Intravascular Coagulation Phenomena Associated with Prevalent Fall in Fibrinogen and Plasminogen during &lt;i&gt;L&lt;/i&gt;-Asparaginase Treatment in Leukemic Children

Legnani, Cristina; Palareti, Gualtiero; Pession, Andrea; Poggi, Maurizio; Vecchi, Vico; Bianchini, Bruno; Coccheri, S.

doi:10.1159/000215802

Cited by 18 publications

(19 citation statements)

References 19 publications

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“…The protein C content at the start of ASP therapy is 147% and 137.5% for the E . Miniero et al [24] Legnani et al [35] O'Meara et al [20] This study This study coli and Erwinia group, respectively. During ASP treatment, however, we observed a steady decline in protein C levels.…”

Section: Discuss 1 0 Nmentioning

confidence: 94%

Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: A randomized study

Risseeuw-Appel

Dekker

Hop

et al. 1994

Med. Pediatr. Oncol.

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A randomized study was done in twenty newly diagnosed children with acute lymphoblastic leukemia. Ten children were treated with Escherichia coli L-asparaginase, and ten with Erwinia chrysanthemi L-asparaginase. L-asparaginase (ASP) treatment started halfway during ALL-induction treatment with vincristine, prednisone, daunorubicin and intrathecal methotrexate. The mean activated partial thromboplastin time (APTT) level in all children demonstrated a significant fall (P < 0.001) from 28.25 sec at diagnosis to 23.0 sec at the start of ASP treatment. In this same time interval, the mean fibrinogen level declined markedly from 3 g/l to 1.2 g/l (P < 0.001), probably due to prednisone therapy. The APTT stayed shortened during ASP therapy, whereas the hypofibrinogenemia recovered significantly faster in the Erwinia group (P < or = 0.01). Factors (F) II, V, VII and X stayed within the normal range, while F VIII and F IX were elevated. During the entire period of induction therapy, the ATIII activity remained within the normal range in both treatment groups. The protein C values, however, demonstrated a steady decline from 140% at start of ASP treatment to a mean of 81% and 93%, respectively, at the end of the ASP therapy in the E. coli and Erwinia group. Five of the ten children treated with E. coli ASP demonstrated protein C levels below 70% at the end of ASP therapy, opposed to none of the Erwinia treated patients (P = 0.03). We suggest that the effect of ASP resulting in decreased coagulation factor synthesis is in part counterbalanced by the effect of prednisone on the coagulation system, when ASP is administered at the end of ALL induction treatment. The overall effect of ASP either of E. coli or of Erwinia on the hemorrhagic system reveals a slight imbalance towards thrombosis, mainly because of a gradual decrease in protein C activity. This imbalance is less pronounced in the Erwinia group.

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Section: Discuss 1 0 Nmentioning

confidence: 94%

Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: A randomized study

Risseeuw-Appel

Dekker

Hop

et al. 1994

Med. Pediatr. Oncol.

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“…We hypothesized that thrombosis during L-asparaginase therapy is associated with low fibrinogen levels. In previous case series and case reports with L-asparaginase-induced thrombosis, low levels of fibrinogen and other clotting factors have occurred, resulting in the need for cryoprecipitate or fresh frozen plasma infusion [1,2,11,12]. No adult study to date has demonstrated an association of thrombosis with low fibrinogen in a large subset of patients.…”

Section: Introductionmentioning

confidence: 99%

Thrombosis associated with l‐asparaginase therapy and low fibrinogen levels in adult acute lymphoblastic leukemia

Beinart

Damon

2004

American J Hematol

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L-Asparaginase is a chemotherapeutic agent commonly used in the treatment of both adult and pediatric acute lymphoblastic leukemia (ALL). A major complication is thrombosis, resulting from reduced synthesis of proteins such as antithrombin III. Hypofibrinogenemia, also a side effect, may be a marker of thrombosis and decreased protein synthesis. A retrospective chart review of identically treated patients revealed 9 thrombotic events among 93 patients (10%), 6 (7%) occurring during treatment cycles including L-asparaginase. Twelve (13%) patients had fibrinogen levels <50 mg/dL. Of these, 3 (25%) suffered a thrombotic event. This results in a specificity of 90% and a relative risk of 10 (P = 0.014). Therefore, a fibrinogen <50 mg/dL may serve as a marker for a hypercoagulable state in ALL patients receiving L-asparaginase. Am.

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“…L-asparaginase (L-ase) is an enzyme whose therapeutic effect in acute lymphoblastic leukaemia (ALL) GIMEMA the type obtained by E. coli (1 1, 12). Moreover, it has been reported that L-ase treatment is the cause of a widespread impairment of the haemostatic system (13)(14)(15)(16)(17)(18)(19)(20)(21)(22) sometimes associated with thrombotic events (5,15,17,18,23,24). While these haemostatic complications are known to be rare in children (8), in adults they seem to be more frequent and more severe (7,25,26), although their real incidence has not been established.…”

Section: Introductionmentioning

confidence: 99%

Incidence of thrombotic complications in adult patients with acute lymphoblastic leukaemia receiving L‐asparaginase during induction therapy: A retrospective study

Gugliotta

Mazzucconi²,

Leone³

et al. 1992

European J of Haematology

106

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The incidence of thrombotic complications chronologically related to L‐asparaginase administration is retrospectively analyzed in 238 adult ALL patients treated according to the GIMEMA protocol ALL 0288. The patients (126 males and 112 females, aged 12–68 years, median 29) received E. coli L‐asparaginase (L‐ase) in the induction phase at a dosage of 6000 U/m2/day × 7 d starting on d 15, as well as vincristine, prednisone, daunorubicin and cyclophosphamide, the last‐named by random 1:1. Ten patients (4.2%) developed thrombotic complications 5–15 d (median lid) after the start of L‐ase treatment. The thrombotic events, which were lethal in 5 patients, involved the cerebral sinus (5 cases), the cerebral arteria (2 cases), the portal vein (1 case), the pulmonary district (1 case), and a deep vein in the lower extremity (1 case). The occurrence of these complications was not related to the general thrombotic risk factors, nor to the main clinical and laboratory data registered at diagnosis and immediately before the start of L‐asparaginase treatment. The present study documents for the first time in a sufficiently large series of adult ALL patients that the incidence and the severity of thrombotic events related to L‐ase administration are relevant and need further consideration.

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Intravascular Coagulation Phenomena Associated with Prevalent Fall in Fibrinogen and Plasminogen during <i>L</i>-Asparaginase Treatment in Leukemic Children

Cited by 18 publications

References 19 publications

Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: A randomized study

Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: A randomized study

Thrombosis associated with l‐asparaginase therapy and low fibrinogen levels in adult acute lymphoblastic leukemia

Incidence of thrombotic complications in adult patients with acute lymphoblastic leukaemia receiving L‐asparaginase during induction therapy: A retrospective study

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