Acquired Clotting Factor Deficits During Treatment with Asparaginase in an Institutional Cohort

Abstract

We invariably see prolongation of activated partial thromboplastin time in patients treated with asparaginase in our clinical practice, but have noted that, contrary to hypofibrinogenemia and low antithrombin, clotting times’ prolongation by asparaginase is largely unreported in the literature and guidelines and is not widely known to clinicians. We report on aPTT prolongations in a small cohort of patients, and on their origin, as investigated by measurements of clotting factors, fibrinogen, and D-dimers before and after asparaginase administration. We observed significant reductions in FIX and FXI (median post-treatment values of 27 IU/dl and 52 IU/dl, respectively), confirming one previous observation. A decrease in FXII was less pronounced but contributed to the prolonged aPTTs (FXII has no effect on in vivo haemostasis). The factor deficits are not due to consumption, as evidenced by unchanged D-dimer levels, and are, therefore, probably caused by disturbed factor synthesis. Our observations and insights contribute to elucidation of the profile of clotting assays during asparaginase treatment, and thus, to optimally monitor for undesirable events or steer situations of therapeutic anticoagulation without the risk of suboptimal or excessive anticoagulation.

Keywords:

• asparaginase
• clotting assays
• acute lymphoblastic leukemia
• NK-cell lymphoma
• bleeding
• thrombosis

Data Sharing Statement

More detailed clinical/laboratory data are available upon request.

Ethics Statement

Report of this case series was approved by the cantonal Ethics Committee of the Canton of Vaud, Switzerland (CER-VD, No 2022-02114). All patients had given consent for anonymous reutilization of data.

Acknowledgments

The authors wish to thank Mr. Francisco-Xavier Gomez, lead laboratory technician at the Hemostasis Laboratory of Lausanne University Hospital.

Author Contributions

Both authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare.

Additional information

Funding

No external funding was relevant to this publication.