Pediatric aspects of hemoatological disorders
 Heritable causes are more common in children than in adults
o Eg: differential for diagnosis of pancytopenia in children must include constitutional forms of bone marrow failure,
like Fanconi’s anemia, in addition to acquired forms of aplasia
 Treatment and prognosis for constitutional forms different from acquired  specific diagnosis cannot be
missed
 Fanconi’s anemia – characterized by increased chromosomal breakage, preparative regimens for BM
transplant must be adjusted to prevent fatal toxicities
o Certain genetic syndromes predispose to hematologic disease in children
 Downs syndrome
 Infants at risk for myeloproliferative syndrome, leukemoid rxn
 10-20 fold increased risk for developing AML/ALL during childhood
 If acquired, most often related to infection or post-infectious response
 One particular challenge in peds involves age-specific normal values
o RBC, WBC, coag factors
Age
Birth-3 days
1 wk
1 mt
2 mts
3-6 mts
6-23 mts

mean and lower limit
of normal Hb
18.5 gm/dL (14.5)
17.5 (13.5)
14.0 (10.0)
11.5 (9.0)
11.5 (9.5)
12.5 (11.0)
mean and lower limit
of normal MCV
108 (98)
107 (89)
104 (85)
96 (77)
91 (74)
77 (70)
Modestly lower levels of Hb
and MCV are normal for
children compared to adults.
Pediatric anemias
o Make sure you know the age-specific normal values, the MCV (microcytic, normocytic, macrocytic differentials),
the reticulocyte count (increased destruction vs decreased production), and peripheral blood smear
o Sickle Cell Disease
 Initial diagnosis – neonatal screening programs
 Preventative care
 Penicillin prophylaxis  b/c of early splenic dysfunction, infants susceptible to invasive
infections with encapsulated organisms
 Progression of disease
 Infants born with normal blood counts, since predominant Hb is fetal
 HbF declines  replaced by HbS  hemolysis increases, Hb falls, reticulocyte count rises
 Values seen at 2 yrs are pretty close to what individual will maintain throughout life
 All organs affected, but during infancy, predominant problems include
 Early splenic dysfunction
o Obstruction of spleen with sickle red blood cells, abnormally inflexible and adhere
abnormally to endothelium
o Acute splenic sequestration occurs when that process this greatly exacerbated over a short
period of time  spleen becomes a trap for RBCs
 Severe bacterial infections
o Sepsis and meningitis
 Dactylitis
o Acute, painful swelling of hands and feet
o Caused by obstruction of small blood vessels
 Acute chest syndrome
o Pneumonia-like illness which can be triggered by pulmonary infection, pulmonary fat
embolism, lung infarction, and sometimes unknown participants
o Highest single cause of mortality in sickle cell disease (but higher in adults than children)
 After infancy, additional problem in children include
 Delays in growth and pubertal development
 Priapism in males
 Hyposthenuria (inability to conc urine)
 Aplastic crisis
 Avascular necrosis (particularly of hips)
 Gall bladder disease
 STROKE - requires chronic transfusion therapy; typical watershed infarct
 Underlying causes of complications include
o
o
o
o
o
o
o
 Vaso-occulsion
 Endothelial cell activation
 Endothelial cell damage
 Chronic inflammation
 Hemolysis
 Treatment
 More effective, more complex, and more aggressive in past 10 yrs
 Hydroxyurea (clinical trials)
 Curative therapy remains elusive
 Selection for BM transplant HLA-matched sibling matches is complex
Iron deficiency
 Think diet first
 Set of physiologic challenges in childhood
 Blood volume must keep pace with increasing body size
 Iron content in unfortified infant foods is very low
 Breast milk iron is very bioavailable, but bioavailability is reduced when infants are taking other
foods along with breast milk
 Cow’s milk is a very poor source of iron and can cause low-grade asymptomatic GI losses of iron in milkprotein allergic patients
 Many children with iron def are consuming excessive amounts of cow’s milk  replaces ironcontaining foods and decreases iron absorption
 Practical treatment: consider therapeutic trial of iron
 Can be diagnostic as well
 Child who has low Hb on anemia screening
 Not recently or currently ill
 Give iron 3-5 mg/kg/day for 4 wks
 Recheck Hb after 4 wks  if up at least 1 gm, diagnosis is confirmed
o If successful, continue with 3 mg/kg/day for another 2 mts
 Dietary counseling
Thalassemia  trait is extremely common
 Grp of disorders involving reduced synthesis of one of the chains involved in synthesis of adult Hb
 α chains
o 2 copies of 2 diff genes
o Mild forms include silent carrier (_a/aa) and trait (_a/_a or __/aa)  do not require
treatment
o Most cases a diagnosis is one of exclusion (rule out iron def, rule out beta thal)
o Screening electrophoresis is normal
 β chains
o 2 copies of one gene
o Genotypes result in range of anemia phenotypes
o Milder situations (b+b or b0b)
o Key diagnostic pt is that std Hb electrophoresis will show an elevated A2 at about 1 yr
Anemia assoc with acute infection
 Normocytic anemia related to acute infection is now the most common cause of anemia in young children
in US
 Usually viral
G6PD deficiency
 Diagnosis freq made in context of moderate to sever acute hemolytic anemia following exposure of child to
oxidant “trigger” (medication or infection or unknown)
 Important cause of neonatal jaundice, even with minimal hemolysis
AIHA
 In children is almost always a post-viral, IgG-mediated event
 Presentation is similarly to G6PD deficiency, although smear typically has spherocytes
 Direct Coombs is positive
 Spontaneous resolution is general rule
Hemolytic disease of fetus/newborn (HDFN)
Hereditary spherocytosis
 Autosomal dominant
 Typically presents during childhood with splenomegaly, mild hemolytic anemia with elevated MCHC,
spherocytes, moderately high reticulocyte count
 Direct Coombs is negative
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 Another cause of neonatal jaundice
 Main consideration is timing of splenectomy and avoidance of gall bladder disease
Pediatric hemostasis
o Hemophilia
 Factor VIII and factor IX do not cross placenta  diagnosis can theoretically be made in immediate
newborn period by checking specific factor levels in cord blood samples
 Majority have known family hx
 Characteristic bleeding (hemarthroses, deep tissue/muscle bleeding, bruising)
 Prolonged PTT and decreased factor levels
 3 things to know b/f treatment:
 Hemophilia A or B?
 Mild, moderate, severe?
 Inhibitor or not?
o ITP
 Typically an acute, transient affliction that improves in several wks and resolves in several months
 Over 80% will resolve within 6 mts, in contrast to adults, for whom disease is usually chronic
 Diagnosis
 Mucocutaneous bruising, epistaxis, gingival/oral bleeding
 Likely caused by abnormal but temporary immune rxn, likely to common viral infection
 CBC  no significant abnormalities of WBC count or Hg
 Smear  normal white and red blood cell morphology
 Treatment
 Goal in children is to prevent serious bleeding while allowing disease process to run its course
 If observation is not an option, first-line treatment include IVIg, steroids, anti-D immune globulin
 temporarily raise platelet count
 Peds hematologists sometimes recommend observation without treatment for children with typical
acute ITP who do not have serious bleeding (b/c of side effects of treatment)
Thrombosis/thrombophilia
o 2 “high risk” stages of childhood for thrombosis are newborn period and adolescence
 Newborns are at high risk likely due to unique imbalances seen in their developing hemostatic systems
 Anticoagulants protein C and S are also vit K-dep and are present in lower levels in 1st few months of life
 Homozygous deficiency of either protein C or protein S  typically presents with purpura
fulminans, CNS damage, and other thromboses
o Spontaneous thrombosis in childhood is rare  typically more than one identifiable factor contributing to event
 Congenital (protein C or S deficiency, antithrombin III deficiency, factor V Leiden, prothrombin G20210A
mutation)
 Infection
 Dehydration
 Surgery
 Trauma
 Cancer
 Renal disease
 Congenital heart disease
 Sickle cell anemia
 Vasculitis
 Inflammatory disease (lupus)
 INDWELLING VASCULAR CATHETER  single most common risk factor for thrombosis in children
 Commonly used for venous access, diagnostic procedures, monitoring critically ill children
o Diagnosis
 Key = clinical suspicion
 Even if acquired risk factors for thrombosis are present (infection, catheter), assays for major congenital
thrombophilias are often performed, esp if clot is severe
 Use of contrast dye = gold std
 Ultrasonography, contrasted CT, MRI
o Treatment
 Options same as for adults, doses and protocols differ
 Std heparin, LMWH and warfarin
 Aspirin may be used following stroke
 Age of patient is important in determining starting dose of anticoagulant (children under 2 mts of age
typically have higher per-kg dose requirements to achieve therapeutic levels
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VERY FEW INSTANCES IN WHICH LONG TERM ANTICOAGULATION IS CONSIDERED IN
CHILDREN
Neutrophil disorders
o Neutropenia in peds
 Autoimmune or antibody-mediated neutropenia occurs fairly frequently in young children and can last for
as long as 2 yrs b/f subsiding
 Transient neutropenia – 2ndary to many common viral infections, very common, does not usually result in
significant infectious morbidity
 Presence of mouth sores or gingival inflammation suggests that the neutronpenia is NOT transient
and further eval is needed
 Chronic primary neutropenia
 Differentiating b/t primary production problem of neutrophils and peripheral destruction often
requires a BM to assess maturation and degree of production
 Complete immunologic work-up required to assess primary immunodeficiency
 Chronic neutropenias resulting from decreased production are most effectively treated with G-CSF
o Neutrophilia
 Acute bacterial infections, corticosteroids
 Reactive neutrophilia – much more common in peds patients than underlying hematologic or oncologic
disease
 Generally assoc with elevation in LAP
 Appearance of immature white cells in peripheral blood  “shift to left”
o Disorders of neutrophil function
 Disorders of neutrophil adhesion (LAD I and II)
 Mediated by abnormalities of leukocyte carbohydrates and glycoproteins (II  CD15 deficiency /
I  CD18 deficiency)
 Usually have numerous bacterial infections and HIGH numbers of neutrophils circulating in blood
 elevation persists even when patient is not overtly infected
 Neutrophils not only don’t get to sites of infection, they also don’t work well
 Sometimes have a hx of delayed umbilical cord separation
 Chronic granulomatous disease (CGD)
 Group of heritable disorders that share the failure of neutrophils, monocytes, macrophages, and
eosinophils to undergo a respiratory burst and generate O2 Neutrophil numbers are normal
 Recurrent pneumonias, skin infections, lymphadenitis
 Staph aureas, Serratia, Aspergillus
 CHILDREN WITH RECURRENT BACTERIAL INFECTIONS SHOULD HAVE FLOW
CYTOMETRY FOR CGD AS PART OF INITIAL WORKUP
Lymphocyte disorders and immunodeficiences
o Lymphocytosis
 Often benign, assoc with infections
 Reactive lymphocytes freq have increased size and cytoplasmic abnormalities which distinguish them from
malignant lymphoid cells
o Lymphopenia
 Leucopenia  consider underlying immunodeficiency as potential cause
 Corticosteroid admin, infections (HIV)
 Many of primary immunodeficiencies are treated by stem cell replacement (BM transplant)