A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study.
BACKGROUND
Thrombotic events (TEs) are serious secondary complications in children with acute lymphoblastic leukemia (ALL) who receive L-asparaginase (ASP) therapy; however, the prevalence of TEs has not been established. The primary objective of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study was to determine the prevalence of TEs. The secondary objective was to detect any association of TEs with the presence of congenital or acquired prothrombotic disorders.


METHODS
Children with ALL were screened for TEs at the end of ASP treatment using bilateral venograms, ultrasound, magnetic resonance imaging, and echocardiography. Symptomatic TEs were confirmed by appropriate radiographic tests. All tests were read by a blinded central adjudication committee.


RESULTS
Twenty-two of 60 children had TEs, a prevalence of 36.7% (95% confidence interval, 24.4-48.8%). TEs were located in the sinovenous system of the brain in 1 patient, the right atrium in 3 patients, and the upper central venous system in 19 patients. TEs detected by venography resulted in 1) 25-100% occlusion, with 1 in 3 patients showing occlusion of > 75% of the greatest vessel dimension, and 2) the presence of collaterals in 60% of patients, with 40% categorized as major. No children with TEs were positive for factor V Leiden or prothrombin gene 20201A, and four of eight children with antiphospholipid antibodies had a TE.


CONCLUSIONS
The prevalence of TEs is exceedingly high in this population, and it is likely that the extent of occlusion is likely clinically significant. No trend was seen toward an association between TEs and the presence of congenital prothrombotic disorders. A trend was seen toward an association between TEs and antiphospholipid antibodies. Carefully designed clinical trials of primary prophylaxis for the prevention of TEs are required in this patient population.
Mitchell
Lesley G
LG
Population Health Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada. lesley.mitchell@sickkids.ca
Andrew
Maureen
M
Hanna
Kim
K
Abshire
Thomas
T
Halton
Jacqueline
J
Anderson
Ron
R
Cherrick
Irene
I
Desai
Sunil
S
Mahoney
Donald
D
McCuster
Patricia
P
Wu
John
J
Dahl
Gary
G
Chait
Peter
P
de Veber
Gabrielle
G
Lee
Kyong-Jin
KJ
Mikulis
David
D
Ginsberg
Jeffrey
J
Way
Cliford
C
D000293:Adolescent; D017152:Antibodies, Antiphospholipid / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000627:therapeutic use*; D001778:Blood Coagulation Disorders / Q000235:genetics; D002405:Catheterization, Central Venous / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005165:Factor V / Q000032:analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control
D017152:Antibodies, Antiphospholipid; D000970:Antineoplastic Agents; D000991:Antithrombins; C095381:factor V Leiden; D005165:Factor V; D001215:Asparaginase