PB0534 - Interference of PLX038 (pegylated topoisomerase inhibitor SN-38) with coagulation assays

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Pedro E. Alcedo Andrade, MD

Hematology Fellow
Division of Intramural Research, National Heart, Lung, and Blood Institute. National Institutes of Health.
Bethesda, Maryland, United States

Co-Author(s)

PD

Parth Desai

Hematology and Oncology Fellow
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Bethesda, Maryland, United States
SN

Samantha Nichols

Physician Assistant
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Bethesda, Maryland, United States
KN

Khanh Nghiem

Researcher
Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health
Bethesda, Maryland, United States
NP

Nisha Patel

Staff Clinician
Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health
Bethesda, Maryland, United States
AD

Alina Dulau-Florea

Staff Hematopathologist. Assistant Research Physician. Director of Coagulation
Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health
Bethesda, Maryland, United States
CP

Christopher Pleyer

Staff Clinician
Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health
Bethesda, Maryland, United States
AT

Anish Thomas

Staff Clinician
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health
Bethesda, Maryland, United States
CB

Charles Bolan

Staff Clinician
Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health
Bethesda, Maryland, United States
RP

Rajiv Pruthi

MBBS
Mayo Clinic
Rochester, Minnesota, United States
SK

Shelley Sahu Kalsi

Deputy Chief of the Hematology Consult Service
National Heart, Lung, and Blood Institute, National Institutes of Health
Bethesda, Maryland, United States

Background: A patient with metastatic breast cancer receiving PLX038, a novel pegylated form of the topoisomerase inhibitor SN-38 (irinotecan active metabolite), showed abnormal pre-procedural coagulation parameters, concerning for an acquired factor inhibitor.

Aims: To describe the interference of PLX038 with coagulation assays.

Methods: After informed consent, citrated blood samples were analyzed for PT, aPTT, aPTT long incubation, aPTT mixing studies, lupus anticoagulant (LAC), dilute Russell viper venom time (DRVVT), factor (F) activities, fibrinogen, thrombin time (TT), vWF:Ag, and vWF:RCo, using testing platforms and reagents shown in Table 1. The aPTT on patients who previously received the drug was retrospectively evaluated.

Results: See Table 1. On the Stago STA-R Evolution analyzer using STA PTT Automate 5, prolonged aPTT did not correct with 50:50 mix, with FVIII, FIX, and FXI activities < 5% and non-parallelism on serial dilution studies. In contrast, on the ACL Advance analyzer all aPTT and factor activity assays, including chromogenic FVIII and FIX, levels were normal. Normal studies on the Stago analyzer included PT, LAC, Fibrinogen, TT, vWF:Ag, vWF:RCo. DRVVT was normal on both analyzers.
All 5 previously treated patients with aPTT evaluations performed on the Stago STA-R Evolution analyzer both before and after PLX038 administration developed newly prolonged aPTT after receiving PLX038.

Conclusion(s): This first description of PLX038 interference with coagulation assays demonstrates a pattern of interference using the STA-PTT assay (micronized silica activator), but not with the HemosIL SynthASil assay (colloidal silica activator), and no abnormalities on several other assays. Other pegylated agents have been shown to have a similar pattern of reagent- and assay-specific interference (PMID: 31809565; 29984531; 19015207). Increasing use of pegylated drugs warrants greater awareness of this effect on routine laboratory parameters to avoid unnecessary testing, prolonged hospitalization, procedure delays, and inappropriate high-risk treatments for acquired factor inhibitors.