Page 2459 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 150 Disorders of Coagulation in the Neonate 2197

levels of fibrinogen despite ACT values that were within the accept- Acquired Thrombophilia
able range of 180 to 220 seconds in the final 24 hours of ECMO.
Thus routine laboratory testing is inadequate for predicting or pre-
venting thrombotic or hemorrhagic complications in pediatric Indwelling Catheters
ECMO patients. Thrombin generation assays, anti-FXa heparin
levels, and thromboelastography have been suggested as alternatives Central venous and arterial access is essential for the advanced care
to the ACT. Data supporting the use of these tests are lacking. provided in modern neonatology. The most common acquired
In neonates with established thrombosis or at risk for thrombosis, thrombotic risk factor in neonates is the presence of an indwelling
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daily FFP infusion is sometimes used as a source of plasminogen and vascular catheter. In a recent literature review by Park et al, the
anticoagulant proteins. Data supporting this approach are lacking. incidence of TE in neonates with central venous catheters was 9.2%.
Length of catheter stay, infusion of blood products, and malposi-
tioned umbilical venous catheters were found to be important risk
Respiratory Distress Syndrome factors. The most frequently reported sites of thrombosis are hepatic
25
veins, right atrium, and inferior vena cava. The incidence of
RDS, also known as hyaline membrane disease, is an acute pulmonary catheter-associated deep vein thrombosis (DVT) is influenced by the
process that is common in premature neonates. The disorder is method of detection. When catheters are used for total parenteral
characterized by hyaline membrane formation and fibrin deposition nutrition, it is estimated that DVT is diagnosed in 1% on clinical
in diffuse areas of atelectasis. Although severe RDS is associated with grounds, in 35% by echocardiography, and in 75% by venography.
increased thrombin generation and decreased levels of AT, interven- Although contrast venography is regarded as the reference standard
tions aimed at addressing these abnormalities have yielded inconclu- for the diagnosis of thrombosis in neonates with central venous
sive results. Plasmin or plasminogen may enhance survival; heparin catheters, ultrasonography is more commonly used because it is
is of uncertain benefit, and AT supplementation may increase mortal- noninvasive, is easy to perform at the bedside, and does not expose
ity. Additional studies are needed to explore the utility of anticoagulant patients to ionizing radiation.
or thrombolytic therapies in RDS. A laboratory profile consistent DVT often causes pain, swelling, and discoloration of the affected
with mild DIC is common in RDS; fibrinogen levels are decreased, limb. Loss of catheter patency, evidence of collateral circulation, and/
and levels of D-dimer are elevated. An unexpected increase in ventila- or unexplained thrombocytopenia should raise the suspicion of DVT.
tory support should raise the suspicion of pulmonary embolism in Prospective imaging studies performed before central access catheter
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this population. removal demonstrate thrombi in up to 86% of patients. Treatment
often begins with removal of the catheter, although consideration of
anticoagulation before catheter removal is warranted, especially in
NEONATAL THROMBOEMBOLIC DISORDERS infants with right-to-left intracardiac or intrapulmonary shunting.
Small catheter-associated thrombi may resolve without specific
The incidence of thromboembolism (TE) has a bimodal peak, with therapy. Larger thrombi or those in locations associated with greater
an increased occurrence in newborns and adolescents. Important risk morbidity (e.g., sinovenous, renal, portal) may warrant short courses
7
factors for the development of neonatal TE include vascular catheter- of heparin or thrombolytic agents. Platelets should never be admin-
ization, a hypercoagulable state conferred by the developing coagula- istered through arterial catheters because of the potential risk for TE.
tion system, and comorbidities such as congenital heart disease,
dehydration, sepsis, congenital nephritic syndrome, necrotizing
enterocolitis, and asphyxia. 3 Disseminated Intravascular Coagulation
Laboratory workup often reveals a hypercoagulable state such as
decreased levels of AT, protein C, and protein S; defective fibrinolysis; Neonates are susceptible to DIC because of their immature antico-
hyperactive platelets; elevated levels of clotting factors (i.e., fibrino- agulant and fibrinolytic systems. Most cases of neonatal DIC are
gen, FVII, FVIII); and the presence of antiphospholipid antibodies associated with tissue ischemia and acidosis secondary to sepsis, low-
or thrombophilic defects, such as FV Leiden or the prothrombin gene output cardiac failure, perinatal asphyxia, severe RDS, or necrotizing
1–3
mutation. A family history of TE or miscarriages may indicate a enterocolitis. Other causes of DIC are conditions that lead to con-
hereditary thrombophilia. sumptive coagulopathy such as large vascular anomalies, severe liver
Consensus guidelines have been developed for the management disease, massive hemolysis, or hereditary thrombophilia. DIC may
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of neonatal TE. Heparin, either unfractionated heparin (UFH) or present with hemorrhage and/or TE. Bleeding in a well-appearing
low-molecular-weight heparin (LMWH), remains the mainstay of neonate is usually the result of an inherited deficiency of a coagulation
treatment in newborns. If the thrombus is limb or life threatening, protein or immune-mediated thrombocytopenia rather than DIC. In
thrombolytic therapy may be considered. Most recommendations are contrast, bleeding in a sick preterm neonate is more likely the result
of low-grade level because the evidence in this patient population is of DIC. Patients with DIC often exhibit a prolonged PT, aPTT, and
derived from case reports, case series, registries, and extrapolation thrombin clotting time, decreased fibrinogen and FVIII levels,
from studies in adults. Large, multicenter, prospective controlled thrombocytopenia, and increased levels of D-dimer (Table 150.6).
clinical trials are needed to generate evidence-based guidelines; such Definitive therapy requires identification and reversal of the
studies are problematic in neonates. trigger for DIC. FFP, platelets (if bleeding is severe), and cryoprecipi-
tate (if the fibrinogen concentration is low) are given to replace the
consumed factors. Reasonable treatment targets include maintaining
Incidence the fibrinogen level over 100 mg/dL, the platelet count over 50 ×
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10 /L, and the PT close to normal. Heparin should be given if there
Current estimates of the incidence of neonatal TE are derived from is TE along with AT concentrate if indicated. Successful treatment
three international registries, each with different inclusion criteria. of DIC depends on reversal of the trigger and provision of aggressive
Registry data from Canada, Germany, and the Netherlands indicate supportive care. Therapy aimed at reversing the coagulopathy has
the incidence of TE in neonates to be 24 per 10,000 NICU admis- little effect on DIC outcome.
sions, 0.51 per 10,000 live births, and 14.5 per 10,000 live births,
respectively. 23–25 Two-thirds of thromboembolic events are venous,
and 80% are either catheter associated or develop after a severe Hereditary Thrombophilia
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illness. Arterial thromboembolic events in neonates usually present
as strokes or emboli to the limbs from catheter-associated thrombi. Spontaneous TE is rare in healthy newborns, and this presentation
Neonatal TE is associated with significant mortality and morbidity. should prompt evaluation for hereditary thrombophilia. Among the