Questions and Answers
What is a common symptom of hereditary spherocytosis?
Which test is used to diagnose paroxysmal nocturnal hemoglobinuria?
What is the primary cause of hemolysis in G6PD deficiency?
Which of the following is a feature of pyruvate kinase deficiency?
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What triggers acute hemolysis in cold autoimmune hemolytic anemia?
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What is the main physiological effect of a mutation in the PIGA gene in paroxysmal nocturnal hemoglobinuria?
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Which condition is associated with a decrease in NADPH levels?
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What type of anemia is characterized by the presence of bite cells on a blood smear?
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What is the preferred treatment for warm autoimmune hemolytic anemia?
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Which of the following is true regarding hemoglobin C disease?
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What factor is essential for protecting red blood cells from complement-mediated lysis in paroxysmal nocturnal hemoglobinuria?
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Which of the following conditions involves intravascular hemolysis due to oxidant injury?
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What is the primary underlying genetic cause of hereditary spherocytosis?
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What symptom is commonly associated with paroxysmal nocturnal hemoglobinuria?
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Which test is utilized to confirm G6PD deficiency?
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Which of the following statements about pyruvate kinase deficiency is accurate?
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What is one of the main clinical features of hemoglobin C disease?
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What is a typical laboratory finding in G6PD deficiency during an oxidative crisis?
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In hereditary spherocytosis, what test is typically used to assess osmotic fragility of RBCs?
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Which statement accurately describes a treatment option for paroxysmal nocturnal hemoglobinuria?
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What is a key characteristic of the red blood cells in pyruvate kinase deficiency?
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Which of the following signs is often associated with G6PD deficiency during hemolysis?
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Which feature is typical in the blood smear of someone with hemoglobin C disease?
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In which condition is an eosin-5 maleimide (EMA) binding test particularly useful?
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During an acute hemolytic episode in G6PD deficiency, what may be falsely normal?
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Which phenomenon occurs when pyruvate kinase deficiency leads to increased levels of 2,3-BPG?
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What complication can arise in patients with paroxysmal nocturnal hemoglobinuria?
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Which of the following mutations is associated with hereditary spherocytosis?
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What is the primary pathophysiological consequence of G6PD deficiency?
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Which diagnosis is confirmed by a blood smear showing spherocytes?
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Which treatment is primarily used for paroxysmal nocturnal hemoglobinuria?
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What is a common sign of pyruvate kinase deficiency in newborns?
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What distinguishes macroangiopathic hemolytic anemia from other types?
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What unusual blood finding can be indicative of G6PD deficiency during oxidative stress?
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What is a major symptom associated with autoimmune hemolytic anemia?
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Which condition is characterized by hemolysis predominantly during nocturnal hours?
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Which condition is likely to show abnormal findings of Heinz and bite cells on a blood smear?
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Study Notes
Hereditary Spherocytosis
- Autosomal dominant disorder characterized by mutations in ankyrin, band 3, protein 4.2, and spectrin.
- Results in defective red blood cell membrane structure causing spherocyte formation.
- Spherocytes lose membrane surface relative to cell volume, leading to increased fragility and dehydration.
- Increased Mean Corpuscular Hemoglobin Concentration (MCHC) due to high hemoglobin concentration.
- Symptoms include aplastic crisis, splenomegaly, and pigmented gallstones.
- Diagnosis involves EMA binding test, decreased mean fluorescent RBCs, osmotic fragility test, and typical blood tests showing decreased MCV and abundant RBC count.
- Treatment typically involves splenectomy.
Paroxysmal Nocturnal Hemoglobinuria
- Caused by a mutation in haematopoietic stem cells.
- Impaired synthesis of GPI anchors due to PIGA gene mutation leads to absence of protective protein attachment on cell membranes.
- Red blood cells are susceptible to complement-mediated intravascular hemolysis, notably at night.
- Symptoms include pain, pink/red urine in the morning, and possible venous thrombosis.
- Diagnosis confirmed through flow cytometry on RBCs.
- Managed with eculizumab, targeting terminal complement protein C5.
G6PD Deficiency
- X-linked recessive condition leading to a defect in G6PD enzyme.
- G6PD is crucial for maintaining NADPH levels, which aid in regenerating reduced glutathione—important for protecting RBCs from oxidative damage.
- Deficiency causes oxidative stress hemolysis, especially triggered by specific drugs or substances like fava beans.
- Symptoms include back pain and hemoglobinuria developing a few days post-oxidant exposure.
- Diagnosis through blood smear revealing Heinz and bite cells; G6PD activity may appear normal during acute hemolysis.
Pyruvate Kinase Deficiency
- Autosomal recessive disorder affecting pyruvate kinase enzyme in glycolysis.
- Lack of ATP production leads to increased RBC rigidity and vulnerability to extravascular hemolysis.
- Compensatory rise in 2,3-bisphosphoglycerate reduces hemoglobin’s oxygen affinity, enhancing oxygen release in active tissues.
- Primarily presents as hemolytic anemia in newborns.
- Diagnosis includes blood smear indicating burr cells.
Hemoglobin C Disease
- Result of glutamic acid-to-lysine mutation in the β-globin gene leading to an autosomal recessive disorder.
- More severe manifestation occurs in homozygous HbC carriers; mild forms in heterozygous states with HbS gene.
- Hemoglobin SC disease results from a combination of the sickle cell trait and hemoglobin C.
- Diagnosis via blood smear displays hemoglobin crystals inside RBCs and target cells.
Autoimmune Hemolytic Anemia
- Etiology can be idiopathic or related to conditions like SLE and certain drugs.
- Warm variant involves IgG antibodies leading to RBC destruction (extravascular hemolysis).
- Cold variant mediated primarily by IgM antibodies triggers agglutination and hemolysis upon cold exposure.
- Symptoms commonly include acute anemia.
- Diagnosis through blood smear showing spherocytes; treatment for warm variant includes steroids and rituximab, while cold variant focuses on avoidance and rituximab.
Drug-Induced Hemolytic Anemia
- Triggered by various medications including antibiotics, antitubercular drugs, chemotherapy, and NSAIDs.
- Mechanism involves both antibody-mediated destruction and oxidative injury from drug metabolism.
- Diagnosis might reveal spherocytes indicating immune hemolysis or bite cells suggesting oxidative hemolysis in a blood smear.
Extrinsic Hemolytic Anemia
- Microangiopathic forms include conditions like DIC, TTP, HUS, SLE, and HELLP syndrome.
- Macroangiopathic forms include hemolysis related to prosthetic heart valves or aortic stenosis.
- Infection-related hemolysis noted in conditions such as malaria and Babesia.
- Diagnosis through blood smear commonly shows schistocytes indicative of extrinsic mechanisms.
Hereditary Spherocytosis
- Inherited condition primarily caused by autosomal dominant mutations.
- Mutations affect proteins like ankyrin, band 3, protein 4.2, and spectrin, resulting in abnormal red blood cell shapes (spherocytes).
- Spherocytes exhibit increased fragility and dehydration due to altered membrane structure, leading to elevated MCHC (Mean Corpuscular Hemoglobin Concentration).
- Common manifestations include splenomegaly, abdominal pain, and risk of aplastic crisis during parvovirus B19 infections.
- Diagnosis involves tests like the Eosin-5 maleimide binding test, osmotic fragility test, and evaluation of RBC count and MCHC.
- Treatment primarily consists of splenectomy to reduce hemolysis.
Paroxysmal Nocturnal Hemoglobinuria (PNH)
- Caused by mutations in hematopoietic stem cells, particularly affecting the PIGA gene.
- PIGA mutations lead to impaired synthesis of GPI anchors, crucial for protective proteins (CD55, CD59) that prevent complement-mediated hemolysis.
- This results in intravascular hemolysis, especially during sleep, leading to symptoms like pink or red urine and pancytopenia.
- Patients may also develop venous thrombosis like Budd-Chiari syndrome and are at risk of aplastic anemia or acute leukemia.
- Diagnosis confirmed via flow cytometry to assess RBC surface proteins.
- Treatment with eculizumab targets terminal complement protein C5.
G6PD Deficiency
- An X-linked recessive condition resulting from a defect in glucose-6-phosphate dehydrogenase (G6PD) enzyme.
- G6PD deficiency leads to decreased NADPH production, impairing the regeneration of reduced glutathione, which protects RBCs from oxidative stress.
- Vulnerable RBCs can undergo hemolysis after exposure to oxidative agents (sulfa drugs, antimalarials, fava beans), causing symptoms like back pain and hemoglobinuria.
- Diagnosis involves blood smear analysis showing Heinz and bite cells, while G6PD activity may appear normal during acute hemolysis.
- Management focuses on removing oxidative stressors and treating hemolysis.
Pyruvate Kinase Deficiency
- An autosomal recessive disorder stemming from defective pyruvate kinase, crucial for glycolysis.
- Insufficient ATP production from this defect leads to increased RBC rigidity and extravascular hemolysis.
- A compensatory rise in 2,3-bisphosphoglycerate (2,3-BPG) reduces hemoglobin's oxygen affinity, aiding oxygen release, but may compromise oxygen delivery to less active tissues.
- Hemolytic anemia is often evident in newborns, marked by distinctive presentation.
- Diagnosis includes blood smear observation for burr cells.
- Treatment revolves around managing hemolytic anemia.
Hemoglobin C Disease
- Result of a mutation in β-globin, causing alterations in hemoglobin structure and leading to hemolysis.
- Various forms exist, with HbSC disease being milder than sickle cell disease (HbSS).
- Patients can present with varying symptoms depending on the severity of the condition.
- Diagnosis typically involves a blood smear showing hemoglobin crystals and target cells.
- Management primarily targets alleviating hemolytic anemia symptoms.
Autoimmune & Drug-induced Hemolytic Anemia
- Autoimmune hemolysis can be idiopathic or triggered by warm and cold autoimmune mechanisms.
- Drug-induced hemolysis often involves antibiotics like penicillins and cephalosporins.
- Conditions causing extrinsic hemolytic anemias include mechanical RBC damage from heart valves or infections such as malaria and Babesia.
- Diagnosis and treatment vary based on the underlying cause and severity of hemolytic anemia.
Hereditary Spherocytosis
- Aetiology involves mutations in genes for ankyrin, band 3, protein 4.2, and spectrin.
- Pathophysiology characterized by defective vertical interactions of RBC membrane proteins, leading to reduced surface area and increased spherical shape.
- Spherocytes are fragile and prone to hemolysis.
- Signs include aplastic crisis, especially after parvovirus B19, splenomegaly, and pigmented gallstones.
- Diagnosis includes EMA binding test, osmotic fragility test, and examination of RBC morphology; elevated MCHC and abundant RBC count noted.
- Treatment involves splenectomy, improving RBC lifespan.
Paroxysmal Nocturnal Haemoglobinuria
- Caused by a mutation in haematopoietic stem cells.
- Critical for GPI anchor biosynthesis, impacting cell membrane integrity.
- Symptoms include hemolysis at night, pain, and venous thrombosis.
- Diagnosed using flow cytometry, revealing negative results on RBC.
- Treatment with eculizumab, targeting complement protein C5.
G6PD Deficiency
- Inherited in an X-linked recessive manner.
- Results in decreased NADPH, weakening RBCs against oxidative stress.
- Symptoms include back pain and hemoglobinuria following oxidant exposure.
- Diagnosis features blood smear showing Heinz and bite cells.
- Treatment focuses on avoiding triggers to prevent hemolysis.
Pyruvate Kinase Deficiency
- An autosomal recessive disorder affecting ATP production in RBCs.
- Secondary increase in 2,3-bisphosphoglycerate, impacting oxygen delivery.
- Hemolytic anemia is evident, particularly in newborns.
- Diagnosis found through blood smear showing burr cells.
Hemoglobin C Disease
- Involves a mutation where glutamic acid is replaced by lysine in β-globin.
- Leads to structural hemoglobinopathy, potentially causing sickle cell disease when homozygous.
- Hemolytic anemia primarily presents in newborns.
- Diagnosis through blood smear shows hemoglobin crystals and target cells.
Autoimmune Haemolytic Anaemia
- Aetiologies include warm and cold autoimmune conditions, often idiopathic.
- Antibodies, mainly IgG, target and destroy RBCs via extravascular hemolysis.
- Symptoms feature acute anemia.
- Diagnosed with a blood smear exhibiting spherocytes and agglutinated RBCs.
- Treatment includes corticosteroids and rituximab for refractory cases.
Drug-Induced Haemolytic Anaemia
- Associated with various antibiotics, antituberculous drugs, and chemotherapy.
- Mechanisms include antibody-mediated destruction and oxidative injury from free radicals.
- Presents as rutin anemia.
- Diagnosis via blood smear displaying spherocytes and bite cells.
Extrinsic Haemolytic Anaemia
Microangiopathic Haemolytic Anaemia
- Causes include DIC, TTP, HUS, SLE, hypertensive emergencies, and HELLP syndrome.
- RBCs experience damage when traversing narrowed or obstructed vessels.
- Diagnosis involves blood smear showing schistocytes.
Macroangiopathic Haemolytic Anaemia
- Typically caused by prosthetic heart valves or aortic stenosis.
- These conditions mechanically destroy RBCs.
- Diagnosis via blood smear showing spherocytes.
Haemolytic Anaemia Due to Infection
- Caused by pathogens such as malaria and Babesia.
- Results in direct destruction of RBCs.
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Description
This quiz covers key concepts related to hereditary spherocytosis and paroxysmal nocturnal hemoglobinuria. Learn about their genetic causes, symptoms, diagnostic methods, and treatment options. Test your understanding of these blood disorders and their implications on health.
