Blood Coagulation Changes under L-Asparaginase Therapy

Deutsch, Erwin; Fischer, M; Frischauf, H; Honetz, N; Lechner, Klaus; Pesendorfer, F; Stych, H.; Weissmann, A

doi:10.1007/978-3-642-99984-0_38

Cited by 15 publications

(12 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reports about the influence of ASNase on AT III synthesis are mostly related to patients receiving a prolonged administration of ASNase (mean total dose 140,000 U) [11][12][13], but the decrease in AT III has been reported to occur precociously from the start of the therapy [9,12], In our cases, a mean decrease in plasma AT III concentration and activity of about 25% occurred after 4 days from only 1 administration of 10,000 U of ASNase, with a return to normal range within 1 week. A second administration of HID ARAC + ASNase within 8 days from the first course seems to prolong this slight decrease in AT III.…”

Section: Discussionmentioning

confidence: 99%

“…High dose Ara-C (HIDARAC) regimen has been re ported to be an effective therapy of acute leukemia [1][2][3]; successively, this schedule has been modified by a sequential administration of asparaginase (ASNase) to obtain a synergic effect between Ara-C and AS Nase [4][5][6]. A mild and transient liver toxicity has been reported in 75% of patients who underwent HIDARAC therapy [6,7], Moreover, liver toxicity oc curs very frequently during ASNase administration [8]; coagulation abnormalities are also frequent [8][9][10], and antithrombin III (AT III) levels are dra matically lowered [9][10][11][12], so that an increased risk of thromboembolism has been noticed [11][12][13]. ASNaseinduced depression in AT III appears to be secondary to a reduced production by the liver, where AT III is synthesized [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antithrombin III during High-Dose Cytosine Arabinoside Therapy with or without Asparaginase

Marra¹,

Pagano²,

Stefano³

et al. 1986

Acta Haematol

View full text Add to dashboard Cite

Fourteen patients with hematologic neoplasia (11 acute myeloid leukemias, 2 non-Hodgkin’s lymphomas and 1 blast crisis of chronic myeloid leukemia) who underwent high-dose cytosine arabinoside (HIDARAC) therapy with or without sequential asparaginase (ASNase) were investigated in order to evaluate liver toxicity and a possible decrease in antithrombin III (AT III) plasma level. AT III was found decreased only in patients who received ASNase, whereas HIDARAC alone did not influence AT III levels. It is pointed out that a single dose of ASNase seems to be sufficient to induce a decrease in AT III. A mild and transient liver toxicity due to HIDARAC therapy does not seem to be of any clinical relevance.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antithrombin III during High-Dose Cytosine Arabinoside Therapy with or without Asparaginase

Marra¹,

Pagano²,

Stefano³

et al. 1986

Acta Haematol

View full text Add to dashboard Cite

show abstract

“…During L-asp therapy decreased levels of various fibrinolytic factors were observed. This can be ascribed to an inhibition of protein synthesis, as is demonstrated for albumin (Deutsch et al, 1970) and thyroxin-binding globulin (Garnick & Larsen, 19 79). Other possibilities are consumption by disseminated intravascular coagulation and liver dysfunction.…”

Section: Discussionmentioning

confidence: 88%

The influence of l-asparaginase therapy on the fibrinolytic system

Vellenga¹,

Kluft²,

Mulder³

et al. 1984

Br J Haematol

View full text Add to dashboard Cite

Summary. Fibrinolytic factors were assessed during L‐asparaginase administration, to study whether their changes may predispose to a haemorrhagic or thrombotic diathesis. The total level of α2‐antiplasmin declined, as well as the ratio of the plasminogen‐binding form of α2‐antiplasmin to the non‐plasminogen‐binding form. After cessation of L‐asparaginase administration, the ratio increased to 1.6 times that of the pretreatment value. These data indicate that the plasminogen‐binding form of α2‐antiplasmin is the form primarily synthesized in vivo. L‐Asparaginase therapy reduced plasma levels of plasminogen and histidine‐rich glycoprotein (HRG) and influenced the equilibrium between HRG, plasminogen and HRG‐plasminogen complex, with a more pronounced decrease of plasminogen (62%±8) and HRG (76%±11) in comparison to the free‐plasminogen levels (51%±6). α2‐Macroglobulin was only slightly influenced by L‐asparaginase and may consequently play a more pronounced role in inhibition. This is suggested by moderate declines in functional tests of plasmin, urokinase and tissue activator inhibition by patients plasma, and by the ratio of inhibition of these enzymes over α2‐antiplasmin. Thus the bleeding tendency described during L‐asparaginase therapy can be ascribed not only to a temporary deficiency of coagulation factors but also to temporary α2‐antiplasmin deficiency.

show abstract

“…The basis for its effect is the depletion of asparagine, an amino acid essential for lymphoblasts. The enzyme also affects the synthesis of proteins, thereby causing a reduction of coagulation proteins (1)(2)(3)(4). Depression of antithrombin, fibrinogen and coagulation factors 11, IX and X is well established (4)(5)(6).…”

mentioning

confidence: 99%

“…The enzyme also affects the synthesis of proteins, thereby causing a reduction of coagulation proteins (1)(2)(3)(4). Depression of antithrombin, fibrinogen and coagulation factors 11, IX and X is well established (4)(5)(6). Recent studies have also reported a decrease in protein C and protein S (5)(6)(7)(8).…”

mentioning

confidence: 99%

Effects of Erwinia‐asparaginase on the coagulation system

Carlsson

Stockelberg

Tengborn

et al. 1995

European J of Haematology

View full text Add to dashboard Cite

l‐Asparaginase treatment during induction therapy in acute lymphoblastic leukaemia (ALL) is known to be frequently complicated by thromboembolic events. It was recently suggested that l‐asparaginase derived from Erwinia chrysanthemi alters the coagulation system less severely than does Escherichia coli asparaginase. In a series of 11 adult patients with ALL, we investigated some parameters of the coagulation system during treatment with Erwinia asparaginase. The doses employed were rather high; all patients below the age of 60 years received 15000 U/m2 daily over 14 days. In accordance with what is known from treatment with E. coli asparaginase, we observed significant lowering of antithrombin as well as of fibrinogen. However, as to fibrinogen indeed a significant decrease had occurred prior to the institution of Erwinia asparaginase treatment. The most striking observation in the present study was that the levels of prothrombin complex, reflecting the function of K‐vitamin dependent coagulation factors II, VII and X, remained within normal ranges during treatment. This indicates that these coagulation factors were not affected by Erwinia asparaginase, an observation at variance with several reports where E. coli asparaginase was investigated. This latter observation was the only finding which could lend support to the view that Erwinia asparaginase affects the coagulation system less than E. coli asparaginase. Finally, one of our patients developed a sinus thrombosis, a severe thrombotic complication.

show abstract

Blood Coagulation Changes under L-Asparaginase Therapy

Cited by 15 publications

References 12 publications

Antithrombin III during High-Dose Cytosine Arabinoside Therapy with or without Asparaginase

Antithrombin III during High-Dose Cytosine Arabinoside Therapy with or without Asparaginase

The influence of l-asparaginase therapy on the fibrinolytic system

Effects of Erwinia‐asparaginase on the coagulation system

Contact Info

Product

Resources

About