lead poisoning
WHOLE BLOOD lead level (not fingerstick)
- Would see ringed sideroblast (immature red blood cell with iron bloated mitochondria surrounding the nucleus)
Causes of vitamin B12 deficiency
- Crohn’s disease, following bowel resection
- Vegetarian diets
- Intrinsic factor deficiency (pernicious anemia)
- Bacterial overgrowth
Causes of folate deficiency
- Goat’s milk
- Make sure to treat with B12 and folate when correcting anemia (can lead to irreversible neurologic damage if you forget the B12)
Signs of hemolysis in the urine
Hemosiderin
Bilirubin
Hemolytic anemia with normal reticulocyte count
Parvovirus infection –> aplastic anemia
Autoimmune hemolysis diagnostic test
Positive Coombs test
Heinz bodies, helmet cells, blister cells
G6PD
- Small, purple granules in the red cell that form as a result of damage to teh hemoglobin molecule
African American or Mediterranean boy (X-linked) with fatigue, back pain, jaundice, anemia, dark urine
G6PD deficiency
- No HSM
- If abdominal pain consider cholelithiasis
Diagnosis for G6PD
- Can’t test right after or during an episode because reticulocytes have a large amount of G6PD and can lead to a false negative
Hereditary spherocytosis diagnostic clues
- Mild/moderate anemia
- Reticulocytosis
- Nonimmune hemolysis so DAT will be negative
- Osmotic fragility testing is classic
Hereditary spherocytosis treatment
- Splenectomy is curative (need to vaccinate against H. flue, S. pneumo, N. meningitidis), do after age 5
- Monitoring if not severe, some may require transfusion
- Need folic acid supplementation
Sickle cell molecular cause
- Amino acid substition at AA 6 of beta globin chain – > valine is substituted for glutamic acid
CBC findings in sickle cell
Normocytic anemia with high reticulocyte count
- Can also have high indirect bili
Sickle cell trait complications
- 8% of African Americans have sickle cell trait on newborn scree
- Need hemoglobin electrophoresis after 3 months of age
- Dehydration with extreme exercise
- Microscopic/gross hematuria
- Increased risk of kidney disease ane renal medullary carcinoma
- Rhabdomyolysis
- Splenic infarction
Sickle cell complications
- Vasoocclussive: acute pain secondary to ischemia and infarction (dactylitis in infants) - rehydration and aggressive pain control
- Sequestration crisis: signs of shock due to pooling of blood in liver/spleen in response to infection, need transfusion
- Aplastic crisis: due to parvovirus infection, need blood transfusions
- Hyperhemolytic crisis: infection as cause
- Priapism
Sickle cell infection prophylaxis
- Give penicillin VK from 2 months of age through age 5
- Pneumococcal vaccine series (functional asplenia)
Howell Jolly bodies
Sickle cell anemia once asplenic
Management of acute chest syndrome
- Chest pain, infiltrate on xray, hypoxia
- Get an ABG
- Tx with transfusion or exchange transfusion
Complication of chloramphenicol
Aplastic crisis
Physical characteristics associated with fanconi anemia
- Presents usually after age 3
- Macrocytic anemia with elevated fetal hemoglobin
- Abnormal skin pigmentation
- Short stature/microcephaly
- Renal abnormalities
- Abnormal thumbs/foreamrs
- Developmental delays
- Eye/ear anomalies
Treatment of fanconi anemia
- RBC/platelet transfusions
- Only cure is bone marrow transplant
Cause of Diamond Blackfan Anemia vs. Transient Erythroblasopenia of Childhood
- DBA caused by arrest in maturaiton of red cells
- TEC caused by suppression of erythroid production
- Both have low hemoglobin and reticulocyte count to start (DBA often presents at birth, TEC in toddlers)
Thumb abnormalities, urogenital defects, craniofacial problems, severe anemia
Diamond Blackfan Anemia (presents at 2-3 months of age usually)
Treatment of TEC vs DBA
- Can use steroids in DBA and need transfusions
- Self resolving for TEC
Cause of febrile nonhemolytic reactions
- Fever and chills
- Reduce risk by leukocyte filtered blood
Cause of hemolytic reactions
Happen if blood is not properly cross matched
Definition of neutropenia
< 1000 in first year of life
< 1500 after that
Common infections with neutropenia
Recurrent mucosal ulcerations (mouth/perirectal), gingivitis, cellulitis, abscess formation, pneumonia, septicemia
- S. aureus, S. epi, gram negatives, enterococci
Classes of drugs that cause neutropenia
Antibiotics and anticonvulsants
Isoimmune neonatal neutropenia
Maternal antibodies against infant’s neutrophils cross placenta
- Mild neutropenia in healthy infant, resolves without treatment
Neutropenia for about a week that occurs once a month with oral ulcers, fever, enlarged lymph nodes, in a kid younger than 10 years old
Cyclic neutropenia - AUTOSOMAL DOMINANT
- Less likely to have invasive infections
- Need serial CBCs for 6 weeks
- Tx with daily GCSF
- Most deaths are from clostridia or gram negative organisms if untreated
Chronic benign neutropenia
- Often incidental finding in a 1-5 year old
- Usually don’t have any symptoms but if they have oral ulcers or infections can use GCSF
- Outgrowth this by age 5
Severe congenital neutropenia
Kostmann syndrome
- Autosomal recessive
- Arrest in development of neutrophils
- SEVERE Infections, need GCSF or bone marrow transplant
Pancytopenia, pancreatic exocrine insufficiency (diarrhea), short stature, recurrent infections, skeletal abnormalities
Schwachman Diamond Syndrome
- Monitor for leukemic transformation
- Treat infections, give pancreatic supplements
Common meds to cause thrombocytopenia
Sulfas, seizure meds, vancomyccin
- ASA and ibuprofen affect platelet function but not the platelet count
Causes of neonatal thrombocytopenia
Sepsis, allo/autoantibodies from mom, MOST COMMON is clumping from improper collection
Neonatal alloimmune thrombocytopenia
- Isolated, transient, severe thrombocytopenia in the first 48 hours of life due to maternal antibodies
- If autoimmune then both mom and baby have low platelets
Complications from ITP and treatment
- Intracranial hemorrhage (headaches or neurological changes)
- Chronic/recurrent ITP (more likely in kids > 10) –> may need splenectomy
- IVIG for treatment if severely low or significantly bleeding
Kasabach Merritt Syndrome
Hemangioma that traps the platelets (localized consumptive coagulopathy) so have thrombocytopenia, bone marrow is normal
- Tx is to control hemangioma
TAR Syndrome
- Thrombocytopenia
- Absent Radius
- Can also ahve renal agenesis
- WBC is usually elevated
- 50% are symptomatic in the first week of life, 90% have symptoms by 4 months of age
Vitamin K dependent factors
2, 7, 9, 10 (extrinsic pathway)
- Deficiency in these creates an elevated PT
Risk factors for early onset vitamin K deficiency
Exclusive breastfeeding and being born at home (no vitamin K shot)
- Tx is vitamin K and FFP if active bleeding
Workup for child with persistent bleeding after a heelstick or circumcision
Workup for hemophilia - congenital factor deficiency
Prolonged PT
VItamin K deficiency (2, 7, 9, 10)
Prolonged PTT
Hemophilia (factors 8 and 9)
Hemophilia A factor deficiency
8 –> X linked recessive (so mostly in boys)
Hemophilia B factor deficiency
9 –> X linked recessive (so mostly in boys)
Bleeding problems with hemophilia
- Bleeding from circumcision/venipuncture
- Deep joint bleeds
- Intracranial bleed
Treatment for hemophilia
Factor replacement
Use of von Willebrand factor
- Leads to normal factor VIII function and platelet aggregation
Symptoms of Von Willebrand’s disease
- Excessive bleeding after dental procedure or tonsillectomy
- Epistaxis
- Girl with menorrhagia
Labs for von Willebrand’s disease
- NORMAL PT
- PTT can be slightly prolonged but is often normal
- VWF activity will be low
Treatment of von Willebrand’s disease
- Often no treatment
- If minor bleeding can do DDAVP (stimulates endogenous release of stored vWF and factor VIII)
- replacement of factor VIII concentrate for major surgery or life threatening bleeds
DIC labs
- Platelets low
- Low fibrinogen
- Elevated D-dimers
- PT/PTT unpredictable
- Thrombin time will be prolonged
Iron deficiency peripheral smear
Microcytosis, hypochromic
Iron deficiency anemia iron studies
- Low iron, MCV, ferritin, RBCs
- High TIBC, RDW
Mentzer index
Used to distinguish thalassemia from iron deficiency anemia
= MCV / RBC
- If > 12 then iron deficiency
- If < 12 then beta thalassemia
