Haematology Flashcards
(420 cards)
1
Q
What is the definition of anemia in children?
A
Reduction in hemoglobin concentration or red cell mass below the normal range for age and sex.
2
Q
What are normal hemoglobin levels in neonates, infants, and older children?
A
Neonate: 14–20 g/dL; Infant (2 months): ~10–11 g/dL; Child: ~11.5–13.5 g/dL.
3
Q
What are the major mechanisms of anemia?
A
Decreased production, increased destruction (hemolysis), or blood loss.
4
Q
What are the key clinical signs of anemia?
A
Pallor, tachycardia, fatigue, murmurs, congestive heart failure signs in severe cases.
5
Q
What is the first step in evaluating a child with anemia?
A
History, physical examination, complete blood count (CBC) with RBC indices.
6
Q
What is the significance of mean corpuscular volume (MCV) in anemia evaluation?
A
Helps classify anemia as microcytic, normocytic, or macrocytic to guide differential diagnosis.
7
Q
What are causes of microcytic anemia?
A
Iron deficiency, thalassemia, lead poisoning, anemia of chronic disease (rarely microcytic).
8
Q
What are causes of normocytic anemia?
A
Acute blood loss, hemolysis, anemia of chronic disease, marrow failure syndromes.
9
Q
What are causes of macrocytic anemia?
A
Vitamin B12 deficiency, folate deficiency, hypothyroidism, bone marrow failure syndromes.
10
Q
What is the role of the reticulocyte count in anemia evaluation?
A
Determines bone marrow response: high = active response, low = impaired production.
11
Q
What does a high reticulocyte count indicate?
A
Suggests blood loss or hemolysis.
12
Q
What does a low reticulocyte count suggest?
A
Suggests decreased red cell production (e.g., marrow suppression, nutritional deficiency).
13
Q
What is the significance of red cell distribution width (RDW)?
A
Increased RDW suggests anisocytosis (variation in RBC size), common in iron deficiency anemia.
14
Q
What laboratory investigations are essential in anemia workup?
A
CBC with indices, reticulocyte count, peripheral smear, iron studies, sometimes bone marrow studies.
15
Q
What is the significance of a blood smear in anemia?
A
Can reveal morphological abnormalities supporting diagnosis (e.g., spherocytes, schistocytes, target cells).
16
Q
What is the approach to anemia based on MCV and reticulocyte count?
A
Classify by MCV (low, normal, high) and reticulocyte response (high vs low).
17
Q
What is the differential diagnosis of microcytic anemia?
A
Iron deficiency, thalassemias, anemia of chronic disease (early stages), lead poisoning, sideroblastic anemia.
18
Q
What are the features of iron deficiency anemia?
A
Low MCV, high RDW, hypochromic microcytic RBCs, low ferritin, high TIBC.
19
Q
What are the features of thalassemia minor?
A
Mild microcytic anemia, normal RDW, target cells on smear, normal or slightly elevated RBC count.
20
Q
What is the differential diagnosis of macrocytic anemia?
A
Vitamin B12 deficiency, folate deficiency, hypothyroidism, Diamond-Blackfan anemia, drugs.
21
Q
What are common causes of normocytic anemia with low reticulocyte count?
A
Anemia of chronic disease, early aplastic anemia, renal failure (low EPO production).
22
Q
What are causes of anemia with elevated reticulocyte count?
A
Hemolysis (hereditary spherocytosis, G6PD deficiency) or acute blood loss.
23
Q
What are signs of hemolysis on laboratory evaluation?
A
Elevated indirect bilirubin, elevated LDH, low haptoglobin, positive Coombs test.
24
Q
What inherited disorders cause hemolytic anemia?
A
Hereditary spherocytosis, G6PD deficiency, sickle cell disease, thalassemia major.
25
What acquired disorders cause hemolytic anemia?
Autoimmune hemolytic anemia, hemolytic uremic syndrome, infections (malaria, parvovirus B19).
26
When should bone marrow examination be considered in anemia?
Unexplained anemia, pancytopenia, suspicion of leukemia, refractory anemia.
27
What is the approach to acute severe anemia?
Stabilization (oxygen, fluids), transfusion if Hb <6–7 g/dL or symptomatic.
28
What is the approach to chronic mild anemia?
Determine cause and severity, monitor, supplement nutrients if deficiency identified.
29
How do infections contribute to anemia?
Parvovirus B19 causes transient red cell aplasia; malaria causes hemolysis and anemia.
30
What are indications for blood transfusion in pediatric anemia?
Symptomatic anemia, Hb <6–7 g/dL, signs of heart failure, severe hypoxia.
31
What is iron deficiency anemia (IDA)?
A microcytic, hypochromic anemia caused by insufficient iron for hemoglobin synthesis.
32
What are the main causes of IDA in children?
Inadequate dietary intake, blood loss (e.g., GI bleeding, heavy menses), rapid growth.
33
What are dietary risk factors for IDA in infants?
Exclusive breastfeeding beyond 6 months without iron supplementation, excessive cow's milk intake.
34
What are key clinical features of IDA?
Pallor, fatigue, irritability, tachycardia, spoon-shaped nails (koilonychia).
35
How does pica relate to iron deficiency?
Pica (eating non-food items like dirt or ice) is associated with iron deficiency.
36
What is the typical MCV in iron deficiency anemia?
Low MCV (<80 fL), typically microcytic anemia.
37
What laboratory findings are typical in IDA?
Low hemoglobin, low MCV, high RDW, low ferritin, low serum iron, high TIBC.
38
What happens to RDW in iron deficiency anemia?
RDW is typically elevated, indicating variable RBC sizes.
39
What are classic peripheral smear findings in IDA?
Microcytosis, hypochromia, anisopoikilocytosis, pencil-shaped cells.
40
How is ferritin affected in IDA?
Ferritin is low in true iron deficiency; it is the best early indicator.
41
What is the role of serum iron and TIBC in IDA diagnosis?
Serum iron is low; TIBC is elevated (iron-binding capacity increases).
42
What are early signs of iron deficiency before anemia develops?
Restlessness, irritability, poor concentration, poor growth.
43
How does iron deficiency affect neurodevelopment in children?
Associated with cognitive delay, impaired learning, behavioral problems.
44
What is the gold standard test for diagnosing IDA?
Low serum ferritin combined with low hemoglobin and microcytosis.
45
What dietary interventions can prevent IDA in infants?
Iron-fortified cereals, iron-fortified formula, meat introduction after 6 months.
46
When is iron supplementation recommended in infancy?
At 4–6 months of age for exclusively breastfed infants.
47
What are sources of dietary iron?
Meats (heme iron), legumes, leafy greens, iron-fortified cereals.
48
What is the recommended iron supplementation dose for prevention?
1 mg/kg/day of elemental iron starting at 4 months for at-risk infants.
49
What is the treatment dose of elemental iron for IDA?
3–6 mg/kg/day of elemental iron divided once or twice daily.
50
How should oral iron be administered for optimal absorption?
On an empty stomach, with vitamin C to enhance absorption.
51
What are common side effects of oral iron therapy?
Nausea, constipation, diarrhea, dark stools.
52
How is response to iron therapy monitored?
Reticulocytosis in 5–7 days, rise in hemoglobin by 2–4 weeks.
53
When should a lack of response to iron therapy prompt further evaluation?
If no Hb improvement after 4 weeks of adherence to iron therapy.
54
What is functional iron deficiency?
Adequate iron stores but impaired utilization due to inflammation or chronic disease.
55
What are causes of iron-refractory iron deficiency anemia (IRIDA)?
Mutation in TMPRSS6 gene causing hepcidin dysregulation and refractory IDA.
56
What is the role of hepcidin in iron regulation?
Hepcidin inhibits intestinal iron absorption and release from macrophages.
57
What infections can cause impaired iron absorption?
Helicobacter pylori infection can impair iron absorption.
58
How does chronic inflammation affect iron metabolism?
Inflammation increases hepcidin, reducing iron availability.
59
When is intravenous iron indicated in pediatric patients?
Severe anemia, intolerance to oral iron, malabsorption, noncompliance.
60
What are the long-term risks of untreated IDA in children?
Neurocognitive deficits, behavioral problems, poor academic performance, growth retardation.
61
What is megaloblastic anemia?
A macrocytic anemia characterized by impaired DNA synthesis leading to large, immature RBC precursors.
62
What is the hallmark blood smear finding in megaloblastic anemia?
Macro-ovalocytes and hypersegmented neutrophils on peripheral blood smear.
63
What are the most common causes of megaloblastic anemia in children?
Vitamin B12 deficiency and folate deficiency.
64
What is the role of vitamin B12 in the body?
Required for DNA synthesis and neurologic function (myelin synthesis).
65
What is the role of folate in the body?
Required for DNA synthesis and rapidly dividing cells (e.g., bone marrow, gut epithelium).
66
What is the pathophysiology of megaloblastic anemia?
Defective DNA synthesis leads to delayed nuclear maturation and cell division, causing large, immature cells.
67
What are key clinical features of vitamin B12 deficiency?
Fatigue, pallor, glossitis, weight loss, neurological symptoms (paresthesias, ataxia, dementia).
68
What are clinical features specific to folate deficiency?
Fatigue, pallor, glossitis, without neurologic findings.
69
What are neurologic manifestations of vitamin B12 deficiency?
Paresthesias, loss of vibration and proprioception, ataxia, cognitive decline.
70
Why are neurologic signs absent in folate deficiency?
Folate is not involved in neurologic pathways like vitamin B12.
71
What are common dietary causes of folate deficiency?
Poor diet, malabsorption, increased demand (pregnancy), chronic alcohol use.
72
What conditions cause vitamin B12 deficiency?
Pernicious anemia, malabsorption (e.g., Crohn's disease), ileal resection, bacterial overgrowth, vegan diet.
73
What is pernicious anemia?
Autoimmune destruction of gastric parietal cells leading to intrinsic factor deficiency.
74
What gastrointestinal disorders can lead to B12 deficiency?
Celiac disease, Crohn’s disease, short bowel syndrome (especially ileal disease).
75
What medications can cause folate deficiency?
Phenytoin, methotrexate, sulfasalazine, trimethoprim.
76
What lab findings suggest megaloblastic anemia?
Low hemoglobin, high MCV (>100 fL), low reticulocytes, hypersegmented neutrophils.
77
What are characteristic RBC indices in megaloblastic anemia?
High MCV, often >100 fL; elevated RDW.
78
What happens to WBCs and platelets in severe megaloblastic anemia?
Leukopenia and thrombocytopenia can be present in severe cases (pancytopenia).
79
What are hypersegmented neutrophils?
Neutrophils with 5 or more nuclear lobes; highly specific for megaloblastic anemia.
80
What is the significance of LDH and indirect bilirubin elevation in megaloblastic anemia?
Reflect ineffective erythropoiesis and intramedullary hemolysis.
81
How is vitamin B12 deficiency confirmed biochemically?
Low serum B12 level, elevated methylmalonic acid and homocysteine levels.
82
What is the Schilling test?
An older test measuring absorption of radioactive B12; rarely used today.
83
Is the Schilling test still routinely used?
No, it has been largely replaced by serum B12 and metabolite measurements.
84
What serum markers are elevated in B12 deficiency but not in folate deficiency?
Elevated methylmalonic acid and homocysteine in B12 deficiency; only homocysteine elevated in folate deficiency.
85
How is folate deficiency diagnosed?
Low serum folate level or low RBC folate level (more reliable).
86
What is the first step in treating megaloblastic anemia?
Correct the specific deficiency (B12 or folate) and treat underlying cause if present.
87
How is vitamin B12 administered for treatment?
Intramuscular injection initially, then maintenance oral therapy in some cases.
88
What is the risk of treating B12 deficiency with folate alone?
It can correct anemia but allow neurologic damage to progress.
89
What is the response timeline after initiating therapy for megaloblastic anemia?
Reticulocytosis within 5–7 days, hemoglobin rise by 2–3 weeks, resolution of symptoms over months.
90
What are causes of combined vitamin B12 and folate deficiencies?
Poor nutrition, chronic alcoholism, malabsorption syndromes, severe gastrointestinal disease.
91
What is hemolytic anemia?
Anemia caused by premature destruction of red blood cells.
92
What are the main mechanisms of hemolysis?
Intrinsic red cell defects or extrinsic factors like antibodies, mechanical damage, toxins.
93
How is hemolytic anemia classified?
Inherited (intrinsic) vs acquired (extrinsic); intravascular vs extravascular.
94
What are common symptoms of hemolytic anemia?
Pallor, jaundice, dark urine, fatigue, splenomegaly.
95
What are lab findings suggestive of hemolysis?
Elevated reticulocyte count, indirect bilirubin, LDH; low haptoglobin, possible hemoglobinuria.
96
What are examples of intrinsic causes of hemolytic anemia?
Hereditary spherocytosis, G6PD deficiency, sickle cell disease, thalassemia.
97
What are examples of extrinsic causes of hemolytic anemia?
Autoimmune hemolysis, infections, toxins, DIC, HUS, hypersplenism.
98
What is hereditary spherocytosis?
A membrane defect causing spherical RBCs that are trapped in the spleen.
99
What are clinical features of hereditary spherocytosis?
Anemia, jaundice, splenomegaly, gallstones, family history.
100
What tests help diagnose hereditary spherocytosis?
Osmotic fragility test, EMA-binding test, blood smear showing spherocytes.
101
What is the treatment for hereditary spherocytosis?
Folic acid, splenectomy in moderate/severe cases, transfusions as needed.
102
What is G6PD deficiency?
X-linked enzymatic defect that leads to oxidative RBC damage and hemolysis.
103
What are triggers of hemolysis in G6PD deficiency?
Infections, certain drugs (sulfa, antimalarials), fava beans.
104
What is the typical blood smear finding in G6PD deficiency?
Bite cells and Heinz bodies.
105
What is the inheritance pattern of G6PD deficiency?
X-linked recessive; mainly affects males.
106
What is autoimmune hemolytic anemia (AIHA)?
Anemia due to autoantibodies targeting red blood cells.
107
What are the types of AIHA?
Warm AIHA (IgG-mediated) and Cold agglutinin disease (IgM-mediated).
108
What is the role of the Coombs test in AIHA?
Direct Coombs (DAT) test detects antibodies or complement on RBCs.
109
What are causes of secondary AIHA?
SLE, infections (EBV, Mycoplasma), malignancy, drugs.
110
What is the treatment for warm AIHA?
Steroids, IVIG, immunosuppressants, splenectomy if refractory.
111
What is cold agglutinin disease?
Hemolysis due to IgM antibodies at low temperatures; often post-infectious.
112
How is cold agglutinin disease managed?
Keep patient warm, treat underlying condition, rituximab for severe cases.
113
What is paroxysmal nocturnal hemoglobinuria (PNH)?
Acquired clonal disorder with complement-mediated intravascular hemolysis.
114
What are features of intravascular hemolysis?
Hemoglobinemia, hemoglobinuria, hemosiderinuria, low haptoglobin.
115
What is microangiopathic hemolytic anemia (MAHA)?
Hemolysis due to mechanical damage to RBCs in small vessels.
116
What are causes of MAHA in children?
HUS, TTP, DIC, severe hypertension, malignancy.
117
What is the hallmark blood smear finding in MAHA?
Schistocytes (fragmented RBCs).
118
What is hemolytic uremic syndrome (HUS)?
A thrombotic microangiopathy often following E. coli O157:H7 infection.
119
What are the classic triad of HUS?
Microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury.
120
How is HUS managed?
Supportive care, dialysis if needed, avoid antibiotics and antidiarrheals during active E. coli infection.
121
What is thalassemia?
A group of inherited disorders caused by decreased synthesis of globin chains in hemoglobin.
122
What are the types of thalassemia?
Alpha-thalassemia and beta-thalassemia.
123
What is the pathophysiology of thalassemia?
Imbalance in globin chain production leads to ineffective erythropoiesis and hemolysis.
124
What is the genetic basis of beta-thalassemia?
Mutations in the HBB gene on chromosome 11 affecting beta-globin production.
125
What are the clinical forms of beta-thalassemia?
Beta-thalassemia major, intermedia, and minor.
126
What are features of beta-thalassemia major?
Severe anemia, transfusion dependence, growth retardation, bone deformities, splenomegaly.
127
At what age does beta-thalassemia major usually present?
Usually after 6 months of age as fetal hemoglobin declines.
128
What are typical lab findings in beta-thalassemia major?
Low Hb, microcytosis, high reticulocytes, elevated indirect bilirubin, elevated LDH, low haptoglobin.
129
What are characteristic findings on peripheral smear in beta-thalassemia?
Microcytosis, target cells, anisopoikilocytosis, basophilic stippling.
130
What are radiologic findings in thalassemia major?
Crew-cut skull, widened diploic space, thinned cortex, expansion of marrow spaces.
131
What is the role of hemoglobin electrophoresis in diagnosis?
Shows increased HbF, increased HbA2 in beta-thalassemia; absent HbA in major.
132
What is the treatment for beta-thalassemia major?
Regular transfusions, iron chelation, folate, splenectomy if needed, stem cell transplant.
133
What is iron overload and why does it occur in thalassemia?
From repeated transfusions and increased intestinal absorption due to ineffective erythropoiesis.
134
What are complications of iron overload?
Cardiomyopathy, liver fibrosis, diabetes, growth failure, hypogonadism.
135
How is iron overload monitored?
Serum ferritin, liver MRI (T2*), cardiac T2* MRI.
136
What is the role of iron chelation therapy?
Prevents organ damage by removing excess iron.
137
What are common iron chelators used in thalassemia?
Deferoxamine (parenteral), deferasirox and deferiprone (oral).
138
What are indications for splenectomy in thalassemia?
Hypersplenism, high transfusion requirement, symptomatic splenomegaly.
139
What is the role of stem cell transplant in beta-thalassemia?
Only curative option; best outcomes in young children with matched donor.
140
What is beta-thalassemia intermedia?
Moderate anemia, occasional transfusions, less severe than major.
141
What are clinical features of beta-thalassemia minor?
Asymptomatic or mild anemia, often discovered incidentally.
142
How is beta-thalassemia minor diagnosed?
Normal iron studies, elevated HbA2 on electrophoresis.
143
How does beta-thalassemia minor differ from iron deficiency anemia?
Thalassemia minor: normal RDW, target cells, increased RBC count; IDA: low ferritin, high RDW.
144
What is alpha-thalassemia?
Decreased synthesis of alpha-globin chains due to gene deletions on chromosome 16.
145
What are the clinical forms of alpha-thalassemia?
Silent carrier (1 deletion), trait (2 deletions), HbH disease (3 deletions), hydrops fetalis (4 deletions).
146
What is Hemoglobin Bart's hydrops fetalis?
Lethal condition due to complete absence of alpha chains; causes intrauterine death.
147
What is Hemoglobin H disease?
Moderate hemolytic anemia with presence of HbH (β4 tetramers).
148
What is silent carrier state in alpha-thalassemia?
Asymptomatic carrier with normal blood count or mild microcytosis.
149
How is alpha-thalassemia diagnosed?
Gap-PCR and DNA analysis; HbH inclusions on smear (brilliant cresyl blue).
150
What is the treatment for alpha-thalassemia?
Supportive; HbH disease may need transfusions; no treatment for trait or silent carrier.
151
What is aplastic anemia?
A bone marrow failure syndrome characterized by pancytopenia and hypocellular marrow.
152
What is the pathophysiology of aplastic anemia?
Destruction or failure of hematopoietic stem cells leads to decreased production of all blood lines.
153
What are the primary types of aplastic anemia?
Inherited (e.g., Fanconi anemia) and acquired (idiopathic, drugs, infections, radiation).
154
What are common acquired causes of aplastic anemia?
Drugs (chloramphenicol, NSAIDs), toxins, viral infections (hepatitis, EBV, HIV), autoimmune disorders.
155
What is Fanconi anemia?
An autosomal recessive disorder causing chromosomal instability and bone marrow failure.
156
What are clinical features of Fanconi anemia?
Short stature, café-au-lait spots, thumb/radial anomalies, pancytopenia, increased malignancy risk.
157
What investigations help diagnose Fanconi anemia?
Chromosomal breakage test (DEB test), genetic testing for FANCA mutations.
158
What is dyskeratosis congenita?
A telomere biology disorder causing marrow failure and mucocutaneous abnormalities.
159
What are features of dyskeratosis congenita?
Abnormal skin pigmentation, nail dystrophy, leukoplakia, pulmonary fibrosis, bone marrow failure.
160
What are common presenting symptoms of aplastic anemia?
Fatigue, infections, mucosal bleeding, bruising, pallor.
161
What lab findings are characteristic of aplastic anemia?
Pancytopenia with low reticulocyte count, normal or slightly elevated MCV, low neutrophils/platelets.
162
What are findings on bone marrow biopsy in aplastic anemia?
Hypocellular marrow with fatty replacement, no blasts or abnormal infiltrates.
163
What is the difference between aplastic anemia and leukemia?
Leukemia has blasts and hypercellular marrow; aplastic anemia has hypocellular marrow without blasts.
164
What infections can cause aplastic anemia?
Hepatitis viruses (non-A-E), EBV, HIV, CMV, parvovirus B19.
165
What drugs are commonly associated with aplastic anemia?
Chloramphenicol, sulfonamides, anticonvulsants, gold salts, chemotherapy agents.
166
What is the role of parvovirus B19 in marrow failure?
Can cause pure red cell aplasia, especially in sickle cell or immunocompromised patients.
167
What is the reticulocyte count in aplastic anemia?
Low due to suppressed erythropoiesis.
168
What are the criteria for severe aplastic anemia (SAA)?
Two of the following: ANC <500/μL, Plt <20,000/μL, Retic <20,000/μL with hypocellular marrow.
169
What are the criteria for very severe aplastic anemia?
Same as SAA with ANC <200/μL.
170
What is the first-line treatment for SAA in children?
Allogeneic hematopoietic stem cell transplant (HSCT) from HLA-matched sibling donor.
171
When is stem cell transplant indicated in aplastic anemia?
First-line for children with matched sibling donor; early transplant improves survival.
172
What is immunosuppressive therapy (IST) for aplastic anemia?
Used when no matched donor available or transplant is contraindicated.
173
Which agents are used in IST?
Antithymocyte globulin (ATG) + cyclosporine ± eltrombopag.
174
What are complications of immunosuppressive therapy?
Infections, serum sickness, renal toxicity, risk of relapse or clonal evolution.
175
What are supportive care measures in aplastic anemia?
Growth factor support, transfusions (irradiated, leukoreduced), infection prophylaxis.
176
Why should blood transfusions be minimized before transplant?
Reduces risk of alloimmunization and graft rejection.
177
What is the prognosis of untreated severe aplastic anemia?
High mortality; median survival <6 months without treatment.
178
What is clonal evolution in aplastic anemia?
Development of clonal disorders like MDS, PNH, AML after IST or over time.
179
What are signs of transformation to MDS or leukemia?
Rising blasts, new cytogenetic abnormalities, worsening cytopenias.
180
How is long-term follow-up done in aplastic anemia?
Regular CBCs, bone marrow assessments, cytogenetics, PNH clone monitoring.
181
What is immune thrombocytopenia (ITP)?
An autoimmune condition causing isolated thrombocytopenia due to destruction of platelets by antiplatelet antibodies.
182
What is the pathophysiology of ITP?
Autoantibodies target platelet surface antigens, leading to destruction in the spleen.
183
What are the typical age and onset of ITP in children?
Most common in children aged 2–7 years; often sudden onset after viral infection.
184
What are the clinical features of ITP?
Petechiae, purpura, mucosal bleeding (epistaxis, oral), rarely serious bleeding.
185
What is the typical platelet count in ITP?
Often <20,000/μL at presentation; normal WBCs and hemoglobin.
186
What is the most common cause of acute thrombocytopenia in healthy children?
ITP (especially post-viral ITP).
187
What viral illnesses commonly precede ITP?
EBV, CMV, varicella, rubella, influenza, COVID-19.
188
What is the difference between acute and chronic ITP?
Acute ITP resolves within 3–12 months; chronic ITP persists >12 months.
189
What is the definition of chronic ITP?
Platelet count <100,000/μL for >12 months without secondary causes.
190
What are the diagnostic criteria for ITP?
Isolated thrombocytopenia with normal WBC and Hb, normal exam except for bleeding signs.
191
What is the role of peripheral smear in ITP evaluation?
To rule out pseudothrombocytopenia, leukemia, and confirm isolated thrombocytopenia.
192
What tests help exclude secondary causes of thrombocytopenia?
ANA, HIV, hepatitis panel, antiphospholipid antibodies if systemic symptoms.
193
When is bone marrow examination indicated in ITP?
If atypical presentation (e.g., hepatosplenomegaly, lymphadenopathy, pancytopenia).
194
What are the red flags that suggest other causes than ITP?
Fever, weight loss, hepatosplenomegaly, lymphadenopathy, pancytopenia suggest leukemia or other causes.
195
What is the natural course of ITP in children?
80–90% of children recover within 6–12 months without treatment.
196
When is treatment indicated in ITP?
Platelet count <10,000/μL or active bleeding, or risk factors (trauma, surgery).
197
What is first-line treatment for ITP in symptomatic patients?
IVIG, corticosteroids, anti-D immunoglobulin (in Rh+ patients).
198
What is the mechanism of IVIG in ITP treatment?
Blocks Fc receptors in macrophages, reducing platelet destruction.
199
What is the role of corticosteroids in ITP?
Suppresses autoantibody production and immune-mediated destruction of platelets.
200
What is the dose and duration of corticosteroids in ITP?
Prednisone 1–2 mg/kg/day for 5–7 days or pulse dexamethasone 0.6 mg/kg/day for 4 days.
201
What are the risks of long-term steroid use?
Weight gain, hypertension, hyperglycemia, growth suppression, mood changes.
202
What are second-line treatments for chronic or refractory ITP?
Rituximab, TPO receptor agonists (eltrombopag, romiplostim), splenectomy.
203
What is the role of splenectomy in ITP?
Considered in chronic ITP unresponsive to medical therapy, usually after age 5.
204
What are the risks of splenectomy in children?
Sepsis from encapsulated organisms, thromboembolism.
205
What vaccinations are required before splenectomy?
Pneumococcal, meningococcal, and Haemophilus influenzae type b vaccines.
206
What is rituximab and how does it work in ITP?
Anti-CD20 monoclonal antibody that depletes B cells and reduces autoantibody production.
207
What are thrombopoietin receptor agonists (TPO-RAs)?
Drugs that stimulate platelet production by mimicking thrombopoietin.
208
What are examples of TPO receptor agonists used in ITP?
Eltrombopag (oral), romiplostim (subcutaneous).
209
What precautions should be taken in children with severe thrombocytopenia?
Avoid trauma, NSAIDs, sports; maintain safe environment; educate family.
210
What is the prognosis of pediatric ITP?
Excellent in most children; majority recover fully, even without treatment.
211
What is hemophilia?
An inherited bleeding disorder due to deficiency of clotting factor VIII or IX.
212
What are the types of hemophilia?
Hemophilia A (factor VIII deficiency) and Hemophilia B (factor IX deficiency).
213
What is the inheritance pattern of hemophilia?
X-linked recessive; affects males, females are usually carriers.
214
What is the pathophysiology of hemophilia A and B?
Impaired thrombin generation due to missing intrinsic clotting factor.
215
What clotting factors are deficient in hemophilia A and B?
Hemophilia A: factor VIII; Hemophilia B: factor IX.
216
What are the severity classifications of hemophilia?
Mild (>5%), moderate (1–5%), severe (<1%) of normal factor activity.
217
What are common clinical features of hemophilia?
Spontaneous bleeding, hemarthrosis, muscle hematomas, prolonged bleeding after injury/surgery.
218
What is hemarthrosis and which joints are most commonly affected?
Bleeding into joints, especially knees, ankles, and elbows.
219
What types of bleeding are uncommon in hemophilia?
Petechiae and mucosal bleeding (more typical of platelet disorders).
220
What is the most serious complication of hemophilia?
Intracranial hemorrhage, especially after trauma.
221
What laboratory tests are used to screen for hemophilia?
Prolonged aPTT, normal PT, bleeding time, and platelet count.
222
What are typical lab findings in hemophilia?
Isolated prolonged aPTT; factor assays confirm specific deficiency.
223
Why is PT normal in hemophilia?
Hemophilia affects the intrinsic pathway; PT tests the extrinsic pathway.
224
How is the diagnosis of hemophilia confirmed?
By factor VIII or IX assay; genetic testing may follow.
225
What are the differences between hemophilia A and B?
Clinically similar; both cause joint and muscle bleeds; differ only by deficient factor.
226
What is the role of genetic testing in hemophilia?
Helps identify carriers, confirm diagnosis, and plan family counseling.
227
How is hemophilia managed acutely during bleeding episodes?
IV infusion of clotting factor concentrates to achieve hemostasis.
228
What are the target factor levels for minor and major bleeds?
Minor bleed: raise factor to 30–50%; major bleed or surgery: raise to 80–100%.
229
What is the role of DDAVP (desmopressin) in hemophilia?
A synthetic vasopressin analog that increases plasma levels of factor VIII and vWF.
230
Which type of hemophilia responds to DDAVP?
Mild hemophilia A only.
231
What are the indications for prophylactic factor replacement?
Severe hemophilia or frequent bleeds; started early in life to prevent joint disease.
232
What are the types of factor replacement therapy?
Plasma-derived or recombinant factor VIII/IX; given on-demand or as prophylaxis.
233
What are inhibitors in hemophilia?
Neutralizing antibodies against factor VIII or IX that reduce treatment efficacy.
234
How are inhibitors detected?
By Bethesda assay.
235
How are bleeding episodes treated in patients with inhibitors?
By bypassing agents like activated prothrombin complex concentrate (aPCC) or recombinant factor VIIa.
236
What is immune tolerance induction therapy?
Therapy to eliminate inhibitors by repeated high-dose factor exposure.
237
What are non-factor therapies for hemophilia?
Emicizumab: a bispecific antibody mimicking factor VIII function (for hemophilia A).
238
What are complications of recurrent joint bleeds?
Chronic synovitis, joint deformity, pain, limited mobility (hemophilic arthropathy).
239
What preventive strategies are important in hemophilia care?
Avoid IM injections, trauma prevention, dental hygiene, hepatitis B vaccination.
240
What is the prognosis of a child with hemophilia today?
With appropriate treatment and prophylaxis, most children have near-normal life expectancy and quality of life.
241
What is von Willebrand disease (vWD)?
An inherited bleeding disorder caused by deficiency or dysfunction of von Willebrand factor.
242
What is the function of von Willebrand factor (vWF)?
Mediates platelet adhesion to damaged endothelium and stabilizes circulating factor VIII.
243
What are the types of vWD?
Type 1 (partial quantitative deficiency), Type 2 (qualitative defects), Type 3 (complete deficiency).
244
What is the most common inherited bleeding disorder?
Type 1 vWD.
245
How is vWD inherited?
Autosomal dominant for types 1 and 2; autosomal recessive for type 3.
246
What is the pathophysiology of vWD?
Defective platelet adhesion and/or reduced factor VIII levels impair clot formation.
247
What are the clinical features of vWD?
Mucocutaneous bleeding, easy bruising, epistaxis, menorrhagia, prolonged bleeding.
248
What type of bleeding is common in vWD?
Platelet-type bleeding: mucosal and skin; coagulation-type: deep tissues, joints.
249
What is the difference between platelet-type bleeding and coagulation-type bleeding?
In von Willebrand Disease (vWD), the bleeding can resemble either platelet-type or coagulation-type bleeding, depending on the subtype and severity:
Platelet-type bleeding occurs due to impaired platelet adhesion caused by defective or deficient von Willebrand Factor (vWF). This is common in Type 1 and Type 2 vWD. It presents with mucocutaneous bleeding, such as nosebleeds, gum bleeding, easy bruising, and heavy menstrual bleeding. Bleeding time is prolonged, but aPTT may be normal or mildly prolonged. Factor VIII levels are usually normal or only slightly reduced.
Coagulation-type bleeding results from significantly reduced Factor VIII levels, which vWF normally protects from degradation. This is seen in severe Type 3 vWD. It leads to deep tissue bleeding, including joint bleeds (hemarthroses), muscle hematomas, and delayed bleeding after surgery or trauma. In this case, aPTT is markedly prolonged, and Factor VIII levels are very low, while bleeding time may be normal or slightly prolonged.
Key Point:
Mild or moderate vWD presents with platelet-type bleeding, while severe vWD (especially Type 3) shows coagulation-type bleeding due to combined vWF and FVIII deficiency.
250
What are the typical bleeding sites in vWD?
Nosebleeds, gum bleeding, menorrhagia, GI bleeding, prolonged post-surgical bleeding.
251
What are the differences between type 1 and type 2 vWD?
Type 1 is a quantitative defect; Type 2 is qualitative (abnormal vWF function).
252
What is type 3 vWD?
Severe form with undetectable vWF and markedly low factor VIII.
253
What is the inheritance pattern of type 3 vWD?
Autosomal recessive.
254
What lab tests are used to evaluate vWD?
vWF antigen, vWF activity (ristocetin cofactor), factor VIII activity, bleeding time.
255
What are the typical lab findings in vWD?
Prolonged bleeding time, decreased vWF activity, ± low factor VIII depending on type.
256
How is bleeding time affected in vWD?
Usually prolonged.
257
What is the ristocetin cofactor assay?
Measures vWF activity by evaluating platelet agglutination with ristocetin.
258
What is the vWF antigen assay?
Quantifies vWF protein in plasma.
259
What is factor VIII activity in vWD?
Reduced in type 3 and sometimes in type 1 and 2N vWD.
260
What are vWF multimer studies used for?
Used to subtype vWD by analyzing vWF molecular weight distribution.
261
What is the role of DDAVP (desmopressin) in vWD?
Increases endogenous release of vWF and factor VIII from endothelial stores.
262
Which types of vWD respond to DDAVP?
Effective in most type 1, some type 2A; not effective in type 3.
263
What are contraindications to using DDAVP?
Type 2B (may worsen thrombocytopenia), type 3 vWD, cardiovascular disease, seizures.
264
What is used for treatment in patients unresponsive to DDAVP?
Plasma-derived vWF-FVIII concentrate.
265
What is the role of antifibrinolytics in vWD?
Useful for mucosal bleeding; includes tranexamic acid, aminocaproic acid.
266
What is the role of estrogen-containing OCPs in vWD?
Used to reduce menorrhagia in adolescent girls with vWD.
267
What precautions are necessary in vWD before surgery?
Ensure adequate hemostasis with DDAVP or vWF-containing concentrates; consult hematology.
268
What is acquired von Willebrand syndrome?
vWD caused by acquired conditions (e.g., malignancy, hypothyroidism, cardiac defects).
269
How is acquired vWD managed?
Treat underlying condition; may use IVIG, DDAVP, or vWF concentrates.
270
What is the prognosis of vWD with treatment?
Excellent with appropriate treatment and precautions; most lead normal lives.
271
What is disseminated intravascular coagulation (DIC)?
A life-threatening condition with widespread activation of coagulation leading to microthrombi and bleeding.
272
What are the pathophysiological mechanisms in DIC?
Uncontrolled thrombin generation leads to fibrin deposition, consumption of platelets and factors, and bleeding.
273
What are common causes of DIC in children?
Sepsis, trauma, malignancy, burns, liver failure, severe infections, transfusion reactions.
274
What are neonatal causes of DIC?
Perinatal asphyxia, sepsis, RDS, NEC, birth trauma, maternal-fetal transfusion.
275
How does sepsis lead to DIC?
Triggers pro-inflammatory cytokines and tissue factor expression leading to systemic coagulation activation.
276
What are clinical features of DIC?
Bleeding (petechiae, oozing), thrombosis, multiorgan dysfunction, shock.
277
What are signs of bleeding in DIC?
Gum bleeding, epistaxis, GI bleeding, hematuria, oozing from lines/wounds.
278
What are signs of thrombosis in DIC?
Peripheral gangrene, renal failure, CNS involvement, respiratory failure.
279
What is purpura fulminans?
A severe manifestation of DIC with hemorrhagic skin necrosis due to microvascular thrombosis.
280
What laboratory abnormalities are typical in DIC?
Prolonged PT/aPTT, low fibrinogen, thrombocytopenia, elevated D-dimer and FDPs.
281
What is the role of D-dimer in DIC?
Elevated due to increased fibrin degradation from widespread clot formation.
282
How is platelet count affected in DIC?
Usually decreased due to consumption.
283
How is PT and aPTT affected in DIC?
Both are typically prolonged due to depletion of clotting factors.
284
What happens to fibrinogen levels in DIC?
Low due to consumption; may be normal early in DIC.
285
What is the role of the ISTH DIC scoring system?
Used to aid diagnosis by scoring platelet count, PT, D-dimer, and fibrinogen.
286
What is the importance of identifying the underlying cause in DIC?
Treating the cause is essential for reversing DIC (e.g., antibiotics in sepsis).
287
What are the principles of DIC management?
Supportive care, treat underlying cause, replace depleted factors and platelets.
288
When should fresh frozen plasma (FFP) be administered in DIC?
If PT/aPTT is prolonged with active bleeding or before invasive procedures.
289
What are indications for cryoprecipitate in DIC?
If fibrinogen <100 mg/dL in active bleeding or high-risk patients.
290
When are platelet transfusions recommended in DIC?
If platelet count <50,000/μL with bleeding; <20,000/μL even without bleeding.
291
What is the target platelet count in bleeding DIC?
Maintain >50,000/μL in bleeding; >100,000/μL for surgery/critical illness.
292
When is heparin used in DIC?
Reserved for life-threatening thrombosis; controversial in acute bleeding DIC.
293
What are risks of using anticoagulants in DIC?
May exacerbate bleeding if not carefully selected and monitored.
294
How is DIC managed in neonates?
Same principles: treat cause, support with plasma/platelets/fibrinogen as needed.
295
What is the role of protein C and antithrombin in DIC?
Their levels are reduced in DIC; replacement may be considered in refractory or purpura fulminans cases.
296
What are complications of untreated DIC?
Multiorgan failure, shock, death; bleeding and thrombotic complications.
297
What is chronic DIC and when does it occur?
A low-grade compensated coagulopathy seen in malignancy, large AVMs, or retained dead fetus.
298
What are differences between acute and chronic DIC?
Acute: rapid decompensation, bleeding and thrombosis; Chronic: mild labs, thrombosis predominates.
299
What is the prognosis in pediatric DIC?
Depends on cause, prompt recognition, and supportive care; neonatal and septic DIC have higher mortality.
300
What are key points for monitoring in DIC?
Monitor platelets, PT/aPTT, fibrinogen, D-dimer; reassess frequently with clinical status.
301
What are the main types of leukemia in children?
Acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (rare).
302
What is the most common childhood leukemia?
Acute lymphoblastic leukemia (ALL).
303
What is the peak age of incidence for ALL?
2–5 years of age.
304
What are the risk factors for childhood leukemia?
Genetic syndromes (Down syndrome), radiation exposure, previous chemotherapy, family history.
305
What are common presenting symptoms of leukemia?
Fever, pallor, fatigue, bruising, bleeding, bone pain, lymphadenopathy.
306
What physical findings are suggestive of leukemia?
Hepatosplenomegaly, lymphadenopathy, pallor, petechiae, fever, sternal tenderness.
307
What is leukostasis?
Hyperviscosity syndrome from very high WBC count causing CNS, pulmonary symptoms.
308
How does bone marrow failure present in leukemia?
Anemia, thrombocytopenia, neutropenia causing fatigue, bleeding, infections.
309
What laboratory findings are seen in acute leukemia?
Anemia, thrombocytopenia, high or low WBC count, circulating blasts.
310
What are typical findings on peripheral smear in leukemia?
Presence of lymphoblasts or myeloblasts depending on leukemia type.
311
How is the diagnosis of leukemia confirmed?
Bone marrow aspirate showing ≥25% blasts confirms acute leukemia.
312
What is the role of flow cytometry in leukemia diagnosis?
Identifies immunophenotype (B-ALL, T-ALL, AML); guides diagnosis and therapy.
313
What cytogenetic abnormalities are associated with favorable prognosis in ALL?
Hyperdiploidy, t(12;21) ETV6-RUNX1 fusion.
314
What cytogenetic abnormalities are associated with poor prognosis in ALL?
t(9;22) BCR-ABL, t(4;11) MLL rearrangements, hypodiploidy.
315
What CNS findings may occur in leukemia?
Headache, vomiting, cranial nerve palsies, seizures (due to CNS leukemia).
316
What is the role of lumbar puncture in leukemia evaluation?
To assess for CNS involvement and for intrathecal therapy.
317
What is the significance of tumor lysis syndrome in leukemia?
Rapid cell lysis leads to hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, AKI.
318
How is tumor lysis syndrome managed?
Aggressive hydration, allopurinol or rasburicase, monitor electrolytes and renal function.
319
What are the phases of ALL treatment?
Induction, consolidation, maintenance, and CNS prophylaxis.
320
What is the purpose of induction therapy?
Achieve complete remission by eradicating leukemic blasts.
321
What is the role of CNS prophylaxis in leukemia?
Prevents leukemic infiltration of the CNS, a sanctuary site.
322
What drugs are commonly used for CNS prophylaxis?
Intrathecal methotrexate ± cytarabine or hydrocortisone.
323
What is minimal residual disease (MRD)?
Detection of residual leukemic cells below morphologic level by flow cytometry/PCR.
324
How is MRD used in leukemia management?
Used to stratify risk, guide therapy intensity, and predict relapse.
325
What are common complications of leukemia treatment?
Infections, bleeding, anemia, mucositis, hepatotoxicity, neurotoxicity.
326
What infections are leukemia patients particularly prone to?
Gram-negative sepsis, fungal infections (Aspergillus, Candida), Pneumocystis jirovecii.
327
How is febrile neutropenia managed in leukemia?
Broad-spectrum IV antibiotics urgently; workup for infection; antifungal if persistent.
328
What is the difference between ALL and AML?
ALL: lymphoblasts, more common in children; AML: myeloblasts, more common in infants/teens.
329
What is the role of stem cell transplant in leukemia?
Considered in high-risk or relapsed cases; not first-line in standard-risk ALL.
330
What is the long-term prognosis of childhood ALL?
Over 85% long-term survival in standard-risk ALL with modern therapy.
331
What are the two main types of lymphomas in children?
Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).
332
What is the most common type of lymphoma in children?
Non-Hodgkin lymphoma (NHL).
333
What is the peak age for Hodgkin lymphoma?
Adolescents, typically 15–19 years.
334
What are the subtypes of Hodgkin lymphoma?
Nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte-depleted.
335
What is the characteristic histological cell in Hodgkin lymphoma?
Reed-Sternberg cell: large binucleated cell with owl-eye nuclei.
336
What is the clinical presentation of Hodgkin lymphoma?
Painless lymphadenopathy (often cervical), fatigue, B symptoms, mediastinal mass.
337
What is the significance of B symptoms in Hodgkin lymphoma?
Associated with more advanced disease and worse prognosis.
338
What are B symptoms?
Fever >38°C, weight loss >10%, night sweats.
339
What are common physical findings in Hodgkin lymphoma?
Cervical/axillary lymphadenopathy, splenomegaly, mediastinal widening.
340
What is the staging system used for Hodgkin lymphoma?
Ann Arbor staging system.
341
What investigations are used to stage lymphoma?
CBC, LDH, CT/PET scan, bone marrow biopsy, lumbar puncture (if CNS symptoms).
342
What is the role of PET-CT in Hodgkin lymphoma?
Used for staging and assessing treatment response.
343
What is the Ann Arbor staging system?
Stage I–IV based on number, location, and systemic symptoms.
344
What is the general prognosis of pediatric Hodgkin lymphoma?
Excellent (>90% survival with combined modality therapy).
345
What is the mainstay of treatment for Hodgkin lymphoma?
Combination chemotherapy ± radiotherapy based on risk/stage.
346
What are late effects of treatment for Hodgkin lymphoma?
Infertility, hypothyroidism, second malignancies, pulmonary and cardiac toxicity.
347
What is non-Hodgkin lymphoma (NHL)?
A group of malignant lymphoproliferative disorders excluding Hodgkin lymphoma.
348
What are the main types of NHL in children?
Burkitt lymphoma, lymphoblastic lymphoma, large cell lymphoma, anaplastic large cell lymphoma.
349
What is the most common NHL subtype in children?
Burkitt lymphoma.
350
What are clinical features of Burkitt lymphoma?
Rapidly growing abdominal mass, jaw mass (endemic form), intussusception, CNS involvement.
351
What are common extranodal sites of NHL in children?
GI tract, CNS, bone marrow, mediastinum.
352
How does T-cell lymphoblastic lymphoma typically present?
With a large anterior mediastinal mass and pleural effusion.
353
What are oncologic emergencies in NHL?
Tumor lysis syndrome, superior vena cava syndrome, airway compression.
354
How is NHL diagnosed?
Lymph node biopsy, flow cytometry, cytogenetics, immunohistochemistry.
355
What are typical findings in Burkitt lymphoma on biopsy?
Starry-sky appearance due to high mitotic activity and macrophages among tumor cells.
356
What is the treatment of pediatric NHL?
Intensive multi-agent chemotherapy.
357
Is surgery used for treatment of NHL?
Only for biopsy or complications; not curative.
358
What are prognostic factors in pediatric NHL?
Stage, LDH level, CNS/BM involvement, tumor burden, response to initial therapy.
359
How is CNS involvement evaluated in lymphoma?
Lumbar puncture and neuroimaging.
360
What is the overall prognosis for pediatric NHL?
Varies by type but >80% long-term survival with appropriate therapy.
361
What is hemophagocytic lymphohistiocytosis (HLH)?
A life-threatening hyperinflammatory syndrome caused by uncontrolled immune activation.
362
What are the types of HLH?
Primary (genetic/familial) and secondary (acquired/reactive).
363
What is primary (familial) HLH?
An inherited form due to mutations affecting cytotoxic lymphocyte function.
364
What are genetic causes of familial HLH?
PRF1, UNC13D, STX11, STXBP2 (affecting perforin/granule exocytosis pathways).
365
What is secondary HLH?
Triggered by infections, malignancies, autoimmune diseases, or immunosuppression.
366
What are common triggers of secondary HLH?
EBV, CMV, HIV, malignancies (especially lymphoma), systemic JIA, lupus.
367
What is the pathophysiology of HLH?
Defective cytotoxic function leads to persistent macrophage and T-cell activation and cytokine storm.
368
What are the hallmark clinical features of HLH?
Prolonged fever, hepatosplenomegaly, cytopenias, hyperferritinemia, liver dysfunction.
369
What are the diagnostic criteria for HLH (HLH-2004)?
5 of 8 criteria: fever, splenomegaly, cytopenias, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis, low NK activity, hyperferritinemia (>500), elevated sCD25.
370
What is the significance of fever in HLH?
Persistent, high-grade fever is an early and consistent feature.
371
What organomegaly is common in HLH?
Hepatosplenomegaly is almost universal.
372
What CNS symptoms may occur in HLH?
Irritability, seizures, altered sensorium, encephalopathy, meningitis-like signs.
373
What hematologic abnormalities are found in HLH?
Bicytopenia or pancytopenia (anemia, neutropenia, thrombocytopenia).
374
What is hemophagocytosis?
Activated macrophages engulfing RBCs, WBCs, platelets in marrow, lymph nodes, or liver.
375
Is hemophagocytosis always present in bone marrow in HLH?
No; it may be absent early or require repeat biopsies to detect.
376
What laboratory markers are characteristic of HLH?
Hyperferritinemia, high triglycerides, low fibrinogen, elevated transaminases, high LDH.
377
What is the role of ferritin in HLH diagnosis?
Ferritin >10,000 ng/mL is highly suggestive; >500 is a diagnostic criterion.
378
What are other elevated markers in HLH?
Elevated sCD25 (soluble IL-2 receptor), low NK activity, high IL-6, IL-10, IFN-γ.
379
What infections are commonly associated with HLH?
Epstein-Barr virus (most common), CMV, HSV, adenovirus.
380
What autoimmune diseases are associated with HLH?
Systemic juvenile idiopathic arthritis, SLE (macrophage activation syndrome).
381
What malignancies are associated with HLH?
T-cell lymphoma and leukemia are common associations.
382
What is the role of NK cell activity in HLH?
Usually decreased or absent; part of diagnostic criteria.
383
What is soluble IL-2 receptor (sCD25) and its role in HLH?
Marker of T-cell activation; elevated in HLH and used diagnostically.
384
How is HLH distinguished from sepsis?
Sepsis may present similarly, but HLH has high ferritin, cytopenias, organomegaly, and persistent inflammation.
385
What is the first-line treatment protocol for HLH?
HLH-94 or HLH-2004 protocols: immunosuppression and cytotoxic therapy.
386
What are the components of HLH-94 or HLH-2004 protocol?
Dexamethasone, etoposide, cyclosporine ± intrathecal therapy (if CNS involved).
387
What is the role of etoposide in HLH?
Kills activated T cells and macrophages, reducing cytokine production.
388
When is hematopoietic stem cell transplant (HSCT) indicated?
In primary HLH or refractory/relapsing secondary HLH after remission induction.
389
What supportive therapies are used in HLH?
Broad-spectrum antibiotics, antivirals, antifungals, transfusions, supportive ICU care.
390
What is the prognosis of HLH?
Poor if untreated; with timely therapy and transplant, survival has improved significantly.
391
What is bone marrow transplantation (BMT)?
A procedure to replace damaged or diseased bone marrow with healthy stem cells.
392
What are the types of hematopoietic stem cell transplants (HSCT)?
Autologous (self), allogeneic (donor), and syngeneic (identical twin).
393
What are sources of hematopoietic stem cells?
Bone marrow, peripheral blood stem cells, umbilical cord blood.
394
What are the main indications for HSCT in pediatrics?
Leukemias, lymphomas, aplastic anemia, immunodeficiencies, hemoglobinopathies.
395
What is an allogeneic transplant?
Stem cells from a genetically matched or partially matched donor.
396
What is an autologous transplant?
Stem cells collected from the patient, used for rescue after high-dose therapy.
397
What is a syngeneic transplant?
Stem cells from an identical twin; no GVHD risk.
398
What are common hematologic diseases treated with HSCT?
ALL, AML, CML, aplastic anemia, MDS, thalassemia, sickle cell disease.
399
What immunodeficiencies are treated with HSCT?
SCID, Wiskott-Aldrich, CGD, severe combined immunodeficiency syndromes.
400
What metabolic disorders can be treated with HSCT?
Hurler syndrome, adrenoleukodystrophy, metachromatic leukodystrophy.
401
What are the types of donors in HSCT?
Matched sibling, matched unrelated, haploidentical, or cord blood donors.
402
What is HLA matching and why is it important?
Prevents rejection and reduces GVHD by matching HLA antigens.
403
What are the risks of mismatched transplants?
Increased risk of graft failure, GVHD, and mortality.
404
What is the conditioning regimen in BMT?
Chemotherapy and/or radiation given before transplant to suppress immunity and clear marrow.
405
What is myeloablative conditioning?
High-dose chemo/radiation fully ablating marrow; allows full donor engraftment.
406
What is reduced-intensity conditioning?
Less toxic regimen for older or comorbid patients; allows mixed chimerism.
407
What are the goals of conditioning?
Create marrow space, suppress immune system, eliminate disease.
408
What is engraftment in HSCT?
The point at which donor cells begin producing blood cells (usually ~2–4 weeks).
409
What is graft-versus-host disease (GVHD)?
An immune-mediated complication where donor T cells attack recipient tissues.
410
What are the types of GVHD?
Acute (<100 days), chronic (>100 days), and overlap forms.
411
What are risk factors for GVHD?
Mismatched donor, older age, unrelated donor, conditioning regimen, T-cell replete grafts.
412
How is GVHD prevented?
Immunosuppressants like methotrexate, cyclosporine, ATG.
413
How is acute GVHD treated?
High-dose steroids, calcineurin inhibitors, biological agents (e.g., ruxolitinib).
414
What is graft failure?
Failure of donor cells to engraft; requires re-transplant or supportive care.
415
What infections are patients susceptible to post-transplant?
Bacterial, fungal, viral (CMV, EBV, HSV), pneumocystis pneumonia.
416
What is CMV reactivation and why is it significant?
CMV can cause pneumonia, colitis, retinitis; requires monitoring and antiviral therapy.
417
What is veno-occlusive disease (VOD)?
Liver sinusoidal obstruction; presents with hepatomegaly, jaundice, fluid retention.
418
What supportive care is needed post-transplant?
Antibiotics, antivirals, antifungals, blood products, nutritional support, isolation.
419
What are long-term complications of HSCT?
Infertility, endocrine disorders, secondary cancers, chronic GVHD, organ dysfunction.
420
What is chimerism and how is it monitored?
Presence of donor vs recipient cells post-transplant; monitored by PCR or FISH.
