Paediatrics Marrow Pg 241-250 (Hematology)
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Questions and Answers

Which of the following is NOT a component required for normal hemostasis?

  • Platelets
  • Red blood cells (correct)
  • Clotting factors
  • Blood vessel

    • Platelet disorders typically present with deep bleeding in muscles and joints.

    False

    What autoimmune condition involves the production of autoantibodies against GP IIb/IIIa receptors on platelets?

    Immune Thrombocytopenic Purpura (ITP)

    Vitamin C deficiency can lead to __________, which is a vascular bleeding disorder.

    <p>scurvy</p> Signup and view all the answers

    Match the bleeding disorder with its associated feature:

    <p>Immune Thrombocytopenic Purpura (ITP) = Presence of autoantibodies against platelets Henoch-Schönlein purpura = Vascular inflammation Scurvy = Vitamin C deficiency Hereditary Hemorrhagic Telangiectasia = Genetic disorder causing blood vessel malformations</p> Signup and view all the answers

    What is the inheritance pattern of Sickle Cell Anemia?

    <p>Autosomal recessive</p> Signup and view all the answers

    Sickle Cell Anemia symptoms typically manifest before the age of 6 months.

    <p>False</p> Signup and view all the answers

    What amino acid is substituted in the β-globin chain of hemoglobin in Sickle Cell Anemia?

    <p>Valine</p> Signup and view all the answers

    In Sickle Cell Anemia, the presence of __________ in red blood cells leads to hemolysis.

    <p>HbS</p> Signup and view all the answers

    Match the following clinical features of Sickle Cell Anemia with their descriptions:

    <p>Icterus = Yellowing of the skin and eyes due to bilirubin Dactylitis = Swelling of fingers and toes Painful vaso-occlusive crises = Characteristic painful episodes Pallor = Paleness due to anemia</p> Signup and view all the answers

    What is the mode of inheritance for β-thalassemia?

    <p>Autosomal recessive</p> Signup and view all the answers

    β-thalassemia major is the least severe form of β-thalassemia.

    <p>False</p> Signup and view all the answers

    What is a key clinical feature associated with β-thalassemia?

    <p>Hepatosplenomegaly</p> Signup and view all the answers

    In β-thalassemia, the α & β chains are produced in a ______ ratio.

    <p>1:1</p> Signup and view all the answers

    Match the β-thalassemia genotype with its corresponding name:

    <p>β/β = Normal β/β⁺ = β-Thalassemia trait (mild) β⁰/β⁰ = β-Thalassemia major/cooley's anemia β+/β⁰ = β-Thalassemia intermedia</p> Signup and view all the answers

    What is the gold standard test for diagnosing hematological conditions?

    <p>High-Performance Liquid Chromatography (HPLC)</p> Signup and view all the answers

    Leukocyte-depleted blood products increase the risk of allergic reactions.

    <p>False</p> Signup and view all the answers

    What is the pre-transfusion target hemoglobin level to reduce deformities and promote growth?

    <p>9-10 g/dL</p> Signup and view all the answers

    The major cause of morbidity and mortality related to repeated blood transfusions is __________.

    <p>Cardiotoxicity</p> Signup and view all the answers

    Match the following iron chelators with their side effects:

    <p>Deferasirox = Mild GI disturbances Deferoxamine = Ototoxicity &amp; retinal toxicity Deferiprone = Neutropenia &amp; cartilage damage</p> Signup and view all the answers

    What does the sickling test involve?

    <p>Adding 2% sodium metabisulphite</p> Signup and view all the answers

    Acute chest syndrome resembles pneumonia and is characterized by a fever and breathing difficulty.

    <p>True</p> Signup and view all the answers

    What is the best diagnostic test for sickle cell disease?

    <p>Hb electrophoresis</p> Signup and view all the answers

    Sickling of cells in the spleen leads to ________ by 6 years of age.

    <p>autosplenectomy</p> Signup and view all the answers

    Match the type of intervention with its use:

    <p>Good hydration = Prevent dehydration Analgesics = Relief of pain episodes PRBC transfusions = Increase blood oxygen carrying capacity Exchange transfusion = Address acute chest syndrome &amp; stroke</p> Signup and view all the answers

    What is the primary age range for the clinical presentation of acute ITP?

    <p>1-7 years</p> Signup and view all the answers

    Lymphadenopathy and splenomegaly are commonly observed in acute ITP.

    <p>False</p> Signup and view all the answers

    Name one treatment option for acute ITP that decreases macrophage activity.

    <p>IV immunoglobulins</p> Signup and view all the answers

    Acute ITP often follows a viral infection that occurs __ to __ weeks prior.

    <p>1, 4</p> Signup and view all the answers

    Match the following conditions to their related causes of thrombocytopenia:

    <p>Aplastic anemia = Bone marrow failure Leukemia = Marrow infiltration Systemic lupus erythematosus (SLE) = Connective tissue disorder Parvovirus infection = Viral infection leading to thrombocytopenia</p> Signup and view all the answers

    Which treatment option is particularly useful in Hemophilia A?

    <p>Cryoprecipitate</p> Signup and view all the answers

    Antibodies to clotting factor are the least serious complication of therapy.

    <p>False</p> Signup and view all the answers

    What is the most common inherited bleeding disorder worldwide?

    <p>von Willebrand Disease (VWD)</p> Signup and view all the answers

    Emicizumab is a monoclonal antibody to ______.

    <p>factor VIII</p> Signup and view all the answers

    Match the types of von Willebrand Disease with their descriptions:

    <p>Type 1 = Most common, partial deficiency of vWF Type 2 = Qualitative defect, severe dysproteinemia Type 3 = Complete absence of vWF, resembles Hemophilia A</p> Signup and view all the answers

    What is a characteristic finding in the red blood cell indices for congenital hemolytic anemia?

    <p>Increased MCHC</p> Signup and view all the answers

    Splenectomy is considered the best treatment modality for congenital hemolytic anemia.

    <p>True</p> Signup and view all the answers

    What is the purpose of lifelong folic acid supplementation in patients with congenital hemolytic anemia?

    <p>To support megaloblastic erythropoiesis due to chronic hemolysis</p> Signup and view all the answers

    The lack of __________ in spherocytes is a key finding on peripheral smear for congenital hemolytic anemia.

    <p>central pallor</p> Signup and view all the answers

    Match the following tests with their corresponding characteristics:

    <p>Osmotic Fragility = Increased Na+ permeability in spherocytes Incubated Osmotic Fragility = Increased sensitivity at 37°C Flow Cytometry = Bending of eosin-5-maleimide to proteins Molecular Testing = Deletion of mutations in RBCs</p> Signup and view all the answers

    Which type of hemophilia is most common?

    <p>Hemophilia A</p> Signup and view all the answers

    Hemophilia B is caused by a deficiency of Factor IX.

    <p>True</p> Signup and view all the answers

    What is the hallmark feature of hemophilia?

    <p>Hemarthrosis</p> Signup and view all the answers

    Hemophilia C is inherited in an __________ manner.

    <p>autosomal recessive</p> Signup and view all the answers

    Match the hemophilia type with its corresponding clotting factor deficiency:

    <p>Hemophilia A = Factor VIII Hemophilia B = Factor IX Hemophilia C = Factor XI</p> Signup and view all the answers

    What is the most common red blood cell enzyme deficiency?

    <p>G6PD Deficiency</p> Signup and view all the answers

    Splenectomy increases the risk of infection by encapsulated bacteria in patients aged 6 years or older.

    <p>True</p> Signup and view all the answers

    What are the two common risk factors for episodic hemolysis in G6PD deficiency?

    <p>Fever and exposure to certain drugs (e.g., Primaquine)</p> Signup and view all the answers

    The absence of ________ macrophages is a consequence of splenectomy.

    <p>splenic</p> Signup and view all the answers

    Match the following conditions with their associated clinical features:

    <p>G6PD Deficiency = Neonatal jaundice and episodic hemolysis Splenectomy = Increased risk of infection by encapsulated bacteria Heinz bodies = Indicative of oxidative stress in RBCs Bite cells = Result from hemolysis due to oxidative damage</p> Signup and view all the answers

    Study Notes

    Bleeding Disorders

    • Normal hemostasis requires blood vessels, platelets, and clotting factors.
    • Vascular etiologies for bleeding disorders include:
      • Vasculitis (e.g., Henoch-Schönlein purpura)
      • Scurvy (vitamin C deficiency)
      • Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu syndrome)

    Platelet vs Coagulation Disorders

    • Platelet disorders typically cause mucocutaneous bleeding, petechiae, and multiple, small ecchymoses.
    • Coagulation disorders predominantly lead to deep bleeding in muscles and joints (hemarthrosis) and single, large ecchymoses.
    • Patients with platelet disorders will experience bleeding after minor trauma, while coagulation disorders may result in delayed bleeding after surgery.

    Immune Thrombocytopenic Purpura (ITP)

    • Pathogenesis:
      • Molecular mimicry:
        • Viral infections, particularly in children aged 1-7, can trigger autoantibody production against GP IIb/IIIa receptors on platelets.
        • Antibody-coated platelets enter the spleen and are recognized by Fc receptors on splenic macrophages leading to lysis of platelets.
        • This results in autoimmune thrombocytopenia.
      • Bone marrow Compensation: Megakaryocyte production increases in response to platelet loss.

    Sickle Cell Anemia

    • Inheritance: Autosomal recessive

    • Incidence: High incidence in tribal populations of Madhya Pradesh and Maharashtra, India.

    • Pathogenesis:

      • Mutation: Mutation in the gene for β-globin chain of hemoglobin.
      • Amino Acid Substitution: Glutamate is replaced by valine at the 6th position of the β-globin chain.
      • HbS Production: Defective HbS is produced (normal Hb: HbA).

    • RBCs with HbS:

      • Clinical Features: Hypoxia, dehydration, fever, and metabolic acidosis can trigger sickling.
      • Sickling: Repeated sickling leads to fragile red blood cells and hemolysis.

    • Clinical Features (Sickle Cell Anemia):

      • Onset: Symptoms manifest after 6 months of age due to the protective effect of HbF (fetal hemoglobin) during the first 6 months.
      • Symptoms: Icterus, pallor, and characteristic painful vaso-occlusive crises.
      • Dactylitis/Hand and Foot Syndrome: Swelling of fingers and toes typically presenting in infancy.

    • Management:

      • Supportive: Most episodes are self-limiting, and implicated drugs should be avoided.
      • Diagnostic Test: Enzyme assay in RBCs confirms decreased enzyme levels.

    β-Thalassemia

    • Mode of Inheritance: Autosomal recessive

    • Types:

      • Reduction or absence of β-globin chain synthesis.
      • Normally, alleles code for β-globin chain.
      • Key:
        • β: Normal
        • β⁺: Decreased production
        • β⁰: No production

    • Genotype & Severity:

      Genotype Name Severity
      β/β Normal Asymptomatic
      β/β⁺ β-Thalassaemia trait (mild) Mild to moderate
      β+/β⁺ Mild to moderate (β+/β° > β+/β+)
      β+/β⁰ β-Thalassaemia intermedia
      β⁰/β⁰ β-Thalassaemia major/cooley's anemia (most severe) Severe (Transfusion every 3-4 weeks)

    • Pathophysiology & Clinical Features:

      • α-Chain Accumulation: Accumulation of α-chains in RBCs leading to cell instability and early destruction.
      • Ineffective Erythropoiesis:
      • Severe Anemia: Transfusion-dependent anemia.
      • Extramedullary Hematopoiesis:
        • Hepatosplenomegaly
        • Skull involvement.
      • Note: α & β chains are typically produced in a 1:1 ratio.

    • Clinical Features:

      • Frontal bossing
      • Depressed nasal bridge
      • Maxillary prominence
      • Dental malocclusion
      • Thalassemic facies
      • Prominent vertical trabeculae
      • Hair-on-end appearance

    • X-Ray (Hair-on-End Appearance): An X-ray of the skull demonstrates a characteristic "hair-on-end" appearance.

    Investigations (Hematology)

    • Peripheral Smear:

      • Nucleated RBCs
      • Microcytic
      • Hypochromic RBCs (Central pallor > 1/3rd)

    • Hemoglobin Electrophoresis: Initial diagnostic test.

    • High-Performance Liquid Chromatography (HPLC): Gold standard test.

    • Management (Supportive):

      • Blood transfusions every 3-4 weeks.
      • Leukocyte-depleted/irradiated blood products reduce the risk of allergic reactions.
      • Pre-transfusion target Hb 9-10 g/dL: Reduces skeletal deformities and promotes growth.

    • Management (Curative): Hematopoietic stem cell transplant.

    Complications of Iron Overload (β-Thalassemia)

    • Risk: Due to repeated transfusions (over 1 year of transfusion), iron overload is a significant concern.

    • Morbidity & Mortality: Major cause of morbidity and mortality (cardiotoxicity).

    • Organ Damage: Liver, spleen, and heart.

    • High Transferrin Saturation:

      • Decreased bacteriostatic properties of lactoferrin.
      • Increased risk of infections (most common: Yersinia enterocolitica).

    • Investigations:

      • Serum ferritin > 1000 pg/L.
      • MRI (Ra or Ra* weighted Ta-weighted cardiac MRI and Liver MRI: Best)

    • Management:

      • Iron chelators:
        • Deferasirox (Oral): Preferred; Causes mild GI disturbances.
        • Deferoxamine (s.c): Side effects: Ototoxicity & retinal toxicity.
        • Deferiprone (Oral): Side effects: Neutropenia & cartilage damage.

    Sickle Cell Anemia - Additional Information

    • Acute Chest Syndrome: Fever and breathing difficulty, resembling pneumonia. Chest X-ray shows new-onset infiltrates.
    • Stroke Episodes: Can occur due to sickling of cells in the brain.
    • Autosplenectomy: Repeated infarcts in the spleen lead to autosplenectomy by age 6, resulting in functional hyposplenism and recurrent infections by encapsulated bacteria.
    • Venous Blockade & Pallor: Venous blockade causes acute pooling of blood, leading to a 22% reduction in hemoglobin, resulting in pallor and shock.
    • Aplastic Crisis: Pancytopenia precipitated by parvovirus B19 infection.

    Investigations (Sickle Cell Anemia)

    • Peripheral Smear: Sickled RBCs.

    • Screening Test:

      • Sickling test: Induction of sickling by adding 2% sodium metabisulphite.

    • Hb Electrophoresis: Initial, best diagnostic test.

    • High-Performance Liquid Chromatography (HPLC): Gold standard test for detecting and quantifying HbS.

    • Sickle Cell Trait: HbA + HbS – Less severe manifestations.

    Management (Sickle Cell Anemia)

    • Good hydration
    • Analgesics for pain episodes
    • PRBC transfusions: Used for Aplastic crisis, sequestration crisis, and to increase blood's oxygen carrying capacity.
    • Exchange transfusion: Used for acute chest syndrome and stroke to remove HbS from circulation. Goal: Hbs concentration < 30%.

    Acute ITP

    • Age: 1-7 years

    • Viral Infection Trigger: Viral infection 1-4 weeks prior to onset.

    • Clinical Features:

      • Sudden onset of mucocutaneous bleeds (petechiae > epistaxis, oral oozing).
      • Child generally appears well.
      • Rare:
        • Gastrointestinal (GI) bleeds
        • Hematuria
        • Central nervous system (CNS) bleeds (Fatal).

    • Lymphadenopathy & Splenomegaly: Usually not seen in acute ITP; If present, evaluate for a different underlying cause, such as leukemia.

    Investigations (Acute ITP)

    • Blood Count:
      • Peripheral smear: Normal-sized and large (young platelets) due to bone marrow compensation.
      • Bone marrow aspiration: Increased megakaryocytes.

    Management (Acute ITP)

    • Supportive Care: Majority of cases are self-limiting.

    • Treatment Decision: Based on clinical symptoms (organ bleeds/increased number of bleeds) and not solely on platelet counts.

    • Treatment Options:

      • IV Immunoglobulins (best): Reduces macrophage activity and platelet destruction.
      • Steroids (Prednisolone): Increases platelet production.
      • Platelet Transfusions: Only used for life-threatening bleeds.

    Other Causes of Thrombocytopenia

    • Aplastic anemia
    • Marrow infiltration (Leukemia/storage disorders)
    • Connective tissue disorders (e.g., SLE)
    • Infections: Parvovirus, EBV, Varicella, Rubella, mumps
    • Drugs:
      • Heparin
      • Valproate, Phenytoin
      • NSAIDs
      • Penicillins & Cephalosporins

    Congenital Hemolytic Anemia

    • Investigations:
      • Peripheral Smear: Lack of central pallor in spherocytes due to loss of surface area during shape change and cellular dehydration.
      • Red blood cell indices: ↑MCHC is characteristic.
      • Screening Tests:
        • Osmotic Fragility: Increased permeability to Na+ in spherocytes.
        • Incubated osmotic fragility: Blood is incubated at 37°C for 24 hours to improve test sensitivity. Osmotic fragility is also seen in other hemolytic disorders.
      • Confirmatory Tests:
        • Flow cytometry: Bending of eosin-5-maleimide (EMA) to proteins.
        • Molecular testing: Deletion of mutations in RBCs.

    Management (Congenital Hemolytic Anemia)

    • Lifelong folic acid supplementation: Given for megaloblastic erythropoiesis due to chronic hemolysis and should be administered to all children with chronic hemolytic anemia.
    • Splenectomy:
      • Best treatment modality: Decreases lysis, increases RBC lifespan, and reduces anemia severity.
      • Laparoscopic partial splenectomy is preferred.
      • Concomitant cholecystectomy if gallstones are present.

    Treatment Options:

    • Fresh Frozen Plasma (FFP):
    • Cryoprecipitate: Contains Factor VIII & fibrinogen. Useful only in Hemophilia A.

    Complications of Treatment (Inherited Bleeding Disorders)

    • Antibodies to clotting factor: Most serious complication, leading to patients stopping responding to factor replacement therapy.

    Treatment (Inherited Bleeding Disorders)

    • Bypass agents: Used to bypass the defective clotting factor in the cascade.

    Bypass Agents:

    • Recombinant Factor Vila
    • Activated Prothrombin Complexes (APCS)/ Factor VIII Inhibitor Bypass Activity (FEIBA)

    Von Willebrand Disease (VWD)

    • Most common inherited bleeding disorder worldwide
    • Inheritance: Mostly autosomal dominant.

    Functions of von Willebrand Factor (vWF)

    • Factor VIII Binding: Binds to factor VIII, increasing its half-life.
    • Platelet-Collagen Bridge: Acts as a bridge between platelets and subendothelial collagen.

    Non-Factor Type (Treatment)

    • Emicizumab: Monoclonal antibody to factor VIII (Hemophilia A only).

    Types of VWD

    Type Description
    Type 1 Most common (80% cases). Quantitative defect.Partial deficiency of vWF.
    Type 2 Qualitative defect.Dysproteinemia: Function of vWF is abnormal, levels are normal.Most severe.
    Type 3 Quantitative defect.Complete absence of vWF.Resembles Factor VIII deficiency (Hemophilia A).

    Consequences of Splenectomy

    • Active Space: The absence of splenic macrophages, which normally remove old or damaged red blood cells, increases the risk of infection by encapsulated bacteria due to a lack of phagocytic function.
    • Risk of Infection: Especially in children less than 6 years of age.
    • Immunization: Post-splenectomy, patients require immunizations with encapsulated organisms to protect against infections.
    • Penicillin Prophylaxis: Penicillin prophylaxis for 2 years post-splenectomy is recommended.

    G6PD Deficiency

    • Most Common RBC Enzyme Deficiency
    • Inheritance: X-linked recessive.
    • Prevalence: Commonly seen in Africans, Mediterranean populations, and Asians.

    Pathophysiology (G6PD Deficiency)

    • HMP Shunt: Glucose-6-phosphate is converted to 6-phosphoglycerate via G6PD, generating NADPH, which is required to maintain reduced glutathione levels.
    • Reduced Glutathione: Levels of reduced glutathione decrease, leading to increased oxidative stress and hemolysis.

    Clinical Features (G6PD Deficiency)

    • Varied Onset:
      • Early: Neonatal jaundice.
      • Late: Episodic hemolysis.
    • Risk Factors for Episodic Hemolysis:
      • Fever
      • Drugs: (Usually begin 2-3 days after drug exposure and are self-limiting):
        • Primaquine
        • Nitrofurantoin
        • Sulfonamides
      • Fava Beans

    Investigations (G6PD Deficiency)

    • Peripheral Smear:
      • Heinz bodies
      • Decreased Hb
      • Bite cells

    Inherited Bleeding Disorders: Hemophilia

    • Gene Defect: Clotting factor defect leading to delayed clot formation and bleeding.
    • Bleeding Manifestations: Hemarthrosis, muscle hematomas, and various types of bleeding.

    Types of Hemophilia:

    Type Clotting Factor Deficiency Mode of Inheritance
    Hemophilia A (m/c) Factor VIII X-linked recessive (males are affected more)
    Hemophilia B Factor IX X-linked recessive (males are affected more)
    Hemophilia C Factor XI Autosomal recessive

    Clinical Features (Hemophilia)

    • Hemarthrosis: Bleeding into a joint.
    • Hallmark Feature: Hemarthrosis is a hallmark feature of hemophilia.
    • Most Common Joint Affected: Knee > elbow, ankle.
    • Target Joint: Repeated bleeds into the same joint.
    • Fibrosis: Restriction of joint movements is a common cause of morbidity.

    Classification (Hemophilia)

    Severity Clotting Factor Activity Spontaneous Bleeds Features
    mild 5-40% Absent Unnoticed until adolescence
    moderate 1-4% Mostly absent Bleeding after trauma or surgery * Hemarthrosis, muscle Hematoma.* Rare bleeds: CNS bleeds
    Severe <1% Frequent Spontaneous bleeds * Hemarthrosis, muscle Hematoma.* Also CNS bleeds, GI bleeds, hematuria

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    Description

    Test your knowledge on hemostasis, Sickle Cell Anemia, and β-thalassemia. This quiz covers important concepts such as inheritance patterns, clinical features, and key components involved in these blood disorders. Challenge yourself to match each disorder with its characteristics and understand the underlying mechanisms.

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