Incidence and outcomes of splanchnic vein thrombosis after diagnosis of COVID-19 or COVID-19 vaccination: a systematic review and meta-analysis

Journal of Thrombosis and Thrombolysis - Coronavirus disease 2019 (COVID-19) and COVID-19 vaccination may cause splanchnic vein thrombosis (SVT), which is potentially fatal. The present study aims...     

Prognostic factors in noncirrhotic patients with splanchnic vein thromboses

OBJECTIVES AND METHODS: Splanchnic vein thrombosis (SVT), not associated with cancer or liver cirrhosis, is a rare event and scanty data are available on its natural history, long-term prognosis, and treatment. In this study 121 SVT patients consecutively seen from January 1998 to December 2005 were included and 95 of them were followed up for a median time of 41 months. Screening for thrombophilic factors was performed in 104 patients. New thrombotic or bleeding episodes were registered and anticoagulant therapy was performed according to preestablished criteria. RESULTS: SVT was an incidental finding in 34 (28.1%) patients; 34 (28.1%) presented with abdominal infarction; 39 (32.2%) had bowel ischemia or acute portal vein thrombosis; 14 (11.6%) had bleeding from portal hypertensive sources. Survival rates at 1, 3, and 7 yr were 95%, 93.3%, and 89.6%, respectively; 87.5% of deaths occurred at onset of SVT as complications of intestinal infarction. Patients with isolated portal vein thromboses had symptoms and intestinal infarction in 16/41 (39%) and 0/41 (0%) of the cases, respectively, whereas superior mesenteric vein thromboses, isolated or not, were associated with symptoms and intestinal infarction in 69/75 (92%) and 34/75 (45%), respectively. During the follow-up 14 (14.7%) suffered from 39 episodes of gastrointestinal bleeding with no deaths. A previous gastrointestinal bleed was associated with new hemorrhagic events during follow-up. New venous thrombotic episodes occurred in 10 of 95 patients (10.5%), of which 73% were in the splanchnic area. Seven out of these 10 patients had a chronic myeloproliferative disease (MPD) and none was on anticoagulation. CONCLUSIONS: Anticoagulant therapy was effective to obtain recanalization of acute SVT in 45.4% of patients and preserved patients from recurrent thrombosis when given lifelong.     

COVID-19 and its effects on the digestive system

Coronavirus disease 2019 (COVID-19) is caused by infection of the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with typical respiratory symptoms. SARS-CoV-2 invades not only the respiratory system, but also other organs expressing the cell surface receptor angiotensin converting enzyme 2. In particular, the digestive system is a susceptible target of SARS-CoV-2. Gastrointestinal symptoms of COVID-19 include anorexia, nausea, vomiting, diarrhea, abdominal pain, and liver damage. Patients with digestive damage have a greater chance of progressing to severe or critical illness, a poorer prognosis, and a higher risk of death. This paper aims to summarize the digestive system symptoms of COVID-19 and discuss fecal-oral contagion of SARS-CoV-2. It also describes the characteristics of inflammatory bowel disease patients with SARS-CoV-2 infection and discusses precautions for preventing SARS-CoV-2 infection during gastrointestinal endoscopy procedures. Improved attention to digestive system abnormalities and gastrointestinal symptoms of COVID-19 patients may aid health care providers in the process of clinical diagnosis, treatment, and epidemic prevention and control.     

Acute upper limb ischemia in a patient with COVID-19

Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mainly present with upper and lower respiratory tract symptoms, with complications related to cytokine storm syndrome and acute respiratory distress syndrome. It has also been described to predispose to venous and arterial thromboembolism; however, limited published data is available regarding thrombosis in coronavirus disease 2019 (COVID-19). Here we are presenting a case of arterial thrombosis in a patient with COVID-19 and a systematic review on coagulopathy associated with COVID-19.     

Clinical presentations,risk factors,treatment and outcomes in patients with splanchnic vein thrombosis: a single-center experience

Splanchnic vein thrombosis (SVT) is an uncommon form of venous thrombosis. Management can be challenging due to underlying conditions, increased bleeding risk, and lack of evidence from clinical trials. We sought to characterize the presentation and management of patients with SVT at a large tertiary hospital. A total of 43 patients’ electronic medical records were reviewed. Median age at diagnosis was 43 (18–71). Sixteen patients had isolated portal vein thrombosis (37.2 %), and 16 (37.2 %) had thrombosis involving multiple splanchnic veins. Abdominal pain was the most common clinical presentation (67.4 %). Thrombophilia was present in 18 patients (41.9 %), nine had underlying liver disease (20.9 %) and seven had inflammatory bowel disease (16.3 %). Thirty-nine (90.7 %) patients were treated with anticoagulation, and 11(25.6 %) of these patients underwent interventional procedures. Thirty (69.8 %) patients remained on indefinite anticoagulation. Results of follow-up imaging at least 1 month after diagnosis were available for 29 patients; imaging showed chronic, stable thrombosis in 14 patients (48.3 %), resolution of thrombosis in 13 patients (44.8 %) and asymptomatic progression in two patients (6.9 %). Recurrent thrombosis occurred in four patients (9.3 %). Major bleeding occurred in eight patients who received anticoagulation (18.6 %), including fatal subdural hematoma in one patient. In this cohort of patients managed by hematologists and gastroenterologists, the majority of patients were treated with anticoagulation. Interventional procedures were higher than in previously reported series. Our study strongly supports the interdisciplinary management of splanchnic venous thrombosis.     

Abdominal and gastrointestinal manifestations in COVID-19 patients: Is imaging useful?

Coronavirus disease 2019 (COVID-19) can be considered a systemic disease with a specific tropism for the vascular system, in which the alterations of the microcirculation have an important pathogenetic role. The lungs are the main organ involved in COVID-19, and severe progressive respiratory failure is the leading cause of death in the affected patients; however, many other organs can be involved with variable clinical manifestations. Concerning abdominal manifestations, the gastrointestinal tract and the hepatobiliary system are mainly affected, although the pancreas, urinary tract and spleen may also be involved. The most common gastrointestinal symptoms are loss of appetite, followed by nausea and vomiting, diarrhea and abdominal pain. Gastrointestinal imaging findings include bowel wall thickening, sometimes associated with hyperemia and mesenteric thickening, fluid-filled segments of the large bowel and rarely intestinal pneumatosis and ischemia. Hepatic involvement manifests as an increase in the enzymatic levels of alanine aminotransferase, aspartate aminotransferase, serum bilirubin and γ-glutamyl transferase with clinical manifestations in most cases mild and transient. The most frequent radiological features are hepatic steatosis, biliary sludge and gallstones. Edematous acute pancreatitis, kidney infarct and acute kidney injury from acute tubular necrosis have been described more rarely in COVID-19. Lastly, splenic involvement is characterized by splenomegaly and by the development of solitary or multifocal splenic infarcts with classic wedge-shaped or even rounded morphology, with irregular or smooth profiles. In summary, the abdominal radiological findings of COVID-19 are nonspecific and with poor pathological correlation reported in the literature. Ultrasound and particularly computed tomography with multiphasic acquisition are the diagnostic methods mainly utilized in COVID-19 patients with abdominal clinical symptoms and signs. Although radiological signs are not specific of abdominal and gastrointestinal involvement, the diagnostic imaging modalities and in particular computed tomography are helpful for the clinician in the management, evaluation of the severity and evolution of the COVID-19 patients.     

Coronavirus disease–2019 and the intestinal tract: An overview

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can progress to a severe respiratory and systemic disease named coronavirus disease–2019 (COVID-19). The most common symptoms are fever and respiratory discomfort. Nevertheless, gastrointestinal infections have been reported, with symptoms such as diarrhea, nausea, vomiting, abdominal pain, and lack of appetite. Importantly, SARS-CoV-2 can remain positive in fecal samples after nasopharyngeal clearance. After gastrointestinal SARS-CoV-2 infection and other viral gastrointestinal infections, some patients may develop alterations in the gastrointestinal microbiota. In addition, some COVID-19 patients may receive antibiotics, which may also disturb gastrointestinal homeostasis. In summary, the gastrointestinal system, gut microbiome, and gut-lung axis may represent an important role in the development, severity, and treatment of COVID-19. Therefore, in this review, we explore the current pieces of evidence of COVID-19 gastrointestinal manifestations, possible implications, and interventions.     

Gastrointestinal symptoms in patients with COVID-19: Is there a relationship with mortality and new variations of SARS-CoV-2?

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although, respiratory symptoms are typical the digestive system is also a susceptible target with gastrointestinal symptoms present even in the absence of respiratory symptoms. The gastrointestinal symptoms of COVID-19 include diarrhea, abdominal pain, anorexia, and nausea among other symptoms. Some questions that remain to be answered include: Do patients with gastrointestinal symptoms have a higher mortality? SARS-CoV-2 variants are already a global reality: Do these variants present with a greater prevalence of gastrointestinal symptoms? Do patients with these symptoms warrant more intensive care unit care?     

Ischaemic jejunal stenosis complicating portal and mesenteric vein thrombosis: a report of two cases.

A major complication of portal and mesenteric vein thrombosis is acute bowel ischaemia resulting in infarction and requiring immediate resection of the involved segment. Sufficient collaterals can prevent acute haemorrhagic infarction, but bowel stenosis due to chronic ischaemia may develop. We report two cases of ischaemic jejunal stenosis occurring 4 weeks after successful treatment of portal and mesenteric vein thrombosis. Diagnosis of high-grade segmental stenosis of the jejunum was established by contrast medium radiography of the gastrointestinal tract. After laparotomy and resection of the stenosed jejunal segment, both patients recovered well from the operation and were released from hospital. Follow-up examinations revealed an unremarkable state of health. Ischaemic bowel stenosis should be considered in patients with recurring abdominal pain after mesenteric and portal vein thrombosis. A close follow-up of every patient after treatment for mesenteric and portal vein thrombosis should be carried out to ensure early diagnosis of this complication.     

Superficial vein thrombosis: risk factors, diagnosis, and treatment

Superficial vein thrombosis (SVT) is a very common disease even though its incidence has never been assessed properly. Until recently, the literature on this topic has been relatively poor, old, and with numerous methodologic drawbacks, probably because this disease was considered benign and trivial. However, the recent recognition of a frequent association with concomitant venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [PE]) and the risk of subsequent VTE complications in patients with isolated SVT has revived interest and has encouraged new clinical research. SVT and VTE share many common predisposing risk factors. Even if varicose veins represent the main cause of SVT, several underlying conditions (e.g., malignancy, thrombophilia, autoimmune diseases) should be sought, especially in idiopathic, migrant, or recurrent SVT of nonvaricose vein patients. The diagnosis is made in a clinical setting but ultrasonography is useful to identify concomitant asymptomatic DVT. Many medical and surgical treatments have been suggested to relieve local symptoms and signs, prevent recurrences, and limit the VTE risk of SVT, but the evidence coming from the limited number of prospective randomized studies does not allow strong recommendations on the optimal treatment of SVT.     

COVID-19 as a trigger of irritable bowel syndrome: A review of potential mechanisms

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.     

Mechanism and potential treatments for gastrointestinal dysfunction in patients with COVID-19

The global coronavirus disease 2019 (COVID-19) has become one of the biggest threats to the world since 2019. The respiratory and gastrointestinal tracts are the main targets for severe acute respiratory syndrome coronavirus 2 infection for they highly express angiotensin-converting enzyme-2 and transmembrane protease serine 2. In patients suffering from COVID-19, gastrointestinal symptoms have ranged from 12% to 61%. Anorexia, nausea and/or vomiting, diarrhea, and abdominal pain are considered to be the main gastrointestinal symptoms of COVID-19. It has been reported that the direct damage of intestinal mucosal epithelial cells, malnutrition, and intestinal flora disorders are involved in COVID-19. However, the underlying mechanisms remain unclear. Thus, in this study, we reviewed and discussed the correlated mechanisms that cause gastrointestinal symptoms in order to help to develop the treatment strategy and build an appropriate guideline for medical workers.     

Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID-19 pandemic

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated coronavirus disease 2019 (COVID-19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID-19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID-19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID-19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.     

Alterations of the gut microbiota in coronavirus disease 2019 and its therapeutic potential

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global health. SARS-CoV-2 infects host cells primarily by binding to angiotensin-converting enzyme 2, which is coexpressed in alveolar type 2 cells and gut epithelial cells. It is known that COVID-19 often presents with gastrointestinal symptoms and gut dysbiosis, mainly characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. In recent years, multiple studies have comprehensively explored gut microbiota alterations in COVID-19 and highlighted the clinical correlation between dysbiosis and COVID-19. SARS-CoV-2 causes gastrointestinal infections and dysbiosis mainly through fecal-oral transmission and the circulatory and immune pathways. Studies have shown that the gut microbiota and its metabolites can regulate the immune response and modulate antiviral effects. In addition, the gut microbiota is closely related to gastrointestinal symptoms, such as diarrhea, a common gastrointestinal symptom among COVID-19. Therefore, the contribution of the gut microbiota in COVID-19 should not be overlooked. Strategies targeting the gut microbiota via probiotics, prebiotics and fecal microbiota transplantation should be considered to treat this patient population in the future. However, the specific alterations and mechanisms as well as the contributions of gut microbiota in COVID-19 should be urgently further explored.     

Prevalence of overt myeloproliferative neoplasms and JAK2 V617F mutation in Korean patients with splanchnic vein thrombosis

Introduction: Myeloproliferative neoplasm (MPN) is known to be a major risk factor of splanchnic vein thrombosis (SVT). Recent studies revealed that a significant proportion of patients with SVT harbor a gain‐of‐function mutation in the JAK2 gene (V617F) with or without MPN. In this study, the authors investigated the prevalence of MPN and JAK2 V617F mutation in Korean patients with SVT. Methods: The study subjects were 26 patients diagnosed as having SVT based on Doppler ultrasound and/or computed tomography from January 2008 to January 2010 (16 men and 10 women; mean age 44 years, range 15–75 years). The clinical and laboratory data were reviewed. The JAK2 V617F mutation was detected by allele‐specific polymerase chain reaction and direct sequencing analyses using DNA from peripheral blood leukocytes. Results: Among 26 study patients, 12 had portal vein thrombosis, five had hepatic vein thrombosis, three had mesenteric, and two had splenic vein thrombosis. Four patients had thrombosis involving more than one splanchnic vein. Two patients (7.7%; 2/26) had overt MPN (essential thrombocythemia). JAK2 V617F was detected in three patients (11.5%) including the two patients with overt MPN. Thus, the prevalence of the JAK2 V617F mutation in patients with SVT but without overt MPN was 4.2% (1/24). Conclusion: The prevalence of overt MPN and that of JAK2 V617F were lower in Korean patients with SVT than in previous reports. Data from a larger number of patients with long‐term follow‐up are needed to reveal the clinical relevancy of JAK2 V617F in Korean patients with SVT.     

Hyperhomocysteinemia and the methylene tetrahydrofolate reductase C677T mutation in splanchnic vein thrombosis

Introduction: The role that hyperhomocysteinemia (HH) and the C677T mutation in 5,10‐methylenetetrahydrofolate reductase (MTHFR) play in splanchnic vein thrombosis (SVT) remains unclear due to this unusual thrombotic location. Objective: To analyse the possible association of HH with the C677T mutation in the MTHFR gene in SVT. Material and methods: We determined homocysteine levels and the C677T MTHFR mutation, along with classical cardiovascular risk factors, in 48 patients with SVT (18 Budd‐Chiari syndrome, 11 mesenteric vein thrombosis, 19 portal vein thrombosis) and 84 controls. Results: In the univariate analysis, patients with SVT showed statistically higher homocysteine levels (P = 0.044). After adjusting for total cholesterol, differences disappeared (P = 0.256). However, no differences in homocysteine levels were observed when comparing the three SVT types (P = 0.199), even after adjusting for age and total cholesterol (P = 0.095). In addition, the prevalence of the TT genotype was no different when controls were compared with patients with SVT (P = 0.253) or with SVT subtypes (P = 0.885). No association was found between HH (>15 μm ) and the TT genotype in cases (P = 0.404), controls (P = 0.178), or in the different SVT subtypes (P = 0.495). Conclusions: Our results suggest that HH and the homozygous genotype in the MTHFR C677T mutation do not seem to play a role in SVT development.     

Progress of local symptoms of superficial vein thrombosis vs. duplex findings

BACKGROUND: Risk of subsequent deep vein thrombosis (DVT) following superficial vein thrombosis (SVT) is not fully appreciated. Mechanisms, time relations and risk factors for DVT arising upon earlier SVT remain unclear. The aim of this study was to analyze time relations between local symptoms of lower limb superficial vein thrombosis, duplex findings and onset of deep vein thrombosis during clinically evident course of SVT. PATIENTS AND METHODS: 46 patients with early (onset less than 72 hours prior to inclusion) clinical diagnosis of SVT, confirmed ultrasonographically were included in this prospective, multicenter study. Progress of pain, erythema and swelling in relation to subsequent ultrasound changes in size and localization of thrombus at 0, 7, 14 and 21 day of study has been recorded. RESULTS: Local symptoms subsided completely during 3 weeks. At that time thrombus disappeared completely only in 26% of cases, in remaining cases decreased in size from average 117.5 mm to 43.0 mm. Thrombus regression was similar to venous blood outflow direction--proximal to femoral area. Thrombus propagation was observed following regression of local symptoms of SVT. 4 cases of DVT (8.7%) were diagnosed at 2-11 days. CONCLUSIONS: Local, clinically detectable symptoms of SVT regress incomparably quicker than thrombus in affected veins. Risk of further thrombus propagation extends well beyond the period of intensive local symptoms of SVT. Regression of thrombus in femoral area requires significantly more time than in popliteal or calf segment. Thrombus propagation is directed with blood flow towards femoral segment.     

Acute mesenteric ischaemia, a highly lethal disease with a devastating outcome

BACKGROUND: Acute mesenteric ischaemia remains a serious condition requiring emergency, surgical management. The mortality rate still remains high, due to the unspecific and delayed diagnosis and ranges from 59% to 100%. Purpose of our study is to present our experience in the management of the disease. PATIENTS AND METHODS: This is a retrospective study of 61 patients treated surgically for acute mesenteric ischaemia, between 1988 and 2004. All patients underwent a laparotomy. 75% of the patients were operated within the first 24 hours and the rest within 48 hours. RESULTS: Superior mesenteric artery embolism occurred in 36 (59%), thrombosis in 21 (34%) and superior mesenteric vein thrombosis in 4 (7%) cases. In 49 (80%) cases, embolectomy or thrombectomy of the superior mesenteric artery with resection of the necrotic segment of the bowel was performed. Twelve cases (20%) were considered inoperable because of massive bowel necrosis. According to our study mortality and morbidity rate amounts to 75% and 80% respectively. No significant difference in the mortality rate between patients with embolism (75%) and thrombosis (76%) was found. However a significant increase of mortality rate was observed when the surgical intervention became afterwards the first 24-hour period. (72% versus 87%). Patients who underwent embolectomy or thrombectomy with bowel resection presented an improved survival rate compared with patients that underwent only bowel resection. (p = 0.019) CONCLUSIONS: Acute mesenteric ischaemia has the characteristics of a highly lethal condition and only early recognition and appropriate treatment can reduce the potential for a devastating outcome. The reduction of time interval from the beginning of symptoms up to the treatment remains the main critical important factor.