Pediatric emergency medicine trisk 559

TABLE 93.10
4T’S SCORE FOR HIT PRETEST PROBABILITY
2
Thrombocytopenia

Timing of fall in
platelet count

1

>50% plt count fall 30–50% plt count
and nadir ≥20K
fall to nadir 10–
cells/μL
19K cells/μL
Onset 5–10 days or >10 days or timing
<1 day (if heparin
unclear or <1 day
exposure within
with recent
30 days)
heparin 31–100
days

0
<30% plt count fall
or nadir ≤10K
cells/μL
Plt count fall <4
days (without
recent heparin

exposure)

Thrombosis or other • New thrombosis
sequelae
• Skin necrosis at
injection site
• Adrenal
hemorrhage
• Anaphylactoid
reaction to IV
heparin bolus

• Progressive or
recurrent
thrombosis on
therapeutic
anticoagulation
• Erythematous skin
lesion at injection
site
• Suspected but not
confirmed
thrombosis

None

Other cause for
No other cause
thrombocytopenia
evident

Possible other cause
evident

Probable/definite
other cause
present

Score 0–3: Low probability of HIT (<5%). Testing not advised.
Score 4–5: Intermediate probability of HIT (10–30%). Consider sending screening test
(HIT antibody screen); discuss with hematology.
Score 6–8: High probability of HIT (20–>80%). Send both tests (HIT antibody screen
and the serotonin release assay).
Modified from Warkentin TE, Linkins LA. Non-necrotizing heparin-induced skin lesions and the 4T’s score. J
Thromb Haemost 2010;8:1483–1485.

Most commonly, HIT develops due to formation of an IgG antibody that recognizes
an antigen formed by the complex of heparin and platelet factor 4 (PF4), a protein
secreted by activated platelets. The antibody mediates destruction of platelets resulting
in thrombocytopenia. HIT more frequently develops in the setting of unfractionated
heparin (UFH) use but can also emerge in patients receiving low–molecular-weight


heparin (e.g., enoxaparin). The typical pattern for HIT is the downtrending of the
patient’s platelet count 5 to 10 days following the initiation of heparin therapy. The
platelet count may fall to 50% of baseline values for the patient, but generally the nadir
is mild to moderate with median counts reported in the 50 to 60 × 103/μL range. If the
patient has had a recent exposure to heparin and had circulating antibodies present at the
time of heparin reinitiation, the platelet count may fall in the first 24 hours. If HIT is
strongly suspected, discontinue heparin therapy immediately and use an alternate

anticoagulant in consultation with a hematologist. Alternative treatment options include
direct thrombin inhibitors such as argatroban and bivalirudin, but studies are currently
limited in pediatric patients.

Nonimmune Thrombocytopenia
Nonimmune etiologies of thrombocytopenia are less common but important to consider
particularly in mild to moderate thrombocytopenia. Platelet production can be affected
by intrinsic defects or absence of megakaryocytes (platelet progenitors), suppression
mediated by infection, medications, toxins, or marrow replacement by malignant cells
such as leukemia or a metastatic solid tumor. Platelet destruction can arise in the setting
of microangiopathic coagulopathies such as DIC, TTP, or HUS. Occult thrombus,
mechanical destruction such as cardiopulmonary bypass, and environmental stressors
such as hypothermia can also result in thrombocytopenia. Platelet sequestration is most
commonly due to splenomegaly. Pseudothrombocytopenia (laboratory artifact when
platelets clump in a specimen) is also a consideration in an otherwise healthy individual
with isolated and unexpected thrombocytopenia.
Severe thrombocytopenia in the setting of a nonimmune process puts a patient at
greater risk of bleeding than ITP. Patients usually respond well to platelet transfusions.
Transfusions should be reserved for severe or persistent bleeding or for significant
trauma. Many affected patients have chronic disorders and require repeated transfusions.
The excessive use of platelet transfusions, whether prepared from multiple, single, or
HLA-matched donors, may contribute to the formation of antiplatelet antibodies. Such
antibodies make subsequent transfusions challenging since platelets are often quickly
destroyed by these alloantibodies leading to a minimal or short-lived increase in the
platelet count. Use single-donor transfusions (apheresis units) and leukocyte-depleted
blood products whenever possible for this patient population, to decrease the risk of
alloimmunization.

THROMBOCYTOSIS
Goals of Treatment

Treatment for thrombocytosis is typically unnecessary in the pediatric population.
Unlike primary thrombocytosis, secondary or reactive thrombocytosis has not been
associated with a significant increased risk of thrombotic or hemorrhagic complications


and empiric antiplatelet therapy is not routinely recommended even for extreme
thrombocytosis.

Clinical Considerations
Clinical Recognition
Thrombocytosis is defined as a platelet count greater than 450 × 103/μL. Primary
thrombocytosis is rare in the pediatric population. Hereditary or familial forms have
been associated with gene variants that encode thrombopoietin and the thrombopoietin
receptors, and transmit in an autosomal dominant fashion. Clonal forms of
thrombocytosis result from myeloproliferative syndromes; these are extremely rare in
children. The pathophysiology and natural history of primary thrombocytosis have been
predominantly explored in the adult population. Evidence of increased risk of
thrombotic and hemorrhagic events has been reported in children but to a lesser degree
than observed in adults. Risk assessment and stratification tools have not been validated
in children. The degree of thrombocytosis can range from mild (>450 × 103/μL) to
extreme (>1,500 × 103/μL) regardless of a primary or secondary etiology. Secondary
thrombocytosis is common and occurs in the setting of infection, inflammation, or other
physiologic stress ( Table 93.11 ).
Clinical Assessment/Diagnostic Testing
Thrombocytosis is usually an incidental finding. Spurious causes of thrombocytosis
such as cell fragments or microorganisms should be excluded by reviewing a peripheral
blood smear. Initial evaluation should focus on identifying an inciting cause. In the
absence of symptoms, laboratory evidence of acute inflammation such as C-reactive
protein, von Willebrand factor (VWF), fibrinogen, and proinflammatory cytokines (IL6) may suggest an underlying inflammatory state. The presence of Howell–Jolly bodies
on peripheral blood film may suggest an asplenic or functionally asplenic state.

TABLE 93.11
ETIOLOGIES OF REACTIVE THROMBOCYTOSIS
Acute infectious disease
Chronic infection (tuberculosis, hepatitis, osteomyelitis)
Autoimmune/inflammatory disease
• Inflammatory bowel disease (IBD)
• Kawasaki disease
• Ankylosing spondylitis
• Rheumatoid arthritis
Medication effect
• Glucocorticoids
• Epinephrine
• Low–molecular-weight heparin
• Vincristine
Malignancy
Tissue damage
• Postprocedure
• Thermal burns
• Trauma
Asplenia or functional asplenia
Iron deficiency
Hemolytic anemia
Acute blood loss
Inflammation
Exercise
Rebound following thrombocytopenia
Management
Patients with asymptomatic thrombocytosis do not require emergency medical therapy

to lower their platelet count; however, they may require treatment directed at the
underlying cause of their thrombocytosis. Patients should follow up with their primary
care provider to ensure platelet count normalization; the platelet count may remain
elevated for weeks to months. Consultation with a pediatric hematologist is advised if
thrombocytosis persists beyond this time frame. The use of antiplatelet (e.g., aspirin) or
cytoreductive agents (e.g., hydroxyurea, anagrelide) should only be started in
consultation with a pediatric hematologist. Evidence for their use and the optimal agent