How to Use Thrombolytic Agents in the Treatment of Neonatal Thrombosis: A Systematic Review

R. Leong¹, J. Patel², N. Samji³, B. Paes^3,4, A.KC Chan⁴, J.-A. Petropoulos⁵, M.D Bhatt⁴

¹Contributed equally as co-first authors, McMaster University, Faculty of Health Sciences, Hamilton, Canada, ²Contributed equally as co-first authors, McMaster University, Faculty of Science, Hamilton, Canada, ³McMaster University, Department of Medicine, Hamilton, Canada, ⁴McMaster University, Department of Pediatrics, Hamilton, Canada, ⁵McMaster University, Faculty of Health Sciences, Hamilton, Canada

Abstract Number: LPB0026

Meeting: ISTH 2021 Congress

Theme: Pediatrics » Thrombosis in Neonates and Children

Background: Among children, neonates have the highest incidence of thrombosis with recent studies reporting up to 15 per 1000 neonatal intensive care unit (NICU) admissions. Thrombolytic agents are used for management of life and/or organ threatening thrombosis in neonates. There is limited literature evaluating dosing, monitoring, efficacy and safety of thrombolytic use in the neonatal population.

Aims: To cumulatively summarize published literature on dosing, administration, monitoring, and duration recommendations proposed by primary studies on tissue plasminogen activator (tPA), streptokinase and urokinase treatment in neonates (≤28 days).

Methods: A systematic literature search was conducted using OVID Medline, Embase, Web of Science, CINAHL, and EBM databases from database inception until June 20, 2020. The initial search yielded 6,411 articles, of which 23 were included for review.

Results: Out of 23 included studies, 15, 4, and 1 studies exclusively reported on the use of tPA, streptokinase, and urokinase, respectively. In total tPA use was reported in 195 patients, streptokinase in 58 patients and urokinase in 14 patients. The reported dosing range for tPA was 0.01-0.6 mg/kg/h, streptokinase was 50-2000 U/kg/h, and urokinase was 1000-20,000 U/kg/h with duration ranging from 30 minutes up to 30 days. Complete and partial resolution rates are reported to be 66-71% and 20-22%, respectively, with recurrence risk in 0-11%. The bleeding risk is significant at 18-44% and mortality reported in 11-15% of neonates. The dosing, efficacy and safety are summarized in Table 1.

	Parameter	tPA	Streptokinase	Urokinase
Numbers	Studies	16	7	3
Numbers	Patients	195	58	14
Dosing & Duration	Dosing	0.01-0.6 mg/kg/h	50-2000 U/kg/h	1000-20,000 U/kg/h
Dosing & Duration	Duration	30 minutes – 30 days	1-11 days	6 hours – 9 days
Efficacy	Recurrence risk	7.4% (2/27)	0% (0/10)	11.1% (1/9)
	Complete resolution	66.1% (78/118)	69.4% (34/49)	71.4% (10/14)
	Partial resolution	20.0% (19/95)	22.4% (11/49)	21.4% (3/14)
Safety	Bleeding risk	18.2% (27/148)	20.7% (12/58)	44.4% (4/9)
Safety	Death	15.3% (18/118)	11.1% (1/9)	11.1% (1/9)

Summary of dosing, efficacy and safety from 23 included studies. Each variable is reported from only the data that was available in the studies.

Conclusions: This is the first study to objectively summarize the efficacy and safety of thrombolytic agents in neonates. Overall, thrombolytic use is associated with up to 69% complete resolution of thrombosis and 11% recurrence risk. The reported bleeding risk is about 28%, which is much higher compared to other anticoagulants. Larger prospective studies are required to elucidate effective dosing regimens and further clarify efficacy and safety of thrombolytic agents.

To cite this abstract in AMA style:

Leong R, Patel J, Samji N, Paes B, KC Chan A, Petropoulos J-, D Bhatt M. How to Use Thrombolytic Agents in the Treatment of Neonatal Thrombosis: A Systematic Review [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/how-to-use-thrombolytic-agents-in-the-treatment-of-neonatal-thrombosis-a-systematic-review/. Accessed December 10, 2023.

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