Antithrombin Iii Deficiency During Asparaginase Therapy

Pitney, W. R.; Phadke, Kalindi; Dean, Shirley

doi:10.1016/s0140-6736(80)91046-6

Cited by 38 publications

(12 citation statements)

References 4 publications

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“…Nevertheless, the etiology of this enhanced thrombotic tendency has not yet been well defined, even though several studies have been performed to elucidate the underlying mechanisms and to show which hemostatic parameters are targets of chemotherapeutic drugs. L-asparaginase has been reported to lower AT-III, plasminogen, and PC levels [23][24][25]. A de-creased level of AT-III activity has been described in patients receiving tamoxifen [17], whereas another report by Auger et al [26] failed to demonstrate decline of either AT-III or PC levels in Stage II breast cancer patients receiving tamoxifen alone as adjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

A prothrombotic state in breast cancer patients treated with adjuvant chemotherapy

Rella

Coviello

Giotta³

et al. 1996

Breast Cancer Res Tr

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Cancer is often associated with abnormal activation of coagulation leading to a prothrombotic state. Some chemotherapeutic agents used for cancer may induce thrombosis but their biological alterations in the hemostatic system are not yet well understood. This study evaluated alterations of coagulative and fibrinolytic parameters following chemotherapy. In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1-21 or 1-8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (TAT), prothrombin fragment F 1 + 2 (F 1 + 2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and PS were also evaluated with immunoenzymatic methods, t-PA, PAI-1, D-D, TAT, and F 1 + 2 were measured with immunoenzymatic methods. All tests were performed immediately before starting therapy and after each cycle. A PC antigen decrease appeared soon after beginning therapy and lasted throughout chemotherapy. The lowest values were present after the first treatment both in the CMF 1-21 group (mean +/- SD = 72.5 +/- 10.8%) and in the CMF 1-8 group (mean +/- SD = 77.2 +/- 6.9%): PC activity was also decreased. PS antigen decreased after the first administration (mean +/- SD = 73.3 +/- 10% in CMF 1-21 group, and 72.5 +/- 4.9% in CMF 1-8 group): PS activity also decreased. PAI-1 antigen levels increased (mean +/- SD = 43.1 +/- 20.4 ng/ml in the CMF 1-21 group, and 37.5 +/- 12.2 ng/ml in CMF 1-8 group) lasting up to the last cycle. CMF provokes a trend toward hypercoagulability; this effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.

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Section: Discussionmentioning

confidence: 99%

A prothrombotic state in breast cancer patients treated with adjuvant chemotherapy

Rella

Coviello

Giotta³

et al. 1996

Breast Cancer Res Tr

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“…The First description of venous throm bosis induced by ¿.-asparaginase treat ment and probably due to AT III deficien cy was reported by Pitney et al in 1980. This complication was found to occur dur ing or within a week after cessation of treatment. The most frequent site of vascu lar occlusion was the ileo-femoral venous district and the incidence was around 10% [Conard et al, 1980;Tura et al, 1981], Very recently, Steinherz et al [1981] re ported 2 children with ALL developing dural sinus thrombosis during induction treatment with vincristine, prednisone and asparaginase.…”

Section: Discussionmentioning

confidence: 99%

“…First, the massive destruc tion of leukaemic blast cells may cause the release of procoagulant material, as is ty pically seen in acute promyelocytic leu kaemia; second, chemotherapy may im pair the synthesis of proteins physiologi cally involved in the neutralization of acti vated procoagulant factors. Following Lasparaginase therapy, a significant de crease of plasma antithrombin III (AT III) has been described and this may ac count for the thromboembolic manifesta tions described in rare cases of acute lym phoblastic leukaemia (ALL) [Pitney et al, 1980;Conard et al, 1980;Vellenga et al, 1980;Turaet al, 1981].…”

Section: Introductionmentioning

confidence: 99%

Fatal Pulmonary Embolism and Antithrombin III Deficiency in Adult Lymphoblastic Leukaemia during L-Asparaginase Therapy

et al. 1983

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We describe 2 adult patients with acute lymphoblastic leukaemia (ALL) who died from pulmonary embolism following L-asparaginase treatment. Since this drug is known to cause a decrease in antithrombin III, the most important protein physiologically involved in the neutralization of thrombin, we studied the behaviour of this inhibitor in 14 ALL patients treated with a protocol including a 14-day course of L-asparaginase. A significant but transient fall of biological and immunological antithrombin III and a concomitant reduction of fibrinogen were documented.

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“…Thromboembolic manifestations have been described following L-ASE therapy with a significant decrease of antithrombin III by other authors [Pitney, 1980;Conard, 1980;Vellenga, 1980;Tura, 1981].…”

Section: Pulmonary Embolism and L-asparaginase Therapymentioning

confidence: 91%