key: cord-0877039-bjmhg6z4
authors: Cui, Songping; Chen, Shuo; Ke, Lihui
title: Reply to ‘Ibuprofen and thromboembolism in SARS‐COV2’
date: 2020-05-29
journal: J Thromb Haemost
DOI: 10.1111/jth.14934
sha: 773f7994f0faa3a2aecb9216da22d5760a1784d3
doc_id: 877039
cord_uid: bjmhg6z4

We appreciate the opportunity to respond to the comments by Drs. Arian Arjomandi Rad, Robert Vardanyan and Natalie R Tas. Non‐steroidal anti‐inflammatory drugs (NSAIDs) are widely used in many countries for the relief of symptoms of pain, inflammation and fever, which reduce the conversion of arachidonic acid to prostaglandins, prostacyclin (PGI2), and thromboxane (Tx) A2 by inhibiting cyclooxygenase (COX). At present, it is recognized that there are two related but different types of COX activity, COX‐1 and COX‐2.

We appreciate the opportunity to respond to the comments by Drs. Arian Arjomandi Rad, Robert Vardanyan and Natalie R Tas. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in many countries for the relief of symptoms of pain, inflammation and fever, which reduce the conversion of arachidonic acid to prostaglandins, prostacyclin (PGI2), and thromboxane (Tx) A2 by inhibiting cyclooxygenase (COX). At present, it is recognized that there are two related but different types of COX activity, COX-1 and COX-2. COX-1 is continuously expressed in most tissues, and platelets containing COX-1 are the main source of TXA2 [1] , which affects vascular smooth muscle contraction and platelet aggregation [2] . COX-2 is mainly expressed in the inflammatory response and is the main source of PGI2 [3] . According to the different selectivity for COX inhibition, NSAIDs are divided into non-selective and COX-2 selective. Ibuprofen is a type of non-selective NSAIDs.

As the authors said before, a number of studies have confirmed that NSAIDs (including ibuprofen) are significantly associated with the occurrence of venous thromboembolism (VTE), especially in selective COX-2 inhibitors, and are related to the dose and duration of administration, but the mechanism is not clear. The primary hypothesis is that NSAID may create an imbalance between PGI2 and TXA2, resulting in a relative increase in TXA2, leaving the body in a hypercoagulable state [4] . Moreover, the reduction of prostaglandin leads to the decrease of thrombomodulin, which increases the incidence of thrombosis [5] .

During COVID-19 's treatment, the use of NSAIDs was very common. In addition to increasing the risk of thrombosis, NSAIDs (including ibuprofen) may also reduce host defense capability during infection [6] . On the one hand, NSAIDs may mask the early symptoms of the disease, leading to delays in diagnosis and treatment; on the other hand, NSAIDs can inhibit the immune response of the body through a variety of ways, leading to disease progression [7] . Even though some studies have shown that NSAIDs may be beneficial to patients with viral infection, it is still necessary to use it with great caution.

In the clinical diagnosis and treatment of novel coronavirus patients, more attention should be paid to the use and management of NSAIDs. Clinicians need to determine whether patients have a history of gastrointestinal ulcers and cardiovascular events, and avoid overdose or long-term medication. Now, more research is really needed to determine the effects of NSAIDs on the incidence of VTE and viral infection in novel coronavirus patients.

This article is protected by copyright. All rights reserved Accepted Article

Human platelet/erythroleukemia cell prostaglandin G/H synthase: cDNA cloning, expression, and gene chromosomal assignment

Cyclooxygenase inhibition and thrombogenicity

Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2

Non-steroidal anti-inflammatory drugs and venous thromboembolism in women

Regulation of thrombomodulin expression in human vascular smooth muscle cells by COX-2-derived prostaglandins

Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells

Italian Society of P. NSAIDs in patients with viral infections, including Covid-19: Victims or perpetrators?

This article is protected by copyright. All rights reserved Accepted Article