Antithrombin Research Articles

Thrombin, protein C, and protein S values in mother-infant dyads in the postpartum period

IntroductionThe objective of the study was to establish the normal range for the levels of antithrombin (AT), protein C (PC), and protein S (PS) in the first week post birth in mother–infant pairings, adjusting for obstetric and perinatal factors, based on 2 different laboratory methods. MethodsDeterminations were carried out in 83 healthy term neonates and their mothers, establishing 3 postpartum age groups: 1−2 days, 3 days, and 4−7 days. ResultsThere were no differences in the levels of any of the proteins between the different age groups in neonates or mothers in the first week post birth. The adjusted analysis found no association with obstetric or perinatal factors. The AT and PC levels were higher in mothers compared to infants (P < .001), while the PS levels were similar in both. Overall, the correlation of maternal and infant protein values was poor, except for the levels of free PS in the first 2 days after delivery. Although we found no differences based on which of the 2 laboratory methods was applied, the absolute values did differ.

Serpin family proteins as potential biomarkers and therapeutic drugs in stroke: A systematic review and meta-analysis on clinical/preclinical studies.

Serpin is a superfamily of serine proteinase inhibitors. They have anticoagulative activities and immunoregulatory effects. The family has been widely studied in stroke patients and animal stroke models. However, results from clinical and preclinical studies are controversial. The systematic review and meta-analysis aimed to determine whether serpin activities are affected by stroke and whether members of the serpin family could be used in stroke treatment. Literature was systematically searched in six databases until September 5, 2022. In the included studies, 47 clinical studies (8276 subjects) reported concentrations of serpin proteins in stroke patients and healthy controls. In total, 41 preclinical studies (742 animals) reported neurological outcomes in animal models with serpin treatment and vehicle. Meta-analysis of clinical studies showed that both ischemic (IS) and hemorrhagic stroke patients had higher thrombin-antithrombin complex (TAT) levels and lower antithrombin (AT) levels which were persistent in the acute and subacute phase of IS. Meta-analysis of preclinical studies reported the efficacy of serpins in treating stroke. C1-INH and FUT175 reduced brain infarct size and improved sensorimotor and motor behavior in a dose- and time-dependent manner in the MCAO models. Our study confirmed the important roles serpin family proteins played in the onset, progression, and treatment of stroke. Among serpins, AT and TAT may be used as blood biomarkers in the early diagnosis of stroke. C1-INH and FUT175 could be potential medications for IS.

Evaluation of acquired antithrombin deficiency in paediatric patients supported on extracorporeal membrane oxygenation.

There remains a paucity of literature regarding best practice for antithrombin (AT) monitoring, dosing and dose-response in paediatric extracorporeal membrane oxygenation (ECMO) patients. We conducted a retrospective cohort study at a quaternary care paediatric intensive care unit in all patients <18 years of age supported on ECMO from 1 June 2011 to 30 April 2020. Adverse events and outcomes were characterized for all ECMO runs. AT activity and replacement were characterized and compared between two clinical protocols. AT activities measured post- vs. pre-AT replacement were compared in order to characterize a dose-response relationship. The final cohort included 191 patients with 201 ECMO runs and 2028 AT activity measurements. The median AT activity was 65% (interquartile range [IQR], 51-82) and 879 (43.3%) measurements met the criteria of deficient. The overall median AT dose and increase in AT activity were 50.6 units/kg/dose (IQR, 39.5-67.2) and 23.5% (IQR, 9.8-36.0), respectively. In the protocol that restricted AT activity measurements to clinical scenarios concerning for heparin resistance, there was significantly higher dosing in conjunction with significantly fewer overall administrations. Approximately one third of AT activity remained deficient after repletion. There was no difference in mechanical complications, reasons for discontinuation of ECMO support, time on ECMO or survival between protocols. There was a high prevalence of AT deficiency in paediatric ECMO patients. An AT replacement protocol based on evaluating heparin resistance is associated with fewer AT administrations, with similar circuit and patient outcomes. Further data are needed to identify optimal dosing strategies.

Valores de antitrombina, proteína C y proteína S en parejas madre-recién nacido durante el posparto

IntroductionThe objective of the study was to establish the normal range for the levels of antithrombin (AT), protein C (PC), and protein S (PS) in the first week post birth in mother-infant dyads, adjusting for obstetric and perinatal factors, based on 2 different laboratory methods. MethodsWe took measurements in 83 healthy term neonates and their mothers, establishing 3 postpartum age groups: 1-2 days, 3 days, and 4-7 days. ResultsThere were no differences in the levels of any of the proteins between the different age groups in neonates or mothers in the first week post birth. The adjusted analysis found no association with obstetric or perinatal factors. The AT and PC levels were higher in mothers compared to infants (P<.001), while the PS levels were similar in both. Overall, the correlation of maternal and infant protein values was poor, except for the levels of free PS in the first 2 days post birth. Although we found no differences based on which of the 2 laboratory methods was applied, the absolute values did differ.

Low Early Antifactor Xa Target Achievement Rate of Low-Molecular-Weight Heparin for Treating Venous Thromboembolism in Patients in Intensive Care.

This study aimed to evaluate whether early antifactor Xa (anti-Xa) achieved the target range when venous thromboembolism (VTE) was treated with low-molecular-weight heparin (LMWH), based on body weight and renal function in patients treated in intensive care units (ICUs). Anti-Xa levels in patients treated with LMWH for VTE in ICU and medical wards between January 1,2021, and June 30,2022, were retrospectively assessed. The demographics, laboratory parameters, and early anti-Xa peak levels of patients were collected. All patients were followed up for 3months to collect VTE recurrence/bleeding events. Univariate and multivariate linear regression analyses were used to identify the factors affecting anti-Xa levels. A total of 108 patients were enrolled in this study, including 70 patients in ICU and 38 patients on medical wards. The early anti-Xa level (0.36 vs 0.61IU/mL, P<.001) and target achievement rate (21.4% vs 39.5%, P=.015) of patients in ICU were lower than those in medical wards. Multivariate linear regression showed that only antithrombin (AT) significantly affected anti-Xa levels in patients in ICU (β=0.008, 95%CI 0.005 to 0.011, P<.001). There was no significant difference in VTE recurrence events (11.8% vs 7.5%, P=.628) and bleeding events (29.4% vs 17.0%, P=.304) between the early anti-Xa within-target group and the early anti-Xa below-target group. Low anti-Xa peak levels are common in patients in ICU. AT activity should be monitored when using LMWH in critically ill patients.

Bushen Huoxue Fang improves recurrent miscarriage in mice by down-regulating the JAK2/STAT3 pathway

To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05). BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.

Impact of SERPINC1 mutation on thrombotic phenotype in children with congenital antithrombin deficiency—first analysis of the International Society on Thrombosis and Haemostasis pediatric antithrombin deficiency database and biorepository

BackgroundThe natural history and genotype–phenotype correlation of congenital antithrombin (AT) deficiency in children are unknown. ObjectivesTo describe the clinical presentation of congenital AT deficiency in children and evaluate its correlation to specific mutations in SERPINC1. MethodsIn 2017, a prospective pediatric database and DNA biorepository for congenital AT deficiency was established. During the pilot phase, the database was opened at 4 tertiary care centers in Canada and US. Approval from research ethics board was obtained at each participating center. Written consent/assent was obtained from guardians/subjects who met eligibility. Demographic/clinical data were uploaded into a database. DNA extraction and SERPINC1 sequencing were centralized for US centers. Standard statistical methods were used to summarize parameters. Probability of VTE-free survival was assessed using the Kaplan–Meier method. ResultsOverall, 43 participants (25 females) from 31 unique kindreds were enrolled. Median age (range) at enrollment was 14.8 years (1-21 years). Median AT activity was 52% (24%-87%), and median AT antigen (n = 20) was 55% (38%-110%). Nineteen (44%) participants had a history of venous thromboembolism (VTE). Median age at VTE diagnosis was 12.8 years (0.1-19.2 years). SERPINC1 sequencing was completed for 31 participants and 21 unique mutations were identified, including 5 novel variants. Probability of 5-year VTE-free survival (95% CI) for carriers of missense mutations (92.0% [95% CI: 71.6%-97.9%]) was significantly higher compared with carriers of null mutations (66.7% [95% CI: 19.5%-90.4%]); p = .0012. ConclusionTo our knowledge, this is the first pediatric study to document a severe thrombotic phenotype in carriers of null mutations in SERPINC1, when compared with carriers of missense mutations; underscoring the importance of genetic testing.

Exploring the Role of Antithrombin in Nephrotic Syndrome-Associated Hypercoagulopathy: A Multi-Cohort Study and Meta-Analysis.

Nephrotic syndrome is associated with an acquired hypercoagulopathy that is thought to drive its predisposition for venous thromboembolism. Previous studies have suggested that urinary antithrombin (AT) loss leading to acquired AT deficiency is the primary mechanism underlying this hypercoagulopathy, but this hypothesis has not been directly tested. The objectives of this study were to test the influence of AT levels on hypercoagulopathy in nephrotic syndrome patient samples and perform meta-analyses to evaluate the likelihood of AT deficiency in patients with nephrotic syndrome. Samples from three independent nephrotic syndrome cohorts were analyzed. AT antigen and activity assays were performed using ELISA and amidolytic assays, respectively. Plasma thrombin generation, albumin, and urine protein-to-creatinine ratios were determined using established methods. Meta-analyses were performed by combining these new data with previously published data. AT levels were not consistently related to either plasma albumin or proteinuria. AT was quantitatively related to hypercoagulopathy in adult nephrotic syndrome, whereas AT activity was inconsistently associated with hypercoagulopathy in childhood nephrotic syndrome. Notably, hypercoagulopathy did not differ between patients with normal AT levels and those with levels below the threshold used to define clinical AT deficiency (<70%). Moreover, ex vivo AT supplementation did not significantly alter hypercoagulopathy in AT-deficient plasma samples. The meta-analyses demonstrated that AT deficiency was not a uniform feature of nephrotic syndrome and was more common in children than adults. These data suggest that AT deficiency plays only a limited role in the mechanisms underlying the acquired hypercoagulopathy of nephrotic syndrome. Moreover, AT deficiency was not present in all patients with nephrotic syndrome and was more likely in children than adults despite the higher risk for venous thromboembolism in adults than children.

Identification of thrombin inhibiting antithrombin-III like protein from Punica granatum using in silico approach and in vitro validation of thrombin inhibition activity in crude protein

Thrombosis is characterized by the formation of clots in the blood vessels. Antithrombin-III deficiency in the blood causes thrombus formation. Supplementing antithrombin-III may serve as anticoagulant therapy. In the present studies, an antithrombin like Protein from Punica granatum has been identified and characterized using in silico approach. Based on sequence homology, an ALPP was selected depending upon its highest binding affinity of −41.28 kcal/mol with thrombin. Thrombin structure complexed with ALPP was docked with TAME using AutoDock Vina. No binding was observed for TAME at Ser195 of thrombin. MD simulation (50 ns) was performed to evaluate the flexibility and stability of docked complexes. In vitro assays with crude protein showed 78% thrombin inhibition at 5 µg and calculated IC50 value was 0.188 µg. The presence of thrombin inhibitors in crude protein was also confirmed by reverse zymography. Thus, it is very likely that the protein identified from P. granatum may act as thrombin inhibitor.

Abstract A089: Antithrombin III and fibrinogen activity as surrogate markers in predicting therapeutic asparaginase activity levels in children with acute lymphoblastic leukemia

Abstract Background. The incorporation of asparaginase has played an important role in improving survival rates in pediatric patients treated for acute lymphoblastic leukemia (ALL). Measuring asparaginase levels is one method to determine the efficacy of this chemotherapy. Determination of antithrombin III (ATIII) and/or fibrinogen (FIB) activity can be clinically useful as indirect asparaginase (ASP) level assessments since serum assays of ASP levels are not widely available, can be costly, and are performed at specialized labs. Previous studies have identified ATIII and FIB as potential markers in characterizing low or undetectable asparaginase activity in pediatric patients with ALL. The objective of this study was to determine whether FIB and ATIII levels can be used as surrogate markers in predicting therapeutic ASP activity in a predominantly Hispanic ALL population. Methods. FIB and ATIII levels were collected prior and 7 days post PEG-asparaginase (PEG) infusion. ASP levels were collected 7 days post-PEG. Mean differences in levels of FIB and ATIII activity were compared using t-tests for means and Mann-Whitney tests for medians. The Spearman correlation was used to evaluate the association between asparaginase activity, FIB, and ATIII levels. Unadjusted odds ratios were calculated to assess the predictive value of differences from baseline to Day 7 in ATIII and FIB levels associated with therapeutic levels (≥ 0.1 IU/mL). Results. Twenty patients were enrolled. The cohort was predominantly Hispanic (60%) and male (68%) with a median age of 8 years [range 2-19]. The median FIB level post-PEG was 155 mg/dL [nl 212-466] and the median ATIII activity level was 61% [nl 84-125] in those with therapeutic ASP levels. A median decrease in FIB and ATIII activity levels of 52% were seen with therapeutic ASP levels. By contrast in those with non-therapeutic levels, the difference was 7% and 28%, respectively. The bivariate correlation between ATIII and 7-day asparaginase levels was significant when controlling for BMI (Spearman’s ρ=0.62, p=0.001); the 7-day association between ASP and FIB was not influenced by BMI (Spearman’s ρ=-0.46, p=0.05). FIB and ATIII were correlated (Spearman’s ρ =.47;p=0.03). Both FIB (OR=0.004[0.0003-0.44]; p=0.02) and ATIII (OR=0.004[0.0002-1.0]; p=0.04) demonstrated reduced odds of higher therapeutic levels compared to lower therapeutic levels when mediated by Hispanic ethnicity. ATIII mean changes baseline to Day 7 were significantly smaller for Hispanic ethnicity [(Hispanic =-0.45(0.18) vs. Non-Hispanic =0.52(0.05); p=0.05)]. There were no significant differences in FIB by Hispanic ethnicity. Conclusions. Decreases in ATIII levels from baseline are associated with reduced odds of therapeutic asparaginase levels while decreased FIB levels may also indicate subtherapeutic levels. Hispanic ethnicity appears to mediate the observed effects from ATIII. ATIII and FIB levels may be important indirect markers in ASP activity monitoring when serum asparaginase assays are unavailable. Citation Format: Sonia Morales, Edith Williams, Kirsten Kasper, Keri Zabokrtsky, Lois Sayrs, Diane Nugent, Van Huynh. Antithrombin III and fibrinogen activity as surrogate markers in predicting therapeutic asparaginase activity levels in children with acute lymphoblastic leukemia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A089.

Efficacy of Serum Antithrombin III Test in Patients With Severe Traumatic Brain Injury.

Immune reactions following traumatic brain injury (TBI) cause many complications, including intravascular dissemination. Antithrombin III (AT-III) plays an important role in suppressing abnormal clot formation and ensuring hemostasis. Therefore, we investigated the efficacy of serum AT-III in patients with severe TBI. This retrospective study included 224 patients with severe TBI who visited a single regional trauma center between 2018 and 2020. AT-III levels were measured immediately after the TBI diagnosis. AT-III deficiency was defined as an AT-III serum level <70%. Patient characteristics, injury severity, and procedures were also investigated. Patient outcomes included Glasgow Outcome Scale scores at discharge and mortality. AT-III levels were significantly lower in the AT-III deficient group (n=89; 48.27% ± 1.91%) than in the AT-III sufficient group (n = 135, 78.90% ± 1.52%) (p < 0.001). Mortality occurred in 72 of the 224 patients (33.04%), indicating that there were significantly more patients in the AT-III-deficient group (45/89, 50.6%) than in the AT-III-sufficient group (27/135, 20%). Significant risk factors for mortality included the Glasgow Coma Scale score (P = 0.003), pupil dilatation (P = 0.031), disseminated intravascular coagulopathy (P = 0.012), serum AT-III level (P = 0.033), and procedures including barbiturate coma therapy (P = 0.010). Serum AT-III levels were significantly correlated with Glasgow Outcome Scale scores at discharge (correlation coefficient = 0.455, p < 0.001). Patients with AT-III deficiency after severe TBI may require more intensive care during treatment, because AT-III levels reflect injury severity and correlate with mortality.

Prognostic Value of Antithrombin Activity Levels in the Early Phase of Intensive Care: A 2-Center Retrospective Cohort Study

To investigate the relationship between antithrombin (AT) activity level and prognosis in patients requiring intensive care. Patients whose AT activity was measured within 24 h of intensive care unit (ICU) admission were enrolled for analysis. The primary endpoint was mortality at discharge. Prognostic accuracy was examined using receiver operating characteristic (ROC) curves and cox hazard regression analysis. Patients were divided into 6 groups based on predicted mortality, and a χ2 independence test was performed on the prognostic value of AT activity for each predicted mortality; P &lt; .05 was considered significant. A total of 281 cases were analyzed. AT activity was associated with mortality at discharge (AT% [interquartile range, IQR]): survivor group, 69 (56-86) versus nonsurvivor group, 56 (44-73), P = .0003). We found an increasing risk for mortality in both the lowest level of AT activity (&lt;50%; hazard ratio [HR] 2.43, 95% confidence interval [CI] 1.20-4.89, P = .01) and the middle-low level of AT activity (≥ 50% and &lt; 70%; HR 2.06, 95% CI 1.06-4.02, P = .03), compared with the normal AT activity level (≥ 70%). ROC curve analysis showed that the prediction accuracy of AT was an area under the curve (AUC) of 0.66 (cutoff 58%, sensitivity 61.4%, specificity 68.2%, P = .0003). AT activity was significantly prognostic in the group with 20% to 50% predicted mortality (AUC 0.74, sensitivity: 24.0%-55.5%, specificity: 83.3%-93.0%). An early decrease in AT activity level in ICU patients may be a predictor of mortality at discharge.

Antithrombin Therapy: Current State and Future Outlook.

Antithrombin (AT) is a natural anticoagulant pivotal in inactivating serine protease enzymes in the coagulation cascade, making it a potent inhibitor of blood clot formation. AT also possesses anti-inflammatory properties by influencing anticoagulation and directly interacting with endothelial cells. Hereditary AT deficiency is one of the most severe inherited thrombophilias, with up to 85% lifetime risk of venous thromboembolism. Acquired AT deficiency arises during heparin therapy or states of hypercoagulability like sepsis and premature infancy. Optimization of AT levels in individuals with AT deficiency is an important treatment consideration, particularly during high-risk situations such as surgery, trauma, pregnancy, and postpartum. Here, we integrate the existing evidence surrounding the approved uses of AT therapy, as well as potential additional patient populations where AT therapy has been considered by the medical community, including any available consensus statements and guidelines. We also describe current knowledge regarding cost-effectiveness of AT concentrate in different contexts. Future work should seek to identify specific patient populations for whom targeted AT therapy is likely to provide the strongest clinical benefit.

Coagulation Factors and Natural Anticoagulants as Surrogate Markers of Preeclampsia and Its Subtypes: A Case-Control Study in a Ghanaian Population.

Preeclampsia (PE) is associated with endothelial injury and hemostatic abnormalities. However, the diagnostic role of coagulation parameters and natural anticoagulants in predicting PE has not been explored in Ghana. This study assessed plasma levels of these factors as surrogate markers of PE and its subtypes. This case-control study included 90 women with PE (cases) and 90 normotensive pregnant women (controls). Blood samples were drawn for the estimation of complete blood count and coagulation tests. The prothrombin time (PT), activated partial thromboplastin time (APTT), and the calculation of the international normalized ratio (INR) were determined by an ACL elite coagulometer while the levels of protein C (PC), protein S (PS), antithrombin III (ATIII), and D-dimers were also measured using the solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) method. All statistical analyses were performed using the R Language for Statistical Computing. Results showed significantly (p < .05) shortened APTT (28.25 s) and higher D-dimer levels (1219.00 ng/mL) among PE women, as well as low levels of PC (1.02 µg/mL), PS (6.58 µg/mL), and ATIII (3.99 ng/mL). No significant difference was found in terms of PT and INR. From the receiver operating characteristic analysis, PC, PS, and ATIII could significantly predict PE and its subtypes at certain cutoffs with high accuracies (area under the curve [AUC] ≥0.70). Most women with PE are in a hypercoagulable state with lower natural anticoagulants. PC, PS, and ATIII are good predictive and diagnostic markers of PE and its subtypes (early-onset PE [EO-PE] and late-onset PE [LO-PE]) and should be explored in future studies.

Thrombin Generation Decrease After LMWH Administration in an Antithrombin-Deficient Pregnant Woman With a Homozygous HBS II Mutation.

The cases of antithrombin (AT)-deficient pregnant women with a homozygous HBS II mutation are relatively rare and are accompanied by an increased thrombophilic risk, which is manifested by increased thrombin generation (TG). It is very difficult to ensure their prophylactic treatment during pregnancy. We aimed to determine the utility of the thrombin generation assay (TGA) and anti-factor Xa (anti-FXa) test to monitor the effects of a prophylactic dose of low-molecular-weight heparin (LMWH) in a 28-year-old woman with homozygous AT deficiency caused by mutation c.391C > T#, (p.Leu131Phe†) in the SERPINC1 gene and to compare the findings with those from a group of pregnant and non-pregnant women also treated with LMWH. TG monitoring was chosen due to severe AT deficiency that was manifested by low levels of anti-FXa activity when monitoring the efficacy of LMWH treatment. A significant decrease in TG was detected in all monitored groups (P < .05). There were no thrombotic complications during the whole pregnancy of the woman with AT deficiency. Consistent monitoring of TG with LMWH anticoagulant therapy administration during pregnancy together with AT administration before and after delivery may improve the overall condition of pregnant women and the quality of their care.

Antithrombin Deficiency: Frequency in Patients with Thrombosis and Thrombophilic Families

Purpose: Antithrombin (AT) deficiency is a well-known inherited risk factor for venous thromboembolism (VTE). However, F V Leiden and F II20210a mutations have drawn much more attention in the recent years. Therefore, we have decided to analyze the frequency of antithrombin deficiency in different cohorts of patients and tried to formulate indications for its testing. Results: Antithrombin deficiency was found in 4% of patients with recurrent VTE ≤ 50 years of age with, in 1% of patients with splanchnic vein thrombosis and in 2% of cases associated with combined oral contraceptives (COC) use or pregnancy. In patients with central venous thrombosis, antithrombin deficiency was not found. Recommendation: We consider antithrombin testing useful in patients with thrombosis occuring up to 45 years of age without any risk factors. Namely, females with VTE in pregnancy and puerperium should be tested as well as females with thrombosis on COC, if VTE occurred within the first year of their use. Conclusion: In spite of degressive interest in thrombophilia work up, we still consider antithrombin testing useful in defined clinical situations.

Predictive Value of D-Dimer and Antithrombin III (ATIII) In the Development of Moderate to Severe Acute Pancreatitis. A Prospective Observational Study

Predictive Value of D-Dimer and Antithrombin III (ATIII) In the Development of Moderate to Severe Acute Pancreatitis. A Prospective Observational Study

Cystathionine-β-synthase and SERPINC1 genes mutation-induced ischemic stroke and multisystem diseases in a young woman: a case report and relevant literature review

Xuanfei Jiang, Dan Shen, Xiangyan Yang, Zhenchan Lu, Huan Huang, Bing Zhang, Honggang Ma

Evaluation of Plasma Level of Anticoagulant Proteins (Protein C, S and Anti thrombin III) in Patients with Acute Lymphoblastic Leukemia

Evaluation of Plasma Level of Anticoagulant Proteins (Protein C, S and Anti thrombin III) in Patients with Acute Lymphoblastic Leukemia

Favourable outcome of multisystem venous thrombosis associated with novel SERPINC1 mutation after treated with dabigatran: a case report with 7-year follow-up

BackgroundMutations in SERPINC1lead to deficiency in antithrombin (AT) which is an endogenous anticoagulant ofnormal hemostasis and could result in venousthromboembolism (VTE). Case presentationA 61-year-old male patientwith recurrent thrombosis returned to the hospital with multiple cerebralthrombosis after voluntary cessationof dabigatran therapy. Laboratory tests revealed a type I AT deficiency in thispatient and further whole exome sequencing (WES) identified a novelheterozygous frameshift duplication (c.233_236dup, p.Val80Alafs*26) in SERPINC1gene. Long-term dabigatran treatment was given and no recurrence or sideeffects were found within the followed 5 years.ConclusionA multisystem VTE patient witha novel SERPINC1 mutation (c.233_236dup, p.Val80Alafs*26) reached a favourableoutcome after dabigatran treatment.