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Clinical Journal of Gastroenterology Jun 2024Nonocclusive mesenteric ischemia (NOMI) is a life-threatening disorder. Early diagnosis is challenging because NOMI lacks specific symptoms. A 52-year-old man who...
Nonocclusive mesenteric ischemia (NOMI) is a life-threatening disorder. Early diagnosis is challenging because NOMI lacks specific symptoms. A 52-year-old man who received extended cholecystectomy with Roux-en-Y hepaticojejunostomy for gallbladder cancer (GBC) presented to our hospital with nausea and vomiting. Neither tender nor peritoneal irritation sign was present on abdominal examination. Blood test exhibited marked leukocytosis (WBC:19,800/mm3). A contrast-enhanced abdominal computed tomography (CT) scan revealed remarkable wall thickening and lower contrast enhancement effect localized to Roux limb. On hospital day 2, abdominal arterial angiography revealed angio-spasm at marginal artery and arterial recta between 2nd jejunal artery and 3rd jejunal artery, leading us to the diagnosis of NOMI. We then administered continuous catheter-directed infusion of papaverine hydrochloride until hospital day 7. Furthermore, the patient was anticoagulated with intravenous unfractionated heparin and antithrombin agents for increasing D-dimer level and decreasing antithrombin III level. On hospital day 8, diluted oral nutrition diet was initiated and gradually advanced as tolerated. On hospital day 21, the patient was confirmed of improved laboratory test data and discharged with eating a regular diet. We experienced a rare case of NOMI on Roux limb after 2 years of extended cholecystectomy with hepaticojejunostomy for GBC, promptly diagnosed and successfully treated by interventional radiology (IVR).
Topics: Humans; Male; Middle Aged; Anastomosis, Roux-en-Y; Mesenteric Ischemia; Gallbladder Neoplasms; Cholecystectomy; Tomography, X-Ray Computed; Postoperative Complications; Radiology, Interventional; Jejunostomy
PubMed: 38528196
DOI: 10.1007/s12328-024-01954-7 -
Perfusion Mar 2024Over the past decade, there has been an increase in the use of recombinant Anti-Thrombin III (AT-III) administration during neonatal and pediatric short- and long-term...
INTRODUCTION
Over the past decade, there has been an increase in the use of recombinant Anti-Thrombin III (AT-III) administration during neonatal and pediatric short- and long-term mechanical support for the replacement of acquired deficiencies. Recombinant AT-III (Thrombate) administration is an FDA licensed drug indicated primarily for patients with hereditary deficiency to treat and prevent thromboembolism and secondarily to prevent peri-operative and peri-partum thromboembolism. Herein we propose further use of Thrombate for primary AT-III deficiency of the newborn as well as for acquired dilution and consumption secondary to cardiopulmonary bypass (CPB).
METHODOLOGY
All patients undergoing CPB obtain a preoperative AT-III level. Patients with identified deficiencies are normalized in the OR using recombinant AT-III as a patient load, in the CPB prime, or both. Patient baseline Heparin Dose Response (HDR) is assessed using the Heparin Management System (HMS) before being exposed to AT-III. If a patient load of AT-III is given, a second HDR is obtained and this AT-III Corrected HDR is used as the primary goal during CPB. Once CPB is initiated, an AT-III level is obtained with the first patient blood analysis. A subtherapeutic level results in an additional dose of AT-III. During the rewarm period, a final AT-III level is obtained and AT-III treated once again if subtherapeutic. A retrospective, matched analysis review of practice analyzing two groups, a Study Group (Repeat HDR, May 2022 onward) and Matched Group (Without Repeat HDR, July 2019 to April 2022), for age (D), weight (Kg) and operation was conducted. The focus of the study was to determine any change in heparin sensitivity identified post AT-III patient bolus load in the HDR (U/mL), Slope (U/mL/s), ACT (s), and total amount of heparin on CPB (U) and protamine (mg) used in each group.
RESULTS
No significance was seen in Baseline AT-III (%), post heparin load HDR (U/mL), first CPB ACT (s), first CPB HDR (U/mL), or total CPB heparin (u/Kg) between the two groups. Statistical significance was seen in Baseline ACT (s), Baseline HDR (U/mL), Baseline Slope (U/mL/s), Post Heparin Load ACT (s), first CPB AT-III (%), and Protamine (mg/Kg) ( < .05). No statistical significance was seen in the Study Intragroup between pre versus post AT-III patient load baseline sample in ACT (s), however significance was seen in HDR (U/mL) and Slope (U/mL/s) ( < .05).
CONCLUSION
Implementation of AT-III monitoring and therapy before and during CPB in conjunction with the HMS allows patients to maintain a steady state of anticoagulation with overall less need for excessive heparin replacement and potentially thrombin activation. The result is obtaining a steady state of anticoagulation, a reduced fluctuation in the heparin and ACT levels and a potential for lower co-morbidities associated with prolonged CPB times.
PubMed: 38503431
DOI: 10.1177/02676591241239819 -
Cureus Feb 2024Deep vein thrombosis (DVT) is caused by a clot (thrombus) formed in the deep veins, usually the legs. The incidence of DVT is notably less prevalent in children than in...
Deep vein thrombosis (DVT) is caused by a clot (thrombus) formed in the deep veins, usually the legs. The incidence of DVT is notably less prevalent in children than in adults. Here, we present a rare case of DVT in an eight-year-old female child with a significant family history involving the untimely death of the maternal aunt. The child presented with pain and edema in the left lower limb causing immobilization without any obvious cause. The clinical features suggested the possibility of DVT. On further evaluation and radiological investigations, the diagnosis of DVT was confirmed. A complete thrombophilia workup was done showing antithrombin (AT) III deficiency. The patient was then started on low-molecular-weight heparin, leading to improvement in the symptoms. Oral rivaroxaban was continued for the patient on discharge.
PubMed: 38496153
DOI: 10.7759/cureus.54157 -
Clinical and Applied... 2024Direct oral factor Xa inhibitors are replacing vitamin K-dependent antagonists as anticoagulation treatment in many clinical scenarios. Trauma centers are noting an...
Direct oral factor Xa inhibitors are replacing vitamin K-dependent antagonists as anticoagulation treatment in many clinical scenarios. Trauma centers are noting an increase in patients presenting on these medications. The 2018 Food and Drug Administration approval of andexanet alfa provides an alternative anticoagulation reversal. Barriers may limit utilization of new medications including a lack of grade 1A evidence supporting the use of prothrombin complex concentrate (PCC) versus andexanet alfa and cost. To evaluate barriers of andexanet alfa utilization by trauma surgeons, a 15-question survey was conducted. There was a 9% completion rate (n = 89). The results revealed 23.5% would choose andexanet alfa as first-line treatment in children, and 25.8% as first-line treatment in adults. The majority of respondents, 64.7% and 67.4%, would use PCC preferentially in children and adults, respectively. Respondents indicated that cost burden was an overriding factor (76.3%); 42.4% cited lack of high-level efficacy data of andexanet alfa for reversal of factor Xa inhibitors. Additional double-blinded multi-institutional randomized controlled trials comparing 4F-PCC and andexanet alfa for factor Xa inhibitor reversal are needed to support efficacy especially with the increased cost associated.
Topics: Adult; Child; Humans; Factor Xa Inhibitors; Factor Xa; Anticoagulants; Antithrombin III; Fibrinolytic Agents; Factor IX; Recombinant Proteins
PubMed: 38494906
DOI: 10.1177/10760296241238013 -
The Journal of Clinical Endocrinology... Mar 2024Breastfeeding is associated with a reduced maternal risk for cardiovascular diseases. Since the underlying mechanisms are still poorly understood, we here examined the...
OBJECTIVE
Breastfeeding is associated with a reduced maternal risk for cardiovascular diseases. Since the underlying mechanisms are still poorly understood, we here examined the impact of breastfeeding on the plasmatic coagulation system in women with and without history of gestational diabetes mellitus (GDM).
METHODS
76 participants of the German Gestational Diabetes Study (PREG; NCT04270578) were examined 14 [interquartile range: 12-26] months after delivery with a 5-point oral glucose tolerance test. Global coagulation tests, prothrombotic coagulation proteins (FII/FVII/FVIII/FIX), antithrombotic proteins (antithrombin, protein C/S) and endothelial markers (von-Willebrand-factor and PAI-1) were determined. The Framingham Risk Score was used to estimate the 10-year cardiovascular risk. The impact of breastfeeding duration on coagulation was analyzed using multivariable linear models.
RESULTS
The mean duration of breastfeeding was 11 [7-14] months. Overall, longer duration of breastfeeding was associated with lower cardiovascular risk (Framingham Risk Score, p=0.05) and was negatively associated with FIX (p=0.018). We detected an interaction between previous GDM and breastfeeding duration for FIX (pInteraction=0.017): only in women with GDM history was the duration of breastfeeding negatively associated with FIX activity (p=0.016). This association persisted in statistical models adjusted for age, body-mass index, insulin sensitivity, and C-reactive protein. The duration of breastfeeding was not associated with anticoagulant proteins and endothelial markers.
CONCLUSION
Longer duration of breastfeeding is associated with lower cardiovascular risk and an improved coagulation profile. Women with GDM history appear to benefit particularly from prolonged breastfeeding.
PubMed: 38487818
DOI: 10.1210/clinem/dgae172 -
International Journal of Molecular... Mar 2024Antithrombin (AT) is the major plasma inhibitor of thrombin (FIIa) and activated factor X (FXa), and antithrombin deficiency (ATD) is one of the most severe...
Antithrombin (AT) is the major plasma inhibitor of thrombin (FIIa) and activated factor X (FXa), and antithrombin deficiency (ATD) is one of the most severe thrombophilic disorders. In this study, we identified nine novel AT mutations and investigated their genotype-phenotype correlations. Clinical and laboratory data from patients were collected, and the nine mutant AT proteins (p.Arg14Lys, p.Cys32Tyr, p.Arg78Gly, p.Met121Arg, p.Leu245Pro, p.Leu270Argfs*14, p.Asn450Ile, p.Gly456delins_Ala_Thr and p.Pro461Thr) were expressed in HEK293 cells; then, Western blotting, N-Glycosidase F digestion, and ELISA were used to detect wild-type and mutant AT. RT-qPCR was performed to determine the expression of AT mRNA from the transfected cells. Functional studies (AT activity in the presence and in the absence of heparin and heparin-binding studies with the surface plasmon resonance method) were carried out. Mutations were also investigated by in silico methods. Type I ATD caused by altered protein synthesis (p.Cys32Tyr, p.Leu270Argfs*14, p.Asn450Ile) or secretion disorder (p.Met121Arg, p.Leu245Pro, p.Gly456delins_Ala_Thr) was proved in six mutants, while type II heparin-binding-site ATD (p.Arg78Gly) and pleiotropic-effect ATD (p.Pro461Thr) were suggested in two mutants. Finally, the pathogenic role of p.Arg14Lys was equivocal. We provided evidence to understand the pathogenic nature of novel mutations through in vitro expression studies.
Topics: Humans; Antithrombins; HEK293 Cells; Anticoagulants; Heparin; Mutation; Antithrombin III Deficiency
PubMed: 38474138
DOI: 10.3390/ijms25052893 -
Annals of Medicine and Surgery (2012) Mar 2024The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the...
Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?
BACKGROUND AND AIMS
The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates.
MATERIALS AND METHODS
Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality.
RESULTS
Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups.
CONCLUSIONS
Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.
PubMed: 38463105
DOI: 10.1097/MS9.0000000000001772 -
Medicine Mar 2024Thrombophilia is a coagulation disorder closely associated with venous thromboembolism. Hereditary antithrombin III (AT III) deficiency is a type of genetic...
BACKGROUND
Thrombophilia is a coagulation disorder closely associated with venous thromboembolism. Hereditary antithrombin III (AT III) deficiency is a type of genetic thrombophilia. In China, genetic thrombophilia patients mainly suffer from deficiencies in AT III, protein S, and protein C. Multiple mutations in the serpin family C member 1 (SERPINC1) can affect AT III activity, resulting in thrombosis.
CASE PRESENTATION
This case presented a 17-year-old adolescent female who developed lower extremity venous thrombosis and subsequently pulmonary embolism (PE) following a right leg injury. A missense mutation in gene SERPINC1 of c.331 T > C, p.S111P was detected on the patient, resulting in a decreased AT III activity and an elevated risk of thrombosis. The patient received anticoagulation treatment for approximately 5 months. During follow-up, the blood clot gradually dissolved, and there have been no recurrent thrombotic events reported thus far.
DISCUSSION
Hereditary AT deficiency can be classified into two types based on the plasma levels of the enzymatic activity and antigen. Type I is a quantitative defect, while Type II is a qualitive defect. Until 2021, 486 SERPINC1 gene mutations have been registered, more than 18% of which are point mutations. The SERPINC1 mutation c.331 T > C in was firstly reported in 2017, which was classified into type I AT III deficiency.
CONCLUSION
Hereditary thrombophilia is a coagulation disorder with a high omission diagnostic rate. Minor mutations in the SERPINC1 gene can also lead to hereditary AT III deficiency, which in turn can cause PE. We emphasized the importance of etiological screening for hereditary thrombophilia in venous thromboembolism patients without obvious high-risk factors. Long-term anticoagulation treatment and avoidance of potential thrombosis risk factors are critical for such patients.
Topics: Adolescent; Humans; Female; Antithrombin III Deficiency; Venous Thromboembolism; Thrombosis; Pulmonary Embolism; Thrombophilia; Anticoagulants
PubMed: 38457560
DOI: 10.1097/MD.0000000000037429 -
Journal of Thrombosis and Haemostasis :... Jul 2024Coagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic...
BACKGROUND
Coagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic complications, and diffuse intravascular coagulation. Microbiome dysbiosis influences the clinical course of COVID-19. However, the role of dysbiosis in COVID-19-associated coagulopathy is not fully understood.
OBJECTIVES
The present study tested the hypothesis that the microbiota-derived proapoptotic corisin is involved in the coagulation system activation during SARS-CoV-2 infection.
METHODS
This cross-sectional study included 47 consecutive patients who consulted for symptoms of COVID-19. A mouse acute lung injury model was used to recapitulate the clinical findings. A549 alveolar epithelial, THP-1, and human umbilical vein endothelial cells were used to evaluate procoagulant and anticoagulant activity of corisin.
RESULTS
COVID-19 patients showed significantly high circulating levels of corisin, thrombin-antithrombin complex, D-dimer, tumor necrosis factor-α, and monocyte-chemoattractant protein-1 with reduced levels of free protein S compared with healthy subjects. The levels of thrombin-antithrombin complex, D-dimer, and corisin were significantly correlated. A monoclonal anticorisin-neutralizing antibody significantly inhibited the inflammatory response and coagulation system activation in a SARS-CoV-2 spike protein-associated acute lung injury mouse model, and the levels of corisin and thrombin-antithrombin complex were significantly correlated. In an in vitro experiment, corisin increased the tissue factor activity and decreased the anticoagulant activity of thrombomodulin in epithelial, endothelial, and monocytic cells.
CONCLUSION
The microbiota-derived corisin is significantly increased and correlated with activation of the coagulation system during SARS-CoV-2 infection, and corisin may directly increase the procoagulant activity in epithelial, endothelial, and monocytic cells.
Topics: Humans; COVID-19; Animals; Male; Female; Middle Aged; Blood Coagulation; Cross-Sectional Studies; SARS-CoV-2; Mice; Human Umbilical Vein Endothelial Cells; A549 Cells; Acute Lung Injury; THP-1 Cells; Aged; Disease Models, Animal; Microbiota; Dysbiosis; Adult; Antithrombin III; Mice, Inbred C57BL; Peptide Hydrolases
PubMed: 38453025
DOI: 10.1016/j.jtha.2024.02.014 -
Blood May 2024Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B),...
Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary end point was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary end points included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor, n = 19; noninhibitor, n = 46) were eligible for ABR analyses. Observed median ABRs were 6.5 (interquartile range [IQR], 2.2-19.6)/4.4 (IQR, 2.2-8.7) with BPA/CFC prophylaxis vs 0.0 (IQR, 0.0-0.0)/0.0 (IQR, 0.0-2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = .0021) and 46.4% (P = .0598) vs BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced 0 treated bleeds with fitusiran vs 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events vs BPA/CFC prophylaxis in PwHA/B, with or without inhibitors, and reported adverse events were generally consistent with previously identified risks of fitusiran. This trial was registered at www.ClinicalTrials.gov as #NCT03549871.
Topics: Humans; Male; Hemophilia B; Adult; Hemophilia A; Middle Aged; Adolescent; Young Adult; Hemorrhage; Child; RNA, Small Interfering; Blood Coagulation Factors; Aged
PubMed: 38452197
DOI: 10.1182/blood.2023021864