Comparative study on the impact of different doses of plasma transfusion on coagulation function using an in vitro model

Introduction

Background

In clinical practice, coagulopathy is commonly used to describe a hypocoagulable state (1), which represents one of the most frequent diagnoses. It manifests as prolonged prothrombin time (PT)/international normalized ratio (INR) and/or activated partial thromboplastin time (APTT), decreased platelet count, and/or reduced fibrinogen levels (FIB) (2,3). At least 30% of critically ill patients in intensive care units exhibit coagulation abnormalities (4,5): PT prolongation occurs in 12–30% (6), thrombocytopenia in 40–67% (3), and INR ≥1.5 in over 66% (3). These abnormalities are commonly observed in critically ill populations such as trauma, liver disease, and sepsis patients (1,7-9), and are closely associated with bleeding, multiple organ dysfunction, and a more than fourfold increase in mortality (3).

Rationale and knowledge gap

Routine coagulation tests, also known as the coagulation panel, including PT, APTT, thrombin time (TT), and FIB/INR, are commonly used clinically to assess coagulation function. These tests are based on the cascade theory of blood coagulation and evaluate the coagulation system by measuring time intervals at different stages, with the endpoint defined as reaching 5% thrombin generation (10,11). However, these tests cannot reflect platelet-endothelial interactions or fibrinolytic activity (6). In recent years, the application of thromboelastography (TEG) has gradually expanded. Based on the cellular model theory of blood coagulation, TEG evaluates the coagulation system by measuring the time and clotting strength at different stages. It not only covers the enzymatic reactions of the coagulation cascade but also reflects the role of cellular components in coagulation. Compared to the isolated endpoint detection of the four coagulation parameters, TEG provides a comprehensive assessment that fully describes the entire coagulation process and offers a detailed evaluation of the influence of various cellular components on coagulation mechanisms. For example, the maximum amplitude (MA) of the clot is primarily influenced by platelets and fibrinogen, with platelets accounting for approximately 80% and fibrinogen for approximately 20% (12). Studies indicate that TEG outperforms conventional coagulation tests in assessing the necessity of blood product transfusions for patients with trauma, liver disease, critical illness, and obstetric conditions (7,13,14). Furthermore, its results can guide the management of perioperative hemostasis (13) and monitor the efficacy of heparin and platelet-related drugs (15).

Transfusion of fresh frozen plasma (FFP) is one therapeutic approach to improve coagulopathy. However, the regulatory standard-dose (10–20 mL/kg) often conflicts with total fluid volume control goals. Moreover, over 40% of patients actually receive low-dose FFP (<10 mL/kg) (16,17), and the efficacy of low-dose FFP remains unclear. Some studies indicate that FFP has a minimal therapeutic effect when the INR is below 2.0. Furthermore, substantial volumes of FFP are required to achieve only a slight reduction in the INR, without restoring the INR to the normal range (18,19).

Objective

This study aims to establish an in vitro model simulating the efficacy of plasma transfusion to identify suitable indicators for evaluating its therapeutic effect when the INR is within or slightly above the upper limit of the normal reference range. The study also seeks to assess whether low-dose FFP transfusion can correct abnormal coagulation test indicators, providing experimental evidence for establishing uniform efficacy standards and formulating blood-saving strategies. We present this article in accordance with the MDAR reporting checklist (available at https://aob.amegroups.com/article/view/10.21037/aob-2025-1-44/rc).

Methods

In vitro plasma transfusion model

The design of this in vitro simulated plasma transfusion model is based on the integration and optimization of five transfusion research paradigms. The technical approach deeply integrates three core principles: proportional scaling, equivalent conversion, and micro-manipulations. Firstly, the study established the FFP dosage gradient framework (20). Secondly, the study introduced patient-plasma mixed-plasma testing (21). Thirdly, the study pioneered equivalence conversion from micro-systems to clinical dosages (22). Fourthly, the study validated 37 ℃ incubation conditions to simulate in vivo metabolic environments (23). Finally, the study developed algorithms for reverse-calculating dosage guided by TEG (24). An in vitro plasma transfusion model was designed by estimating the transfusion volume based on the patient’s TEG reaction time (R) value prior to plasma transfusion. This estimation also considered sample.

The in vitro simulated plasma transfusion model design in this study is as follows: first, patients were categorized based on the estimated transfusion volume calculated using body weight, pre-transfusion TEG R value, and a preset criterion (R >10 min). Second, the required plasma volume was calculated using the target estimated transfusion volume, patient weight, and residual blood sample volume after TEG testing. Next, precisely measured FFP was added to the residual blood sample post-TEG testing. The mixture was thoroughly agitated for 10 seconds and incubated at 37 ℃ for 5 min to simulate the in vivo circulatory environment. Finally, a 1,000 µL aliquot of the mixture was subjected to a second TEG test.

In accordance with the Chinese national standard WS/T 623-2018 (25), the plasma transfusion dose ranges between 10 and 20 mL/kg. The low-dose regimen (<5 to >10 mL/kg) reflects the empirical volume typically administered when only a single unit of plasma is transfused in routine clinical practice. Thus, in this study, the low-dose means 5 mL/kg < transfusion dose <10 mL/kg, and the standard-dose is 10 mL/kg ≤ transfusion dose ≤20 mL/kg.

For specimens meeting the inclusion criteria, the plasma addition volume is calculated using Eqs. [1–3]. The experiments are conducted using an in vitro simulated plasma transfusion model, following the operational procedure illustrated in Figure 1.

Bloodvolume(mL)=weight×75[1]

Plasmaadditionvolume(μL)=(plasmaapplicationvolume×2,000)/bloodvolume[2]

Plasmatransfusiondose(mL/kg)=plasmaapplicationvolume/weight[3]

Figure 1 Experimental procedure. TEG, thromboelastography; FFP, fresh frozen plasma.

Study subjects

Patients who underwent TEG and routine coagulation testing based on clinical needs at Nanfang Hospital Zengcheng Campus from November 1, 2021, to August 31, 2025, were collected.

Inclusion criteria: (I) age ≥18 years; (II) underwent TEG testing; and (III) TEG-citrated kaolin (CK) R value >10.0 min.

Exclusion criteria: (I) missing clinical data (weight, plasma transfusion volume); (II) patients receiving plasma transfusions due to blood loss; (III) specimens collected using heparin; and (IV) antiplatelet drugs (clopidogrel, warfarin, etc.).

Sample size determination: this study was an exploratory study in order to conduct an ex vivo simulated transfusion with in vitro assessment and to preliminarily validate the feasibility. The sample size was calculated based on consideration of the following factors. (I) This study used a paired sample for the TEG parameters compared with before vs. after transfusion in the same patient. Paired design sample size was less than the independent sample size. (II) According to the initial trial results, it was planned to use a non-parametric test method. With an effect size ranging from 0.5 to 0.8, α=0.05, and a power (1 − β) of 0.80, calculations performed using G*Power suggest that a minimum of 19 pairs are required. (III) Patients were required to have a TEG-CK R value >10.0 min, which limited the number of samples available. After comprehensively considering its exploration, the need for data statistics, operability, etc., the total sample size was finally decided to be 24 cases. It should be pointed out that due to the relatively small sample size, the results of the study were mainly used as exploratory analysis and hypothesis formulation research, and the large samples of multi-center studies would be needed in the future.

Specimen requirements

This study measured TEG, requiring venous blood collection for testing, typically from the median cubital vein. Clinical nurses routinely disinfected the local skin with iodine, inserted a sterile negative pressure blood collection needle obliquely into the vein, collected 3 mL of blood using a 1:9 sodium citrate anticoagulant vacuum collection tube, inverted the tube three times to thoroughly mix blood with sodium citrate, placed vertically, and delivered to the Blood Transfusion Medicine Department for testing within 1 hour of collection. Blood samples were kept at room temperature for at least 10 min before testing.

TEG testing

Add 1,000 µL of sample to the kaolin-activated tube. Dispense 20 µL of CaCl₂ (product No. CaCl₂-05) into the test cup. Add 340 µL of kaolin-activated sample to the test cup. Perform testing using the TEG 5000 system (Haemonetics Corporation, Boston, MA, USA).

Calculation formulas

The normal range of human adult blood volume is usually 75 mL/kg (26). Patient’s blood volume can be done by this proportion. Noting that this is a calculated estimate of blood volume, and it uses standard values. In a clinical setting, we see individual volumes may be different due to variations in age, sex, illness, and hydration status. For example, males typically have higher blood volume (approximately 75 mL/kg) than females (approximately 65 mL/kg), elderly patients may have reduced blood volume, and critically ill patients may experience blood volume changes due to fluid loss or fluid resuscitation. This study adopted a fixed calculation standard value of 75 mL/kg to ensure uniformity of method, but it may produce certain systematic errors, which need to be taken into account in the interpretation of the results. From a 3 mL submitted specimen, 1,000 µL of sample were used on the TEG test, leaving 2,000 µL of blood sample for plasma to be added to in vitro simulated plasma transfusion blood samples (anticoagulated with sodium citrate). The volume calculation formulas of R, clot formation time (K), clot formation rate (Alpha angle), maximum amplitude (MA), clot lysis percentage at 30 min (LY30), and coagulation index (CI) are:

ΔR(min)=Rafterinvitrosimulatedplasmatransfusion−Rbeforeplasmatransfusion[4]

ΔK(min)=Kafterinvitrosimulatedplasmatransfusion−Kbeforeplasmatransfusion[5]

ΔAlphaangle(degree)=Alphaangleafterinvitrosimulatedplasmatransfusion−Alphaanglebeforeplasmatransfusion[6]

ΔMA(mm)=MAafterinvitrosimulatedplasmatransfusion−MAbeforeplasmatransfusion[7]

ΔLY30(%)=LY30afterinvitrosimulatedplasmatransfusion−LY30beforeplasmatransfusion[8]

ΔCI=CIafterinvitrosimulatedplasmatransfusion−CIbeforeplasmatransfusion[9]

Limitations of calculation formulas in this study: the plasma addition volume calculation assumes that (I) all patients have the same blood volume of 75 mL/kg; (II) plasma is evenly distributed in blood samples; (III) the in vitro dilution ratio equals the patient’s in vivo plasma concentration after transfusion.

Quality control measures

In order to ensure the reliability and repeatability of the experiment, this study adopts the following quality control measures: (I) all TEG tests were carried out by trained and certified two laboratory technicians in accordance with relevant operating procedures to reduce operator error; (II) all tests were performed in a strictly controlled laboratory with a constant temperature of 22 to 24 ℃ to ensure the stability of testing conditions; (III) the FFP used in this research is obtained from clinical blood bank, meeting the relevant national standards (stored at −20 ℃ or below and thawing at 37 ℃ water temperature for 20 min), and the plasma product comes from the qualified donor and meets the requirements of quality testing; (IV) all patients’ blood sample test will be performed within an hour after the sample was collected, and the in vitro simulated plasma transfusion test will be completed within 2 hours of blood sample collection. In the process of storing blood samples, to avoid the impact of storage time on coagulation function.

Data collection

General and clinical data of study subjects were collected, specifically:

• Basic information: patient ID, gender, ABO blood type, RhD blood type, age, weight, pregnancy/delivery history, transfusion history;
• Relevant medical history: disease diagnosis;
• Plasma transfusion therapy: plasma application volume, plasma distribution volume, plasma transfusion start time, plasma transfusion end time;
• Routine coagulation test results: APTT, PT, FIB, and INR;
• TEG test results: R, K, Alpha angle, MA, LY30, and CI;
• Medication history and timing information: current medications used for coagulation function (such as anticoagulants, antiplatelets, antibiotics, etc.), time from when symptoms started until taking blood, from when last medication was given until taking blood, current course of the disease (acute phase, steady phase, recovery phase).

It is worth noting that due to the non-interventional design of this study, although patients were excluded from receiving heparin and antiplatelet drugs (such as clopidogrel, warfarin, etc.), other medications (such as certain antibiotics) may affect coagulation function, thereby introducing certain limitations.

Statistical analysis

Statistical analysis in this study was performed using SPSS 25.0 software. Age, TEG parameters, and routine CIs were treated as continuous variables; all other clinical characteristics were categorical. The Shapiro-Wilk test was firstly applied to assess the normality of distribution for each continuous variable. P>0.05 indicated a normally distributed variable, while P<0.05 indicated a non-normally distributed variable. Categorical variables are summarized as n (%). Continuous variables following a normal distribution are presented as mean ± standard deviation (SD), whereas those with a non-normal distribution are expressed as median [25^th percentile (P25), 75^th percentile (P75)]. Comparisons were performed using nonparametric tests (Mann-Whitney U or Kruskal-Wallis H). Two-tailed P<0.05 indicated statistically significant differences.

Ethical consideration

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Nanfang Hospital (No. NFEC-202406-K26-01) and individual consent for this retrospective analysis was waived.

Results

Clinical information of study subjects

This study included patients who underwent TEG testing based on clinical needs from November 1, 2021 to August 31, 2025. A total of 24 patients met the inclusion criteria and were divided into low-dose (5 mL/kg < transfusion dose <10 mL/kg) and standard-dose (10 mL/kg ≤ transfusion dose ≤20 mL/kg) groups based on plasma transfusion dose. Table 1 presents the clinical information of the study subjects. Among the 16 patients receiving low-dose (>5–<10 mL/kg) plasma transfusion, the male-to-female ratio was 11:5. Their ages ranged from 37 to 82 years, with a mean age of 58.1±13.1 years. All females had given birth, and 12 patients (75.0%) had previous transfusion history before testing. INR values were concentrated between 1.1 and 1.5 in 7 cases, accounting for 43.6%. Among the 8 patients receiving standard-dose (10–20 mL/kg) plasma transfusion, the male-to-female ratio was 6:2, with ages ranging from 48 to 84 years and a mean age of 61.9±11.4 years. All females had given birth, and 5 patients (62.5%) had previous transfusion history before testing. A total of 5 patients with 1.1< INR ≤1.5 accounted for 50.0%. Detailed information is shown in Table 1.

Coagulation function changes with two different transfusion doses

The pre-plasma transfusion values for each indicator across different dosage groups are shown in Figures 2,3. Differences in all 10 test indicators were not statistically significant (P>0.05). This indicates no differences in coagulation factor function, fibrinogen, platelet, or fibrinolytic function before plasma transfusion between the two groups. Therefore, since there were no significant baseline differences, all six TEG parameters were suitable for dose-comparison analysis, as shown in Figure 2.

Figure 2 Comparison of TEG parameters R (A), K (B), Alpha angle (C), MA (D), LY30 (E), and CI (F) before plasma transfusion at different doses. Alpha angle, clot formation rate; CI, coagulation index; deg, degree; K, clot formation time; LY30, clot lysis percentage at 30 min; MA, maximum amplitude; R, reaction time; TEG, thromboelastography.

Figure 3 Comparison of routine coagulation parameters APTT (A), PT (B), FIB (C), and PT-INR (D) before plasma transfusion at different doses. APTT, activated partial thromboplastin time; FIB, fibrinogen levels; INR, international normalized ratio; PT, prolonged prothrombin time.

Compared to pre-plasma transfusion, the blood sample with in vitro simulated low-dose plasma transfusion showed significantly shortened R values (P=0.001). This indicates that plasma transfusion improved patients’ coagulation factor function from a hypocoagulable state. The K value shortened, the Alpha angle increased, and the CI values increased significantly significant differences, indicating overall improvement in coagulation function. MA values and LY30 showed no statistically significant differences (P>0.05). Details are shown in Figure 4.

Figure 4 Comparison of coagulation function R (A), K (B), Alpha angle (C), MA (D), LY30 (E), and CI (F) before and after following low-dose (>5–<10 mL/kg) plasma transfusion in an in vitro model. Each solid line connecting two points represents the change in the parameter in the in vitro plasma transfusion model. Alpha angle, clot formation rate; CI, coagulation index; deg, degree; FFP, fresh frozen plasma; K, clot formation time; LY30, clot lysis percentage at 30 min; MA, maximum amplitude; R, reaction time.

Figure 5 shows the changes in TEG parameters before and after in vitro simulated standard-dose. Comparing TEG parameters before and after transfusion, the only decreased significantly significant difference was the R value. Specifically, the R value decreased significantly (P=0.04). K values, Alpha angle values, MA values, LY30, and CI showed no statistically significant differences, indicating that changes in fibrinogen function, platelet function, and fibrinolytic function were not significant before and after plasma transfusion. Based on the changes in measured indicators before and after simulated transfusion in both the low-dose and standard-dose groups, the R value was selected as the evaluation metric for the study on selecting different INR transfusion doses prior to transfusion.

Figure 5 Comparison of coagulation function R (A), K (B), Alpha angle (C), MA (D), LY30 (E), and CI (F) before and after following standard-dose (10–20 mL/kg) plasma transfusion in an in vitro model. Each solid line connecting two points represents the change in the parameter in the in vitro plasma transfusion model. Alpha angle, clot formation rate; CI, coagulation index; deg, degree; FFP, fresh frozen plasma; K, clot formation time; LY30, clot lysis percentage at 30 min; MA, maximum amplitude; R, reaction time.

Coagulation function after plasma transfusion in different INR groups

For INR analyses, patients were first dichotomized at the institutional transfusion trigger (>1.5) and subsequently split into equal-width strata. The frequency distribution across strata is shown in Table 2; the grouping-three solution provided the most balanced allocation and was therefore adopted for further analyses.

There was no statistically significant difference in ΔR improvement across INR segments between the low- and standard-dose groups (χ²_low-dose=5.600, P_low-dose=0.13; χ²_{standard-dose}=2.431, P_{standard-dose}=0.30). The details were presented in Table 3. This indicates no difference in improvement with low-dose plasma transfusion within the INR range of 0.8–2.3, nor with standard-dose plasma transfusion within the INR range of 0.8–1.9. To further define the applicable INR range for low-dose plasma, we compared ΔR changes between the two doses within the same INR segment. The difference in ΔR changes between low-dose and standard-dose plasma transfusion was not statistically significant (Z_{1.1< INR ≤1.5}=0.036, P_{1.1< INR ≤1.5}=0.85; Z_{1.5< INR ≤1.9}=1.190, P_{1.5< INR ≤1.9}=0.28). This indicates that within the INR range of 1.1–1.9, low-dose plasma can improve the R value while reducing plasma usage, as detailed in Table 3.

Figure 6 shows the change of ΔR measured by TEG during in vitro simulated plasma transfusion. When comparing low-dose with standard-dose plasma transfusion, the median ΔR values differed. However, these differences were not statistically significant (P=0.83), indicating that both transfusion doses have comparable efficacy in improving coagulation factor function. Therefore, low-dose plasma transfusion can enhance coagulation status while conserving blood resources.

Figure 6 Comparison of ΔR changes in in vitro simulation of different doses of plasma transfusion. R, reaction time.

Combining data from Figure 6 and Table 3 in vitro simulations of plasma transfusion at both low-dose and standard-dose within the INR range from 1.1 to 1.9 demonstrated the improvement in coagulation factor function. No significant difference was observed in the degree of improvement in ΔR values between the low-dose and standard-dose groups. Low-dose plasma transfusion enhances coagulation status while conserving blood resources.

Discussion

Main research findings and clinical significance

This study employed an in vitro simulated plasma transfusion model to identify TEG parameters suitable for evaluating plasma transfusion efficacy in patients with INR level within or slightly above the upper limit of the normal reference range (Table 4). It also explored the therapeutic effects of low-dose plasma transfusion. The research data demonstrate that TEG can accurately reflect the mechanisms by which plasma transfusion. The research data demonstrate that TEG can accurately reflect the mechanisms by which plasma transfusion affects coagulation status, with significant statistical differences observed in the R value. The patient’s INR level falls within the range of 1.1 to 1.9. Plasma transfusion assessed by TEG can evaluate treatment efficacy, and low-dose administration yields similar results to standard-dose while reducing blood usage.

Differences in sensitivity between TEG and conventional coagulation assays in efficacy assessment and their mechanisms

Within the INR range of 1.1–1.9, TEG R values reflect improvements in coagulation following plasma transfusion earlier and more sensitively than INR, PT, and APTT indicators. This stems from fundamental differences in technical principles; conventional tests rely on platelet-depleted plasma, detecting isolated coagulation endpoints along a linear cascade model. They exhibit an “all-or-nothing” response to factor activity, requiring activity reduction to 30–50% before INR prolongation becomes detectable (27,28); thus, they fail to capture subtle fluctuations in early thrombin generation rates (29,30). TEG, however, utilizes whole blood and integrates platelet, red blood cell, and plasma interactions through a cellular model. The R value quantitatively measures the dynamic mechanical changes from coagulation initiation to fibrin clot formation in real time (12,31,32). Mild coagulation factor deficiencies, insufficient to prolong INR, nonetheless slow thrombin generation, which TEG linearly records as prolonged R values, providing a quantifiable target for plasma therapy during the window period before PT or APTT changes become apparent.

Complementary role of R value in addressing INR evaluation limitations

Stratified analysis revealed that in patients with R >10 min and 1.1< INR ≤1.9, low-dose plasma significantly shortened the R value. This suggests the R value is applicable for assessing efficacy when INR is normal or slightly elevated, challenging the traditional view that “plasma is ineffective when INR <2.0” (18,19,33). Previous studies using INR as the endpoint showed only 12% of patients achieved complete normalization. Moreover, when INR <1.6, 10–15 mL/kg plasma reduced INR by an average of only 0.24, with 45.5% remaining above 1.5 (18,34). The baseline INR of plasma units (approximately 1.3) further diminished the correction magnitude (19). This study confirms that the R value within this range is sensitive to both low-dose and standard-dose plasma transfusion, suggesting previous conclusions may have obscured plasma’s substantive improvement in the coagulation initiation phase. Therefore, under restrictive transfusion strategies such as limiting plasma volume to minimize fluid overload, the R value should serve as a necessary supplement to INR to accurately identify the laboratory benefits of low-dose plasma.

Clinical rationale and application value of low-dose plasma transfusion strategy

Despite guidelines recommending 10–20 mL/kg, 40% of plasma transfusions were <10 mL/kg, with some cohorts receiving only 3.8 mL/kg (17), highlighting the tension between adequate dosage recommendations and fluid management constraints. This study confirms that within the INR range of 1.1–1.9, low-dose plasma improves R values comparably to the standard-dose, indicating a non-linear dose-response relationship. The mechanism may be that when factor deficiency is not severe, the body has already partially compensated, reducing the need for higher plasma volumes to achieve coagulation improvement. Thus, the coagulation status has passed the steep phase of the curve and entered a plateau phase. At this point, further increasing the transfusion volume yields only marginal benefits while significantly increasing the risk of volume overload (19,35). Regarding safety, limiting transfusion volume 10 mL/kg is intended to reduce transfusion-associated acute lung injury (TRALI), circulatory overload, and allergic reactions (33,36). Concerning efficacy, achieving 25–30% of normal clotting factor concentration suffices for hemostasis (37), enabling a low-dose plasma transfusion strategy to meet replacement goals while conserving resources. From a health economics perspective, the low-dose strategy provides evidence-based justification for addressing the prevalent issue of “under-dosing” in transfusions, promoting plasma transfusion from “guideline standards” toward “personalized precision”. However, these conclusions are strictly limited to individuals with R >10 min and mild-to-moderate INR abnormalities, as the efficacy and safety in other populations remain to be validated. Future large-scale randomized controlled trials are needed to validate its generalizability and long-term safety.

Technological innovations and clinical prospects of in vitro plasma simulation methods

This model utilizes pre-transfusion patient samples without additional reagents, thereby eliminating immunogenic risks and reducing costs. Its adjustable dosage is particularly suitable for patients with renal or cardiac insufficiency requiring strict volume control. By shifting efficacy prediction to the decision-making stage, it reduces plasma consumption and risks such as TRALI, offering strategic value during blood shortages. However, the in vitro environment cannot replicate the metabolism and distribution kinetics of endogenous factors, necessitating validation of predictive accuracy through large-scale studies. Furthermore, the model currently provides only quantitative data on R value improvement without establishing a direct correlation with bleeding outcomes. Clinical application requires a comprehensive assessment based on the patient’s overall condition.

Future research directions

The study has obtained initial results, but there are also several important restrictions. The sample size should be expanded to enhance the reliability and applicability of the results and assess their generalizability. Additionally, future studies should focus on evaluating changes in coagulation function following plasma transfusion in different populations, such as the elderly and patients with comorbidities, to provide a basis for individualized treatment.

Conclusions

As for the research methodology, in vitro simulated plasma transfusion experimental method was selected. By doing 24 persons’ TEG test, the R, K, Alpha angle, MA, and CI were recorded. And then the patients, according to the INR and the transfusion dose, were clarified, and the impacts on blood coagulation were analyzed.

According to our results of transfusing plasmas, the coagulation ability was greatly enhanced in patients after transfusion, especially the R changed also statistically significant it showed that plasma transfusion could be beneficial for increasing coagulation factors. In this study, it was also found that patients with 1.1< INR ≤1.9 before plasma transfusion prior to plasma transfusion demonstrated the improved coagulation factor function following extracorporeal simulated plasma transfusion. Comparative results across different transfusion doses indicated that while both groups showed positive effects on coagulation factor function, the degree of improvement was not significantly different. This suggested that low-dose plasma transfusion (>5–<10 mL/kg) could positively influence patients’ coagulation status in clinical practice. Looking ahead, research on extracorporeal simulated plasma transfusion holds vast potential for further exploration. The impact of plasma transfusion on coagulation function changes will be validated in larger clinical samples in the future.

Acknowledgments

The authors thank Dr. Ling Zhang for her helpful suggestions for this study (Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China).

Footnote

Reporting Checklist: The authors have completed the MDAR reporting checklist. Available at https://aob.amegroups.com/article/view/10.21037/aob-2025-1-44/rc

Data Sharing Statement: Available at https://aob.amegroups.com/article/view/10.21037/aob-2025-1-44/dss

Peer Review File: Available at https://aob.amegroups.com/article/view/10.21037/aob-2025-1-44/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aob.amegroups.com/article/view/10.21037/aob-2025-1-44/coif). C.L. serves as an unpaid Associate Editor-in-Chief of Annals of Blood from November 2016 to October 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Medical Ethics Committee of Nanfang Hospital (No. NFEC-202406-K26-01) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Expert Consensus Group on Diagnosis and Treatment of Acute Hemorrhagic Coagulopathy. Expert Consensus on Diagnosis and Treatment of Acute Hemorrhagic Coagulopathy. Chinese Journal of Emergency Medicine 2020;29:780-7.
2. Sabouri M, Vahidian M, Sourani A, et al. Efficacy and safety of fibrinogen administration in acute post-traumatic hypofibrinogenemia in isolated severe traumatic brain injury: A randomized clinical trial. J Clin Neurosci 2022;101:204-11. [Crossref] [PubMed]
3. Song JC, Zhang W, Zhang L, et al. Consensus of Chinese experts on standardized evaluation of coagulation dysfunction in severe patients. Medical Journal of Chinese People's Liberation Army 2022;47:107-17.
4. Yang L, Stanworth S, Hopewell S, et al. Is fresh-frozen plasma clinically effective? An update of a systematic review of randomized controlled trials. Transfusion 2012;52:1673-86; quiz 1673. [Crossref] [PubMed]
5. Ren Q, Wang J, Tian L, et al. Research progress of evidence-based medicine in clinical practice of plasma transfusion. Chinese Journal of Blood Transfusion 2022;35:119-23.
6. Hashim YM, Dhillon NK, Rottler NP, et al. Correcting Coagulopathy With Fresh Frozen Plasma in the Surgical Intensive Care Unit: How Much Do We Need to Transfuse? Am Surg 2022;88:2030-4. [Crossref] [PubMed]
7. Rout G. Thromboelastography-guided Blood Product Transfusion in Cirrhosis Patients With Variceal Bleeding: A Randomized Controlled Trial. J Clin Gastroenterol 2020;54:255-62. [Crossref] [PubMed]
8. Liu YX. Influence of different placement time of FFP/FP after ablation on coagulation time and Angel angle in thromboelastography. Chinese Journal of Health Laboratory Technology 2020;30:3055-6, 3060.
9. Meli A, De Falco S, Novembrino C, et al. The role of inflammation and antithrombin supplementation on thromboelastographic parameters during veno-venous ECMO for respiratory failure. Perfusion 2024;39:66S-76S. [Crossref] [PubMed]
10. O'Keefe D, Lim HY, Tham J, et al. Assessing maternal clotting function with novel global coagulation assays: A prospective pilot study. Int J Lab Hematol 2021;43:458-67. [Crossref] [PubMed]
11. Kohli R, Shingina A, New S, et al. Thromboelastography Parameters Are Associated with Cirrhosis Severity. Dig Dis Sci 2019;64:2661-70. [Crossref] [PubMed]
12. Lin C, Zhang J, Yang X, et al. Use of thromboelastography to monitor effects of the hemocoagulase on the blood coagulation in patients after thoracic surgery. Ann Palliat Med 2020;9:2090-5. [Crossref] [PubMed]
13. Wang P, Yang H, Wang G, et al. Predictive value of thromboelastography parameters combined with antithrombin III and D-Dimer in patients with recurrent spontaneous abortion. Am J Reprod Immunol 2019;82:e13165. [Crossref] [PubMed]
14. Griffiths S, Woo C, Mansoubi V, et al. Thromboelastography (TEG®) demonstrates that tinzaparin 4500 international units has no detectable anticoagulant activity after caesarean section. Int J Obstet Anesth 2017;29:50-6. [Crossref] [PubMed]
15. Gui R, Huang X, Zhou M, et al. Establishment of the Normal Reference Range of Thrombelastogram among the Healthy Population and Pregnants in China. Iran J Public Health 2019;48:841-8.
16. Liu RN, Wang DQ. Current Realities and Novel Improvements of Plasma Transfusion. Journal of Clinical Transfusion and Laboratory Medicine 2024;26:180-6.
17. Lu Y, Sun G, Liu X, et al. Plasma Transfusion in Patients With Cirrhosis in China: A Retrospective Multicenter Cohort Study. Transfus Med Rev 2017;31:107-12. [Crossref] [PubMed]
18. Carson JL, Ness PM, Pagano MB, et al. Plasma trial: Pilot randomized clinical trial to determine safety and efficacy of plasma transfusions. Transfusion 2021;61:2025-34. [Crossref] [PubMed]
19. Chen LF, Tan CR, Zhuang JM, et al. Analysis on Factors Influencing Posttransfusion Effectiveness in Plasma Transfusion of 4423 Cases-Times. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020;28:290-5. [Crossref] [PubMed]
20. Only AJ Jr, DeChristopher PJ, Iqal O, et al. Restoration of Normal Prothrombin Time/International Normalized Ratio With Fresh Frozen Plasma in Hypocoagulable Patients. Clin Appl Thromb Hemost 2016;22:85-91. [Crossref] [PubMed]
21. Chinese Society on Thrombosis and Hemostasis. Chinese expert consensus on operation procedure and result interpretation of APTT mixing test. Chinese Journal of Laboratory Medicine 2021;44:690-7.
22. Pérez-Ferrer A, Navarro-Suay R, Viejo-Llorente A, et al. In vitro thromboelastometric evaluation of the efficacy of frozen platelet transfusion. Thromb Res 2015;136:348-53. [Crossref] [PubMed]
23. Längst E, Crettaz D, Delobel J, et al. In vitro-transfusional model for red-blood-cell study: the advantage of lowering hematocrit. Blood Transfus 2023;21:277-88. [Crossref] [PubMed]
24. Tian Y, Lai D, Ji CF, et al. Transfusion therapy selection guided by TEG extracorporeal correction model: a single-center study. Chinese Journal of Thrombosis and Hemostasis 2023;29:31-6.
25. National Health Commission of the People's Republic of China. Transfusion of whole blood and blood components: WS/T 623-2018. Beijing: Standards Press of China; 2018.
26. Ma HP, Jiang QQ, Wang J, et al. Clinical study on heparin effective dose predicted by in vitro heparin concentration progressive in patients undergoing heart surgery. The Journal of Practical Medicine 2017;33:3906-11.
27. Rassi AB, d'Amico EA, Tripodi A, et al. Fresh frozen plasma transfusion in patients with cirrhosis and coagulopathy: Effect on conventional coagulation tests and thrombomodulin-modified thrombin generation. J Hepatol 2020;72:85-94. [Crossref] [PubMed]
28. Premkumar M, Mehtani R, Divyaveer S, et al. Clinical Validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF. J Clin Transl Hepatol 2021;9:210-9. [Crossref] [PubMed]
29. Mallett SV. Clinical Utility of Viscoelastic Tests of Coagulation (TEG/ROTEM) in Patients with Liver Disease and during Liver Transplantation. Semin Thromb Hemost 2015;41:527-37. [Crossref] [PubMed]
30. Soundar EP, Besandre R, Hartman SK, et al. Plasma is ineffective in correcting mildly elevated PT-INR in critically ill children: a retrospective observational study. J Intensive Care 2014;2:64. [Crossref] [PubMed]
31. Mao XJ, Feng J. Clinical Application of Thromboelastography in Diagnosis and Treatment of Patients with Multiple Injuries. Medical Recapitulate 2019;25:2248-52.
32. Jing J, Wang WT, Chang Y, et al. Comparison of Efficacy between Thrombelastography and Conventional Coagulation Tests and Analysis of Their Correlation for Patients with Abnormal Coagulation Function. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020;28:629-35. [Crossref] [PubMed]
33. Jia Q, Brown MJ, Clifford L, et al. Prophylactic plasma transfusion for surgical patients with abnormal preoperative coagulation tests: a single-institution propensity-adjusted cohort study. Lancet Haematol 2016;3:e139-48. [Crossref] [PubMed]
34. Bi L, Luo T, Liu X, et al. Progress in the application of fresh frozen plasma in critically ill. Journal of Clinical Anesthesiology 2022;38:313-7.
35. Lu W. A Concise Synopsis of Current Literature and Guidelines on the Practice of Plasma Transfusion. Clin Lab Med 2021;41:635-45. [Crossref] [PubMed]
36. Khandelwal A, Minuk L, Liu Y, et al. Plasma transfusion practices: A multicentre electronic audit. Vox Sang 2022;117:1211-9. [Crossref] [PubMed]
37. Hartmann J, Murphy M, Dias JD. Viscoelastic Hemostatic Assays: Moving from the Laboratory to the Site of Care-A Review of Established and Emerging Technologies. Diagnostics (Basel) 2020;10:118. [Crossref] [PubMed]