Transcript Thrombocytopenia in neonates

Thrombocytopenia in
neonates
Adapted from a presentation by
Bronwyn Waddell, MS 4
NICU Sub-internship
9-17-04
Definition
 Thrombocytopenia < 150,000/µL (150 x
109/L)
– Rare in general population (<1%); 22% in NICU
– Many healthy newborns b/w 100,000 150,000/µL.
– Average platelet counts lower in preterm infants
• Reflects increase during gestation, from 187,000 to
274,000/µL at 15 and 40 weeks
– Severe reductions (<50,000/µL) and/or persistent
thrombocytopenia can result in bleeding.
– Severe and/or persistent thrombocytopenia
requires evaluation, even in an asymptomatic
infant.
Evaluation of the
thrombocytopenic neonate
 Based on recognizing typical patterns
– 1) Immune
– 2) Infectious
– 3) Genetic
– 4) Drug-induced
– 5) Disseminated intravascular coagulation
– 6) Placental insufficiency
– 7) Miscellaneous
Algorithm in Evaluation
 Does thrombocytopenia fit pattern of
pathophysiologic process? (Table 1)
– Proceed to confirmatory testing
 Further evaluation is indicated if
– It does not fit one of these patterns
– The dx is not confirmed by appropriate
testing
– It is more severe/prolonged than fits dx
– It does not respond to appropriate tx
Category Subtype
Severity
Onset
Resolution Mechanism
Immune
Alloimmune
Autoimmune
Severe
Moderate
Early
Early
Days - wks Incr.
Wks - mos consumption
Infection
Bacterial
Viral
Fungal
Variable
Variable
Severe
Variable
Early
Late
1-7 days
Variable
2-7 days
Chromosomal
Bone marrow
failures
Familial TCP
Moderate
Severe
Early
Early
Days - wks Decreased
Variable
production
Mild-mod
Early
Never
Drugs
Modsevere
Late
8 days
(med)
Variable
DIC
Severe
Variable
Variable
Inc consump
PIH/
IUGR
Mild-mod
Early
7-10 days
Dec prodxn
NEC
Mod-sev
Late
7-10 days
Inc consump
Genetic
disorder
Mixed
Evaluation in early thrombocytopenia:
Mild to Moderate
 Neonate with early thrombocytopenia (<72
hrs)
– First distinguish b/w mild-mod and severe
• Mild (100-150 x 109/L) or moderate (50-100 x
109/L).
• PIH and IUGR are common causes of early
thrombocytopenia among premature infants
• Generally, resolves spontaneously by day 7-10
of life
• Other labs include PT, PTT, D-dimers, cx
Evaluation in early severe
thrombocytopenia
 Severe/prolonged should trigger evaluation
for other disease processes
– Well-appearing infant: most common cause in
immediate post-natal period is immune
thrombocytopenia from anti-plt Ab across placenta
– Ill-appearing infant: consider other causes
• Sepsis, DIC (freq post severe perinatal asphyxia)
• Viral infections and congenital toxoplasmosis
 If tests fail to confirm dx, base further w/u on
PE, response to plt transfusion, and
mechanistic eval
Physical Examination
 Dysmorphic features suggestive of
chromosomal disorders provide dx clues:
– Trisomy 21, 13, 18, Turner, Noonan
syndrome, DiGeorge/velocardiofacial
syndrome
– HSM, abd masses (renal v thrombosis),
forearm/thumb abnormalities
(TAR/Fanconi’s)
– Decreased pronation/supination of forearm
(congenital amegakaryocytic TCP
w/proximal radial-ulnar synostosis)
Increased destruction
 Immune thrombocytopenia (0.3%)
– Neonatal alloimmune thrombocytopenia (NAIT)
• Mom forms IgG class antiplatelet Ab against the "foreign" antigen
(dad’s)
• Clinical features: mom asx, baby may have petechiae,
ecchymosis
• Labs: plts (often < 10,000/µL), antigen testing of parents’ plts,
mother's serum for antiplatelet alloantibody
• Management: well, term infants transfused if plt <20,000/µL or
if bld
– Transfusion threshold higher (<50,000/µL) in preterm/term infants
who are ill or have risk factors.
• Initial evaluation: head CT to r/o hemorrhage (10-20%)
• Adequate plt counts maintained during 1st 72-96 hrs (highest
bld risk)
• Tx with high-dose intravenous gamma-globulin (IVIG) may be
effective
Increased Destruction:
Immune Thrombocytopenia
 Autoimmune thrombocytopenia:
– Mediated by maternal Ab that react with maternal and infant
platelets.
– Occurs in maternal autoimmune disorders, including ITP and SLE
– Dx apparent from mother's PMH and maternal thrombocytopenia
– Mothers of infants with unexplained neonatal thrombocytopenia
autoimmune disorder?
– Healthy women w/o hx of autoimmune d/o sometimes develop
gestational thrombocytopenia that usually is mild, transient, and
benign.
 Clinical features: Petechiae, bruising, and bleeding.

– 90% infants have moderately severe thrombocytopenia in range of 20,000 to
50,000/µL
– Risk in infant correlates with severity of ITP in the mother:
• Mother s/p splenectomy, plts < 50 in preg, or older sibling w/neonatal
affects
– Plts decrease sharply during the several days after birth; nadir at 2-5 days
Management: transfusion, IVIG, or prednisone for severe TCP or clinical
bleeding
– Plt trx may not be as effective as in NAIT: autoAb usually react w/donor
Drug related
thrombocytopenia
 Drug-related thrombocytopenia:
– Mechanism is accelerated plt destruction caused by drugdependent Abs.
– BM suppression may occur post chemo to mom or newborn
infant
– Maternal thrombocytopenia post drug exposure mediated by
IgG
 Infant's platelet count should be monitored if exposed to
quinidine, penicillins, digoxin, and antiepileptic drugs;
indomethacin, heparin-induced thrombocytopenia less common
 Management — If drug-associated thrombocytopenia is
suspected, the offending agent should be withdrawn.
– Transfusions should be given for low platelet counts
(<20,000/µL) or for bleeding.
– If an immune-mediated condition is suspected, IVIG can be
used while awaiting confirmation.
Peripheral Consumption
 Hypersplenism: thrombocytopenia may be associated with an
enlarged spleen.
– Underlying disorders: hemolytic anemia, congenital hepatitis,
congenital viral infection, and portal vein thrombosis
– Management: Dx and tx of underlying cause.
• Plt transfusions PRN. Splenectomy if bleeding uncontrollable.
 Kasabach-Merritt: DIC, hemangiomas (kaposiform
hemangioendotheliomas)
– shortened platelet survival caused by sequestration of plts in AVM.
– Lesions noted at birth in approximately 50 % of patients
• Trunk (including retroperitoneum), arms and shoulder, lower
extremity, and cervicofacial
– Severe thrombocytopenia, hypofibrinogenemia, elevated fibrin
degradation products, and fragmentation of red blood cells
– Management: resolution of hemangioma, support hemostasis w/trx
– Tx: prednisone, interferon alpha, surgery, embolization, vincristine,
cyclophosphamide, actinomycin D
Peripheral Consumption

Disseminated intravascular coagulationthrombosis and hemorrhage.
– Complication of underlying illness, typically sepsis, asphyxia, MAS, severe
RDS.
– Dx suggested by associated illness, clinical presentation, and presence of
microangiopathic changes on the peripheral blood smear.
– Confirming labs: prolonged PT and PTT, decreased fibrinogen, increased
D-dimer
– Tx: directed at the underlying cause of DIC: platelets and FFP to maintain
plt >50,000/µL and PT time within physiologic range. Fibrinogen
concentration is maintained >100 mg/dL with infusion of cryoprecipitate.

Infection: bacterial, viral, and fungal organisms.
– Bacterial mechanisms for thrombocytopenia include DIC, endothelial
damage, antibody-mediated, and platelet aggregation caused by adherence
of bacterial products to platelet membranes.
• Decreased plt production due to injury to megakaryocytes in BM also
possible
– Viral: congenital rubella and cytomegalovirus.
• Mechanisms include platelet aggregation, loss of sialic acid from the platelet
membrane caused by viral neuraminidase, and megakaryocyte degeneration.
• Splenomegaly and reticuloendothelial hyperactivity may play a role.
 Management: tx underlying infection, platelet transfusions if associated
bld
Peripheral Consumption
 Necrotizing enterocolitis: GI necrosis in 2-10% of infants <1500 g.
– thrombocytopenia from platelet destruction
– In early stages, declining plts correlate with necrotic bowel and
worsening disease.
– Levels of cytokines, including platelet activating factor (PAF), are
increased in premature infants with NEC and correlate w/ disease
severity
– Intestinal damage and inflammatory cell recruitment result from a
cascade of cellular events that may be mediated at least in part by
PAF
 Thrombosis: low plts often accompanies thrombosis in newborns.
– Patients should be evaluated for a thromboembolic disorder if
thrombocytopenia cannot be explained by other conditions.
Decreased platelet production
 Often associated with genetic disorders: result in isolated
thrombocytopenia or syndrome
 Thrombocytopenia-absent radius syndrome: severe
thrombocytopenia and bilateral absent radii; thumbs are always
present
– Also hypoplasia or absence of the ulna, or abnormal or absent
humerus.
– Congenital heart disease, usually ASD or TOF, occurs in 1/3 of pts
– plt <10,000 - 30,000/µL at birth-1st postnatal week in 59 %
– Mortality is significant in neonate and early infancy, primarily due to
ICH.
• If pt survives this period, spontaneous resolution usually occurs after 1st
year
– Tx: supportive with platelet transfusions given when needed.

Fanconi anemia: thrombocytopenia from FA is rare in the
neonatal period.
– Pancytopenia typically diagnosed at six to nine years old
– Condition recognized in newborn by characteristic congenital
malformations in 60-70%:
• Hypopigmented spots, abnormality of thumbs, microcephaly, café-au-lait
spots, and urogenital abnormalities; short stature of prenatal onset
Our DNCC Guidelines for
platelet transfusion
 Transfuse 10-15 mL/kg leukoreduced,
irradiated platelets over 0.5-1 hour for:
–
–
–
–
Infants w/o signs of acute bld, but plt <20,000
Infant w/hemorrhage and plt <50,000
Consider w/bld and plt <100,000, esp ICH risk
Consider trx at predetermined value (20-100)
depending on infant’s status (d/w attending)
Transfusion precautions
 Neonates should receive 10-15 ml/kg of
CMV-safe (CMV Ab-) or leukoreduced
plts
– Increases count by >50 x 109
 Neonates are at increased risk for
transfusion-associated GVHD
– Irradiated bld products for
immunodeficiency, intrauterine or
exchange transfusions, or blood trx from
relative or HLA-selected donor
Conclusion: Neonatal
Thrombocytopenia
 Common in NICU (sick and premature)
 Differentiate and tx based on severity
 Recognition of etiology based on typical
patterns associated with specific
pathophysiologic processes
 Work up and treat per algorithm and
current clinical guidelines
– Pursue immune etiology in infant
w/persistent thrombocytopenia
Sources/References
 Sola M. Evaluation and treatment of severe and prolonged
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thrombocytopenia in neonates. Clin Perinatol; 2004:31(1)
Saxonhouse M, Sola M. Platelet function in term and preterm
neonates. Clin Perinatol 2004;31(1)
Andrew et al. A randomized, controlled trial of platelet
transfusions in thrombocytopenic premature infants. J Pediatr
1993;123:285-91.
Murray NA. Evaluation and treatment of thrombocytopenia in the
neonatal intensive care unit. Acta Paediatr Suppl 2002;91:74-81.
Sola, MC, Del Vecchio, A, Rimsza, LM. Evaluation and
treatment of thrombocytopenia in the neonatal intensive care
unit. Clin Perinatol 2000; 27:655.
Jones, KL. Smith's Recognizable Patterns of Human
Malformations, 5th ed. WB Saunders, Philadelphia 1997
Tomer et al. Autologous platelet kinetics in patients with severe
thrombocytopenia. J Lab Clin Med 1991;118:546-54.
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