Pediatrics (week 10): Hematology
Hematology
for final know anemias, lead poisoning
ANEMIA
MC: Iron deficiency Anemia
Affects 3% of white children, 15% of AA children at one year of age
Another 20% are iron deficient, but not anemic
Etio: rapid growth, relative Fe insuff in diet
exclusive breastfeeding after 6mo thought to be insuff for Fe, not much in breastmilk
Assess at 9-12 mo for Fe def
DDX: cu def, thalassemias (hemoglobinopathies are screened on new infant panel)
Sx: growth delay, heart murmur
PE: often N, mb pallor or nail spooning, pica
Labs: CBC- ferritin, Fe, transferrin saturation
DX: Screen hemoglobin at 9 months, 5 years, 14 years
Complic: Neuro dysfx c irrit, poor attention span, decr scholastic performance, permanent? not known
Tx: use supps for first 30-60 days then rely on diet change for longterm
Tx: ferrous so4 or glycinate 3-6mg/kg, recheck CBC in 30-60 days, she likes ITI liquid Fe or OTC kids floridex
Tx: Fe-rich foods: meat, fish, poultry, raisins, dried frt, sweet potatoes, lima, chili beans, green peas, PB
Tx: Supplement iron at 1mg/kg/day for infants who are exclusively breastfed past 6 months.
MACROCYTIC NORMOCHROMIC ANEMIA
B-12 or Folate deficiency Anemia
Not common, but can be seen in children of mothers with B-12 deficiency
Alert: Vegans, pernicious anemia
Tx: both mom and baby
Tx: folic acid for mom and baby, she uses this for alpha thal as well
HEMOGLOBINOPATHIES
Thalassemia refers to a decreased production of a globin chain resulting in microcytic anemia
Pathophys: Decr intracellular hemoglobin and microcytosis due to gene defect
-->Unpaired globin chains precipitate on the RBC membrane causing hemolysis and splenomegaly
-->Ineffective erythropoiesis cause hepatosplenomegaly and bony changes
RBC lifespan shortened as a result of hemolysis and splenic sequestration
ά-Thalassemia:
Severity depends on how many genes the individual has (Normal is 4 genes)
a_/aa (3 genes), silent carrier (more common in AA), No anemia, normal CBC
a_/a_ (2 genes), trait (more common in AA), Hemoglobin Bart, Mild microcytic anemia, usually asymptomatic
a_/_ _ (1 gene)
i.Hemoglobin H disease (more common in Southeast Asians)
ii.Moderate microcytic anemia, splenomegaly
d._ _/_ _ (0 genes)
i.Hydrops fetalis (more common in Southeast Asians)
ii.Death in utero as a result of severe anemia
Β-Thalassemia
1.Normal is 2 genes
a.Heterozygous (1 gene)
i.Mild anemia with significant hypochromia and microcytosis
b.Homozygous (0 genes)
i.Severe life-threatening anemia that becomes clinically apparent after 6 months of age when the fetal blood is replaced by adult blood
ii.Severe hypochromic, microcytic anemia
v.Complications
1.Most due to homozygous β-thalassemia
a.Skeletal abnormalities
b.Growth retardation
c.Congestive heart failure
d.Gallstones
e.Iron overload
vi.Labs
1.CBC-MCV, MCH and MCHC decreased
2.RDW normal
3.Hemoglobin
a.9-12 g/dL in ά- and β-thalassemia trait
b.6-10 g/dL in Hemoglobin H disease
c.7-10 g/dL in β-thalassemia intermedia
d.<5 g/dL in β-thalassemia major
vii.Treatment
1.Folic acid daily
II.Henoch-Schölein Purpura
a.Definition
i.Immunologically-mediated
ii.Purpuric
iii.Systemic vasculitis involving the small blood vessels of the skin GI tract, joints and kidneys
b.Pathophysiology
i.Most cases associated with recent URI, usually strep throat
c.Epidemiology
i.13.5 cases per 100,000
ii.Year-round occurrence
iii.Most common in Caucasians, Japanese and Native Americans
d.Signs/symptoms
i.Recent URI
ii.Low-grade fever
iii.Hypertension
iv.Rash that is petechial or purpuric in a pressure-dependent, symmetric distribution
1.lateral malleoli, ventral surfaces of feet, buttocks, elbows
v.Joint pain or swelling
1.transient, nondeforming nonmigratory arthritis of knees, ankles, wrists, elbows, and digits
vi.Nonpitting subcutaneous edema of scalp, periorbital region, hands and feet
vii.Abdominal pain which is often colicky and intermittent. Abdomen is often tender to palpation without rebound tenderness.
e.Labs
i.CBC-may see Leukocytosis
ii.ESR, IgA elevated
iii.Normal PT and PTT, C3, ANA
iv.Urinalysis
1.Screen for kidney complications
2.May see gross hematuria
3.Proteinuria is common
v.Stool guaiac
1.Indicates GI involvement
vi.Abdominal ultrasound
1.Screening for intussusception
f.Complications
i.Persistent hypertension
ii.Kidney disease
iii.Intussusception
iv. Bowel perforations, ischemia and infarctions
v.Appendicitis
vi.Protein losing enteropathy
g.Prognosis
i.Generally excellent
ii.33% chance of recurrence within 6 weeks
iii.Most have only 1-3 episodes of purpura
iv.GI tract disease accounts for the most significant morbidity in the short term
v.Renal involvement is the cause of the most serious long-term morbidity.
h.Treatment
i.Analgesics and NSAIDS for pain
ii.Steroids as needed
iii.Aggressive therapy with steroid and/or immunosuppressants with >50% crescentic glomerulonephritis
iv.Refer to nephrologists for consultation if 2+ proteinuria. Hospitalization needed for abdominal complications or for IV fluids or parenteral nutrition
i.Follow up
i.See the patient weekly during the acute phase for history, BP, UA
ii.Urine chemistry
III.Hemophilia
a.Heredity bleeding disorder caused by the absence, severe deficiency or defective functioning of plasma coagulation factors VIII (Hemophilia A) or IX (Hemophilia B)
b.Epidemiology
i.Sex linked recessive disorder so primarily affects men
ii.1 in 5,000 have Hemophilia A
iii.1 in 30,000 have Hemophilia B
c.Pathophysiology
i.Impaired ability to generate thrombin and fibrin so there is elayed formation of an abnormal clot
ii.Frequent joint bleeding
d.Diagnosis
i.Prenatal diagnosis by chorionic villous sampling or amniocentesis
ii.Cord blood testing
iii.Otherwise, be suspicious if prolonged bleeding time or unusual bruising or bleeding
e.Labs
i.PT and PTT
ii.Factor VIII and IX assays
f.Complications
i.Hemophilic arthropathy
ii.Intracranial bleeding
iii.Airway compromise
iv.Life-threatening hemorrhages due to GI, post-traumatic or perioperative bleeds
g.Management
i.Need to be under the care of a hematologist for both long-term management and emergency care
LEAD POISONING
MC pediatric environmental health problem, most commonly with inorganic lead
Children absorb lead more efficiently through GI than adults
children more like to ingest lead through hand-to-mouth activity
back yard chickens and peeling houses mb a source of lead
pre 1980 housing, house dust and paint chips-->child toxicity
SCREENING at 6 months of age if significant risk factors (old paint, renovations), 12mo if not
DX: CDC: lead >10 μg/dL or higher by blood lead test, either venous or capillary
Dx: level of 3-4 still concerning, tx anyway
Dx: CBC may show anemia
Dx: I will use hair for chronic exposure because serum only shows acute exposure
F/U: Redraw every 3-4 months for levels of 10-19μg/dL, monthly if above 20μg/dL
Sx: often asx, Anorexia, intermittent abdominal pain, constipation, sporadic vomiting
Sx: Change in mental/developmental status, pica
Complic: Acute encephalopathy, Seizures, Coma, death, Mental retardation
Complic: Lead adversely affect neurologic, hematologic, GI, rental and reproductive systems
Sx: Cognitive, behavioral, attentional, and neurodevelopmental impairment
Sx: Anemia, Abdominal colic
Tx: avoid continuing exposure, get away from old paint, test water, look into pipes
Tx: chelate c EDTA or DMSA for levels >45μg/dL; Can be considered for levels of 25-45μg.
Tx: Ca, Mg, Fe, minerals compete with Pb for absorption
Tx: monitor each 2-3 mo to be sure blood levels going down
LYMPHOMA
Hodgkin Lymphoma
Malignant enlargement of the lymph nodes
characterized by a pleomorphic cellular infiltrate with multinucleated giant cells (Reed Sternberg cells)
2 peaks of incidence:
--Before adolescence in developing countries, mid to late 20s in US
--Late adulthood
Risk: EBV infection (3x risk)
Familial clustering
Sx: Painless lymphadenopathy with nodes that are firmer and less mobile than inflammatory nodes
Sx: Mediastinal mass causing nonproductive cough or difficulty breating
Sx: Hepatosplenomegaly
Sx: fatigue, anorexia, weight loss, Fever, night sweats
Dx: CBC, ESR for screening, Lymph node biopsy for diagnosis
Dx: she usu waits a week for a large LN to go down, if it does then no worries
Tx: Chemo and radiation
Prog c tx: 88-100% survival for early stage disease, 54-94% with advanced stage disease
Non-Hodgkin Lymphoma
Malignant proliferation of cells of lymphocytic or histiocytic lineage
spreads in a pattern similar to the migration of noral lymphoid tissue
#3 mc childhood malignancy, 1.0-1.5 per 100,000 children
Hx: EBV
Small noncleaved-cell lymphomas (40-50%)
Burkitt and Burkitt-like
Variety of B cell markers present
Lymphoblastic lymphomas (30%)
T-cell origin
Large cell lymphomas (20%)
B-cell origin
Sx: Fever, weight loss, anorexia, fatigue
Lump in neck that does not respond to antibiotics
Abdominal mass with pain, swelling, change in bowel habits, nausea or vomiting
T-cell lymphomas
Mediastinal tumor symptoms such as cough, hoarseness, dyspnea, orthopnea and chest pain, anxiety, confusion, lethargy, HA, distorted vision, syncope, sense of fullness of ears
Bleeding or bruising, bone pain, pallor, fatigue
PE
Small non-cleaved-cell lymphomas
Intra-abdominal mass involving ileocecal region, appendix or ascending colon. Acute abdomen, Lymphadenopathy in inguinal or iliac region
b.In endemic burkitt lymphoma, jaw tumors are the most frequent
c.Orbital tumors in children
2.Lymphoblastic lymphoma
a.Mediastinal mass with pleural effusion
b.Swelling, plethora, and cyanosis of the face, neck and upper extremities; diaphoresis and stridor and wheezing
3.Large cell lymphoma
a.Mediastinum, bone, inguinal nodes, and skin affected
vi.Labs
1.lymph node biopsy, bone marrow aspirate and biopsy for diagnosis
vii.Prognosis
1.Favorable: stages I and II with primary site being head and neck, peripheral nodes, or abdominal site
2.Unfavorable: Stage III or IV, parameningeal stage II, stage IV with CNS involvement. Incomplete initial remission within 2 months
VI.Leukemia
a.Acute Lymphoblastic Leukemia
i.Malignant disorder lymphoblasts in which a single malignant lymphoblast undergoes clonal proliferation. The result is overgrowth and crowding out of normal bone marrow precursors, invasion of nohematopoietic tissues and suppression of differentiation of normal cells.
1.Acute leukemia is the most common cancer of childhood
2.Incidence is 1 in 1700 children under 15 years old
ii.Signs and symptoms
1.Easy bruising and bleeding
a.Thrombocytopenia
2.Bone pain, arthralgia, limp
a.Infiltrative disease of marrow
3.fatigue and pallor
a.anemia
4.stridor, orthopnea, shortness of breath, any respiratory distress
a.Mediastinal mass, pleural effusion
5.Lymphadenopathy, hepatosplenomegaly
iii.Labs
1.CBC
a.Leukocytosis >10,000/mm³ in 50% of cases
b.>50,000/mm³ in 20% of cases
c.Neutropenia and thrombocytopenia
2.Bone marrow aspirate
a.>25% leukemic lymphoblasts id diagnositic
3.Prognosis
a.95% remission
b.Long-term survival 80% (65% for high risk group)
for final know anemias, lead poisoning
ANEMIA
MC: Iron deficiency Anemia
Affects 3% of white children, 15% of AA children at one year of age
Another 20% are iron deficient, but not anemic
Etio: rapid growth, relative Fe insuff in diet
exclusive breastfeeding after 6mo thought to be insuff for Fe, not much in breastmilk
Assess at 9-12 mo for Fe def
DDX: cu def, thalassemias (hemoglobinopathies are screened on new infant panel)
Sx: growth delay, heart murmur
PE: often N, mb pallor or nail spooning, pica
Labs: CBC- ferritin, Fe, transferrin saturation
DX: Screen hemoglobin at 9 months, 5 years, 14 years
Complic: Neuro dysfx c irrit, poor attention span, decr scholastic performance, permanent? not known
Tx: use supps for first 30-60 days then rely on diet change for longterm
Tx: ferrous so4 or glycinate 3-6mg/kg, recheck CBC in 30-60 days, she likes ITI liquid Fe or OTC kids floridex
Tx: Fe-rich foods: meat, fish, poultry, raisins, dried frt, sweet potatoes, lima, chili beans, green peas, PB
Tx: Supplement iron at 1mg/kg/day for infants who are exclusively breastfed past 6 months.
MACROCYTIC NORMOCHROMIC ANEMIA
B-12 or Folate deficiency Anemia
Not common, but can be seen in children of mothers with B-12 deficiency
Alert: Vegans, pernicious anemia
Tx: both mom and baby
Tx: folic acid for mom and baby, she uses this for alpha thal as well
HEMOGLOBINOPATHIES
Thalassemia refers to a decreased production of a globin chain resulting in microcytic anemia
Pathophys: Decr intracellular hemoglobin and microcytosis due to gene defect
-->Unpaired globin chains precipitate on the RBC membrane causing hemolysis and splenomegaly
-->Ineffective erythropoiesis cause hepatosplenomegaly and bony changes
RBC lifespan shortened as a result of hemolysis and splenic sequestration
ά-Thalassemia:
Severity depends on how many genes the individual has (Normal is 4 genes)
a_/aa (3 genes), silent carrier (more common in AA), No anemia, normal CBC
a_/a_ (2 genes), trait (more common in AA), Hemoglobin Bart, Mild microcytic anemia, usually asymptomatic
a_/_ _ (1 gene)
i.Hemoglobin H disease (more common in Southeast Asians)
ii.Moderate microcytic anemia, splenomegaly
d._ _/_ _ (0 genes)
i.Hydrops fetalis (more common in Southeast Asians)
ii.Death in utero as a result of severe anemia
Β-Thalassemia
1.Normal is 2 genes
a.Heterozygous (1 gene)
i.Mild anemia with significant hypochromia and microcytosis
b.Homozygous (0 genes)
i.Severe life-threatening anemia that becomes clinically apparent after 6 months of age when the fetal blood is replaced by adult blood
ii.Severe hypochromic, microcytic anemia
v.Complications
1.Most due to homozygous β-thalassemia
a.Skeletal abnormalities
b.Growth retardation
c.Congestive heart failure
d.Gallstones
e.Iron overload
vi.Labs
1.CBC-MCV, MCH and MCHC decreased
2.RDW normal
3.Hemoglobin
a.9-12 g/dL in ά- and β-thalassemia trait
b.6-10 g/dL in Hemoglobin H disease
c.7-10 g/dL in β-thalassemia intermedia
d.<5 g/dL in β-thalassemia major
vii.Treatment
1.Folic acid daily
II.Henoch-Schölein Purpura
a.Definition
i.Immunologically-mediated
ii.Purpuric
iii.Systemic vasculitis involving the small blood vessels of the skin GI tract, joints and kidneys
b.Pathophysiology
i.Most cases associated with recent URI, usually strep throat
c.Epidemiology
i.13.5 cases per 100,000
ii.Year-round occurrence
iii.Most common in Caucasians, Japanese and Native Americans
d.Signs/symptoms
i.Recent URI
ii.Low-grade fever
iii.Hypertension
iv.Rash that is petechial or purpuric in a pressure-dependent, symmetric distribution
1.lateral malleoli, ventral surfaces of feet, buttocks, elbows
v.Joint pain or swelling
1.transient, nondeforming nonmigratory arthritis of knees, ankles, wrists, elbows, and digits
vi.Nonpitting subcutaneous edema of scalp, periorbital region, hands and feet
vii.Abdominal pain which is often colicky and intermittent. Abdomen is often tender to palpation without rebound tenderness.
e.Labs
i.CBC-may see Leukocytosis
ii.ESR, IgA elevated
iii.Normal PT and PTT, C3, ANA
iv.Urinalysis
1.Screen for kidney complications
2.May see gross hematuria
3.Proteinuria is common
v.Stool guaiac
1.Indicates GI involvement
vi.Abdominal ultrasound
1.Screening for intussusception
f.Complications
i.Persistent hypertension
ii.Kidney disease
iii.Intussusception
iv. Bowel perforations, ischemia and infarctions
v.Appendicitis
vi.Protein losing enteropathy
g.Prognosis
i.Generally excellent
ii.33% chance of recurrence within 6 weeks
iii.Most have only 1-3 episodes of purpura
iv.GI tract disease accounts for the most significant morbidity in the short term
v.Renal involvement is the cause of the most serious long-term morbidity.
h.Treatment
i.Analgesics and NSAIDS for pain
ii.Steroids as needed
iii.Aggressive therapy with steroid and/or immunosuppressants with >50% crescentic glomerulonephritis
iv.Refer to nephrologists for consultation if 2+ proteinuria. Hospitalization needed for abdominal complications or for IV fluids or parenteral nutrition
i.Follow up
i.See the patient weekly during the acute phase for history, BP, UA
ii.Urine chemistry
III.Hemophilia
a.Heredity bleeding disorder caused by the absence, severe deficiency or defective functioning of plasma coagulation factors VIII (Hemophilia A) or IX (Hemophilia B)
b.Epidemiology
i.Sex linked recessive disorder so primarily affects men
ii.1 in 5,000 have Hemophilia A
iii.1 in 30,000 have Hemophilia B
c.Pathophysiology
i.Impaired ability to generate thrombin and fibrin so there is elayed formation of an abnormal clot
ii.Frequent joint bleeding
d.Diagnosis
i.Prenatal diagnosis by chorionic villous sampling or amniocentesis
ii.Cord blood testing
iii.Otherwise, be suspicious if prolonged bleeding time or unusual bruising or bleeding
e.Labs
i.PT and PTT
ii.Factor VIII and IX assays
f.Complications
i.Hemophilic arthropathy
ii.Intracranial bleeding
iii.Airway compromise
iv.Life-threatening hemorrhages due to GI, post-traumatic or perioperative bleeds
g.Management
i.Need to be under the care of a hematologist for both long-term management and emergency care
LEAD POISONING
MC pediatric environmental health problem, most commonly with inorganic lead
Children absorb lead more efficiently through GI than adults
children more like to ingest lead through hand-to-mouth activity
back yard chickens and peeling houses mb a source of lead
pre 1980 housing, house dust and paint chips-->child toxicity
SCREENING at 6 months of age if significant risk factors (old paint, renovations), 12mo if not
DX: CDC: lead >10 μg/dL or higher by blood lead test, either venous or capillary
Dx: level of 3-4 still concerning, tx anyway
Dx: CBC may show anemia
Dx: I will use hair for chronic exposure because serum only shows acute exposure
F/U: Redraw every 3-4 months for levels of 10-19μg/dL, monthly if above 20μg/dL
Sx: often asx, Anorexia, intermittent abdominal pain, constipation, sporadic vomiting
Sx: Change in mental/developmental status, pica
Complic: Acute encephalopathy, Seizures, Coma, death, Mental retardation
Complic: Lead adversely affect neurologic, hematologic, GI, rental and reproductive systems
Sx: Cognitive, behavioral, attentional, and neurodevelopmental impairment
Sx: Anemia, Abdominal colic
Tx: avoid continuing exposure, get away from old paint, test water, look into pipes
Tx: chelate c EDTA or DMSA for levels >45μg/dL; Can be considered for levels of 25-45μg.
Tx: Ca, Mg, Fe, minerals compete with Pb for absorption
Tx: monitor each 2-3 mo to be sure blood levels going down
LYMPHOMA
Hodgkin Lymphoma
Malignant enlargement of the lymph nodes
characterized by a pleomorphic cellular infiltrate with multinucleated giant cells (Reed Sternberg cells)
2 peaks of incidence:
--Before adolescence in developing countries, mid to late 20s in US
--Late adulthood
Risk: EBV infection (3x risk)
Familial clustering
Sx: Painless lymphadenopathy with nodes that are firmer and less mobile than inflammatory nodes
Sx: Mediastinal mass causing nonproductive cough or difficulty breating
Sx: Hepatosplenomegaly
Sx: fatigue, anorexia, weight loss, Fever, night sweats
Dx: CBC, ESR for screening, Lymph node biopsy for diagnosis
Dx: she usu waits a week for a large LN to go down, if it does then no worries
Tx: Chemo and radiation
Prog c tx: 88-100% survival for early stage disease, 54-94% with advanced stage disease
Non-Hodgkin Lymphoma
Malignant proliferation of cells of lymphocytic or histiocytic lineage
spreads in a pattern similar to the migration of noral lymphoid tissue
#3 mc childhood malignancy, 1.0-1.5 per 100,000 children
Hx: EBV
Small noncleaved-cell lymphomas (40-50%)
Burkitt and Burkitt-like
Variety of B cell markers present
Lymphoblastic lymphomas (30%)
T-cell origin
Large cell lymphomas (20%)
B-cell origin
Sx: Fever, weight loss, anorexia, fatigue
Lump in neck that does not respond to antibiotics
Abdominal mass with pain, swelling, change in bowel habits, nausea or vomiting
T-cell lymphomas
Mediastinal tumor symptoms such as cough, hoarseness, dyspnea, orthopnea and chest pain, anxiety, confusion, lethargy, HA, distorted vision, syncope, sense of fullness of ears
Bleeding or bruising, bone pain, pallor, fatigue
PE
Small non-cleaved-cell lymphomas
Intra-abdominal mass involving ileocecal region, appendix or ascending colon. Acute abdomen, Lymphadenopathy in inguinal or iliac region
b.In endemic burkitt lymphoma, jaw tumors are the most frequent
c.Orbital tumors in children
2.Lymphoblastic lymphoma
a.Mediastinal mass with pleural effusion
b.Swelling, plethora, and cyanosis of the face, neck and upper extremities; diaphoresis and stridor and wheezing
3.Large cell lymphoma
a.Mediastinum, bone, inguinal nodes, and skin affected
vi.Labs
1.lymph node biopsy, bone marrow aspirate and biopsy for diagnosis
vii.Prognosis
1.Favorable: stages I and II with primary site being head and neck, peripheral nodes, or abdominal site
2.Unfavorable: Stage III or IV, parameningeal stage II, stage IV with CNS involvement. Incomplete initial remission within 2 months
VI.Leukemia
a.Acute Lymphoblastic Leukemia
i.Malignant disorder lymphoblasts in which a single malignant lymphoblast undergoes clonal proliferation. The result is overgrowth and crowding out of normal bone marrow precursors, invasion of nohematopoietic tissues and suppression of differentiation of normal cells.
1.Acute leukemia is the most common cancer of childhood
2.Incidence is 1 in 1700 children under 15 years old
ii.Signs and symptoms
1.Easy bruising and bleeding
a.Thrombocytopenia
2.Bone pain, arthralgia, limp
a.Infiltrative disease of marrow
3.fatigue and pallor
a.anemia
4.stridor, orthopnea, shortness of breath, any respiratory distress
a.Mediastinal mass, pleural effusion
5.Lymphadenopathy, hepatosplenomegaly
iii.Labs
1.CBC
a.Leukocytosis >10,000/mm³ in 50% of cases
b.>50,000/mm³ in 20% of cases
c.Neutropenia and thrombocytopenia
2.Bone marrow aspirate
a.>25% leukemic lymphoblasts id diagnositic
3.Prognosis
a.95% remission
b.Long-term survival 80% (65% for high risk group)