The Application of Viscoelastic Testing in Patient Blood Management

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Two main points of feedback: 1) add constructive suggestions to the fair criticism of the lack of standardization, 2) consider broadening the base of references and including more original work.

Ad 1) The authors rightly raise issues with and criticisms of VET. It would be great to offer constructive proposals on how to address them. The cost issue will have to be addressed by or in conjunction with the manufacturers, but the issue of lack of consistency deserves further discussion. First, is the lack of consistency necessarily a problem, or a feature of the technology? In other words, why do we expect a lab test to have similar normal reference ranges in different patient populations? Why would the treatment cutoff be the same for different clinical situations? Has that ever been shown or proven for INR, or other "standard coag tests". Maybe it is actually a strength of the technology that it provides functional results, and it is upon us to better interpret them. Second and in line with that, the author raise a valid point that interpretation across sites may be difficult because the approach could be different. It would be great to share a bit more how the field could move to more consistency. There are certainly efforts to harmonize the approach or to develop algorithms that could be used to increase homogeneity in research output. Two recent examples are pasted below for CV surgery and Trauma patients:
- Sarani B, Callum J, Neal MD, Meizoso JP, Spinella PC, Leeper C, Saillant N, Thurston B, Moore EE, Winfield R, Brooks A, Kornblith LZ. Goal-directed transfusion algorithm for trauma patients with severe hemorrhage using TEG 6S: Results of a Delphi consensus survey and expert panel recommendations. J Trauma Acute Care Surg. 2025 Apr 2. doi: 10.1097/TA.0000000000004606. Epub ahead of print. PMID: 40170216.
- Maxey-Jones C, Seelhammer TG, Arabia FA, Cho B, Cardonell B, Smith D, Leo V, Dias J, Shore-Lesserson L, Hartmann J. TEG® 6s-Guided Algorithm for Optimizing Patient Blood Management in Cardiovascular Surgery: Systematic Literature Review and Expert Opinion. J Cardiothorac Vasc Anesth. 2025 May;39(5):1162-1172. doi: 10.1053/j.jvca.2025.02.011. Epub 2025 Feb 8. PMID: 40016048.
Lastly, it would be helpful to further build on the differences of lab and plasma-based tests, versus whole blood tests. To apply the same expectations is comparing apples with pears and does neither justice.

Ad 2) Many references stem from a special issue of Transfusion, they are mostly review articles. The reader could benefit from a broader base of references, highlighting other reviews in high-impact journals in the relevant clinical areas as well as more original research articles. The objective is simply to broaden the base of references in service to the reader.

Author Response

Comment 1.1

“Add constructive suggestions to the fair criticism of the lack of VET standardization.”
Reply 1.1: We expanded Section 5.2 (Roadmap to Harmonization and Consistency) to summarize two 2025 Delphi‑based algorithms (TEG 6s in trauma and cardiac surgery) and outlined concrete steps for multi‑center validation and manufacturer collaboration (see Page 5, lines 129‑142).
Changes in the text: New sub‑heading “5.2 Roadmap to Harmonization”; two paragraphs and Table 5 added.

Comment 1.2

“Broaden the base of references and include more original work beyond the Transfusion special issue.”
Reply 1.2: We replaced 14 review citations with recent original studies and high‑impact meta‑analyses across trauma, obstetrics, cardiac and liver surgery (see reference list, numbers 4, 7, 8, 9, 10, 12, 13, 15, 17, 22, 23, 24, 29, 33, 35, 36).
Changes in the text: Reference list updated; in‑text citations amended throughout to replace secondary sources with primary sources.

Comment 1.3

“Differentiate plasma‑based CCTs from whole‑blood VET—‘apples and pears’.”
Reply 1.3: Section 2 now explicitly contrasts cellular vs. plasma components, adds Figure 2 (schematic of sample matrices) and clarifies why identical reference ranges are neither expected nor desired (see Page 3, lines 65‑78).
Changes in the text: Figure 2 inserted; explanatory paragraph added.

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for allowing me to review the manuscript "The Application of Viscoelastic Testing in Patient Blood Management" 

Strengths 
The purpose is evident; it highlights the role of VET in PBM and integrates the rationale for VET use by contrasting it with conventional coagulation tests (CCTs), underscoring its value. The progression from PBM principles to VET benefits and implementation barriers is logical and well-articulated, and it issues the potential of VET while also noting the real-world limitations. The clinical use of viscoelastic testing (VET) within transfusion optimization and Patient Blood Management (PBM) is highly relevant, especially with a growing emphasis on precision medicine. It covers a wide range of VET applications, including cardiac surgery, trauma, obstetrics, oncology, and critical care, backed by appropriate references. Addresses both benefits and limitations of VET (e.g., cost, standardization), which reflects good scholarly integrity.

Major corrections 

While the manuscript addresses an important and timely topic regarding the use of viscoelastic testing (VET) in clinical practice, several key issues must be addressed to strengthen its scientific rigour and clarity:

Although the review discusses viscoelastic testing, it refers to the concept in general terms and fails to adequately distinguish or describe the specific technologies available, such as thromboelastography (TEG), rotational thromboelastometry (ROTEM), and more recent platforms like Quantra and ClotPro. Including a concise comparative description of these technologies, their parameters (e.g., clot time, maximum clot firmness), and clinical differences would enhance the reader's understanding and reinforce the relevance of the discussion.

While the manuscript contrasts VET with conventional coagulation tests (CCTs), it does not sufficiently demonstrate VET's diagnostic or clinical superiority. The text would benefit from citing comparative studies or meta-analyses that illustrate the improved sensitivity, predictive value, or clinical outcomes associated with VET in various settings, such as trauma, obstetrics, or cardiovascular surgery.

The discussion of clinical scenarios is helpful, however it is presented relatively weak,  stronger references could be included to support the utility of VET. For example, there is robust evidence supporting the use of VET in massive haemorrhage protocols, liver transplantation, and postpartum haemorrhage that is currently underutilized or only briefly mentioned, also the authors should address the importance of VET technology on Goal-Directed coagulation management. 

Minor corrections 

The final paragraph reads more like a continuation of the discussion rather than a conclusive summary. A stronger conclusion should highlight the clinical value of VET, summarize key limitations, and propose future directions for integration into standardized care.

Although PBM is mentioned, the manuscript does not position VET within the second pillar of PBM, minimizing blood loss and optimizing hemostasis. Clarifying this connection would help demonstrate how VET fits into evidence-based strategies for reducing unnecessary transfusions and improving patient outcomes.

 

Comments on the Quality of English Language

The manuscript would benefit from editing. Several sentences are overly long or contain redundant language with some words slightly informal or vague for a scientific paper.

Author Response

Major Corrections

Comment 2.1

“Distinguish specific VET technologies (TEG, ROTEM, Quantra, ClotPro) and compare parameters.”
Reply 2.1: We introduced Table 3 (side‑by‑side technical comparison) (Page 4, lines 87‑90).
Changes in the text: Table 3 added; terminology standardised.

Comment 2.2

“Demonstrate VET’s diagnostic/clinical superiority with comparative studies or meta‑analyses.”
Reply 2.2: Added multiple RCTs and meta‑analyses illustrating reduced transfusion requirements and improved outcomes in trauma and cardiac surgery (4, 7, 8, 9, 10, 12, 13, 15, 17, 22, 23, 24, 29, 33, 35, 36).
Changes in the text: Citations 4, 7, 8, 9, 10, 12, 13, 15, 17, 22, 23, 24, 29, 33, 35, 36 inserted; replaced reviews that were there in prior draft

Comment 2.3

“Strengthen clinical‑scenario discussion (massive hemorrhage, liver Tx, PPH) and link to goal‑directed algorithms.”
Reply 2.3: Added a discussion on previous usage of goal directed algorithms (Page 5, lines 128‑134).

Changes in the text: Text describing goal directed algorithms

Minor Corrections

Comment 2.4

“Conclusion reads like discussion—make it stronger.”
Reply 2.4: Conclusion condensed to one decisive paragraph (Page 23, lines 233-237).
Changes in the text: Conclusion rewritten.

Comment 2.5

“Explicitly position VET within PBM Pillar 2.”
Reply 2.5: Added linkage sentence at end of Introduction (Page 2, lines 19‑20).
Changes in the text: Intro modified.

Comment 2.6

“English language—sentence length & redundancy.”
Reply 2.6: Manuscript passed through professional copy‑edit; long sentences split and informal words replaced (global changes throughout).

Reviewer 3 Report

Comments and Suggestions for Authors

Dear authors,

thank you for sharing the present review. 

Here you try to give an overview of VETs and their use in coagulation management. 

Although the topic is interesting, it feels you did not read literature correctly leading to (partially) wrong statements and interpretations. There are many repetitions across the paragraphs. 

The description of the assays/tests is missing and/or inadequate. 

Please find some comments in the attached file (but I did not put all)...

 

Comments for author File: Comments.pdf

Author Response

Comment 3.1

“Literature not always read correctly; repetitions; assay descriptions inadequate.”
Reply 3.1: We removed various duplicate content, expanded assay description in Section 3 with step‑by‑step methodology, and corrected
Changes in the text: multiple parts of sections rewritten; Figure 1 legend updated.

Comment 3.2

“Added PDF with further marginal notes (not all shown).”
Reply 3.2: Every marginal note in the attached PDF was addressed

Changes in the text: Multiple minor edits (spelling, reference format) across manuscript.

 

Items flagged by reviewers that required only wording tweaks

Line in previous draft	Reviewer note	Action taken
189 ("traditional")	Replace “conventional” → “traditional”	Corrected
37‑39 (disease list)	“These are all transmissible—summarize.”	We chose to keep it to illustrate all the kinds of diseases
Table 1 legend	“and they stop once clot formation starts…”	Clarified in legend
97‑99	Close sentence	Punctuation fixed

 

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors cover all my previous concerns and I accept as it is