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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 Fanconis anemia, in addition to acquired forms of aplasia
Treatment and prognosis for constitutional forms different from acquired specific diagnosis cannot be
missed
Fanconis 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 mean and lower limit mean and lower limit


of normal Hb of normal MCV Modestly lower levels of Hb
Birth-3 days 18.5 gm/dL (14.5) 108 (98) and MCV are normal for
1 wk 17.5 (13.5) 107 (89) children compared to adults.
1 mt 14.0 (10.0) 104 (85)
2 mts 11.5 (9.0) 96 (77)
3-6 mts 11.5 (9.5) 91 (74)
6-23 mts 12.5 (11.0) 77 (70)

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
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
o 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
Cows milk is a very poor source of iron and can cause low-grade asymptomatic GI losses of iron in milk-
protein allergic patients
Many children with iron def are consuming excessive amounts of cows milk replaces iron-
containing 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
o Thalassemia trait is extremely common
Grp of disorders involving reduced synthesis of one of the chains involved in synthesis of adult Hb
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
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
o 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
o 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
o 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
o Hemolytic disease of fetus/newborn (HDFN)
o 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
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
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 dont get to sites of infection, they also dont 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)