Antithrombin deficiency after prolonged asparaginase treatment in children with acute lymphoblastic leukemia.
Children with acute lymphoblastic leukemia (ALL) have several risk factors for deep venous thromboses (DVTs) such as central venous catheters and asparaginase (ASP), related antithrombin (AT) deficiency. After introduction of a new standard and intermediate-risk ALL treatment protocol with prolonged continuous ASP treatment, two symptomatic DVTs in 10 patients were observed at the Children's Hospital, Helsinki, Finland. To prevent further thrombotic complications yet ensuring continuous exposure to ASP, an AT substitution strategy was adopted in Helsinki. The same ALL treatment protocol is used without AT substitution in the other Nordic countries. In this retrospective study, we describe the effect of prolonged ASP treatment on AT and fibrinogen levels in children without AT substitution in Stockholm, Sweden (n = 39) and the AT substitution in children with AT activity below 0.55 kIU/l in Helsinki (n = 36, intervention group). The intervention group is compared with children treated similarly earlier in Helsinki without AT substitution (n = 10). The median lowest AT activity during the ASP treatment without AT substitution was 0.55 kIU/l. Fibrinogen level of 1.0 g/l or less was found in 14% of all routine samples during the ASP treatment. In the intervention group, 23 (64%) received AT concentrate. Two (20%) children had symptomatic DVT before initiation of the AT substitution and two (6%) thereafter. We conclude that most children are exposed to low AT activity during ASP treatment predisposing to thrombosis. The effect of prophylactic AT substitution remains unclear.
aChildren's Hospital, Helsinki University Central Hospital, Helsinki, Finland bChildhood Cancer Research Unit, Karolinska Institute cDepartment of Blood Coagulations Disorders, Karolinska University Hospital, Stockholm, Sweden dUnit of Coagulation Disorders, Division of Haematology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Susanna
S
Ranta
Mats M
MM
Heyman
Kirsi
K
Jahnukainen
Mervi
M
Taskinen
Ulla M
UM
Saarinen-Pihkala
Tony
T
Frisk
Stefan
S
Söderhäll
Pia
P
Petrini
Anne M-T
AM
Mäkipernaa
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D020152:Antithrombin III Deficiency / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy*; D012307:Risk Factors
D000970:Antineoplastic Agents; D005340:Fibrinogen; D001215:Asparaginase