Coagulation Factor Abnormalities Research Articles

The Role of Tripartite Motif Family Proteins in Chronic Liver Diseases: Molecular Mechanisms and Therapeutic Potential.

The worldwide impact of liver diseases is increasing steadily, with a consistent upswing evidenced in incidence and mortality rates. Chronic liver diseases (CLDs) refer to the liver function's progressive deterioration exceeding six months, which includes abnormal clotting factors, detoxification failure, and hepatic cholestasis. The most common etiologies of CLDs are mainly composed of chronic viral hepatitis, MAFLD/MASH, alcoholic liver disease, and genetic factors, which induce inflammation and harm to the liver, ultimately resulting in cirrhosis, the irreversible final stage of CLDs. The latest research has shown that tripartite motif family proteins (TRIMs) function as E3 ligases, which participate in the progression of CLDs by regulating gene and protein expression levels through post-translational modification. In this review, our objective is to clarify the molecular mechanisms and potential therapeutic targets of TRIMs in CLDs and provide insights for therapy guidelines and future research.

Isolated Presentation of Hemi-Retinal Vein Occlusion Secondary to Vaping

Retinal Vein Occlusions (RVOs) in young adults in the absence of underlying vasculopathic diseases require an extensive work up to rule out underlying etiologies such as abnormal clotting factors, medication side effects, or lifestyle risks. Commonly, lifestyle risk factors include cigarette smoking, alcohol consumption, and recreational drug use. Patients often do not recognize vaping or use of electronic cigarettes as a social danger, so unless specifically asked, use of such products often goes unreported. This case demonstrates a strong correlation between retinal vein occlusion and vaping in a young adult with a negative systemic work up.

Coagulation disorders in children with acute pancreatitis at the Vietnam National Children's hospital

Various hematological abnormalities including coagulation factor abnormalities, leukocytosis, acute hemolytic anemia, thrombocytopenia, thrombotic thrombocytopenic purpura, and disseminated intravascular coagulopathy have been reported in acute pancreatitis patients. The purpose of this descriptive cross - sectional study was to describe characteristics of coagulation disorders in 96 children with acute pancreatitis at the Vietnam National Children's Hospital. rom January 2022 to March 2023. Results showed that the mean age of children was 6.2 ± 3.2 years old, and the boy to girl ratio was 1.2 to 1, 69.8% of children had coagulation disorders. Of the 67 children who had abnormal coagulation tests, 64.2% had hypercoagulability, 35.8% had mixed hypercoagulability, 28.4% had fibrinolysis and 25.4% had disseminated intravascular coagulation. Most coagulation disorders cases showed no clinical manifestations and only 3.1% had thrombosis and hemorrhage. The factors associated with coagulopathy were hyperlipidemia and pancreatic necrosis. In conclusion, although coagulation disorders showed up in a high percentage of children with acute pancreatitis, they are difficult to be recognized based on clinical manifestations. This highlights the importance of early identification based on hemostasis testing, as it can lead to better overall management and treatment.

Comparision of coagulation profile trends in case of liver cirrhosis with HCC versus cirrhosis without HCC: Analysis of 150 cases in a tertiary health care

The physiology of haemostasis and blood coagulation is intimately linked to the hepatic function. Liver disorders can be associated with deranged coagulation profile, thrombocytopenia, and dysfibrinogenemia. In hepatocellular injury, both quantitative and qualitative abnormalities in coagulation factors are often seen. Hepatocellular carcinoma (HCC), peculiar as both cancer and liver cirrhosis to dismay the haemostatic balance towards a prothrombotic state. Our study aims to assess the hemostatic changes and the comparision of coagulation profile trends that occur in cases of liver cirrhosis with HCC versus cirrhosis without HCC: The present study is the hospital based cross-sectional study in a tertiary care centre, New Delhi. A maximum 150 cases of liver cirrhosis with and without hepatocellular carcinoma (HCC) studied from Dec 2017 to Nov 2019 and analysed for parameters related to coagulation i.e. prothrombin time (PT/INR), fibrinogen level and platelet count 1 day prior to the liver transplant. Statistical analysis used: Statistical analysis was done using SPSS 20.0. Comparisons between groups frequencies were made using Chi-square test. P< 0.05 was considered as significant.: Prothrombin time was found to be increased in all the cirrhotic patients (both with and without HCC). Decrease in the level of fibrinogen was observed in 90 % cases of cirrhosis with HCC and 80% of cases of cirrhosis without HCC. Platelet count were almost in normal range among majority of the cirrhosis cases both with and without HCC (86.0% and 75.0% respectively).No significant difference was observed in prothrombin time, fibrinogen level and platelet count among the cases with and without hepatocellular carcinoma (p>0.05).: All the cases showed haemostatic abnormalities in the form of hypofibrinogenemia and increase PT/INR. There is no significant difference in the coagulation profile in cases of cirrhosis with HCC in comparison to cases of cirrhosis without HCC.

Recurrent Leg Deep Vein Thrombosis in a Female with Atypical Right-Sided Variant of May Thurner Syndrome and Factor V Leiden Mutation

I ntroduction: May-Thurner syndrome (MTS) is a condition in which the right common iliac artery presses on the left common iliac vein, causing it to narrow over time. Right-sided MTS is a rare event. We present this unique case of recurrent right leg deep vein thrombosis in a female with atypical right sided variant of MTS and Factor V Leiden mutation. Case Presentation: A 34-year-old lady with with no signficiant past medical history presented to the hospital with right lower leg edema, tingling, and discolouration. She was taking oral contraceptive pills. Vitals were unremarkable. Doppler studies revealed right lower extremity deep vein thrombosis in the right external iliac vein, common iliac vein and common femoral vein. She was started on an intravenous heparin drip and subsequently had a thrombectomy procedure. She was subsequently discharged home on apixaban anticoagulation. We opted to request a hypercoagulable and vasculitis workup in light of the extensive thrombosis, despite the OCP risk factor, and discovered a heterozygous Factor V Leiden mutation. She returned to the hospital 2 days later with worsening right leg pain. Repeat Doppler studies demonstrated acute right femoral and popliteal deep vein thrombosis. CT angiography of abdomen and pelvis revealed significant right femoral vein DVT that extends into the External iliac vein, common iliac vein, and IVC to at least slightly below renal vein level. Invasive Radiology was consulted and she had a venogram and intravascular ultrasound (IVUS) which showed high-grade right common iliac vein and IVC stenosis (>90%) at L4 superior endplate. Iliac stenting and angioplasty improved iliac and inferior IVC diameters. Patient also underwent thrombectomy & IVC filter placement. The diagnostic venography revealed a popliteal-to-proximal femoral vein rethrombosis. This was treated with tissue plasminogen activator (TPA) by 8 French power pulse AngioJet and a mechanical thrombectomy. This resulted in partial clearing of the common femoral vein with persistent narrowing and thrombosis of the popliteal vein. TPA was infused at 1 mg/hour with a 5 French McNamara lysis catheter over the popliteal region.Patient transferred to ICU for overnight intravenous thrombolysis. The patient was then re-initiated on the heparin drip and then bridged to therapeutic warfarin. Discussion: MTS is a phenomenon commonly described as an acquired stenosis of the left common iliac vein secondary to compression by the right common iliac artery 1. It has been associated with genetic clotting factor abnormalities, repeated pregnancies, postpartum, contraceptive pills, prolonged immobilization, scoliosis, anti-phospholipid syndrome, COVID-19, and recurrent DVT 2. In patients with left lower-limb DVT, the incidence of MTS is about 20-50%. Right lower limb DVT in patients with right sided variant of MTS is rare. Right lower limb DVT with right sided variant of MTS with co-existing Factor V Leiden mutation is even rarer. Ultrasound imaging typically cannot detect the high pelvic abnormalities seen in MTS. Contrast venography, MRI, or IVUS are needed to diagnose MTS 4. As was the case in our patient, venography should be done to evaluate stenosis and iliac vein compression hemodynamics after thrombus removal. Treatment of MTS depends on the presentation, severity of symptoms, and whether the patient has developed DVT. Conservative treatment such as compression stockings can be used for patients who are asymptomatic or have mild symptoms. For patients with moderate symptoms or DVT, endovascular treatment with stenting is recommended 5. Conclusion: This is a very atypical presentation of MTS variation affecting the right lower extremity with limited description in the literature. To our knowledge, this is the first case presentation of right sided MTS resulting in a DVT in a patient with factor V Leiden mutation. MTS is a potentially treatable and often-overlooked pathology. In the era of expanded endovascular management of MTS, recognition of this disease entity is essential for early diagnosis and treatment.

Blood Cell Parameters Combined with Inflammatory Markers in the Early Diagnosis of Pulmonary Embolism

Venous thrombosis is a semi-solid formation of blood components that coalesce in the venous system, and the pathological process of its formation is called venous thrombosis. The deep veins of the lower extremities are a common site of prevalence, and the clinical diagnosis of lower extremity deep vein thrombosis can occur independently or as a complication of other diseases. There is a clear link between inflammation and coagulation/anticoagulation, with inflammatory mechanisms upregulating pro-inflammatory factors, downregulating natural anticoagulant substances, and inhibiting fibrinolytic activity; systemic inflammation is a strong pro-thrombotic stimulus; and in vivo, natural anticoagulant substances not only prevent thrombosis, but also deter inflammatory processes. The interconnection between inflammation and coagulation plays an important role in venous thrombosis. In this study, we analyzed the relationship between inflammatory markers CRP and Fg, FVIII:C and FIX:C by measuring plasma CRP concentration, Fg level, FVIII:C and FIX:C levels in patients with DVT diagnosed by ultrasound, and explored the role and mechanism of inflammatory response and coagulation factor abnormalities and the interaction between them in the development of DVT. In this paper, human blood DNA was extracted by phenol-chloroform-isoamyl alcohol extraction, and CRP 1059G/C gene polymorphism was detected by polymerase chain reaction-restriction enzyme segment length polymorphism (PCR-RFLP) nucleotide typing technique, and the genotypes of each subject were distinguished according to the bands seen by gel electrophoresis, and the frequency of each genotype was counted. Plasma CRP concentrations were measured by immunoturbidimetric assay, FVIII:C and FIX:C levels were measured by phase I assay, and plasma Fg levels were measured by coagulation assay in 59 cases (38 males and 21 females, aged 21-82 years, mean 49.67±11.12 years) and 26 controls (17 males and 9 females, aged 32-67 years, mean 50.13±8.96 years). The above indexes were compared between the two groups, and the correlation between CRP and FVIII:C, FIX:C and Fg was analyzed. Polymerase chain reaction-restriction enzyme segment length polymorphism nucleotide typing technique was used to detect the relationship between CRP 1059G/C gene polymorphism and DVT, to further search for risk factors of venous thrombosis, thus providing new ideas for the future prevention and treatment of this disease in clinical practice.

Cerebrovascular Accident Complicating Diabetic Ketoacidosis in a Nigerian Adolescent: A Case Report and Review of the Literature

Cerebrovascular accident (CVA) is a rare neurological complication of diabetic ketoacidosis (DKA) in the paediatric population. The risk of developing CVA in DKA patients is often increased due to abnormalities in coagulation factors, platelet activation, blood volume and flow, and vascular reactivity. Cerebral oedema, the most common neurological complication of DKA, may also predispose to CVA. We report the case of a -12-year-old adolescent with DKA complicated by CVA. She developed features of right hemispheric CVA while on admission and had radiological confirmation of an ischaemic CVA. This report highlights that cerebrovascular accidents in DKA can easily be missed or confused with cerebral oedema.

MON-LB127 Pulmonary Embolism in the Setting of Diabetic Ketoacidosis. an Under-Recognized Complication

The relation between Diabetic Ketoacidosis and Venous Thromboembolism is important to appreciate for early recognition and management. 90 year old female with Type 2 DM was brought to the ER after a syncopal episode. Family reported the patient to be lethargic with a decreased appetite for one week. On arrival, patient had a blood pressure of 84/44 mmHg. Oxygen saturation was 89% at room air and improved to 93% on supplemental O2. Patient was afebrile with a respiratory rate of 16 and heart rate 89/minute. On exam, she was dehydrated with decreased skin turgor, dry oral mucosa. Labs revealed blood glucose of 621 mg/dL, Bicarbonate 16 mmol/L, B-Hydroxybutyrate 5.00 mmol/L, Anion Gap 21, pH of 7.26 on ABG. Urinalysis was suggestive of a urinary tract infection. After initiation of IV antibiotics and insulin, she was transferred to the intensive care unit. In the ICU, her blood pressure failed to improve with fluid resuscitation, ultimately requiring vasopressors. Due to hypotension with hypoxia, CT Chest was performed which revealed extensive bilateral PE. She was started on IV heparin infusion. Pro-Brain Natriuretic Peptide was elevated at 4,716 pg/mL. Echocardiogram confirmed right heart strain with severely dilated right ventricle, positive McConnell’s sign, systolic and diastolic septal flattening and an estimated RSVP 67mmHg consistent with moderately severe pulmonary hypertension. Tissue plasminogen activator was recommended however given the patient’s age and functional status; family decided against systemic thrombolysis. Duplex ultrasound of her lower extremities also showed bilateral acute deep venous thrombosis. She was continued on intravenous anticoagulation and eventually was able to come off vasopressors. As the patient’s blood glucose levels improved and her anion gap closed, she was transitioned to basal/bolus insulin and transferred to the general medical floor. She was started on Apixaban and discharged home per family’s request after her code status was changed to DNR-Comfort Care Arrest.Pulmonary embolism is a serious venous thromboembolic event that is rarely reported in association with DKA. Proposed mechanisms include some of the same mechanisms implicated in arterial thrombosis, namely abnormalities in coagulation factors, increased platelet aggregation, impaired fibrinolysis and endothelial injury due to hypertonicity. Also, severe dehydration associated with DKA may contribute by virtue of increased red blood cell rigidity and increased blood viscosity establishing DKA as an underlying cause or contributing factor of pulmonary thromboembolism2.1 Langevin C et al Presumed paradoxical embolus in a patient with diabetic ketoacidosis Int J Gen Med 2015;8:297–301 2015 Sep 182 Scordi Bello I et al Fatal Pulmonary Thromboembolism in Patients with Diabetic Ketoacidosis A Seven-Case Series and Review of the Literature Acad Forensic Pathol 2016;6(2):198–205

Diagnosis and management of hemophilia

Hemophilia A and B are hereditary coagulation disorders caused by functional and quantitative abnormalities of coagulation factor VIII (FVIII) in hemophilia A and coagulation factor IX (FIX) in hemophilia B. A definitive diagnosis is made through the measurement of FVIII or FIX activity and ruling out other pathological conditions or diseases with decreased FVIII or FIX activity. Severity is classified as severe, moderate, and mild according to factor activity level. Moreover, as frequency of hemorrhage and severity are usually correlated, severe patients have a high risk of intracranial hemorrhage during infancy as well as joint damage due to recurrent hemarthrosis. However, there are some non-severe patients who have symptoms like bleeding and joint damage. Therefore, it is necessary to determine the treatment strategy not only based on severity but also on bleeding symptoms. The treatment for hemophilia is mainly replacement therapy using clotting factor concentrates (standard or extended half-life), such as prophylaxis or on-demand therapy for bleeding. However, there are also clinical problems, such as venous access and development of inhibitors. Recently, a non-factor agent has emerged as a new treatment option. Thus, the management of hemophilia is on a turning point.

Phenotypes and genotypes of mitochondrial aminoacyl‐tRNA synthetase deficiencies from a single neurometabolic clinic

Mitochondrial aminoacyl‐tRNA synthetases play a major role in protein translation, synthesis, and oxidative phosphorylation. We reviewed all patients diagnosed with mitochondrial aminoacyl‐tRNA synthetase deficiencies diagnosed in a single neurometabolic clinic. We report five patients with mitochondrial aminoacyl‐tRNA synthetase deficiencies including DARS2, EARS2, PARS2, and RARS2 deficiencies. Siblings with DARS2 deficiency presented with global developmental delay within the first year of life. DARS2, EARS2, PARS2, and RARS2 deficiencies were identified by whole exome sequencing. We report coagulation factor abnormalities in PARS2 deficiency for the first time. We also report symmetric increased signal intensity in globus pallidi in FLAIR images in brain MRI in EARS2 deficiency for the first time. One patient with RARS2 deficiency had compound heterozygous variants in RARS2. One of those variants was an intronic variant. We confirmed the pathogenicity by mRNA studies. Mitochondrial aminoacyl‐tRNA synthetase deficiencies are diagnosed by molecular genetic investigations. Clinically available non‐invasive biochemical investigations are non‐specific for the diagnosis of mitochondrial aminoacyl‐tRNA synthetase deficiencies. A combination of brain MRI features and molecular genetic investigations should be undertaken to confirm the diagnosis of mitochondrial aminoacyl‐tRNA synthetase deficiencies.

Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study

BackgroundMetabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic β-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement.MethodsWater T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression.ResultsPlasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma.ConclusionsWater T2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual’s metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.

Individual clotting factor contributions to mortality following trauma.

Acute traumatic coagulopathy affects 20% to 30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aimed to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma. This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between February 2005 and February 2015. Factors II, V, VII, VIII, IX, and X and protein C activity on admission and mortality status at 28 days were assessed. Predictors of 28-day mortality in univariate analysis were included in multiple logistic regression controlling for traumatic brain injury (TBI), acidosis, age, and mechanism of injury. Principal component analysis was utilized to identify phenotypic coagulation. Complete coagulation factor data were available for 876 (61%) of 1,429 patients. In multiple logistic regression, factors V (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.76-0.97), VIII (OR, 0.97; 95% CI, 0.95-0.99), and X (OR, 0.79; 95% CI, 0.68-0.92) and protein C (OR, 1.17; 95% CI, 1.05-1.30) significantly predicted 28-day mortality after controlling for age, base deficit, mechanism of injury, and TBI. Principal component analysis identified two significant principal components (Phenotypes 1 and 2) that accounted for 66.3% of the total variance. Phenotype 1 (factors II, VII, IX, and X and protein C abnormalities) explained 49.3% and was associated with increased injury, coagulopathy, TBI, and mortality. Phenotype 2 (factors V and VIII abnormalities) explained 17.0% and was associated with increased coagulopathy, blunt injury, and mortality. Only Phenotype 2 remained significantly associated with 28-day mortality in multiple logistic regression. Principal component analysis identified two distinct phenotypes within the entirety of global clotting factor abnormalities, and these findings substantiate the crucial association of factors V and VIII on mortality following trauma. This may be the first step toward identifying unique phenotypes after injury and personalizing hemostatic resuscitation. Prognostic study, level III.

Coagulation factor abnormalities related to discordance between anti-factor Xa and activated partial thromboplastin time in patients supported with continuous-flow left ventricular assist devices

High levels of discordance between activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-FXa) have been reported in patients with continuous-flow left ventricular assist devices (CF-LVADs). We sought to determine the biochemical basis for discordance by simultaneous measurement of coagulation factors with aPTT and anti-FXa. Consecutive CF-LVAD patients admitted for intravenous unfractionated heparin (IV-UFH) therapy were studied. IV-UFH was monitored based on an anti-FXa. International normalized ratio (INR), aPTT, lactate dehydrogenase, and coagulation factors II, V, VII, VIII, IX, X, XI, and XII were measured simultaneously with anti-FXa. The discordance rate between anti-FXa and aPTT was 74.7% overall (568 of 760 samples from 62 patients). In samples in which coagulation factors were simultaneously measured, the discordance rate was 66% (49 of 74 samples from 52 patients). In patients with INR ≤ 1.0 the discordance level was 31.8% vs 82.7% with INR > 1.8. No difference was observed in the rate of discordance between samples with low vs normal vitamin K-dependent factors (65.9% vs 64.7%, p = 0.99). Low factor XII was found in 15%; of these, 90.9% exhibited anti-FXa/aPTT discordance. Low factor V was found in 8.2%, and all were discordant. Factor VIII was elevated in 97% of samples, and 65.7% were discordant. In addition to the effects of warfarin administration on aPTT, the influence of other factors, such as low factor XII or V, may contribute to the discordance between aPTT values and anti-FXa. Coagulation factor levels may assist in individualization of anti-coagulation targets while patients implanted with CF-LVADs are on IV-UFH.

Congenital thrombophilia

Congenital thrombophilia is a thrombotic diathesis caused by a variety of genetic abnormalities in blood coagulation factors or their inhibitory factors associated with physiological thrombus formation. Patients with congenital thrombophilia often present with unusual clinical episodes of venous thrombosis (occasionally combined with pulmonary embolism, known as venous thromboembolism) at a young age and recurrence in atypical vessels, such as the mesenteric vein and superior sagittal sinus, often with a family history of this condition. Studies in Japan as well as in western countries have shown congenital thrombophilia to be caused by a wide variety of genetic abnormalities in natural anticoagulant proteins, such as antithrombin, protein C, and protein S. However, there may still be many unknown causes of hereditary thrombosis. We recently reported a case of hereditary thrombosis induced by a novel mechanism of antithrombin resistance, that is, congenital thrombophilia caused by a gain-of-function mutation in the gene encoding the coagulation factor prothrombin.

DMP1-CDG (CDG1e) with Significant Gastrointestinal Manifestations; Phenotype and Genotype Expansion.

The literature describes eight cases of mutations in the DPM1 gene generating DMP1-CDG, causing similar phenotype of early onset seizures, microcephaly and developmental delay. Investigations of these patients revealed associated abnormal findings on brain imaging, elevated CK, abnormal clotting factors and mildly deranged serum transaminases. We describe the ninth case of DMP1-CDG, whose clinical presentation includes severe gastrointestinal involvement, i.e. food protein induced enterocolitis syndrome (FPIES). Gastrointestinal manifestations (GIT) of the congenital glycosylation disorders have included deranged liver function, hepatomegaly, liver fibrosis, steatosis and protein-losing enteropathy. This is the first report of a congenital glycosylation disorder being associated with FPIES.

Anticoagulation in patients with pulmonary arterial hypertension: An update on current knowledge

Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk.

Mo1824 miR-511-3p, Embedded in the Macrophage Mannose Receptor Gene, Contributes to Experimental Colitis

Approximately 40% of inflammatory bowel diseases (IBD) are associated with thromboembolic events causing significant rate of morbidity and mortality. These extra intestinal events of IBD are initiated by the qualitative and quantitative abnormalities in both coagulation and fibrinolytic factors producing states of hypercoagulability. Nevertheless, the interrelationship between IBD pathogenesis and hypercoagulability condition is not well understood (Figure 1). Here we examine the role of a coagulable state triggered by impaired fibrinolysis in the development of chronic colonic inflammation. Plasminogen (Plg) is the primary fibrinolytic enzyme, becomes activated to serine protease plasmin to dissolve the fibrin clot and to counterbalance hypercoagulability. The rapidity of IBD is caused by combining the effects of genetic and environmental factors. Our data show that when fed with a high fat diet (HFD, 45% milk fat), mouse knockout of Plg (Plg-/mice) developed continuous lesions in the colon with multiple inflammatory polyps (as of 8 weeks, n=15) bearing ulcers. This pathophysiology was not observed in HFD fed wild type (Plg+/+) mice and standard chow diet fed Plg+/+ and Plg-/mice. The increased inflammatory cell infiltration in the colon of HFD fed Plg-/mice was corroborated with increased levels of pro-inflammatory cytokines (IL-6, IL-17 & TNF alpha). In addition, HFD-fed Plg-/mice expressed reduced levels of colonic epithelial tight junctions (Claudin1, Occludin and ZO1), a finding compatible with an impaired epithelial barrier function, compared to Plg+/+ mice. Moreover, HFD fed Plg-/mice showed increased levels of plasma endotoxin, an indicator of impaired intestinal barrier function, compared with HFD-fed Plg+/+ mice. All these pathologies of HFD fed Plg-/mice were associated with excessive fibrin deposition in both vascular and extravascular space in the colon compared with HFD fed Plg+/+ mice providing a link between fibrin deposition and inflammation. Altogether, our present data imply that fibrinolytic pathway plays a crucial role in colon homeostasis and defects in this pathway can cause impaired colon barrier function and sustained colonic inflammation. In depth exploration of this pathway will provide a clue towards the potential role of Plg in colon homeostasis. This study will also challenge current paradigms on the relationship between coagulation abnormalities and IBD, which presume that these abnormalities are a consequence rather than a cause of the disease.

Mo1825 The Interaction of Enteric Bacterial Effectors With Host Engulfment Pathway in Phagocytes Regulates the Pathogenesis of Infection

Approximately 40% of inflammatory bowel diseases (IBD) are associated with thromboembolic events causing significant rate of morbidity and mortality. These extra intestinal events of IBD are initiated by the qualitative and quantitative abnormalities in both coagulation and fibrinolytic factors producing states of hypercoagulability. Nevertheless, the interrelationship between IBD pathogenesis and hypercoagulability condition is not well understood (Figure 1). Here we examine the role of a coagulable state triggered by impaired fibrinolysis in the development of chronic colonic inflammation. Plasminogen (Plg) is the primary fibrinolytic enzyme, becomes activated to serine protease plasmin to dissolve the fibrin clot and to counterbalance hypercoagulability. The rapidity of IBD is caused by combining the effects of genetic and environmental factors. Our data show that when fed with a high fat diet (HFD, 45% milk fat), mouse knockout of Plg (Plg-/mice) developed continuous lesions in the colon with multiple inflammatory polyps (as of 8 weeks, n=15) bearing ulcers. This pathophysiology was not observed in HFD fed wild type (Plg+/+) mice and standard chow diet fed Plg+/+ and Plg-/mice. The increased inflammatory cell infiltration in the colon of HFD fed Plg-/mice was corroborated with increased levels of pro-inflammatory cytokines (IL-6, IL-17 & TNF alpha). In addition, HFD-fed Plg-/mice expressed reduced levels of colonic epithelial tight junctions (Claudin1, Occludin and ZO1), a finding compatible with an impaired epithelial barrier function, compared to Plg+/+ mice. Moreover, HFD fed Plg-/mice showed increased levels of plasma endotoxin, an indicator of impaired intestinal barrier function, compared with HFD-fed Plg+/+ mice. All these pathologies of HFD fed Plg-/mice were associated with excessive fibrin deposition in both vascular and extravascular space in the colon compared with HFD fed Plg+/+ mice providing a link between fibrin deposition and inflammation. Altogether, our present data imply that fibrinolytic pathway plays a crucial role in colon homeostasis and defects in this pathway can cause impaired colon barrier function and sustained colonic inflammation. In depth exploration of this pathway will provide a clue towards the potential role of Plg in colon homeostasis. This study will also challenge current paradigms on the relationship between coagulation abnormalities and IBD, which presume that these abnormalities are a consequence rather than a cause of the disease.

Ovarian and Renal Vein Thrombosis: A Rare Cause of Fever Outer the Postpartum Period.

Although there is no other underlying disease, women can sometimes experience rare and serious diseases such as ovarian vein thrombosis (OVT) and renal vein thrombosis (RVT) after giving birth. The widespread development of thrombosis is treated for the first time in this study. Stasis, coagulation factor abnormalities, and intimal damage to the venous thrombosis risk can increase during pregnancy. It was mentioned that it diagnoses an abnormality in the hypercoagulability half of women with OVT. Despite the hypercoagulant abnormality observed in pregnant women, it was very unusual that the renal vein thrombosis led to this complication. It can lead to severe complication of OVT which can even cause death. It was the first time that the renal vein and ovarian vein thrombosis were observed in the postpartum period, and there was no coagulation abnormality. It is known that the thrombus in the postpartum period can be observed with the fever of unknown origin. The problematic, but rarely observed, postpartum disease such as ovarian venous thrombosis (OVT) is generally observed in the right ovarian vein. In this disease, avoiding the resulting laparotomy heparin and intravenous antibiotics is best solution for the patient. If it is to be noted a fever for unknown reasons, that it be thrombosis.

Platelet Hyper-Aggregation and Abnormalities of Coagulation Factors in Young Diabetic Patients

Diabetic vascular disease is conveniently divided into two main categories: microvascular diseases and macrovascular diseases. The changes involving the smallest blood vessels - the capillary and pre-capillary arteriolesare microvascular changes. The cross sectional case-control study was done on forty young diabetic patients for their platelet aggregation response to ADP, plasma fibrinogen and vWF in relation to the age and BMI matched 10 nondiabetic control subjects (Age in years : 23.7 ± 2.26 in control vs 24.33 ± 3.29 in subjects, and BMI in kg/m2. The lipid profile, C-peptide, C-peptide: glucose and other anthropometric measurements of the diabetic and control subjects were also measured to find out any possible correlation. The platelet aggregation with ADP in diabetics was found to be significantly higher (in diabetics 76.56 ± 16.92 percent compared to controls 62.90 ± 12.35 percents; (P< 0.27). Plasma fibrinogen and plasma von Willebrand factors were found to be significantly higher in young diabetics compared to the non-diabetic counterparts (Plasma fibrinogen in mg/l; 1075.90 ± 455.16 in control vs 1569.15 ± 731.42 in diabetic, P<0.048; plasma vWF in iu/ml; 1.372 ± 0.340 in control vs 1.884 ± 0.51 in diabetic, P<0.001). Fasting plasma glucose was higher and C-peptide - glucose ratio lower in diabetic subjects compared to the controls (Fasting plasma glucose in mmol/l; 3.48 ± 0.38 in control vs 16.02 ± 8.58 in diabetic; C-peptide-glucose ratio 0.426 ± 0.133 in controls vs 0.116 ± 0.105 in diabetics, P<.001). Thus hyperglycemia, endothelial dysfunction, elevated vWF and insulin resistance were supposed to be interlinked. DOI: http://dx.doi.org/10.3329/medtoday.v25i2.17920 Medicine Today 2013 Vol.25(2): 56-59