The Conundrum of "Warfarin Hypersensitivity": Prolonged Partial Thromboplastin Time From Factor IX Propeptide Mutation

Arunabh Sekhri; Adriana Lisinschi; Muhammad Furqan; Chandrasekar Palaniswamy; Nikhil Mukhi; Ridhi Gupta; John C Nelson

doi:10.1097/MJT.0000000000000077

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The Conundrum of "Warfarin Hypersensitivity": Prolonged Partial Thromboplastin Time From Factor IX Propeptide Mutation

Journal article

Peer reviewed

The Conundrum of "Warfarin Hypersensitivity": Prolonged Partial Thromboplastin Time From Factor IX Propeptide Mutation

Arunabh Sekhri, Adriana Lisinschi, Muhammad Furqan, Chandrasekar Palaniswamy, Nikhil Mukhi, Ridhi Gupta and John C Nelson

American journal of therapeutics, Vol.23(3), pp.e911-e915

05/2016

DOI: 10.1097/MJT.0000000000000077

PMID: 24832385

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Abstract

Carboxylation of glutamic acid residues of vitamin K dependent clotting factors (II, VII, IX, and X) is essential to their biological functioning. Binding of these factors to γ-glutamyl carboxylase enzyme for carboxylation reaction is mediated by wild-type propeptide, a small sequence of amino acids that precede the actual polypeptide. Missense mutations at certain residue severely decrease the affinity of mutated propeptide for the enzyme. Such mutations are reported to occur at codon-10 of factor IX propeptide, a clinically silent metabolic event in normal conditions. However in the presence of warfarin, such mutations and resultant decrease affinity of factor IX propeptide for the enzyme that causes severe selective decrease in factor IX activity. This can potentially leads to life-threatening bleeding complications and known as one of the causes of warfarin hypersensitivity. It is imperative to recognize such cases early on to avoid additional warfarin therapy. Recurrent bleeding episodes, subtherapeutic to therapeutic range international normalized ratio values with relatively prolong partial thromboplastin time should raise the suspicion of underlying factor IX propeptide mutations.

Protein Precursors - genetics

Humans

Middle Aged

Warfarin - adverse effects

Factor IX - genetics

Male

Anticoagulants - adverse effects

Mutation, Missense - genetics

International Normalized Ratio

Partial Thromboplastin Time

Drug Hypersensitivity - genetics

Polymorphism, Single Nucleotide - genetics

Hemorrhage - chemically induced

Details

Title: Subtitle: The Conundrum of "Warfarin Hypersensitivity": Prolonged Partial Thromboplastin Time From Factor IX Propeptide Mutation
Creators: Arunabh Sekhri - Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY
Adriana Lisinschi
Muhammad Furqan
Chandrasekar Palaniswamy
Nikhil Mukhi
Ridhi Gupta
John C Nelson
Resource Type: Journal article
Publication Details: American journal of therapeutics, Vol.23(3), pp.e911-e915
DOI: 10.1097/MJT.0000000000000077
PMID: 24832385
ISSN: 1075-2765
eISSN: 1536-3686
Language: English
Date published: 05/2016
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984094363702771

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