The Effect of Fresh Frozen Plasma On the Incidence of Venous Thromboembolism and Haemorrhages in Children with Acute Lymphoblastic Leukaemia

Venous thromboembolism (VTE) and haemorrhages frequently occur during asparaginase (ASP) treatment in paediatric patients treated for acute lymphoblastic leukaemia (ALL). These complications cause significant morbidity and mortality. The effect of fresh frozen plasma (FFP) to prevent these complications in ALL patients is not entirely clear. The aims of this study were to assess the effect of FFP on the incidence of VTE and haemorrhages and the plasma levels of antithrombin (AT) and fibrinogen (FG) during the induction phase in paediatric ALL patients treated according to the Dutch Childhood Oncology Group ALL IX or ALL X protocol. In addition, we compared the incidences of VTE and haemorrhages and the plasma levels of AT and FG between both ALL protocols.

A retrospective observational cohort study was performed among paediatric patients, aging from 0 to 18 years, with newly diagnosed ALL receiving induction therapy according to the ALL IX or ALL X protocol between February 1997 and January 2012. Treatment during the induction phase of the ALL IX protocol, day 0–49, included dexamethasone and 4 doses of 6 000 IU/m² ASP intravenously over a period of 2 weeks (day 29–40). FFP supplementation was recommended if FG levels were < 1.0 g/L. Treatment during the induction phase of the ALL X protocol, day 0–64, included prednisone and 8 doses of 5 000 IU/m²ASP intravenously over a period of 3 weeks (day 12–33). In the ALL X protocol, FFP supplementation was recommended if FG levels were < 0.6 g/L. Medical records were reviewed and all VTE and haemorrhages during induction treatment were recorded. Plasma levels of AT (normal value: 80–140%) and FG (normal value: 0.7–4 g/L) and the frequency of FFP supplementation during the induction phase were also recorded.

In this study, 199 patients were included. During the induction phase, VTE and haemorrhages occurred in 7 (3.5%; 95% CI: 1.0–6.2%) and 2 (1%; 95% CI: 0.4–2.4%) of the 199 paediatric ALL patients treated according to both ALL protocols, respectively. Four VTE occurred in the central nervous system (57%) and 3 VTE were central venous line (CVL) related (43%) and occurred in the subclavian vein. Both haemorrhages were intracranial. 42% of all paediatric ALL patients received FFP supplementation. No statistical significant effect of FFP supplementation was seen on the incidence of VTE and haemorrhages. The mean AT and FG levels significantly decreased after ASP administration from 130% to a minimum of 78% and from 1.6 g/l to a minimum of 0.9 g/l, respectively. In general, the AT and FG levels did not increase by FFP supplementation.

The paediatric patients treated according to the ALL IX protocol (n=94) consisted of significantly less male, younger patients, and less T-ALL patients than patients of the ALL X protocol (n=105). The incidence of VTE during the induction phase was significantly lower in children treated according to the ALL IX protocol (n=1), including dexamethasone and 24 000 IU/m² ASP than in those included in the ALL X protocol (n=6) treated with prednisone and 40 000 IU/m²ASP (p=0.038). 25% of the ALL IX patients and 62% of the ALL X patients received FFP. After the third and fourth administration of ASP, the FG plasma levels were significant higher in the ALL IX protocol than in the ALL X protocol (p= 0.034 and 0.01, respectively).

FFP has no significant effect on the incidence of VTE and haemorrhages and the plasma level of AT and FG during the induction phase in paediatric ALL patients treated according to the Dutch Childhood Oncology Group ALL IX or ALL X protocol. VTE occurred significantly less often in ALL IX patients treated with dexamethasone and 24 000 IU/m² ASP than in ALL X patients treated with prednisone and 40 000 IU/m² ASP.

No relevant conflicts of interest to declare.