5.1 -Disorders of the Blood

Summary

HEMATOLOGY AND ONCOLOGY: ANEMIA IN THE PEDIATRIC POPULATION

COMPARISON OF ANEMIAS OF INADEQUATE PRODUCTION (INEFFECTIVE ERYTHROPOIESIS)

COMPARISON OF PURE RED CELL APLASIAS & PANCYTOPENIAS

COMPARISON OF HEMOLYTIC ANEMIAS (INCREASED DESTRUCTION)

GENERAL PRINCIPLES AND EVALUATION BASICS

• In Anemia, the condition is defined as a reduction of hemoglobin concentration or RBC volume below the range for healthy persons of the same age and sex.
• Physiologic Adjustments to Anemia include increased cardiac output, augmented oxygen extraction, shunting of blood to vital organs, and increased concentration of 2,3-DPG.
• The Oxygen-Dissociation Curve in anemia demonstrates a "Shift to the Right," which reduces hemoglobin's affinity for O2 to facilitate better tissue transfer.
• A Limited Hematologic Evaluation for anemic children consists of a CBC with red cell indices, platelet count, reticulocyte count, and peripheral blood smear (PBS) examination.
• In the History of an Anemic Child, diet is a "red flag" if a 1-year-old is exclusively consuming cow's milk.
• Regarding Drug-Induced Anemia, ASA/NSAIDs may cause GI bleeding, while Chloramphenicol and TMP-SMX are known to cause marrow injury.
• In Physical Examination for Anemia, the presence of tachycardia, tachypnea, and hemic murmurs signifies severe anemia or acute blood loss.
• The MCV (Mean Corpuscular Volume) indicates average RBC size; the lower limit for children 2-10 years is calculated as 70 + age in years.
• The MCHC (Mean Corpuscular Hemoglobin Concentration) represents the amount of hemoglobin relative to the size of the cell; it is uniquely increased in Hereditary Spherocytosis.
• A Normal Peripheral Blood Smear shows RBCs with a central pallor occupying no more than 1/3 of the cell, roughly the size of a lymphocyte nucleus.
• Reticulocyte Count provides crucial information on the rate of red cell production; a low count indicates decreased production, while a high count indicates loss or destruction.
• The Reticulocyte Index (Corrected Retic) must be calculated in anemic patients using the formula: Observed Retic % x (Patient Hct / 0.45).
• The Absolute Reticulocyte Count normal range is 40,000 to 100,000; the formula is RBC (x10¹²) x (Retic # / 1000 RBC) x 1000.

INADEQUATE PRODUCTION ANEMIAS

• In Iron Deficiency Anemia (IDA), anemia in term infants solely due to dietary causes usually occurs between 9-24 months of age.
• Regarding Neonatal Iron Stores, term infants are rarely iron deficient during the first 4-6 months because iron is recycled from high fetal Hgb; stores are depleted sooner in premature infants.
• The Stages of Iron Deficiency begin with "Pre-latent" (low ferritin only), then "Latent" (low serum iron, high TIBC), and finally "IDA" (low Hb and MCV).
• Iron Deficiency Anemia labs typically show microcytic hypochromic cells, increased RDW, high TIBC, and low ferritin; iron studies are often not required if the history is classic.
• Treatment of IDA involves 3-6 mg/kg/day of elemental iron; Hgb should increase by 1 g/dL within one month of therapy.
• Once Hgb normalizes in Iron Deficiency Anemia, iron therapy must continue for an additional 2-3 months to replete tissue stores.
• Megaloblastic Anemia in children who drink goat's milk is typically caused by folate (B9) deficiency.
• In Anemia of Chronic Disease, the primary mechanism is functional iron deficiency where iron is "locked" in macrophages by cytokines, leading to low serum iron but elevated/normal ferritin.
• Physiologic Anemia of Infancy is a normal process occurring in the first week of life and persisting for 6-8 weeks in term infants, requiring only observation.

BONE MARROW FAILURE SYNDROMES (PANCYTOPENIAS)

• Severe Aplastic Anemia (SAA) Criteria: Bone marrow cellularity <25% PLUS two of the following: ANC <500, Platelets <20,000, or Absolute Retic <20 x 10⁹/L.
• The treatment of choice for Acquired Aplastic Anemia with a matched sibling donor is a Bone Marrow Transplant, which carries a >85% survival rate.
• In Fanconi Anemia, patients often present with short stature, thumb anomalies (absent/triphalangeal), and radial malformations.
• Dyskeratosis Congenita is distinguished by a classic triad of clinical findings: reticulated skin hyperpigmentation, dystrophic nails, and oral leukoplakia.
• Pearson Syndrome is a rare mitochondrial disorder characterized by macrocytic anemia, exocrine pancreatic dysfunction, and failure to thrive.

HEMOLYTIC ANEMIAS (INCREASED DESTRUCTION)

• Hereditary Spherocytosis (HS) is the most common red cell membrane defect and is usually inherited in an Autosomal Dominant (70-80%) fashion.
• The Confirmatory Test for Hereditary Spherocytosis is the Osmotic Fragility Test (OFT); the definitive treatment for severe cases is a splenectomy after age 7.
• Regarding G6PD Deficiency, it is the most common enzymatic defect among Filipinos (3.9% incidence) and follows an X-linked inheritance pattern.
• In G6PD Deficiency, hemolysis is "episodic" and triggered by oxidative stress, such as infections, fava beans, or drugs like Nitrofurantoin and Antimalarials.
• The Thalassemias are characterized by an imbalance in globin chain production (alpha or beta), leading to precipitation of excess chains that damage the RBC membrane.
• In Beta-Thalassemia Major, patients develop "chipmunk facies" due to bone marrow expansion and extramedullary hematopoiesis.
• The Most Important Complication of Thalassemia treatment is iron overload (hemosiderosis) due to chronic transfusions, necessitating iron chelation therapy.
• The Hallmark of Autoimmune Hemolytic Anemia (AIHA) is a positive Direct Coombs Test.
• In Wilson Disease, hemolytic anemia can occur due to the toxic effects of copper on the RBC membrane, often associated with Kayser-Fleischer rings.

DISTINGUISHING ENTITIES: EXAM DIFFERENTIATORS

1. IDA vs. Thalassemia Trait: Both are microcytic, but Iron Deficiency Anemia has a high RDW and low ferritin, whereas Thalassemia has a normal/low RDW, high RBC count, and normal ferritin.
2. DBA vs. TEC: Diamond-Blackfan Anemia presents at <6 months with congenital anomalies and high ADA; TEC presents at >1 year in a previously healthy child with normal ADA.
3. HS vs. AIHA: Both show spherocytes on PBS, but Hereditary Spherocytosis has a positive family history and positive OFT, whereas AIHA has a positive Direct Coombs test.
4. Aplastic Anemia vs. Leukemia: Both present with pancytopenia, but Aplastic Anemia shows a "fatty," hypocellular marrow, while Leukemia shows a "packed" marrow with blasts.
5. Fanconi Anemia vs. SAA: Fanconi Anemia is an inherited pancytopenia with physical defects (thumbs, height); Acquired Aplastic Anemia typically has a preceding trigger (drugs/virus) and no skeletal anomalies.
6. G6PD vs. HS: G6PD Deficiency causes acute, episodic hemolysis with "bite cells" and dark urine; Hereditary Spherocytosis causes chronic hemolysis with constant splenomegaly and microspherocytes.
7. IDA vs. ACD: Iron Deficiency Anemia has high TIBC and low Ferritin; Anemia of Chronic Disease has low/normal TIBC and high/normal Ferritin.
8. Megaloblastic vs. IDA: Megaloblastic Anemia is macrocytic (High MCV); IDA is microcytic (Low MCV).
9. Folate vs. B12 Deficiency: Both are megaloblastic, but Vitamin B12 deficiency is more likely to have neurological symptoms (though both were grouped as Megaloblastic in common goats' milk context).
10. Physiologic Anemia vs. Pathologic Anemia (Neonate): Physiologic Anemia occurs at 6-8 weeks and is asymptomatic; anemia in the first week of life is usually pathologic (blood loss/hemolysis).
11. Spherocytes vs. Microspherocytes: Found in both HS and AIHA; they represent RBCs that have lost surface area, making them fragile and lacking central pallor.
12. Target Cells: These are the hallmark PBS finding for Hemoglobinopathies like Thalassemia and Hgb C.
13. MCHC in HS: A High MCHC (>36) is a highly specific clue for Hereditary Spherocytosis.
14. Mentzer Index Hint (not explicitly in text but implied): In Thalassemia, the RBC count is often high despite low Hgb, whereas in IDA, the RBC count is typically low.
15. TEC Recovery: In the recovery phase of Transient Erythroblastopenia of Childhood, the MCV may temporarily increase because of the sudden influx of large reticulocytes.
16. Drug Triggers (Marrow): Chloramphenicol causes aplastic anemia (marrow failure), whereas Nitrofurantoin causes hemolysis only in G6PD deficient patients.
17. Hypersegmentation: If you see Neutrophils with >5 lobes on PBS, the diagnosis is Megaloblastic Anemia.
18. Basophilic Stippling: Though not highlighted as a "hallmark" in this specific text, it is associated with Lead Poisoning and Thalassemia.
19. Splenectomy Timing: In HS and Thalassemia, splenectomy is generally deferred until after age 6-7 to reduce the risk of post-splenectomy sepsis.
20. Goat Milk Anemia: High yield exam fact: Goat's Milk = Folate deficiency = Megaloblastic Anemia.
21. X-Linked Anemias: G6PD Deficiency is X-linked; therefore, it is significantly more common in males.

QA

HEMATOLOGY AND ONCOLOGY: ANEMIA IN THE PEDIATRIC POPULATION

PURE RED CELL APLASIAS & PANCYTOPENIAS

HEMOLYTIC ANEMIAS (INCREASED DESTRUCTION)

GENERAL PRINCIPLES AND EVALUATION BASICS

INADEQUATE PRODUCTION ANEMIAS (SUPPLEMENTAL)

BONE MARROW FAILURE SYNDROMES (SUPPLEMENTAL)

HEMOLYTIC ANEMIAS (SUPPLEMENTAL)

DISTINGUISHING ENTITIES: EXAM DIFFERENTIATORS

5.2 -Disorders of the Blood pt 2

Summary

text

HEMOSTASIS AND BLEEDING DISORDERS

THE COAGULATION CASCADE & SCREENING

• Partial Thromboplastin Time (PTT) measures the Intrinsic Pathway (Factors XII, XI, IX, VIII) and the Common Pathway (I, II, V, X).
• Prothrombin Time (PT) measures the Extrinsic Pathway (Factor VII) and the Common Pathway (I, II, V, X).
• PTT Prolongation with Bleeding usually indicates a deficiency in Factors VIII, IX, or XI.
• PTT Prolongation without Bleeding suggests a deficiency in Factor XII, Prekallikrein (PreK), or High Molecular Weight Kinogen (HMWK).
• Isolated Prolonged PT specifically suggests a Factor VII deficiency.
• The Common Pathway involves Factors X, V, II (Prothrombin), and I (Fibrinogen); Factor Xa activates prothrombin to thrombin.
• Factor XIII is required to crosslink and stabilize the Fibrin Clot; it is NOT measured by standard PT or PTT.
• Vitamin K Dependent Factors include Factors II, VII, IX, and X (Mnemonic: 1972).

DIFFERENTIAL DIAGNOSIS BY LAB SCREEN

CLINICAL EVALUATION OF BLEEDING

• Petechiae are skin bleeds < 2 mm in size, usually signifying low platelet counts.
• Purpura are skin bleeds between 2 mm and 1 cm.
• Ecchymoses (bruises) are skin bleeds > 1 cm.
• Hematomas are bleeds > 1 cm that usually involve deep subcutaneous tissue.
• Mucosal Bleeding (Epistaxis, Menorrhagia, Petechiae) is the clinical phenotype of Platelet/Primary Hemostasis disorders.
• Deep Tissue Bleeding (Hemarthrosis, Hematoma, Delayed surgical bleeding) is the clinical phenotype of Coagulation Factor/Secondary Hemostasis disorders.

HEMOPHILIA (A & B)

• Hemophilia Severity is classified by factor activity: Severe (< 1%) involves spontaneous bleeds; Moderate (1-5%) involves bleeds with mild trauma; Mild (5-40%) involves bleeds only with major trauma/surgery.
• Hemarthrosis in Hemophilia most commonly occurs in hinged joints: ankle, knees, and elbows.
• Mixing Study distinguishes factor deficiency from inhibitors; if the PTT corrects with normal plasma, it indicates a Factor Deficiency.
• Hemophilia A Treatment Dosage: 1 unit/kg of Factor VIII raises plasma levels by 2% (2 IU/dl); the half-life is 8-12 hours.
• Hemophilia B Treatment Dosage: 1 unit/kg of Factor IX raises plasma levels by 1% (1 IU/dl); the half-life is 18-24 hours.
• Management Principle: For suspected life-threatening bleeds (e.g., ICH), treat first (Even IF IN DOUBT) before performing diagnostic tests.
• Supportive Care (RICE): Rest, Ice, Compression, and Elevation are standard for acute bleeding episodes.
• Hemophilia Precautions: Patients must avoid IM injections, aspirin, and NSAIDs.

VON WILLEBRAND DISEASE (VWD)

• Von Willebrand Disease (VWD) is the most common inherited bleeding disorder (1-3% of population).
• Von Willebrand Factor (VWF) serves two roles: it glues platelets to damaged endothelium and protects Factor VIII from degradation.
• Menorrhagia (heavy menses) is one of the most important and frequent complications of VWD in women.
• Blood Type O individuals normally have lower VWF levels, which must be considered during diagnosis.
• VWD Type 1 is a partial quantitative deficiency of VWF and is the most common type; treated with Desmopressin.
• VWD Type 2 involves a qualitative/dysfunctional VWF.
• VWD Type 3 is the total absence of VWF; clinically severe and presents with low Factor VIII levels.
• VWF Assay is the definitive test for diagnosis.

IMMUNE THROMBOCYTOPENIA (ITP)

• Immune Thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children.
• ITP Pathogenesis involves autoantibodies (IgG) against platelet surface glycoproteins (GP IIb/IIIa or GP Ib/IX), leading to splenic destruction.
• Clinical Presentation of ITP is an abrupt onset of petechiae/bruising in an otherwise healthy/well child (toddler/school age).
• ITP History often includes a viral infection or immunization 1-2 weeks prior to symptoms.
• Physical Exam in ITP should be negative for splenomegaly or lymphadenopathy; presence of these "red flags" suggests leukemia or other causes.
• ITP Diagnosis is largely a diagnosis of exclusion; CBC shows isolated thrombocytopenia (< 100 x 10⁹/L) with normal to large platelets.
• Bone Marrow Examination is not required for typical ITP but is used to rule out other causes if features are atypical or if steroids fail.
• ITP Management: Most cases (80%) resolve spontaneously within 3-6 months; observation is preferred for mild bleeding.
• Acute ITP Pharmacotherapy: If treatment is needed, short-course corticosteroids, IVIG, or Anti-D are used.
• Splenectomy is reserved for severe persistent or chronic ITP cases.

OTHER HEMOSTATIC DISORDERS

• Thrombosis in Children is rare compared to adults and usually secondary to critically ill states, cancer, or estrogen use.
• Late Vitamin K Deficiency occurs after the neonatal period, often in breastfed infants or those with malabsorption/liver disease.
• DIC (Disseminated Intravascular Coagulation) is a thrombotic microangiopathy causing consumption of clotting factors and platelets.
• DIC Diagnosis shows prolonged PT, prolonged PTT, and low Platelets (all deranged).
• DIC Treatment: The priority is treating the underlying trigger (infection/malignancy) and correcting shock/acidosis.
• Tranexamic Acid is an antifibrinolytic used to manage mucosal bleeding (epistaxis, oral bleeds) in various disorders.

COMPARISON AND DIFFERENTIATION FOR EXAMS

• ITP vs. Leukemia: ITP presents in a well-appearing child with isolated low platelets; Leukemia presents with an unwell child, weight loss, bone pain, and hepatosplenomegaly.
• Hemophilia vs. VWD: Hemophilia presents with deep tissue bleeds (hemarthrosis) and is X-linked (males); VWD presents with mucosal bleeds (menorrhagia/epistaxis) and affects both sexes.
• Hemophilia A vs. Hemophilia B: Indistinguishable by symptoms; Hemophilia A is Factor VIII deficiency and common; Hemophilia B is Factor IX deficiency and less common.
• Primary vs. Secondary Hemostasis: Primary (Platelets) causes immediate bleeding/petechiae; Secondary (Factors) causes delayed/deep bleeding and large hematomas.
• PT vs. PTT: PT is the best screen for Factor VII and Warfarin monitoring; PTT is the best screen for the intrinsic pathway (8, 9, 11, 12) and Heparin monitoring.
• VWD vs. Hemophilia A Lab Check: Both can show low Factor VIII, but VWD also has low VWF levels, whereas Hemophilia A has normal VWF.
• ITP Platelet Size: In ITP, platelets are normal to large; small platelets may suggest Wiskott-Aldrich Syndrome (WAS).
• Vitamin K Deficiency vs. Liver Disease: Both prolong PT/PTT; Vitamin K deficiency usually responds to Vitamin K administration, while Liver disease may not and often includes low platelets.
• Mixing Study Correction: If PTT corrects, it's a deficiency; if it does not correct, an inhibitor (like Lupus anticoagulant or anti-factor VIII) is present.
• Factor VIII vs. Factor IX Response: 1 unit/kg of Factor VIII provides double the percentage rise (2%) compared to Factor IX (1%).
• VWD Type 1 vs. Type 3: Type 1 is mild and quantitative; Type 3 is severe with near-total VWF absence and very low Factor VIII.
• Petechiae vs. Ecchymosis: Petechiae are pin-point (< 2mm); Ecchymoses are large bruises (> 1cm).
• Hemostatsis Components: Platelet problems affect number or function; Clotting factor problems involve deficiency or inhibitors; Vessel problems involve connective tissue or injury.
• Initial Screen for Bleeding Disorder: Always includes CBC with Platelets, PT, and PTT.
• Bleeding Phenotype of VWD: Characterized by Easy bruising, Epistaxis, and Menorrhagia (Platelet-like bleeding).
• Treatment Priority in DIC: You must treat the underlying cause; factor replacement is only supportive.
• Factor Assay: This is the confirmatory test for Hemophilia after a prolonged PTT is found.
• Treatment Priority in Hemophilia: Bleeds must be treated within 2 hours; head injuries require immediate factor infusion even before imaging.
• ITP "Well Child" Rule: If the child has significant petechiae but feels fine and the rest of the physical exam is normal, ITP is the top differential.
• Antifibrinolytic Contraindication: While generally used for mucosal bleeds, they are usually avoided in hematuria due to risk of obstructive clots.

QA

5.3 - Neoplasms of the Blood

Summary

text

CHILDHOOD CANCER AND HEMATOLOGIC MALIGNANCIES

GENERAL ONCOLOGY AND CHEMOTHERAPY

• Childhood cancer comprises mostly of leukemias, lymphomas, and brain tumors, whereas carcinomas and melanomas are more characteristically seen in adolescents.
• In childhood malignancies, the most common type of cancer overall is leukemia.
• In Leukemia or Neuroblastoma with bone marrow infiltration, patients often present with fever, persistent infections, and neutropenia.
• In Lymphomas (Hodgkin and Non-Hodgkin), hallmark systemic findings include Fever of Unknown Origin (FUO), weight loss, night sweats, and painless lymphadenopathy.
• In Brain tumors, common manifestations include headaches and visual disturbances resulting from increased intracranial pressure.
• In Retinoblastoma, the signature clinical finding is leukokoria (white pupillary reflex).
• In Neuroblastoma, periorbital ecchymosis ("raccoon eyes") is often present, representing metastatic disease.
• In Anterior mediastinal masses (such as gest cell tumors and lymphomas), patients often present with cough, stridor, and tracheobronchial compression.
• In Neuroblastoma, gastrointestinal symptoms can include a palpable abdominal mass or diarrhea.
• In Osteosarcoma and Ewing’s sarcoma, musculoskeletal symptoms like bone pain, limping, and arthralgia are primary features.
• In Brain tumors, Craniopharyngioma, or Langerhans cell histiocytosis, neuroendocrine involvement may manifest as diabetes insipidus and poor growth.
• At Cisplatin (Cp), the primary chemotherapy side effects are ototoxicity, nephrotoxicity, and high emetic potential.
• At Bleomycin (B), the most concerning chemotherapy-related toxicity involves lung disturbances (pulmonary fibrosis).
• At Doxorubicin (D), the dose-limiting chemotherapy side effect is cardiac toxicity.
• At Methotrexate (Mtx), chemotherapy side effects commonly include liver toxicity.
• At Irinotecan (Ir), a major chemotherapy side effect is severe diarrhea.

ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)

• In Acute Lymphoblastic Leukemia (ALL), the disease represents the most common malignant neoplasm in childhood, accounting for 31% of all childhood malignancies.
• In Acute Lymphoblastic Leukemia (ALL), the peak age of incidence is 2 to 3 years of age.
• In Acute Lymphoblastic Leukemia (ALL), the B-cell immunophenotype is more common (85%) and carries a better prognosis compared to the T-cell phenotype (15%).
• In Acute Lymphoblastic Leukemia (ALL), hyperdiploidy (extra chromosomes) is associated with a better prognosis, while hypodiploidy is unfavorable.
• In Acute Lymphoblastic Leukemia (ALL), the translocation t(12;21) (p13;q22) ETV-RUNX1 is the most common and carries a favorable prognosis.
• In ALL Morphology L1 Type, lymphoblasts are small, uniform, and monotonous with scant cytoplasm; this is the most common type in children.
• In ALL Morphology L2 Type, lymphoblasts are large and heterogeneous, often variable in size and shape, and can be mistaken for AML.
• In ALL Morphology L3 (Burkitt Type), cells show deeply basophilic cytoplasm with characteristic cytoplasmic vacuoles and round nuclei.
• At ALL risk stratification, Standard Risk is defined as age 1–9.99 years and a initial WBC < 50,000/µL.
• At ALL risk stratification, High Risk is defined as age <1 year or ≥10 years, and/or an initial WBC > 50,000/µL.
• In Acute Lymphoblastic Leukemia (ALL), boys historically had a poorer prognosis due to risks of testicular relapse and higher T-cell ALL incidence, though modern intensive therapy has narrowed this gap.
• In Acute Lymphoblastic Leukemia (ALL), the definitive diagnosis requires a Bone Marrow Aspiration (BMA) showing >25% lymphoblasts.
• In Acute Lymphoblastic Leukemia (ALL), Serum LDH is measured to assess tumor burden; higher levels indicate greater burden.
• In Acute Lymphoblastic Leukemia (ALL), a Chest X-ray must be performed to check for an anterior mediastinal mass.
• In Acute Lymphoblastic Leukemia (ALL), a Lumbar Puncture is required after diagnosis to assess for CNS involvement.
• In ALL Chemotherapy phase: Induction, the goal is the induction of remission.
• In ALL Chemotherapy phase: Consolidation, the goal is to reinforce remission in the CNS and marrow compartments.
• In ALL Chemotherapy phase: Interim Maintenance and Delayed Intensification, the goal is to further reduce residual leukemia in the marrow.
• In ALL Chemotherapy phase: Maintenance, the goal is to reduce the overall risk of relapse; total treatment typically takes 2-3 years.
• In Acute Lymphoblastic Leukemia (ALL), supportive care includes "Double Hydration," allopurinol for uric acid, and Pneumocystis jirovecii prophylaxis.

ACUTE MYELOGENOUS LEUKEMIA (AML)

• In Acute Myelogenous Leukemia (AML), the relative frequency increases significantly during adolescence, representing 36% of leukemias in 15-19 year olds.
• In Acute Myelogenous Leukemia (AML), risk factors include ionizing radiation, Down syndrome, Fanconi anemia, and prior exposure to alkylating agents or epipodophyllotoxins.
• In Acute Promyelocytic Leukemia (APL), signs and laboratory findings of Disseminated Intravascular Coagulation (DIC) are common.
• In Acute Myelogenous Leukemia (AML), "blueberry muffin" lesions (subcutaneous nodules) may be observed.
• In AML (especially Monocytic Subtype), infiltration of the gingiva (gums) is a characteristic clinical finding.
• In Acute Myelogenous Leukemia (AML), Chloromas or Granulocytic Sarcomas (leukemic masses) can fill soft tissue spaces in the eyes, gums, or skin.
• In Acute Myelogenous Leukemia (AML), diagnosis is confirmed by Bone Marrow Aspiration showing >20% blasts.
• In Acute Myelogenous Leukemia (AML), favorable cytogenetic features include t(8;21), t(15;17), and Inv (16).
• In Acute Myelogenous Leukemia (AML), unfavorable cytogenetic features include Monosomies 7 and 5, and 11q23 abnormalities.

CHRONIC (CML) AND JUVENILE MYELOMONOCYTIC LEUKEMIA (JMML)

• In Chronic Myelogenous Leukemia (CML), 99% of cases are associated with the t(9;22)(q34;q11) translocation, known as the Philadelphia chromosome.
• In Chronic Myelogenous Leukemia (CML), patients often present with hyperleukocytosis (WBC >100,000) and normal or elevated platelet counts.
• In CML Treatment, Imatinib (or Dasatinib) is an oral tyrosine kinase inhibitor that inhibits BCR-ABL and often requires lifelong administration.
• In Juvenile Myelomonocytic Leukemia (JMML), the disease typically affects children younger than 2 years of age and presents with massive splenomegaly, monocytosis, and no Philadelphia chromosome.
• In Juvenile Myelomonocytic Leukemia (JMML), mutations often lead to activation of the RAS oncogene pathway (NF1, PTPN11).
• In Juvenile Myelomonocytic Leukemia (JMML), transplant is the only curative intent treatment, though survival is generally very poor.

LYMPHOMAS

• In Lymphoma, it is the most common cancer in adolescents aged 15-19 years.
• In Hodgkin Lymphoma (HL), the hallmark finding is the Reed-Sternberg cell, described as a large cell with multiple or multilobulated nuclei.
• In Hodgkin Lymphoma (HL), physical examination typically reveals painless, non-tender, firm, and "rubbery" cervical or supraclavicular lymphadenopathy.
• At Hodgkin Lymphoma (HL) "B symptoms", the triad consists of unexplained fever >38°C, weight loss >10% in 6 months, and drenching night sweats.
• In Hodgkin Lymphoma (HL) staging, Stage I involves a single node region, while Stage IV indicates diffuse metastasis to extralymphatic organs.
• In Non-Hodgkin Lymphoma (NHL), the disease is categorised by high-grade, aggressive behavior; 70% of pediatric patients have Stage III-IV disease at diagnosis.
• In Burkitt Lymphoma (NHL Subtype), characteristics include t(8;14) translocation, mature B-cell phenotype (CD19, CD20 positive), and a "starry sky" appearance (suggested by rapid turnover).
• In Non-Hodgkin Lymphoma (NHL), the disease frequently presents as an oncologic emergency like Superior Vena Caval (SVC) Syndrome or Tumor Lysis Syndrome (TLS) due to rapid cell turnover.
• In NHL St. Jude Staging, any primary intrathoracic mass (mediastinal, pleural) is automatically classified as Stage III.
• In Non-Hodgkin Lymphoma (NHL), radiation therapy is reserved for special circumstances like CNS involvement in LBL, airway obstruction (SMS), or paraplegia.

ONCOLOGIC EMERGENCIES (HYPERLEUKOCYTOSIS & TLS)

• At Hyperleukocytosis, the condition is defined as a total WBC count greater than 100,000 cells/mm³.
• In Hyperleukocytosis Management, aggressive hydration with 3L/m²/day of IVF (D5 0.45 NaCl) is required, and transfusion of Packed Red Blood Cells (PRBC) must be avoided to prevent further increasing viscosity.
• In Hyperleukocytosis Management, platelets should ideally be maintained at 50,000 to prevent intracranial hemorrhage.
• At Tumor Lysis Syndrome (TLS), the condition involves the rapid release of intracellular metabolites (Potassium, Phosphorus, Nucleic acids) exceeding renal excretory capacity.
• In Tumor Lysis Syndrome (TLS), diagnosis requires two or more of: Uric acid >8 mg/dL, Potassium >6 meq/dL, Phosphorus >2.1 mmol/L, or Calcium <1.75 mmol/L (or 25% change from baseline).
• In Tumor Lysis Syndrome (TLS), hyperkalemia is characterized by widened QRS and peaked T-waves on ECG.
• In Tumor Lysis Syndrome (TLS), hypocalcemia presents with tetany, seizures, a prolonged QTc interval, and + Trousseau/Chovestek signs.
• In Tumor Lysis Syndrome (TLS) Management, alkalinization of urine is now avoided to prevent precipitation of xanthine calculi and calcium phosphate in renal tubules.
• At Rasburicase (recombinant urate oxidase), the drug effectively reduces existing uric acid (unlike Allopurinol which only blocks new formation).
• In Tumor Lysis Syndrome (TLS), dialysis is indicated for potassium >6 meq/L, phosphate >10 mg/dL, or volume overload/anuria unresponsive to medical therapy.

DIFFERENTIATION AND COMPARISONS FOR EXAMS

1. In Acute Leukemia Diagnosis, ALL requires >25% lymphoblasts in the bone marrow, whereas AML requires >20% blasts.
2. In Leukemia vs. ITP, Leukemia typically presents with pancytopenia and organomegaly, while ITP presents with isolated thrombocytopenia and a normal-sized spleen.
3. In CML vs. JMML, the Philadelphia chromosome t(9;22) is present in 99% of CML cases but is notably absent in JMML.
4. In CML vs. Acute Leukemia, CML usually presents with extreme hyperleukocytosis but with normal or elevated platelet counts, unlike the thrombocytopenia typical of acute forms.
5. In Hodgkin vs. Non-Hodgkin Lymphoma, Hodgkin usually presents with slow, firm, rubbery nodal enlargement, while Non-Hodgkin presents with a very rapidly progressing mass and higher risk of SVC syndrome.
6. In Hodgkin Lymphoma Staging, Stage II refers to nodes on the same side of the diaphragm, while Stage III refers to involvement on both sides of the diaphragm.
7. In NHL Staging, a single side of the diaphragm involvement is Stage II, but any intrathoracic/mediastinal mass is automatically Stage III.
8. In Hyperleukocytosis risk, Myeloblasts (AML) are bigger and "stickier" than Lymphoblasts (ALL), causing leukostasis at lower counts (~200k in AML vs ~300k in ALL).
9. In Allopurinol vs. Rasburicase, Allopurinol prevents the formation of new uric acid, while Rasburicase breaks down pre-existing uric acid.
10. In Tumor Lysis Syndrome (TLS), the classic metabolic quadriad is Hyperuricemia, Hyperkalemia, Hyperphosphatemia, and Hypocalcemia (Secondary).
11. In ALL Morphology, L1 cells are small and uniform (most common in children), L2 cells are large/heterogeneous (mimic AML), and L3 cells are basophilic with vacuoles (Burkitt type).
12. In AML special findings, Gingival hyperplasia/infiltration is most specific for the monocytic subtype (M4/M5).
13. In Leukemia Skin findings, "Blueberry muffin" lesions are associated with AML, while "Chloromas" are specifically localized collections of myeloblasts.
14. In ALL cytogenetics, t(12;21) is the most common and "good" prognosis, while t(9;22) in ALL is associated with "poor" prognosis.
15. In Pediatric vs. Adult Cancers, pediatric cancers are predominantly blast-based (leukemias/sarcomas), while adult cancers are predominantly epithelial (carcinomas).
16. In Hodgkin Lymphoma biopsy, Excision biopsy is preferred over needle biopsy to allow for proper subtyping and immunostaining.
17. In Burkitt Lymphoma genetics, the characteristic translocation is t(8;14) involving the MYC oncogene.
18. In ALL Support, double hydration is standard, but in Hyperleukocytosis, PRBC transfusions are avoided as they worsen blood viscosity and risk stroke.
19. In JMML Diagnosis, the patient is usually <2 years old with monocytosis; in CML Diagnosis, the patient can be older and has the Philadelphia chromosome.
20. In Hyperuricemia Presentation, patients may show microscopic hematuria due to uric acid crystals in the renal tubules.

QA

5.4 - Childhood Cancer

Summary

text

I. PEDIATRIC ABDOMINAL AND SOLID TUMORS

• In pediatric abdominal masses, age is the most important factor for narrowing differentials: Neonates usually have congenital malformations, children 1-5 years usually have Wilms or Neuroblastoma, and adolescents often have lymphoma or germ cell tumors.
• For adolescent females with abdominal masses, practitioners must always consider pregnancy as a differential diagnosis.
• Most pediatric abdominal malignancies are asymptomatic and found accidentally by parents during bathing or by physicians during well-child checkups.
• A thrombocytosis (platelets as high as 1.5 million) in a child with a liver mass is a hallmark finding of Hepatoblastoma due to tumor production of thrombopoietin.
• In Neuroblastoma, periorbital hemorrhage or "raccoon eyes" occurs due to tumor infiltration of the skull or orbital bones.
• Horner’s Syndrome (meiosis, ptosis, enophthalmos, anhidrosis) in Neuroblastoma indicates cervical sympathetic chain involvement.
• Wilms Tumor is associated with specific syndromes including WAGR (Wilms, Aniridia, GU anomalies, Retardation), Denys-Drash, and Beckwith-Wiedemann Syndrome.
• A biopsy is strictly discouraged/contraindicated in Wilms Tumor as it results in tumor seeding and upstaging of the disease.
• Hypertension in a child with Wilms Tumor is common and is driven by increased renin production or renal artery obstruction.
• Stage MS Neuroblastoma is a unique category for children <18 months where metastasis is confined to skin, liver, or bone marrow and may undergo spontaneous regression.
• Beckwith-Wiedemann Syndrome predisposes children to Wilms Tumor, Hepatoblastoma, and Adrenal Carcinoma.
• Klinefelter Syndrome is specifically associated with an increased risk of mediastinal Germ Cell Tumors.
• AFP (Alpha-fetoprotein) levels normally remain high in infants until approximately 8 months of age, which must be considered when diagnosing Germ Cell Tumors.

II. BRAIN TUMORS, BONE TUMORS, AND RETINOBLASTOMA

• Brain tumor location varies by age: In the 1st year of life, tumors are typically supratentorial; between 1-10 years, they are primarily infratentorial (e.g., Medulloblastoma); after age 10, they are again mostly supratentorial.
• Parinaud Syndrome (upward gaze palsy, light-near dissociation/Pseudo-Argyll Robertson pupil) is a hallmark of tumors in the pineal region.
• Diencephalic Syndrome, characterized by failure to thrive and emaciation despite normal intake, is seen in tumors of the suprasellar and third ventricular regions.
• Retinoblastoma survivors, particularly those with hereditary forms (RB1/TP53 mutations), have a significantly increased risk of developing Osteosarcoma later in life.
• Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma, frequently presenting as a small round blue cell tumor requiring immunohistochemistry (desmin, myogenin) for diagnosis.
• Botryoid Rhabdomyosarcoma is a variant that appears like a "bunch of grapes" and is typically found in mucosal-lined cavities like the vagina or bladder.
• Alveolar Rhabdomyosarcoma is associated with the PAX-FOXO1 transcript and carries the poorest prognosis among the histologic types.

III. PEDIATRIC BLOOD TRANSFUSIONS

• The 30-minute rule in blood banking states that RBC units left at room temperature for >30 minutes cannot be returned to storage for reissue.
• The 4-hour rule requires that the infusion of any blood component must be completed within 4 hours of removal from controlled storage to prevent bacterial proliferation.
• In pediatric blood transfusion, the only compatible IV fluid to be given concomitantly with PRBCs is 0.9% Normal Saline.
• Fever is NOT a contraindication to starting a blood transfusion; however, a temperature rise of >1°C during/after is classified as a Febrile Non-hemolytic Transfusion Reaction.
• Emergency Release of Blood (when group is unknown) should utilize Type O RBCs and Type AB Platelets/Plasma.
• Pediatric Massive Transfusion is defined as replacing >50% of total blood volume in 3 hours or >100% in 24 hours.
• Routine premedication (Acetaminophen/Diphenhydramine) for blood transfusions is generally considered a poor practice as evidence suggests it is not effective prophylaxis for first-time reactions.
• In Hema-Oncology patients, a Lumbar Puncture usually requires a platelet threshold of 20k-40k/uL.
• For Autoimmune Hemolytic Anemia (AIHA), transfusion should never be withheld if life-threatening anemia is present, even if crossmatching is incompatible.

IV. DIFFERENTIATING CLINICAL PEARLS (EXAM FOCUS)

1. Neuroblastoma vs. Wilms Tumor: Neuroblastoma occurs in younger children (<1 yr), often crosses the midline, and has calcifications on CT; Wilms occurs older (2-3 yrs), remains in the renal flank (rarely crosses midline), and shows the "Claw Sign."
2. Osteosarcoma vs. Ewing Sarcoma Imaging: Osteosarcoma presents with a "Sunburst" pattern at the metaphysis; Ewing Sarcoma presents with "Onion-skinning" at the diaphysis.
3. Acute Lymphoblastic Leukemia (ALL) Risk Stratification: Standard Risk is age 1-10 years and WBC <50,000; High Risk is age <1 year or >10 years, or WBC >50,000.
4. AFP vs. B-HCG Markers: AFP is elevated in Yolk Sac Tumors and Hepatoblastoma; B-HCG is elevated in Choriocarcinoma.
5. Supratentorial vs. Infratentorial Brain Tumors: Infratentorial tumors (Medulloblastoma/Astrocytoma) dominate the 1-10 year old age group; Supratentorial tumors dominate infancy and adolescence.
6. Small Round Blue Cells: This is a common histologic finding for Neuroblastoma, Ewing Sarcoma, Rhabdomyosarcoma, and Retinoblastoma; differentiation requires IHC (e.g., desmin for Rhabdo, PAS for Ewing).
7. Thrombocytosis in Tumors: If an abdominal mass is present, thrombocytosis points toward Hepatoblastoma; if pancytopenia is present, it suggests bone marrow infiltration (likely Neuroblastoma or Leukemia).
8. Tumor Marker "Normal Value" Trap: In Teratomas and Germinomas, tumor markers (AFP/HCG) are typically Normal; do not rule them out based on markers alone.
9. Claw Sign vs. Midline Crossing: The Claw Sign is specific for an intra-renal tumor (Wilms); encasing major vessels and crossing the midline is classic for Neuroblastoma.
10. Leukocoria (White Reflex): While the differential is broad, in pediatric oncology, this is Retinoblastoma until proven otherwise.
11. Opsoclonus-Myoclonus ("Dancing Eyes/Feet"): Although less emphasized in this text, it is a paraneoplastic syndrome highly associated with Neuroblastoma.
12. Renin elevation: This is the primary cause of hypertension in Wilms Tumor, distinguishing it from catecholamine-induced hypertension in Neuroblastoma.
13. WAGR Syndrome: The "A" stands for Aniridia (absence of iris), which is a major red flag for underlying Wilms Tumor.
14. Botryoid variant: If the question mentions a "bunch of grapes" in a child's vagina or bladder, the answer is Embryonal Rhabdomyosarcoma.
15. PRBC Volume Calculation: Always remember 10 mL/kg raises Hb by 2 g/dL; this is a frequent calculation on boards.
16. VMA/HVA vs. Hematuria: Urine catecholamines (VMA) are for Neuroblastoma; Hematuria is for Wilms.
17. Most Common Malignancy: Leukemia is #1 overall; Brain Tumors are #2 overall; Neuroblastoma is the #1 extracranial solid tumor.
18. Age-Specific Findings: If a mass is found in a neonate, it is likely a congenital malformation; if found at age 2, it is likely Wilms.
19. Pancytopenia in Solid Tumors: In Neuroblastoma, 75% are metastatic at diagnosis, often involving the bone marrow, causing pancytopenia similar to leukemia.
20. Parinaud Syndrome pupil: In Pineal tumors, the pupil reacts to accommodation but not to light (Pseudo-Argyll Robertson pupil).

QA

text | Count | Question | Answer | | :--- | :--- | :--- | | I. | PEDIATRIC ABDOMINAL AND SOLID TUMORS | | | 1 | What is the origin of Neuroblastoma? | Sympathetic chain/adrenal medulla | | 2 | What is the origin of Wilms Tumor (Nephroblastoma)? | Embryonic renal precursor cells | | 3 | What is the origin of Hepatoblastoma? | Precursors of hepatocytes | | 4 | What are the origins of Germ Cell Tumors (GCT)? | Gonads or Midline structures | | 5 | What is the peak age for Neuroblastoma? | Infants <1 year
75% are <4 years old. | | 6 | What is the peak age for Wilms Tumor (Nephroblastoma)? | 2-3 years old
80% are <5 years old. | | 7 | What is the peak age for Hepatoblastoma? | Mean age 1 year
80% are <3 years old. | | 8 | What is the peak age for Germ Cell Tumors (GCT)? | Bimodal
Infancy and adolescence. | | 9 | List common signs/symptoms (5): Neuroblastoma | 1) Pain
2) Raccoon eyes
3) SubQ nodules
4) weight loss
5) Opsoclonus-myoclonus | | 10 | List common signs/symptoms (3): Wilms Tumor (Nephroblastoma) | 1) Asymptomatic flank mass
2) HTN
3) hematuria | | 11 | List common signs/symptoms (3): Hepatoblastoma | 1) Asymptomatic mass
2) anorexia
3) weight loss | | 12 | List common signs/symptoms (2): Germ Cell Tumors (GCT) | 1) Midline mass
2) precocious puberty (if HCG+) | | 13 | Describe key imaging findings (3): Neuroblastoma | 1) Heterogeneous mass
2) Crossing midline
3) calcifications/hemorrhage | | 14 | Describe key imaging findings (2): Wilms Tumor (Nephroblastoma) | 1) "Claw sign"
2) Does NOT cross midline | | 15 | Describe key imaging finding: Hepatoblastoma | Solid liver mass | | 16 | Describe key imaging locations (2): Germ Cell Tumors (GCT) | 1) Sacrococcygeal
2) Mediastinal | | 17 | What are the diagnostic tumor markers: Neuroblastoma | Urine VMA and HVA | | 18 | What specific tumor marker is used for Wilms Tumor? | None specific | | 19 | What are the hallmark markers/labs (2): Hepatoblastoma | 1) High AFP
2) Thrombocytosis | | 20 | What tumor markers are used for Germ Cell Tumors (GCT)? (2) | 1) AFP (Yolk sac)
2) B-HCG (Choriocarcinoma) | | 21 | Describe the pathology findings (2): Neuroblastoma | 1) Small round blue cells
2) Rosettes | | 22 | Describe the triphasic histology of Wilms Tumor: (3) | Blastemal, stromal, epithelial | | 23 | Describe the histology of Hepatoblastoma: (2) | Epithelial or Mixed | | 24 | List the pathologic types of Germ Cell Tumors (GCT): (4) | 1) Teratomas
2) Germinomas
3) Yolk Sac
4) Choriocarcinoma | | 25 | What is the management for Neuroblastoma? (4) | Surgery, Chemo, Radiation, Stem cell rescue | | 26 | What is the management for Wilms Tumor? (2) | Upfront surgery or Pre-op chemo | | 27 | What is the management for Hepatoblastoma? (3) | Complete resection, Chemo, Transplant | | 28 | What is the management for Germ Cell Tumors (GCT)? (2) | Surgical excision + Chemotherapy | | 29 | What is the most important factor for narrowing differentials in pediatric abdominal masses? | Age | | 30 | Differentials for pediatric abdominal masses: Neonates | Congenital malformations | | 31 | Differentials for pediatric abdominal masses: Children 1-5 years | Wilms or Neuroblastoma | | 32 | Differentials for pediatric abdominal masses: Adolescents | Lymphoma or germ cell tumors | | 33 | What differential must be considered for adolescent females with abdominal masses? | Pregnancy | | 34 | How are most pediatric abdominal malignancies discovered? | Accidentally | | 35 | What lab finding in a liver mass child is a hallmark of Hepatoblastoma? | Thrombocytosis
Due to tumor production of thrombopoietin. | | 36 | What causes "raccoon eyes" in Neuroblastoma? | Tumor infiltration
Of the skull or orbital bones. | | 37 | List the components of Horner’s Syndrome in Neuroblastoma: (4) | Meiosis, ptosis, enophthalmos, anhidrosis | | 38 | What does Horner's Syndrome indicate in Neuroblastoma? | Cervical sympathetic chain involvement | | 39 | List syndromes associated with Wilms Tumor: (3) | 1) WAGR
2) Denys-Drash
3) Beckwith-Wiedemann | | 40 | Why is biopsy contraindicated in Wilms Tumor? | Tumor seeding
Leads to upstaging of the disease. | | 41 | What drives Hypertension in Wilms Tumor? | 1) Renin production
2) Renal artery obstruction | | 42 | Define Stage MS Neuroblastoma: | Metastasis confined to skin/liver/marrow | | 43 | List malignancies associated with Beckwith-Wiedemann Syndrome: (3) | Wilms, Hepatoblastoma, Adrenal Carcinoma | | 44 | What tumor is specifically associated with Klinefelter Syndrome? | Mediastinal Germ Cell Tumor | | 45 | Until what age do AFP levels normally remain high in infants? | 8 months of age | | II. | BRAIN TUMORS, BONE TUMORS, AND RETINOBLASTOMA | | | 46 | What is the incidence rank of Brain Tumors in pediatric cancer? | 2nd most common | | 47 | What is the incidence of Retinoblastoma? | Most common intraocular tumor | | 48 | What is the incidence of Osteosarcoma (OS)? | Most common bone tumor | | 49 | What is the incidence rank of Ewing Sarcoma (EWS)? | 2nd most common bone tumor | | 50 | List key findings (3): Brain Tumors (General) | 1) Morning headache
2) vomiting
3) papilledema | | 51 | List key findings (2): Retinoblastoma | 1) Leukocoria (white reflex)
2) Strabismus | | 52 | Describe findings for Osteosarcoma (OS): (2) | 1) Bone pain
2) Metaphysis swelling | | 53 | Describe findings for Ewing Sarcoma (EWS): (2) | 1) Bone pain
2) Diaphysis swelling | | 54 | What is the standard imaging for Brain Tumors? | MRI with Gadolinium | | 55 | Describe imaging for Retinoblastoma: | Chalky white-gray retinal mass | | 56 | Describe imaging for Osteosarcoma (OS): (2) | 1) "Sunburst" pattern
2) Codman triangle | | 57 | Describe imaging for Ewing Sarcoma (EWS): | "Onion-skinning" (periosteal reaction) | | 58 | What defines the pathology of Retinoblastoma? (2) | 1) Small round blue cells
2) Flexner-Wintersteiner rosettes | | 59 | What defines the pathology of Osteosarcoma (OS)? | Malignant osteoid production | | 60 | What defines the pathology of Ewing Sarcoma (EWS)? | Small round blue cells (PAS+) | | 61 | What procedure is strictly contraindicated in Retinoblastoma? | Biopsy | | 62 | Typical location of Brain tumor: 1st year of life | Supratentorial | | 63 | Typical location of Brain tumor: 1-10 years old | Infratentorial (e.g., Medulloblastoma) | | 64 | Typical location of Brain tumor: After age 10 | Supratentorial | | 65 | List the features of Parinaud Syndrome: (2) | 1) Upward gaze palsy
2) light-near dissociation | | 66 | Parinaud Syndrome is a hallmark of tumors in what region? | Pineal region | | 67 | Describe Diencephalic Syndrome features: (2) | 1) Failure to thrive
2) Emaciation | | 68 | Diencephalic Syndrome is seen in tumors of what regions? | Suprasellar/third ventricular regions | | 69 | Retinoblastoma survivors have an increased risk of what later in life? | Osteosarcoma | | 70 | What is the most common pediatric soft tissue sarcoma? | Rhabdomyosarcoma | | 71 | Identify IHC markers (2) for Rhabdomyosarcoma: | 1) Desmin
2) myogenin | | 72 | Describe Botryoid Rhabdomyosarcoma: | "Bunch of grapes" appearance | | 73 | Which histology of Rhabdomyosarcoma has the poorest prognosis? | Alveolar Rhabdomyosarcoma | | 74 | What transcript is associated with Alveolar Rhabdomyosarcoma? | PAX-FOXO1 transcript | | III. | PEDIATRIC BLOOD TRANSFUSIONS | | | 75 | What is the dose of PRBC (Red Cells)? | 10 - 15 mL/kg | | 76 | What is the dose of Platelets? | 5 - 10 mL/kg | | 77 | What is the dose of FFP (Plasma)? | 10 - 15 mL/kg | | 78 | What is the effect of PRBC (Red Cells) at 10 mL/kg? | Raises Hb by 2 g/dL | | 79 | What is the transfusion trigger for PRBC (Red Cells) if stable? | Hb <7 g/dL | | 80 | Identify triggers (3) for Platelet transfusion: | 1) <10k stable
2) <20k sepsis
3) <50k surgery | | 81 | What is the trigger for FFP (Plasma) transfusion? | Bleeding + PT/PTT >1.5x normal | | 82 | Define the 30-minute rule for RBC units: | Cannot be returned to storage | | 83 | Define the 4-hour rule for blood transfusion: | Must be completed within 4 hours | | 84 | What is the only compatible IV fluid for pediatric blood transfusion? | 0.9% Normal Saline | | 85 | Define Febrile Non-hemolytic Transfusion Reaction: | Temperature rise >1°C | | 86 | Emergency Release of Blood: Which types for unknown groups? | Type O RBCs; Type AB Platelets | | 87 | Define Pediatric Massive Transfusion: | Replacing >100% volume in 24 hours | | 88 | Why is routine premedication for blood transfusion considered poor practice? | Evidence suggests it is ineffective prophylaxis | | 89 | Platelet threshold for Lumbar Puncture in Hema-Onco? | 20k-40k/uL | | 90 | Policy for Autoimmune Hemolytic Anemia (AIHA) transfusion: | Never withhold if life-threatening | | IV. | DIFFERENTIATING CLINICAL PEARLS | | | 91 | Neuroblastoma vs. Wilms Tumor location: | Neuroblastoma crosses midline; Wilms renal flank | | 92 | Osteosarcoma vs. Ewing Sarcoma pattern: | Osteosarcoma sunburst; Ewing onion-skinning | | 93 | ALL: Criteria for Standard risk (2) | 1) Age 1-10 years
2) WBC <50,000 | | 94 | AFP vs. B-HCG: Which tumor marker for Yolk Sac? | AFP | | 95 | Supratentorial vs. Infratentorial: Dominant age 1-10 years | Infratentorial | | 96 | Small Round Blue Cells: List examples (4) | Neuroblastoma, Ewing, Rhabdo, Retino | | 97 | Abdominal mass + thrombocytosis suggests: | Hepatoblastoma | | 98 | Status of AFP/HCG in Teratomas and Germinomas: | Typically normal | | 99 | What finding is specific for Wilms Tumor imaging? | Claw Sign | | 100 | What is the significance of Leukocoria in pediatric oncology? | Retinoblastoma until proven otherwise | | 101 | Paraneoplastic syndrome associated with Neuroblastoma: | Opsoclonus-Myoclonus ("Dancing Eyes/Feet") | | 102 | Primary cause of hypertension in Wilms Tumor: | Renin elevation | | 103 | What does the "A" stand for in WAGR Syndrome? | Aniridia (absence of iris) | | 104 | Pediatric mass described as a "bunch of grapes": | Botryoid Rhabdomyosarcoma | | 105 | Formula for PRBC Volume Calculation effect: | 10 mL/kg raises Hb by 2 g/dL | | 106 | VMA/HVA vs. Hematuria: Which points to Wilms? | Hematuria | | 107 | What is the #1 extracranial solid tumor? | Neuroblastoma | | 108 | If an abdominal mass is found in a neonate, it is likely: | Congenital malformation | | 109 | Reason for pancytopenia in Neuroblastoma: | Bone marrow infiltration | | 110 | Describe the pupil in Parinaud Syndrome: | Pseudo-Argyll Robertson pupil
Reacts to accommodation, not to light. |

5.5 - Pediatric Resuscitation

Summary

text

SYSTEMATIC APPROACH TO PEDIATRIC CRITICAL CARE

ASSESSMENT TOOLS (INITIAL, PRIMARY, SECONDARY, TERTIARY)

PRIMARY ASSESSMENT: AIRWAY AND BREATHING DETAILS

• An Airway is classified as Clear (no intervention), Maintainable (needs positioning/suctioning), or Unmaintainable (needs intubation).
• The minimum parameters for Breathing assessment are:
  1. Rate of breathing
  2. Effort of breathing
  3. Air entry/Breath sounds
  4. Oxygen saturation
• In Respiratory Distress, signs include increased work of breathing, nasal flaring, head bobbing, grunting, and retractions.
• Respiratory Failure occurs when the body's metabolic demand for oxygen is not met by breathing, eventually leading to respiratory arrest.

PRIMARY ASSESSMENT: CIRCULATION, DISABILITY, AND EXPOSURE

• Compensated Shock manifests with signs of poor perfusion (tachycardia, delayed CRT) but maintaining a normal systolic BP for age.
• Hypotensive Shock is characterized by impaired perfusion and a systolic BP below the lower limit for age.

MANAGEMENT OF RESPIRATORY DISTRESS AND FAILURE

• The Oropharyngeal Airway (OPA) is used ONLY for unconscious patients without a gag reflex; size is measured from the corner of the mouth to the angle of the mandible.
• The Nasopharyngeal Airway (NPA) is for conscious or semi-conscious patients with a gag reflex; size is measured from the tragus of the ear to the tip of the nose.
• NPA Contraindications include basal skull fractures (potential cranial entry) or coagulation defects.
• The “C-E” grip is the standard technique for Bag-Mask Ventilation (BMV) to ensure a tight seal and jaw lift.
• In Bag-Mask Ventilation, the bag should only be squeezed enough to see chest rise; over-squeezing can cause barotrauma (pneumothorax).

ENDOTRACHEAL INTUBATION (ETT)

• Endotracheal Intubation is the most secure airway method; indications include GCS < 8, failure to oxygenate/ventilate, or anticipatory (e.g., GBS).
• The SOAP MM mnemonic for intubation preparation stands for:
  1. Suction
  2. Oxygen
  3. Airway (equipment/size)
  4. People
  5. Monitor
  6. Medications
• The Formula for Cuffed ETT size is (Age in Years / 4) + 3.5.
• The Formula for Uncuffed ETT size is (Age in Years / 4) + 4.
• The Estimated ETT Depth (lip-to-tip) is calculated as ETT Size x 3.
• The DOPE Mnemonic is used to troubleshoot sudden deterioration in an intubated patient:
  • D: Displacement
  • O: Obstruction
  • P: Pneumothorax
  • E: Equipment failure

SHOCK: TYPES AND PATHOPHYSIOLOGY

• The earliest compensatory mechanism for decreased cardiac output in shock is Tachycardia.
• Septic Shock is unique as it encompasses three shock types: hypovolemic (capillary leak), distributive (vasodilation via NO), and cardiogenic (inflammatory depression of contractility).
• Shock Physiology involves the equation: Blood Pressure = Cardiac Output x Systemic Vascular Resistance.
• In Dissociative Shock (e.g., CO poisoning), O2 delivery is impaired because O2 cannot be released from hemoglobin to tissues, despite normal circulation.

MANAGEMENT OF SEPTIC SHOCK (TIME-SENSITIVE)

• Initial Fluid Bolus in Shock is 10-20 cc/kg given over 15 to 20 minutes.
• The Preferred Fluid Order for shock resuscitation is:
  1. Sterofundin (Isotonic electrolyte solution)
  2. Acetated Ringer's (Buffer usable directly)
  3. Lactated Ringer's (Liver must process buffer)
  4. NSS (Risk of hyperchloremic metabolic acidosis)
• If IV access cannot be established within the first 90 seconds, an Intraosseous (IO) line should be inserted immediately.
• Signs of Fluid Overload/Congestion to monitor during resuscitation include new-onset crackles, hepatomegaly, and edema.
• Inotropes (Epinephrine/Norepinephrine) are indicated if the patient remains in shock after 3 fluid boluses (fluid-resistant shock).
• Hydrocortisone (5mg/kg) is used in catecholamine-resistant shock to treat potential adrenal crisis/insufficiency.

DIFFERENTIAL DIAGNOSIS AND COMPARISONS

1. Upper vs. Lower Airway Obstruction: Upper presents with stridor (inspiratory), while Lower presents with wheezing (expiratory).
2. Compensated vs. Hypotensive Shock: Compensated has Normal SBP, whereas Hypotensive has Low SBP; both show poor perfusion signs (tachycardia, delayed CRT).
3. OPA vs. NPA: OPA is for patients WITHOUT a gag reflex; NPA is for patients WITH a gag reflex.
4. Head Tilt-Chin Lift vs. Jaw Thrust: Head Tilt is for medical cases; Jaw Thrust is for suspected Trauma/C-spine injuries.
5. Cuffed vs. Uncuffed ETT: Cuffed is now generally recommended to prevent air leaks and ensure better ventilation; Uncuffed size formula adds +4 to age/4 while Cuffed adds +3.5.
6. Hypovolemic vs. Distributive Shock Preload: In Hypovolemic, preload is low due to loss of volume; in Distributive, preload is low due to "relative" hypovolemia from massive vasodilation.
7. Respiratory Distress vs. Failure: Distress includes increased effort (tachypnea, flaring); Failure includes inadequate gas exchange (hypoxemia, hypercarbia) and can lead to gasping or agonal breathing.
8. LR vs. AR Fluids: Acetated Ringer's is preferred in shock because the buffer is used directly; Lactated Ringer's requires liver perfusion to convert lactate to bicarbonate.
9. Cardiac Arrest Etiology (Adult vs. Peds): Pediatric arrest is usually Respiratory/Secondary; Adult arrest is usually Sudden Cardiac/Primary.
10. Displacement (D) vs. Obstruction (O) in DOPE: Displacement is the tube moving out (check with breath sounds/XR); Obstruction is the tube blocked by secretions or biting (check with suction catheter).
11. Pneumothorax vs. Ventilator Failure in DOPE: Pneumothorax results in deterioration regardless of bagging/ventilator; Ventilator Failure shows improvement when switched from the machine to manual bagging.
12. Normal SBP Calculation (1-10 years): Calculated as (Age x 2) + 70; anything below this is hypotensive.
13. LPD vs. DCB Auscultation: Lung Parenchymal Disease has crackles/rales; Disordered Control of Breathing may have entirely absent or irregular breath sounds.
14. Septic Shock vs. Other Distributive Shocks: Sepsis typically presents with a history of fever/infection, whereas Anaphylaxis presents with allergen exposure and Neurogenic with trauma history.
15. Preload vs. Afterload Manipulation: Fluid boluses increase Preload; Vasopressors (like Epinephrine) increase Afterload via vasoconstriction.
16. Pneumothorax vs. Gastric Distension: Pneumothorax shows decreased breath sounds and hyper-resonance; Gastric Distension (from ETT in esophagus) shows gurgling in the stomach and abdominal swelling.
17. Inotropes vs. Steroids in Shock: Inotropes (Epi) increase contractility/tone directly; Steroids (Hydrocortisone) are given if inotropes fail to address potential adrenal insufficiency.
18. Nasal Cannula vs. NRM Flow: Cannula is low flow (max 4L); NRM is high flow (requires 11-15L to keep reservoir bag inflated).
19. Initial vs. Primary Assessment: Initial is a "first-look" (ABC only); Primary is a hands-on examination (ABCDE with vitals).
20. Tachycardia Interpretation: Tachycardia is the first sign of compensation in shock but must be differentiated from pain, fever, or medication effects (e.g., Albuterol).

QA

text

SYSTEMATIC APPROACH TO PEDIATRIC CRITICAL CARE

ASSESSMENT TOOLS (INITIAL, PRIMARY, SECONDARY, TERTIARY)

PRIMARY ASSESSMENT: AIRWAY AND BREATHING DETAILS

PRIMARY ASSESSMENT: CIRCULATION, DISABILITY, AND EXPOSURE

MANAGEMENT OF RESPIRATORY DISTRESS AND FAILURE

AIRWAY ADJUNCTS AND VENTILATION

ENDOTRACHEAL INTUBATION (ETT)

SHOCK: TYPES AND PATHOPHYSIOLOGY

MANAGEMENT OF SEPTIC SHOCK (TIME-SENSITIVE)

DIFFERENTIAL DIAGNOSIS AND COMPARISONS

5.6 - Neurologic Emergencies and Stabilization

Summary

RAPID SEQUENCE INTUBATION (RSI) AND AIRWAY MANAGEMENT

PHARMACOLOGY OF RSI

• Atropine is used in Rapid Sequence Intubation to prevent bradycardia and decrease secretions which might obstruct the airway.
• Lidocaine is administered during Intubation to prevent the patient from straining, which would otherwise increase intracranial pressure and risk herniation.
• The Sniffing Position is the gold standard for patient alignment during intubation, often requiring a shoulder roll in infants to compensate for a prominent occiput.
• The Sellick Maneuver involves applying pressure to the cricoid cartilage to visualize the glottis or prevent aspiration; it is NOT a routine maneuver and is used only if visualization is difficult.
• Straight blades (Miller) are typically used in pediatric intubation to address the floppy epiglottis, while curved blades (Macintosh) are more common in adults.
• Confirmation of Endotracheal Tube (ETT) placement is achieved via auscultation, observation of chest rise, vital sign monitoring, and ultimately a chest X-ray.

INTRAOSSEOUS (IO) CANNULATION

• Intraosseous (IO) access allows for the administration of any IV drug, resuscitation fluids, and even obtaining marrow for lab studies (electrolytes, ABG, cultures).
• Technique for IO Cannulation involves directing the needle caudad (10-15 degrees away from the growth plate) using a twisting motion until a "pop" or decrease in resistance is felt.
• Confirmation of IO needle placement is definitive if the needle stands firmly on its own, bone marrow is aspirated, and fluid flushes easily without subcutaneous swelling.
• Compartment Syndrome is a potential complication of IO access caused by the extravasation of fluids into the subcutaneous tissue.
• Fat emboli are a rare risk of IO access; practitioners are advised not to push aspirated marrow back into the cavity.

NEUROLOGIC EMERGENCIES AND TBI

TBI MANAGEMENT STRATEGIES

• Cerebral Perfusion Pressure (CPP) targets are age-dependent: 50 mmHg (2-6y), 55 mmHg (7-10y), and 65 mmHg (11-16y).
• Hyperthermia must be avoided in brain injury as it increases cellular metabolic demand and worsens tissue hypoxia.
• Hypercarbia (High CO2) causes cerebral vasodilation, increasing intracranial blood volume and subsequently increasing ICP.
• Modified Pediatric Glasgow Coma Scale (GCS) is used for children <2 years old to account for non-verbal development scores.
• Cranial CT Scanning in patients <2 years old (PECARN) is indicated if GCS ≤14, there is altered mental status, or a palpable skull fracture.
• Cranial CT Scanning in patients ≥2 years old is indicated if GCS ≤14, there is altered mental status, or signs of a basilar skull fracture (Raccoon eyes/Battle sign).
• Hypertonic Saline (HTS) is often preferred over Mannitol for pediatric cerebral edema as it helps maintain volume while targeting high-normal sodium (145-155).
• Anticonvulsant prophylaxis (e.g., Levetiracetam) prevents early post-traumatic seizures (within 1 week) but does not prevent late-onset epilepsy.

BASIC LIFE SUPPORT (BLS) AND CPR

• Chest Recoil must be complete between compressions to allow for atrial refilling (diastole).
• Rescue Breaths should be delivered over 1 second, ensuring visible chest rise while avoiding excessive ventilation (which increases intrathoracic pressure).
• Jaw-Thrust Maneuver is the mandatory technique for opening the airway in any patient with suspected cervical spine injury.
• Two Thumb-Encircling Hands Technique is the preferred compression method for infants when there are two rescuers.
• Gasping is not normal breathing; it is a sign of cardiac arrest and acidosis requiring immediate CPR.
• AED Analysis: If the rhythm is shockable, clear the patient, deliver the shock, and immediately resume CPR starting with compressions (do not check pulse).
• Unwitnessed Collapse in children requires the lone rescuer to perform 2 minutes (5 cycles) of CPR before leaving to activate EMS or get an AED.
• Witnessed Collapse in children allows the lone rescuer to leave immediately to activate EMS/get an AED because the cause is likely a sudden primary cardiac arrhythmia.

DIFFERENTIATION AND COMPARISON FOR EXAMS

• Etomidate vs. Ketamine: Both are used for hemodynamically unstable patients, but Etomidate is avoided in sepsis (adrenal suppression) while Ketamine is preferred for asthma (bronchodilatory).
• Succinylcholine vs. Rocuronium: Succinylcholine has a faster/shorter onset but dangerous side effects in hyperkalemic or burned patients; Rocuronium is the safer, non-depolarizing alternative.
• Head Tilt-Chin Lift vs. Jaw Thrust: Head tilt is standard, but Jaw Thrust must be used if cervical spine injury is suspected to prevent spinal cord damage.
• Primary vs. Secondary Brain Injury: Primary injury is structural/irreversible damage occurring at impact; Secondary injury is physiological (edema, ischemia) and is the target of medical management.
• 1-Rescuer vs. 2-Rescuer Peds CPR: The compression-to-breath ratio changes from 30:2 (1-rescuer) to 15:2 (2-rescuer) to prioritize oxygenation in children.
• Infant vs. Child Pulse Checks: Check the brachial artery in infants (under 1 year) and the carotid/femoral artery in children (>1 year).
• Mannitol vs. Hypertonic Saline (HTS): HTS acts as a volume expander and is preferred in hypotension; Mannitol is an osmotic diuretic that may cause hypovolemia.
• SIADH vs. Cerebral Salt Wasting (CSW): Both cause hyponatremia after brain injury; SIADH involves fluid retention (euvolemic/hypervolemic), while CSW involves massive sodium loss in urine (hypovolemic).
• Decorticate vs. Decerebrate Posturing: Both indicate brain injury; Decorticate (flexion) suggests damage above the brainstem, while Decerebrate (extension) indicates a more severe brainstem injury/herniation.
• Straight vs. Curved Blades: Straight blades (Miller) physically lift the epiglottis (better for peds); Curved blades (Macintosh) are placed in the vallecula to indirectly lift the epiglottis (Standard for adults).
• Witnessed vs. Unwitnessed Peds Arrest: Witnessed = Get help/AED first. Unwitnessed = Do 2 minutes of CPR first.
• Normal Ventilation vs. Hyperventilation in TBI: Target normal PaCO2 (35-45) for maintenance; target low PaCO2 (25-30) ONLY as a temporary rescue for acute herniation.
• Hypoxia vs. Hyperoxia in TBI: Both are harmful; hypoxia starves brain tissue, while hyperoxia produces oxygen radicals that facilitate secondary brain injury.

QA