228 Section V ■ Vascular Access

procedure such as lumbar puncture is

required, skip two doses of LMWH, and

measure anti-FXa level prior to the procedure.

(g) If an immediate antidote is required, protamine may be administered. The dose is usually a 1:1 ratio with LMWH; administration

of the dose may be done in 2 to 3 aliquots

with monitoring of anti-FXa levels (18).

(3) Thrombolytic agents

(a) Thrombolytic agents should be considered

in the presence of extensive or severe thrombosis when organ or limb viability is at risk.

(b) The use of streptokinase and urokinase has

been superseded by rTPA.

(c) rTPA acts by converting fibrin-bound plasminogen to plasmin, which then proteolytically cleaves fibrin within the clot to fibrin

degradation products. rTPA is nonantigenic

and has a short half-life. Supplementation

with plasminogen in the form of fresh frozen

plasma enhances the thrombolytic effect.

(d) Thrombolysis does not inhibit clot propagation, so anticoagulation may be necessary.

The administration of heparin, either concomitantly or following thrombolytic therapy, has not been adequately evaluated in

neonates.

(e) Dosage: A wide variety of dosage protocols

have been used (3,12,14,19,20).

 i. High-dose protocol: Continuous infusion

of rTPA 0.1 to 0.6 mg/kg/h for 6 hours.

 ii. Low-dose protocol: Continuous infusion

of rTPA 0.01 to 0.06 mg/kg/h over 24 to

48 hours. Simultaneous infusion of

UFH at 10 U/kg/h.

iii. Catheter-directed thrombolysis: Infusion

of low doses of rTPA through a catheter

with the tip adjacent to or within the

thrombus. Initial bolus dose ranges

from 0 to 0.5 mg/kg, followed by infusion of 0.015 to 0.2 mg/kg/h.

(f) Monitoring

 i. Measure thrombin time, fibrinogen

and plasminogen levels, and fibrin split

products or d-dimers prior to therapy, 3

to 4 hours after initiation of fibrinolytic

therapy, and one to three times daily

thereafter.

 ii. Imaging studies every 4 to 12 hours during fibrinolytic therapy to allow discontinuation of treatment as soon as clot

lysis is achieved.

iii. Fibrinolytic response is measured by a

decrease in fibrinogen concentration

and increase in levels of fibrindegradation products, but the correlation between these hemostatic parameters and efficacy of thrombolysis is poor.

Maintain fibrinogen levels of at least

100 mg/dL.

E. Complications of Anticoagulation/

Fibrinolytic Therapy

1. Hemorrhagic complications (1,21,22)

a. Intracerebral hemorrhage: Incidence approximately

1% in term neonates, 13% in preterm neonates,

increasing to 25% in preterm infants treated in the

first week of life. Data in preterm infants is confounded by the risk of “spontaneous” intraventricular hemorrhage (21).

b. Other major hemorrhage: Gastrointestinal, pulmonary

c. Bleeding from puncture sites and recent catheterization sites: Bleeding and hematoma at the site

of the indwelling catheter for LMWH has been

noted (1)

d. Hematuria

2. Embolization

Dislodgement of intracardiac thrombus, causing

obstruction of cardiac valves or main vessels, or pulmonary or systemic embolization (23).

F. Surgical Intervention (24,25)

Early consultation is recommended because surgical management may be required concomitantly, particularly for

life- or limb-threatening emergencies.

1. Thrombectomy

2. Microvascular reconstruction

3. Decompressive fasciotomy

4. Mechanical disruption of thrombus, using soft wires

and balloon angioplasty in conjunction with continuous site-directed thrombolytic infusion into the clot.

5. Amputation

References

1. Van Elteren HA, Veldt HS, te Pas AB, et al. Management and

outcome in 32 neonates with thrombotic events. Int J Pediatr.

2011; 2011:217564.

2. Brotschi B, Hug MI, Latal B, et al. Incidence and predictors of

indwelling arterial catheter related thrombosis in children.

J Thromb Haemost. 2011;9:1157.

3. Saxonhouse MA, Burchfield DJ. The evaluation and management of postnatal thromboses. J Perinatol. 2009;29:467.

4. Haase R, Merkel N. Postnatal femoral artery spasm in a preterm

infant. J Pediatr. 2008;153:871.