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\begin{document}

\title{The association between thrombin-activated fibrinolytic inhibitor levels
and risk of recurrent spontaneous abortion based on anti-thyroid
antibodies status: a retrospective case-control study}



\author[1]{Jing Dong}%
\author[1]{Pengsen Mou}%
\author[1]{Weiming Hou}%
\author[1]{Peng Zhang}%
\author[1]{Guoze Zhang}%
\author[1]{Yuxin Yao}%
\author[1]{Jiaxin Guan}%
\author[2]{ying wang}%
\affil[1]{China Medical University School of Public Health}%
\affil[2]{Shengjing Hospital of China Medical University}%


\vspace{-1em}



  
  \date{June 11, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
\textbf{OBJECTIVE:} The objective of this study was to investigate the
relationship between plasma levels of thrombin-activated fibrinolytic
inhibitor (TAFI) and recurrent spontaneous abortion (RSA) in varying
conditions of anti-thyroid antibodies (ATA), and to provide appropriate
recommendations for RSA prevention. \textbf{Design:} Retrospective
case-control study. \textbf{Setting:}Department of Obstetrics and
Gynecology, Shengjing Hospital, China Medical University.
\textbf{Sample:} There were 1068 subjects in this retrospective study,
including 402 RSA patients and 666 controls. \textbf{Methods:} Collected
case records from the Department of Obstetrics and Gynecology from
January 2020 to March 2022 for comparative analysis between cases and
controls. \textbf{Main outcome measures:} Patients' socio-demographic
factors, plasma TAFI levels, ATA status, including thyroid peroxidase
antibodies (Anti-TPO) and thyroglobulin antibodies (Anti-TG), thyroid
function, coagulation function, and so on. Multivariate adjusted
conditional logistic regression and restricted cubic spline (RCS) models
were applied to evaluate odds ratios (ORs) and their 95\% confidence
intervals (CIs) between plasma TAFI levels and the risk of RSA under
different ATA conditions according to the normal reference range of
plasma TAFI levels (24-35ug/ml). \textbf{Results:} Compared to normal
TAFI levels (as reference), low TAFI levels (\textless{}24ug/ml) had a
significantly increased risk of RSA, which was shown in the Anti-TPO
positive group (OR, 2.15; 95\% CI, 1.221-3.785; P=0.008), Anti-TPO
negative group (OR, 1.429; 95\% CI, 1.032-1.98; P = 0.032), and Anti-TG
positive group (OR, 2.215; 95\% CI, 1.265-3.878; P = 0.005). In
addition, the RSC model showed that plasma TAFI levels showed a linear
negative dose relationship with the risk of RSA. \textbf{Conclusions:}
The study indicates that pregnant women with plasma TAFI levels below
the normal range, especially those who are ATA positive, are at a higher
risk of developing RSA. These findings suggest the need to develop
prevention recommendations.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Recurrent spontaneous abortion (RSA) is defined as two or more
consecutive clinical pregnancy failures that affect 1-5\% of women of
reproductive age \textsuperscript{1}. RSA has a significant negative
impact on women's physical and psychological health and is a serious
reproductive problem whose incidence has been on the rise in recent
years \textsuperscript{2}. Currently, RSA is known to have various
causes, including genetic, thrombotic, infectious factors, immune and
endocrine dysfunction, and anatomical abnormalities of the reproductive
tract \textsuperscript{3, 4}. Thrombin-activated fibrinolysis inhibitor
(TAFI) is the main inhibitor of fibrinolysis, and it plays an important
role in RSA due to its role in the coagulation and fibrinolytic system
as well as in inflammation \textsuperscript{5}.

TAFI is a procarboxypeptidase that is synthesized primarily by the liver
and is present in the circulation as an inactive
zymogen\textsuperscript{6}. TAFI can be activated by thrombin,
thrombin-thrombin regulatory protein, and plasma proteins. The activated
form of TAFI cleaves its C-terminal lysine or arginine residue from the
peptide substrate, resulting in partial degradation of fibrin from the
C-terminal lysine residue \textsuperscript{7, 8}. This mechanism enables
TAFI to exert antifibrinolytic effects \textsuperscript{9}. In vivo
studies have shown that fibrin degradation products may induce apoptosis
in trophoblast cells, leading to embryonic cell death and fetal loss in
mice \textsuperscript{10}. However, the association of TAFI with RSA is
less studied and controversial. A case-control study in Italy provided
evidence that high activity TAFI levels are associated with a reduced
risk of early recurrent fetal loss \textsuperscript{11}, while another
Dutch case-control study showed that TAFI was not associated with
RSA\textsuperscript{12}.

Additionally, TAFI may play a broad role in the regulation of
inflammation. Its activated form inactivates several inflammatory
mediators by removing the C-terminal arginine, including bradykinin,
bovine toxin C3a and C5a \textsuperscript{9, 13}. And inflammation is
closely associated with thyroid autoimmunity (TAI), which is defined as
the presence of anti-thyroid antibodies (ATA), including thyroid
peroxidase antibodies (Anti-TPO) and thyroglobulin antibodies (Anti-TG)
\textsuperscript{14}. It is generally accepted that Anti-TPO positive
women are at higher risk of incidental miscarriage, preterm birth, and
postpartum thyroid disease\textsuperscript{15, 16}. Some studies have
shown that patients with RSA have higher levels of Anti-TPO
\textsuperscript{17}. Furthermore, it has been shown that TAI is
associated with resistance to fibrinolysis ex vivo and C3 plasma levels
\textsuperscript{18}. Therefore, there may be an association between ATA
and TAFI in terms of inflammation.

To our knowledge, limited previous research has been conducted to
investigate the relationship between plasma levels of TAFI and RSA in
varying conditions of ATA. Therefore, the objective of this study is to
investigate this association among 1,068 pregnant Chinese women (402
cases and 666 controls) and to explore independent risk factors for RSA
in the presence of different conditions of ATA. Furthermore, this
research aims to analyze the influence of TAFI and ATA on RSA in terms
of inflammation, to provide suitable recommendations for the diagnosis
of RSA.

\textbf{Materials and Methods}

\emph{Study population and data source}

We conducted a retrospective case-control study to investigate the
effect of TAFI on RSA in Anti-TPO, Anti-TG negative, and positive
pregnant women, using gestational examination data from January 2020 to
March 2022 from the Department of Obstetrics and Gynecology, Shengjing
Hospital, China Medical University. We defined RSA as the occurrence of
two or more miscarriages with the same partner before 24 weeks of
gestation. All patients underwent a standardized diagnostic protocol,
and those who received a confirmed diagnosis of RSA by the hospital were
included in this study. Ultimately, we included 402 patients with RSA
and 666 normal pregnant women. The study was approved by the Ethics
Committee of Shengjing Hospital, China Medical University.

\emph{Exposure and outcome variables}

We extracted clinical and laboratory data from the electronic medical
records using the case information management system at Shengjing
Hospital, China Medical University. These include maternal age, plasma
TAFI levels, maximum platelet aggregation rate (including ADP,
Arachidonic acid {[}AA{]}), coagulation measurements (prothrombin time
{[}PT{]}, prothrombin time activity {[}PTA{]}, activated partial
thromboplastin time {[}APTT{]}, fibrinogen content {[}FIB{]}, Thrombin
clotting time {[}TT{]}, D-dimer), blood cell tests (lymphocyte
percentage {[}LYMPH{]}, monocyte percentage {[}MONO{]}, basophil
percentage {[}BASO{]}, Red cell distribution width -CV value
{[}RDW-CV{]}, Red cell distribution width -SD value {[}RDW-SD{]}),
thyroid function tests (free triiodothyronine {[}FT\textsubscript{3}{]},
free thyroxine {[}FT\textsubscript{4}{]}, thyroid stimulating hormone
{[}TSH{]}, thyroid peroxidase antibodies {[}Anti-TPO{]}, thyroglobulin
antibody {[}Anti-TG{]}), thromboelastography tests (reaction time
{[}R{]}, clotting time {[}K{]}, Angle, maximum amplitude {[}MA{]},
coagulation index {[}CI{]}, estimated percentage of lysis {[}EPL{]},
lysis after 30 min {[}LY30{]}). In this study, we measured plasma TAFI
using an ELISA assay with an AU480 fully automated biochemical analyzer
from Beckman Coulter, USA, and a TAFI quantitative assay kit from
Liaoning Mediatek Biotechnology Co. Normal range of plasma TAFI
reference hospital plasma TAFI normal range: 24-35ug/mL.

\emph{Statistical tests}

Continuous variables were described using mean and standard deviation
(SD) or median and interquartile range (IQR). One-way analyses were
performed after the Shapiro-Wilk normality test, and independent samples
t-tests and Mann-Whitney U tests were used to compare differences
between the two groups for parametric and nonparametric variables,
respectively. The threshold of statistical significance was set at a
p-value \textless{} 0.05. All data analyses were performed using R
software (https: www.r-project.org, version 4.1.3) and SPSS 21.0 (SPSS
Inc., Chicago, IL, USA).

Stepwise logistic regression is used to analyze the independent risk
variables for RSA in each group. To evaluate the relationship between
TAFI and RSA, binary logistic regression was used, with the normal
reference range of TAFI as a reference. The adjusted confounders were
the variables screened by the multifactorial regression analysis.

Unconditional logistic regression models were conducted in stratified
analysis by age, coagulation indicators, thyroid function indicators.
Restricted cubic spline models with four knots were used to explore the
potential association between TAFI and RSA under different antibody
conditions. The four knots include the TAFI 1st percentile, 24ug/mL,
35ug/mL, and the TAFI 99th percentile.

\textbf{Results}

\emph{Comparison of baseline characteristics of RSA patients and normal
pregnant women with different ATA}

In the overall population, there were 1068 study subjects, of whom 402
(37.6\%) were RSA patients, and 666 (62.4\%) were normal pregnant women.
Among the study subjects, 253 (23.7\%) tested positive for Anti-TPO, and
273 (25.6\%) tested positive for Anti-TG, with a higher proportion of
individuals testing negative for both antibodies. The correlation
between variables and RSA in the overall population is presented in
Supplementary Table S1. ADP, AA, R, K, CI, EPL, and LY30 did not show
statistical significance, while the remaining variables demonstrated
statistical significance.

Table 1 and Table 2 demonstrate the baseline characteristics of RSA
patients versus normal pregnant women. In terms of plasma TAFI levels,
all groups, regardless of the status of antibodies, exhibited
significantly lower levels in RSA patients compared to normal pregnant
women with statistical significance. The median TAFI level in normal
pregnant women was approximately 25 ug/mL, which was about 2 ug/mL
higher than that of RSA patients. Interestingly, the Anti-TPO negative
group had higher levels of plasma TAFI compared to the Anti-TPO positive
group in both cases and controls.

Regarding the age of the study population, the results of both tables
indicated that RSA patients were older than normal pregnant women.
However, statistically significant differences were observed only in the
Anti-TPO negative and Anti-TG positive groups. With regards to the
platelet aggregation function indicators (ADP and AA), Only AA showed
statistically significant in the Anti-TG negative group.

With regard to coagulation, the results were similar across antibody
states. In the Anti-TPO negative and Anti-TG negative groups, all
coagulation parameters (PT, PTA, APTT, FIB, TT, DD) showed statistically
significant differences.

Concerning blood cell tests and thyroid function, the results of the
analysis were the same in the two negative groups, and the analysis of
the results was similar in the two positive groups. In both negative
groups, except for MONO, all blood cell tests (LYMPH, MONO, BASO,
RDW-CV, RDW-SD) and thyroid function indicators (FT\textsubscript{3},
FT\textsubscript{4}, TSH) showed statistically significant differences.
In both positive groups, LYMPH showed statistical differences in both
groups. BASO showed statistical differences only in the Anti-TPO
positive group, while FT\textsubscript{3} showed statistical differences
only in the Anti-TG positive group.

On the aspect of thromboelastography indexes, the results of the
analysis of the two positive groups were the same as those of the two
negative groups. Only LY30 was statistically different in the two
positive groups. In both the Anti-TPO negative and Anti-TG negative
groups, Angle and MA showed statistically significant differences.

\emph{Multifactorial logistic analysis of independent risk factors for
RSA}

The factors independently associated with RSA in different groups are
shown in Table 3. In the overall population, TAFI, DD, and RDW-CV
variables were shown to be protective factors, all other variables were
considered risk factors. The regression analysis results showed that the
\selectlanguage{greek}β-\selectlanguage{english}coefficient of plasma TAFI level was -0.04 {[}odds ratio (OR) 0.961;
95\% CI, 0.936-0.987; P = 0.004{]}.

In the Anti-TPO positive and Anti-TG positive populations, relatively
few factors were independently associated with RSA. In the Anti-TPO
positive group, TAFI (OR, 0.943; 95\% CI, 0.896-0.992; P = 0.025{]},
LYMPH (OR. 1.034; 95\% CI, 1.003-1.066; P =0.03), and LY30 (OR, 0.162;
95\% CI, 0.035-0.738; P=0.019) were independent predictors of RSA. In
the Anti-TG positive group, TAFI (OR, 0.937; 95\% CI, 0.884-0.992; P =
0.027), age (OR, 1.133; 95\% CI, 1.057-1.215; P \textless{} 0.001), Fib
(OR, 0.593; 95\% CI, 0.393-0.893; P = 0.012). FT\textsubscript{3}(OR,
2.205;95\% CI, 1.307-3.722; P=0.003), and LY30(OR, 0.433;95\% CI,
0.238-0.788; P=0.012) were independent predictors of RSA. In the
Anti-TPO negative group, TAFI (OR, 0.965; 95\% CI, 0.935-0.996; P =
0.028), and age (OR, 1.067; 95\% CI, 1.026-1.11; P = 0.001) were
independent predictors of RSA. It is worth noting that TAFI was shown to
be an independent protective factor for RSA in all four groups, except
in the Anti-TG negative group.

\emph{Correlation between plasma TAFI levels and risk of RSA}

Table 4 shows the correlations between plasma TAFI levels explored in
the binary logistic regression model and the risk of RSA. The total
population was divided into three groups according to the normal range
of plasma TAFI levels: normal levels of plasma TAFI were defined as
24-35ug/ml, TAFI<24ug/mL, TAFI>35ug/mL. The adjusted covariates for
each group were the variables that were statistically significant by
logistic regression. Compared with TAFI levels of 24-35ug/ml. In the
Anti-TPO positive group, the risk of RSA was significantly increased in
those with TAFI \textless{}24 (OR, 2.15; 95\% CI, 1.221-3.785; P=0.008).
This result was also seen in the Anti-TPO negative group and the Anti-TG
positive group. In the Anti-TPO negative group, the risk of RSA was
increased in those with TAFI \textless{}24 (OR, 1.429; 95\% CI,
1.032-1.98; P=0.032); in the Anti-TG positive group, the risk of RSA was
significantly increased in those with TAFI \textless{}24 (OR, 2.215;
95\% CI, 1.265-3.878; P=0.005). It is important to note that in the
Anti-TPO negative group, the OR for the increased risk of RSA in the
TAFI \textless{}24 population was smaller than in the two-positive
group.

As shown in Fig1, the multivariate adjusted spline regression model
showed a linear negative dose response relationship between TAFI and RSA
in all subgroups, with P values for nonlinearity all greater than 0.05.
Of note, in the two positive subgroups, OR value was approximately less
than 1 when TAFI levels were within the normal reference range of 24-35
ug/mL. However, when TAFI levels were below 24 ug/mL, the OR value
increased and was higher than that in the two negative subgroups. On the
other hand, when TAFI levels were above 35 ug/mL, an increasing TAFI
level was found to be associated with a higher risk of RSA, but the
trend is not obvious. This trend was not observed in the two negative
subgroups.

\emph{The impact of TAFI on RSA in specific subgroups.}

Similar results were observed in the stratified analysis by age, BMI,
PT, PTA, APTT, TT, DD, FT\textsubscript{3}, FT\textsubscript{4}, TSH,
Anti-Tpo, and Anti-TG. As shown in Figure 2, The correlation between
TAFI and the risk of RSA is more significant in participants with
age\textgreater{}32, PT\textgreater{}10.9s, PTA[?]109\%, APTT
\textgreater{}32.1s, TT [?]16.2s, DD [?]90ug/ml,
FT\textsubscript{3}\textgreater{}4.42pmol/L, FT\textsubscript{4}
[?]13.08pmol/L, TSH \textgreater{}1.64uIU/mL, and Anti-TPO negative.

\textbf{Discussion:}

\emph{Main Findings}

Previous studies have shown a link between TAFI and RSA, but there has
been controversy. These studies tend to focus on the potential effects
of TAFI on RSA in terms of coagulation and fibrinolysis. And the
presence of ATA in the body can lead to inflammatory reactions, which
has caught our attention. Therefore, we conducted a retrospective
case-control study to explore the effect of TAFI levels on RSA under
different conditions of ATA, and found that when the plasma TAFI level
is below the normal range of TAFI, there is a high risk of RSA in the
Anti-TPO positive, Anti-TPO negative, and Anti-TG positive populations.
There is a dose-response relationship between plasma TAFI levels and the
risk of RSA, which is significantly associated.

\emph{~Interpretation}

A possible explanation for our findings is that TAFI is involved in
regulating the immune response and complement-mediated vascular
inflammation. High TAFI levels suppress the inflammatory response in
vivo and reduce the incidence of miscarriage. TAFI regulates the levels
of inflammatory mediators such as C3a, C5a, bradykinin, and bone
bridging proteins and suppresses inflammation in vivo by inactivating
inflammatory mediators\textsuperscript{19, 20}. For instance, it has
been shown that there is a significant negative correlation between
serum TAFI and C3a levels\textsuperscript{21}. Some investigators have
identified a role for TAFI in inflammation, and their results suggest
that TAFI plays an important role during pneumococcal meningitis, which
is likely to be mediated through inhibition of the complement system,
and influences the occurrence of inflammation \textsuperscript{22}. The
presence of ATA in the body leads to an inflammatory and immune
response, and a recent meta-analysis suggests that they may increase the
risk of pregnancy failure, although the exact mechanism is not yet
known\textsuperscript{23}. ATA can cause thyroid cell damage through
activation of the complement system and
cytotoxicity\textsuperscript{24}, which are associated with the outcome
of pregnancy failure. It is reasonable to speculate that TAFI may exert
a protective effect on RSA by inhibiting the inflammation caused by ATA.
In the study population of two positive groups, there were more
inflammatory mediators, and when TAFI was at a low level
(\textless{}24ug/mL), the anti-inflammatory ability was weaker, which
presented as a risk factor.

It is worth noting that when the plasma TAFI level is lower than the
normal range of TAFI, the risk of RSA in the Anti-TPO negative
population is also increased, but the OR value of 1.429 is significantly
smaller than that of the two positive groups. We speculate that this is
related to coagulation and fibrinolysis system disorders. A possible
explanation for this result is that a low fibrinolytic state may be
beneficial for pregnancy. The fibrinolytic system plays an important
role in helping with placental implantation, fetal growth, and
development during pregnancy \textsuperscript{25}. An animal experiment
had shown that degradation products of fibrinogen can cause apoptosis of
mouse trophoblast cells, leading to fetal loss \textsuperscript{10}.
Reducing the activation of TAFI can enhance the degradation of
fibrinogen, thereby increasing fibrinogen degradation products.
Therefore, low levels of TAFI can increase the risk of RSA.

This outcome is supported by several studies on TAFI levels and the risk
of RSA. Several European case-control studies provide evidence that high
levels of TAFI may be associated with a decreased risk of
RSA\textsuperscript{11, 26, 27}. These findings have important
implications for the prevention and management of RSA. However, there
are studies in the Netherlands and Turkey that show no association
between the level of TAFI and RSA \textsuperscript{12, 28}. In contrast,
a retrospective case-control study conducted in Spain showed that
patients with RSA had statistically significantly higher TAFI antigen
levels compared to other groups \textsuperscript{29}. The observed
differences in the risk of RSA associated with TAFI levels may be
attributed to several reasons. Firstly, varying definitions of RSA exist
across studies. Some studies define RSA as three or more consecutive
pregnancy losses\textsuperscript{11, 28, 29}, whereas other studies
define RSA as two or more consecutive pregnancy losses. When different
definitions are used to diagnose or study RSA, it can result in
different populations being included in the study, thereby reducing the
reliability of the comparative results. Secondly, different studies have
used different methods to measure TAFI levels. Some studies used a
colorimetric assay\textsuperscript{11, 12}, and the enzyme-linked
immunosorbent assay (ELISA) method is used in most studies. It is worth
mentioning that the different sensitivity of ELISA for various isoforms
of TAFI can lead to large differences in TAFI levels among studies
\textsuperscript{30, 31}. Lastly, TAFI levels may vary by geographic
region. Despite the differing conclusions of these studies, our
dose-response correlation further supports the notion that increased
plasma TAFI levels reduce the risk of RSA in our study population.

In addition, The magnitude of the associations between TAFI and RSA was
different in subgroups by age, coagulation indicators, and thyroid
function indicators. Age and thyroid function were reported as potential
influencing factors of TAFI levels. Specifically, a study indicated a
positive correlation between TAFI levels and age \textsuperscript{32}.
Furthermore, TSH levels were identified as predictors of TAFI levels,
and fibrinolytic activity was reduced in patients with impaired thyroid
function \textsuperscript{33, 34}.

\emph{~Strengths and Limitations}

To our knowledge, the present study is the first to examine the
relationship between TAFI and the risk of RSA based on the ATA profile.
However, this study has several limitations worth mentioning. First, as
a single-center study, there are some bias in testing TAFI and other
indicators only in patients from a single study center. Second, all
participants in this study were from Liaoning province, China, and
extrapolation of our results to other populations with different
demographic characteristics or to other regions should be done with
caution. Third, confounding due to unknown or unmeasured factors, such
as maternal medication use during pregnancy, cannot be excluded. Last,
our study did not measure inflammatory mediators levels to further
validate. More large cohort studies are needed in the future to further
investigate and validate our results, and to study whether inflammatory
mediators play a key role in RSA. In addition, the pathological
mechanisms by which low TAFI levels lead to an increased risk of RSA
need to be further investigated.

\textbf{Conclusions:}\begin{CJK}{UTF8}{gbsn}　　\end{CJK}\selectlanguage{english}In summary, our study suggests that pregnant
women with plasma TAFI levels below the normal range, especially in
ATA-positive populations, are at higher risk for RSA. Therefore,
pregnant women with low TAFI levels and ATA-positive should be vigilant
for the occurrence of RSA, which has made a certain contribution to the
prevention of RSA.

\textbf{Data availability}

The data underlying this article will be shared upon reasonable request
to the corresponding author.

\textbf{Authors' roles}

\textbf{Concept or design:} PM, WH, YW, JD; \textbf{Acquisition of
data:} PM, WH, YW; \textbf{Analysis or interpretation of data:} PM, WH,
PZ, GZ, YY, JG; \textbf{Drafting of the manuscript:} PM, WH, JD;
\textbf{Critical revision of the manuscript for important intellectual
content:} PM, WH, PZ, GZ, YY, JG, YW, JD. All authors had full access to
the data, contributed to the study, approved the final version for
publication, and take responsibility for its accuracy and integrity. All
authors read and approved the final manuscript

\textbf{Funding}

No fundings.

\textbf{Conflict of interest}

None declared.

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\textbf{Figure and table legends}

\textbf{Fig 1} Multivariable-adjusted association of TAFI with risk of
RSA by restricted cubic regression. The shaded area represents a 95\%
confidence interval. The solid blue line symbolizes the odds ratio (OR),
and the red vertical line indicates the TAFI value corresponding to an
OR of 1. Adjustment of covariates is based on variables with
statistically significant effects in the multivariate logistic
regression analysis of each group.

\textbf{Fig 2} Unconditional logistic regression models were conducted
in stratified analysis by age (median), BMI (median), PT (median), PTA
(median), APTT (median), TT (median), DD (median), FT3 (median), FT4
(mean), TSH (median), Anti-TPO (negative or positive), Anti-TG (negative
or positive). All models were adjusted for Age, PT, DD, LYMPH, RDW-CV,
FT3, FT4, TSH, and Angle, except for the stratifying variables per se.

\textbf{Table 1} Basic characteristics of pregnant women in the case
group and control group (Anti-TPO positive and Anti-TPO negative
groups).

\textbf{Table 2} Basic characteristics of pregnant women in the case
group and control group (Anti-TG positive and Anti-TG negative groups).

\textbf{Table 3} Multifactorial logistic analysis of independent risk
factors for RSA in different groups.

\textbf{Table 4} Correlation between plasma TAFI levels and risk of RSA
under different groups (normal range of TAFI as reference).

\textbf{Table S1} Correlation of variables with RSA in the overall
population.

\textbf{Hosted file}

\verb`figure word.docx`  available at \url{https://authorea.com/users/621348/articles/644964-the-association-between-thrombin-activated-fibrinolytic-inhibitor-levels-and-risk-of-recurrent-spontaneous-abortion-based-on-anti-thyroid-antibodies-status-a-retrospective-case-control-study}

\textbf{Hosted file}

\verb`table word.docx`  available at \url{https://authorea.com/users/621348/articles/644964-the-association-between-thrombin-activated-fibrinolytic-inhibitor-levels-and-risk-of-recurrent-spontaneous-abortion-based-on-anti-thyroid-antibodies-status-a-retrospective-case-control-study}

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