Mesenteric Artery Thrombosis Research Articles

A Rare Case of Superior Mesenteric Artery Thrombosis With Gangrenous Bowel in a Patient With Mitral Valve Replacement in a Hypocoagulable State

A Rare Case of Superior Mesenteric Artery Thrombosis With Gangrenous Bowel in a Patient With Mitral Valve Replacement in a Hypocoagulable State

Clinical case of effective treatment of invasive mycosis caused by polyresistant strain of Candida auris

The objective was to demonstrate a clinical case of effective treatment of a patient with invasive mycosis caused by Candida auris with drug resistance to antifungal drugs by a combination of micafungin and amphotericin B lipid complex.Materials and methods. International databases such as MEDLINE, EMBASE, Web of Science and Scopus until 2023 were used for the analysis.Results. We have demonstrated the effective case of treatment of invasive candidiasis caused by the polyresistent pathogen Candida auris with the combination of micafungin and amphotericin B in the patient who underwent mitral valve replacement, which was complicated by acute aortic dissection, acute thrombosis of the superior mesenteric artery, septic shock and a number of other nosocomial infections.Conclusion. Due to the high resistance of Candida auris to all antifungal drugs currently existing in the world, the combination of several antifungal drugs is an advantage over monotherapy. However, given the lack of approved standards and guidelines for the treatment of patients with this infection, and insufficient clinical experience in the management of such patients, further search for effective treatment regimens for infections caused by Candida auris and the development of new antifungal agents that can overcome the resistance of this pathogen are necessary.

COVID‐19 with multi‐organ arterial and venous thrombosis. A case report

AbstractThis case illustrates a late complication of viral pneumonia, likely due to COVID‐19, characterized by simultaneous acute arterial and venous thrombosis in multiple organs. The patient experienced myocardial infarction with left ventricular thrombus, pulmonary embolism, acute limb ischemia, superior mesenteric artery thrombosis, renal artery thrombosis, and deep vein thrombosis, posing significant challenges in both management and determining the etiology.

A rare cause of abdominal pain in pregnancy - mesenteric artery thrombosis and miscarriage in a 34-year-old patient

BackgroundMesenteric arterial thrombosis is an extremely rare thrombotic event, especially during pregnancy, that can cause rapid fatal consequences unless the patient receives early definitive treatment.Case presentationWe report the case of a 34-year-old female presenting in her seventh week of gestation with severe abdominal pain who was promptly diagnosed with mesenteric artery occlusion amidst incipient miscarriage. The patient underwent a successful mesentery artery embolectomy, recovered and was later diagnosed with elevated factor VIII activity.ConclusionThe diagnosis of mesenteric ischemia should be considered in pregnant women presenting with severe abdominal pain and any prior predisposing factors. Our case highlights the pivotal role of the emergency physician in maintaining a high index of suspicion coupled with timely and determined action. The prognosis of this high mortality condition depends on prompt diagnosis, early definite management and successful multidisciplinary cooperation.

Angiopoietin-like protein 2 inhibits thrombus formation.

Acute myocardial infarction is mainly caused by a lack of blood flood in the coronary artery. Angiopoietin-like protein 2 (ANGPTL2) induces platelet activation and thrombus formation in vitro through binding with immunoglobulin-like receptor B, an immunoglobulin superfamily receptor. However, the mechanism by which it regulates platelet function in vivo remains unclear. In this study, we investigated the role of ANGPTL2 during thrombosis in relationship with ST-segment elevation myocardial infarction (STEMI) with spontaneous recanalization (SR). In a cohort of 276 male and female patients, we measured plasma ANGPTL2 protein levels. Using male Angptl2-knockout and wild-type mice, we examined the inhibitory effect of Angptl2 on thrombosis and platelet activation both in vivo and ex vivo. We found that plasma and platelet ANGPTL2 levels were elevated in patients with STEMI with SR compared to those in non-SR (NSR) patients, and was an independent predictor of SR. Angptl2 deficiency accelerated mesenteric artery thrombosis induced by FeCl3 in Angptl2-/- compared to WT animals, promoted platelet granule secretion and aggregation induced by thrombin and collogen while purified ANGPTL2 protein supplementation reversed collagen-induced platelet aggregation. Angptl2 deficiency also increased platelet spreading on immobilized fibrinogen and clot contraction. In collagen-stimulated Angptl2-/- platelets, Src homology region 2 domain-containing phosphatase (Shp)1-Y564 and Shp2-Y580 phosphorylation were attenuated while Src, Syk, and Phospholipase Cγ2 (PLCγ2) phosphorylation increased. Our results demonstrate that ANGPTL2 negatively regulated thrombus formation by activating ITIM which can suppress ITAM signaling pathway. This new knowledge provides a new perspective for designing future antiplatelet aggregation therapies.

A Rare Case of Peritonitis in a Patient on CAPD for Nine Years

We report a case of peritonitis due to multi-drug-resistant Escherichia coli in a patient with diabetic kidney disease on continuous ambulatory peritoneal dialysis for nine years. As the peritonitis did not resolve with conventional medical therapy, a contrast-enhanced CT was done, which showed superior mesenteric artery thrombosis with bowel ischemia. The peritoneal dialysis catheter was removed, and appropriate antibiotics were continued as per International Society for Peritoneal Dialysis guidelines. A year later, the patient while on maintenance hemodialysis presented with obstructive jaundice due to a growth in the ampulla of vater.

Peritoneal dialysis-associated peritonitis, caused by superior mesenteric artery thrombosis with intestinal necrosis: a case report.

Peritoneal dialysis (PD)-associated peritonitis is a common complication of PD. Enteric peritonitis is defined as peritonitis arising from an intestinal or intra-abdominal organ source. The delay in the diagnosis or treatment of enteric peritonitis has been reported to increase mortality. Therefore, the early consideration of enteric peritonitis, particularly in cases of culture-negative peritonitis, is imperative. A 67-year-old Japanese man who had been undergoing PD for 3years, was admitted to our hospital with a diagnosis of PD-associated peritonitis. A month previously, he experienced a bleeding gastric ulcer, which led to severe anemia (hemoglobin 6.3mg/dL), followed by thrombocytosis. On admission, peritoneal fluid analysis showed a high white blood cell count (WBC: 8,570 /µL), with neutrophils predominating (74.5%). Cultures of both his dialysis effluent and blood were negative. After admission, the WBC count of the dialysis effluent gradually decreased alongside antibiotic therapy, but the patient's abdominal pain did not improve. After 4days, enhanced computed tomography showed superior mesenteric artery (SMA) thrombosis and intestinal necrosis. Therefore, emergency intestinal resection and PD catheter removal were performed, and then antithrombosis therapy was initiated. Because the patient's abdominal pain was improved and platelet count and D-dimer concentration were reduced by these treatments, he was discharged from the hospital after 47days. Thus, we report a rare case of culture-negative PD-associated peritonitis, which was caused by SMA thrombosis and intestinal necrosis. It is likely that combination of severe calcification of SMA and prolonged thrombocytosis secondary to the severe anemia contributed to the thrombosis.

Acute mesenteric ischemia in covid-19 disease: A case report

This case report explores acute mesenteric ischemia (AMI) in COVID-19 patients, showcasing this as a significant vascular complication from the infection. We discuss two instances of COVID-19-associated AMI, validated through comprehensive imaging and lab tests. The first case is a 54-year-old male with pre-existing hypertension and diabetes who presented with severe abdominal pain and symptoms consistent with COVID-19. The second involves a 65-year-old female with a history of heart disease, similarly, displaying acute abdominal symptoms. Surgical exploration in both cases confirmed mesenteric arterial thrombosis, indicative of a hypercoagulable state induced by COVID-19. These findings emphasize the need for healthcare providers to consider gastrointestinal symptoms as potential indicators of severe COVID-19 complications. Early recognition and appropriate diagnostic imaging are crucial in managing these cases effectively, potentially reducing mortality. The paper highlights the broader systemic effects of COVID-19, stressing the importance of vigilance and rapid response to manage not only the primary respiratory symptoms but also the less common but equally critical vascular complications like AMI. This study contributes to a growing body of evidence that COVID-19 can cause severe systemic complications, necessitating a comprehensive approach to treatment and management.

Percutaneous Mechanical Thrombectomy Using the AcoStream Thrombus Aspiration System for Acute Superior Mesenteric Artery Embolism

BackgroundThis study was performed to summarize our experience in treating acute superior mesenteric artery embolism (SMAE) by percutaneous mechanical thrombectomy (PMT). MethodsBetween January 2023 and October 2023, 18 patients presenting with acute mesenteric ischemia (AMI) were admitted to our center, including 11 cases of superior mesenteric artery embolism (SAME), 3 cases of superior mesenteric artery thrombosis (SMAT) and 4 cases of superior mesenteric vein thrombosis (SMVT). We retrospectively reviewed 8 patients (4 males and 4 females; range, 51–79 years; mean, 62.50 ± 9.67 years) who underwent treatment of acute SMAE using the AcoStream system. The patients had no obvious evidence of intestinal necrosis as shown by peritoneal puncture or computed tomography (CT). Thrombectomy was performed on the superior mesenteric artery (SMA) using an 8F AcoStream thrombus aspiration system (Acotec, China). The demographics, risk factors, therapeutic effect, complications, mortality, and follow-up of the study population were assessed. ResultsThe technical success rate was 100%. After 1-3 passes (2.38 ± 0.92) and aspiration thrombectomy, complete thrombus removal was achieved in 7 (87.50%) patients. 1 patient received an adjunctive catheter-directed thrombolysis (CDT) due to partial thrombus removal. Thrombolysis was conducted for 2 days, resulting in complete resolution of the thrombus. The other 7 patients did not receive adjunctive endovascular intervention due to complete thrombus removal and no residual stenosis. No distal embolization or device-related complications were noted during the procedure. After the procedure, sufficient clinical improvement was seen in 6 patients within 1-2 days. 2 patients showed no significant improvement of their symptoms. Laparotomy was performed on day 1 and day 2 after thrombectomy in patients 3 and 7, respectively. Intestinal necrosis was diagnosed operatively and intestinal resection was performed. All patients were discharged 6–15 days (9.50 ± 3.07) after admission without perioperative complication or death. The mean follow-up period was 5.00 ± 3.30 months (range, 1-10 months), and the follow-up rate was 100%. During the follow-up, all patients remained symptom-free. CTA images showed good flow in the trunk and branches of the SMA in all patients. ConclusionsPMT using the AcoStream system is a minimally invasive, safe, and effective technique for acute SMAE. Early application of PMT can achieve immediate revascularization of the SMA and have the potential advantage of avoiding laparotomy or reducing the extension of enterectomy, as it could theoretically restore intestinal perfusion in less time than open revascularization. If the symptoms do not improve after PMT, exploratory laparotomy should be scheduled as soon as possible. Further studies are necessary on this field to confirm these findings.

Acute superior mesenteric artery thrombosis in a 34-year-old male with thrombophilia: a case report

Introduction: Thrombophilic state, marked by extensive formation of blood clots within the vascular system poses a formidable peril, leading to loss of circulatory integrity and systemic well-being. Superior mesenteric artery (SMA) thrombosis is a serious medical disorder characterized by the obstruction of the arterial blood flow to the gastrointestinal tract, which is associated with significant morbidity and mortality. The condition has a plethora of etiological causes. Vague abdominal pain is a common clinical manifestation, and there is a very high mortality rate.Case Presentation: A 34-year-old Pakistani male presented with rapidly worsening acute abdominal pain over a 10-hour period. Clinical examination revealed elevated blood pressure, while other vital signs remained within normal limits. Abdominal examination findings were inconclusive compared to the patient's severe abdominal pain complaint. Contrast-enhanced CT scan indicated a large thrombus in the superior mesenteric artery with radiological features suggestive of intestinal ischemia, extending from the duodeno-jejunal flexure to the mid-transverse colon. Subsequently, the patient underwent exploratory laparotomy with extensive bowel resection and received anticoagulant therapy. He subsequently experienced compensated right lower limb ischemia, treated conservatively with high-dose anticoagulant therapy. Within days, bowel anastomotic leak developed, requiring multiple surgeries. Eventually, the patient progressed to septic shock, followed by multiorgan failure, culminating in a fatal cardiac arrest.Conclusion: Acute mesenteric ischemia, a rare abdominal emergency with an incidence of 6 per 100,000, is associated with a substantial mortality rate, ranging from 58% to 93% among diagnosed cases. The challenges posed by SMA thrombosis include diagnostic complexities, as it frequently manifests with symptoms disproportionate to clinical signs, and results in catastrophic complications, necessitating high suspicion index and prompt intervention.

Superior Mesenteric Artery Thrombosis and Intestinal Ischemia in Chronic Kidney Disease

We describe the case of an elderly female with a complex medical history, including hypertension, chronic kidney disease, hypothyroidism, and multiple cardiovascular and pulmonary conditions, who presented to the emergency department with abdominal pain. Due to the patient’s chronic kidney disease, two non-contrast CT scans initially ordered showed unremarkable results. The decision to order a third CT scan with contrast finally demonstrated a thrombus in the superior mesenteric artery with potential bowel ischemia. The patient’s condition deteriorated rapidly during the discovery of mesenteric artery thrombosis and extensive gangrenous bowel during surgery. Due to the irreversibility of the bowel ischemia, the patient was placed on comfort measures and passed away.

Retraction: Superior Mesenteric Artery Thrombosis Following Severe COVID-19 Pneumonia.

[This retracts the article DOI: 10.7759/cureus.19954.].

Factors that may affect the outcome of acute occlusive mesenteric ischemia. A single-center study

BackgroundAcute mesenteric ischemia is a rare but lethal disease. Acute occlusive mesenteric ischemia consists of mesenteric artery embolism, mesenteric artery thrombosis, and mesenteric vein thrombosis. This study aimed to investigate the factors that may affect the outcome of acute occlusive mesenteric ischemia.MethodsData from acute occlusive mesenteric ischemia patients admitted between May 2016 and May 2022 were reviewed retrospectively. Patients were divided into 2 groups according to whether complications(Clavien‒Dindo ≥ 2) occurred within 6 months of the first admission. Demographics, symptoms, signs, laboratory results, computed tomography angiography features, management and outcomes were analyzed.Results59 patients were enrolled in this study. Complications(Clavien‒Dindo ≥ 2) occurred within 6 months of the first admission in 17 patients. Transmural intestinal necrosis, peritonitis, white blood cell count, percentage of neutrophils, percentage of lymphocytes, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, creatine kinase isoenzyme, cardiac troponin I, laparoscopic exploration rate, open embolectomy rate, enterostomy rate, length of necrotic small bowel, length of healthy small bowel, surgical time and intraoperative blood loss differed significantly between groups. Creatine kinase isoenzyme (OR = 1.415, 95% CI: 1.060–1.888) and surgical time (OR = 1.014, 95% CI: 1.001–1.026) were independent risk factors associated with complications(Clavien‒Dindo ≥ 2).ConclusionsOur analysis suggests that acute occlusive mesenteric ischemia patients with a creatine kinase isoenzyme level greater than 2.22 ng/mL or a surgical time longer than 156 min are more likely to experience complications’(Clavien‒Dindo ≥ 2) occurrence within 6 months of the first admission.

Thrombosis of acute superior mesenteric artery in a patient with breast cancer receiving toremifene therapy: a case report and literature review

It is widely recognized that cancer itself is related to increased risk of thromembolism. Venous thromboembolism is relatively common in breast cancer patients, but arterial thrombosis, especially acute superior mesenteric artery thrombosis (SMAT) associated with chemotherapy or endocrinotherapy, rarely occurs in breast cancer patients. There were few reports about acute SMAT in cancer patients who underwent chemotherapy, but no reports of acute SMAT caused by endocrine-therapy. We reported a 54-year-old patient with acute SMAT during toremifene treatment after breast cancer surgery. She underwent 4 cycles chemotherapy of TC regimen, then accepted toremifen endocrinotherapy because of positive estrogen receptor. She suffered from acute SMAT after 2 months toremifen treatment. Therefore, we consider that this case of acute SMAT may be a rare adverse event of toremifen. In view of the high risk and rarity of acute SMAT caused by toremifene, we suggest that except for venous thrombosis, arterial thrombosis in special position (ATSP) should be kept in mind during use of toremifene. Once a thrombotic event occurs, toremifene should be stopped immediately.

Aortic endarterectomy in patients with severe multivessel paravisceral and aortoiliac occlusive disease

ObjectiveAortic endarterectomy (AE), once a treatment of choice for aortoiliac occlusive disease, is now rarely performed in favor of endovascular procedures or open aortobifemoral bypass. However, in select patients with paravisceral or aortoiliac occlusive disease, AE remains a viable alternative for revascularization, either as a primary procedure or after prior interventions have failed. Here, we evaluated outcomes for an extended series of patients undergoing paravisceral or aortoiliac endarterectomy, demonstrating that these procedures can be an excellent alternative with acceptable morbidity and mortality in properly selected patients. MethodsA single institution retrospective review of 20 patients who underwent AE from 2017 to 2023 was performed. ResultsFive patients (25%) underwent paravisceral endarterectomy and 15 (75%) underwent aortoiliac endarterectomy. There were no perioperative mortalities. One paravisceral patient died 3 months postoperatively from complications of pneumonia. Three patients in the paravisceral group required reinterventions; one acutely due to thrombosis of the superior mesenteric artery (SMA) requiring extension of the endarterectomy and patch angioplasty on postoperative day 0, one due to stenosis at the distal edge of the endarterectomy 1 month postoperatively, successfully treated with SMA stenting, and one at 10-month follow-up due to SMA stenosis at the distal aspect of the endarterectomy, also successfully treated with SMA stenting. With these reinterventions, the 1-year primary patency in the paravisceral group was 40%, primary-assisted patency was 80%, and secondary patency was 100%. In the aortoiliac group, 1-year primary, primary-assisted, and secondary patency were 91%, 91%, and 100%, respectively. One patient developed iliac thrombosis 10 days postoperatively owing to an intimal flap distal to the endarterectomy site. She and one other patient, a young man with an undefined hypercoagulable disorder, ultimately required neoaortoiliac reconstructions at 18 and 32 months postoperatively, respectively (the latter in the setting of stopping anticoagulation). The remaining 13 patients experienced no complications. All patients had rapid resolution of clinical symptoms, and median postoperative ankle-brachial indexes of 1.06 on the right and 1.00 on the left, representing a median improvement from preoperative ankle-brachial indexes of +0.59 on the right and +0.56 on the left (P < .01 and P < .01). ConclusionsIn this series of 20 patients undergoing paravisceral and infrarenal aortoiliac endarterectomy, AE was associated with no perioperative mortality, relatively low and manageable morbidity, and excellent clinical outcomes in patients with both paravisceral and aortoiliac occlusive disease. SMA-related early reintervention was not uncommon in the paravisceral group, and attention should be given particularly to the distal endarterectomy site. AE remains a viable treatment for severe multivessel paravisceral or aortoiliac occlusive disease isolated to the aorta and common iliac arteries in select patients.

Acute Mesenteric Ischemia: Basic concepts, Diagnosis, Treatment Options and Outcomes.

Acute mesenteric ischemia (AMI) is a group of diseases in which blood flow to the intestine is interrupted by occlusive or nonocclusive causes that include mesenteric arterial embolism, mesenteric arterial thrombosis, and mesenteric venous thrombosis. AMI risk factors include advanced age, Caucasian race, history of systemic arterial hypertension, arterial fibrillation, chronic kidney disease, and congestive heart failure. The clinical triad is characterized by the sudden onset of severe abdominal pain accompanied by gastrointestinal symptoms in the presence of an identified embolic source. Diagnosis is commonly made using computed tomography angiography, where the obstruction is observed directly in occlusive causes. Treatment involves fluid resuscitation and restoring mesenteric artery circulation using endovascular or surgical procedures. The mortality rate varies depending on the patient's clinical history and treatment approach, with a higher risk associated with open surgery. Lifelong anticoagulation or antiplatelet therapy may be necessary to prevent recurrence. Follow-up evaluations are recommended to monitor for restenosis and to prevent acute myocardial infarction.

Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis.

Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbβ3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

Mitochondrial pyruvate dehydrogenase kinases contribute to platelet function and thrombosis in mice by regulating aerobic glycolysis.

Resting platelets rely on oxidative phosphorylation (OXPHOS) and aerobic glycolysis (conversion of glucose to lactate in the presence of oxygen) for their energy requirements. In contrast, platelet activation exhibits an increased rate of aerobic glycolysis relative to OXPHOS. Mitochondrial enzymes pyruvate dehydrogenase kinases (PDKs) phosphorylate the pyruvate dehydrogenase (PDH) complex to inhibit its activity, thereby diverting the pyruvate flux from OXPHOS to aerobic glycolysis upon platelet activation. Of four PDK isoforms, PDK2 and PDK4 (PDK2/4) are predominantly associated with metabolic diseases. Herein, we report that the combined deletion of PDK2/4 inhibits agonist-induced platelet functions, including aggregation, integrin αIIbβ3 activation, degranulation, spreading, and clot retraction. Additionally, collagen-mediated PLCγ2 phosphorylation and calcium mobilization were significantly reduced in PDK2/4-/- platelets, suggesting impaired GPVI signaling. The PDK2/4-/- mice were less susceptible to FeCl3-induced carotid and laser-induced mesenteric artery thrombosis without any effect on hemostasis. In adoptive transfer experiments, thrombocytopenic hIL-4Rα/GPIbα-transgenic mice transfused with PDK2/4-/- platelets exhibited less susceptibility to FeCl3 injury-induced carotid thrombosis compared to hIL-4Rα/GPIbα-Tg mice transfused with WT platelets, suggesting a platelet-specific role of PDK2/4 in thrombosis. Mechanistically, the inhibitory effects of PDK2/4 deletion on platelet function were associated with reduced PDH phosphorylation and glycoPER in activated platelets, suggesting that PDK2/4 regulates aerobic glycolysis. Finally, using PDK2 or PDK4 single KO mice, we identified that PDK4 plays a more prominent role in regulating platelet secretion and thrombosis compared to PDK2. This study identifies the fundamental role of PDK2/4 in regulating platelet functions and identifies PDK/PDH axis as a potentially novel antithrombotic target.

Spontaneous Renal Artery, Superior Mesenteric Artery and Distal Splenic Artery Thrombosis: An Unusual Case of Acute Abdomen

Spontaneous Renal Artery, Superior Mesenteric Artery and Distal Splenic Artery Thrombosis: An Unusual Case of Acute Abdomen

Mitochondrial calcium uniporter b deletion inhibits platelet function and reduces susceptibility to arterial thrombosis

BackgroundMitochondrial calcium uniporter b (MCUb) is a negative regulator of the mitochondrial calcium uniporter (MCU) and is known to limit mitochondrial calcium ion (Ca2+) uptake. The role of MCUb in platelet function remains unclear. ObjectivesUtilizing MCUb−/− mice, we examined the role of MCUb in regulating platelet function and thrombosis. MethodsPlatelet activation was evaluated in agonist-induced standardized in vitro assays. Susceptibility to arterial thrombosis was evaluated in FeCl3 injury–induced carotid artery and laser injury–induced mesenteric artery thrombosis models. The glycolytic proton efflux rate and oxygen consumption rate were measured to evaluate aerobic glycolysis. ResultsUpon stimulation, MCUb−/− platelets exhibited reduced cytoplasmic Ca2+ responses concomitant with increased mitochondrial Ca2+ uptake. MCUb−/− platelets displayed reduced agonist-induced platelet aggregation and spreading on fibrinogen and decreased α and dense-granule secretion and clot retraction. MCUb−/− mice were less susceptible to arterial thrombosis in FeCl3 injury–induced carotid and laser injury–induced mesenteric thrombosis models with unaltered tail bleeding time. In adoptive transfer experiments, thrombocytopenic hIL-4Rα/GPIbα-transgenic mice transfused with MCUb−/− platelets were less susceptible to FeCl3 injury-induced carotid thrombosis compared with hIL-4Rα/GPIbα-Tg mice transfused with wild type platelets, suggesting a platelet-specific role of MCUb in thrombosis. MCUb−/− stimulated platelets exhibited reduced glucose uptake, decreased glycolytic rate, and lowered pyruvate dehydrogenase phosphorylation, suggesting that mitochondrial Ca2+ mediates bioenergetic changes in platelets. ConclusionOur findings suggest that mitochondrial Ca2+ signaling and glucose oxidation are functionally linked in activated platelets and reveal a novel role of MCUb in platelet activation and arterial thrombosis.