Gastrointestinal Bleeding in Congenital Bleeding Disorders.

Gastrointestinal bleeding (GIB) is serious, intractable, and potentially life-threatening condition. There is considerable heterogeneity in GIB phenotypes among congenital bleeding disorders (CBDs), making GIB difficult to manage. Although GIB is rarely encountered in CBDs, its severity in some patients makes the need for a comprehensive and precise assessment of underlying factors and management approaches imperative. Initial evaluation of GIB begins with assessment of hematological status; GIB should be ruled out in patients with chronic anemia, and in presentations that include hematemesis, hematochezia, or melena. High-risk patients with recurrent GIB require urgent interventions such as replacement therapy for treatment of coagulation factor deficiency (CFD). However, the best management strategy for CFD-related bleeding remains controversial. While several investigations have identified CBDs as potential risk factors for GIB, research has focused on assessing the risks for individual factor deficiencies and other CBDs. This review highlights recent findings on the prevalence, management strategies, and alternative therapies of GIB related to CFDs, and platelet disorders.

Impairment in selenocysteine synthesis as a candidate mechanism of inducible coagulopathy in COVID-19 patients.

Coagulopathy has recently been recognized as a recurring complication of COVID-19, most typically associated with critical illness. There are epidemiological, mechanistic and transcriptomic evidence that link Selenium with SARS-CoV-2's intracellular latency. Taking into consideration the vital role of selenoproteins in maintaining an adequate immune response, endothelial homeostasis and a non-prothrombotic platelet activation status, we propose that impairment in selenocysteine synthesis, via perturbations in the aforementioned physiological functions, potentially constitutes a mechanism of coagulopathy in COVID 19 patients other than those developed in critical illness.

Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study.

OBJECTIVE: Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. METHODS: A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. RESULTS: A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. CONCLUSION: COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable.

[Complex management of type 2 heparin-induced thrombocytopenia in patients with major bleeding tendency: two case report]. / Prise en charge de la thrombopénie induite par l'héparine immuno-allergique de type 2 au travers de deux cas cliniques chez des patients à risque hémorragique majeur.

Type 2 heparin-induced thrombocytopenia (HIT 2) is a rare pro-thrombotic disorder occurring in patients treated with heparin. It is defined as a clinical-biological syndrome associating the sudden onset of a thrombocytopenia, characterized by a drop of more than 50% of the initial platelet count, and thrombosis. We report two cases of HIT 2 occurring in patients with major bleeding tendency. The first HIT occurred in a patient whose management, in accordance with current guidelines, made it possible to control the thrombocytopenia and the anticoagulation despite the complexity of adapting and monitoring treatments in the context of recent cerebral hemorrhage. The second refers to an autoimmune HIT, which occurred in a patient whose management required the use of alternative therapies to the standard treatments suggested for HIT 2, to correct the severe refractory thrombocytopenia.

Herbal medicines for metabolic diseases with blood stasis: A protocol for a systematic review and meta-analysis.

BACKGROUND: Herbal medicines have the potential to be alternative treatments for metabolic diseases. This systematic review will assess the efficacy of herbal medicines in treating metabolic diseases with blood stasis. METHODS AND ANALYSIS: We will search MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, 2 Korean medical databases (OASIS, NDSL), a Chinese database (China National Knowledge Infrastructure, CNKI), and a Japanese database (J-STAGE) for relevant literature. We will include all randomized controlled trials (RCTs) or quasi-RCTs evaluating the effectiveness of herbal medicine. Participants of both sexes and of any age with clinically diagnosed metabolic disease with blood stasis will be included. Primary outcomes will include Blood-stasis syndrome score, TC, TG, HDL-C and LDL-C. Secondary outcomes will Blood pressure, FBS. ECG, prevalence rate of heart disease, and response rate. The risk of bias will be assessed using the Cochrane tool for assessing risk of bias. DISCUSSION: The findings of this study will provide a summary of the current state of evidence regarding the effectiveness of types of herbal medicine in managing metabolic disease with blood stasis. In addition, this review will be expected to provide a base for clinical trials to confirm the efficacy of herbal medicine for treatments of metabolic disease with blood stasis. TRIAL REGISTRATION NUMBER: PROSPERO 2018 CRD42018090179.

Thromboelastometry as an Alternative Method for Coagulation Assessment in Pediatric Patients Undergoing Invasive Procedures: A Pilot Study.

INTRODUCTION: Standard coagulation tests (activated partial thromboplastin time [aPTT] and prothrombin time [PT]) are used for the assessment of coagulation profile in critically ill pediatric patients undergoing invasive interventions such as insertion of central venous catheter, tonsillectomy, laparotomy, etc. However, these tests do not reflect the profile of whole blood coagulation. Rotational thromboelastometry (ROTEM) as a point of care (POC) viscoelastic test may serve as an alternative method. Due to its ability to assess coagulation profile of the whole blood, it might yield normal results despite prolonged aPTT/PT results. The aim of this study was to find out if there was any severe bleeding during or after invasive procedures if ROTEM test was normal despite prolonged values of aPTT/PT in pediatric patients. MATERIALS AND METHODS: We retrospectively analyzed data for the years 2015 to 2017 for pediatric patients with prolonged values of aPTT or PT and normal ROTEM tests-internal thromboelastometry (INTEM) (assessing internal pathway of coagulation) and external thromboelastometry (EXTEM) (assessing external pathway of coagulation)-and we looked for severe bleeding during or after invasive procedures. RESULTS: In 26 pediatric patients (children from 2 months to 17 years old), we found that INTEM and EXTEM tests showed normal coagulation despite prolonged values of aPTT ratio with a median of 1.47 (minimum 1.04 and maximum 2.05), international normalized ratio with a median of 1.4 (minimum 0.99 and maximum 2.10), and PT ratio with a median of 1.30 (minimum 0.89 and maximum 2.11). In these patients, no severe bleeding was observed during interventions or postoperatively. CONCLUSION: Our data support using thromboelastometry method as an alternative coagulation test for the assessment of coagulation profile in pediatric patients undergoing surgical or other invasive procedures, especially using it as a POC test. All invasive procedures in our study were performed without severe bleeding despite prolonged values of PT/aPTT with normal ROTEM results. It seems that ROTEM assessment of coagulation may lead to decreased administration of fresh frozen plasma and shorten time of patient preparation for intervention.

Iron deficiency and anemia in patients with inherited bleeding disorders.

Patients with inherited bleeding disorders are predisposed to acute and chronic blood loss, which places them at high risk of iron deficiency anemia (IDA). The clinical effects of iron deficiency (ID) and IDA in the general population are significant and include low energy, reduced cardiovascular health, impaired cognition and reduced health-related quality of life. However, the incidence and impact of ID and IDA in patients with bleeding disorders is largely unknown. Here we review our approach to the diagnosis and management of iron deficiency in patients with inherited bleeding disorders. Given their risk of future iron losses, we propose more aggressive iron supplementation and higher target ferritin values in patients with ID and ongoing bleeding.

Small intestinal bacterial overgrowth (SIBO) and vitamin K-responsive coagulopathy: a previously unrecorded association.

A 17-year-old woman, with a history of three operations on the upper gut in early life and intermittent diarrhoea, presented with a history of epistaxis and leg ecchymosis for the previous 3 months. Initial investigation revealed mild anaemia, low serum albumin, moderately elevated aminotransferases and an exceedingly prolonged prothrombin time (PT) which was promptly shortened to normal by intravenous vitamin K. Additional investigations revealed a grossly abnormal glucose hydrogen breath test, a dilated duodenum and deficiencies of vitamins A, D and E. Repeated courses of antimicrobial agents caused prompt but transient shortening of PT and eventually a duodenal-jejunal anastomosis was performed. Since then, up to 36 months later, the patient has been in good general health and PT has been consistently normal with no vitamin K supplementation. Small intestinal bacterial overgrowth has previously been associated with several conditions but this is the first description of its association with vitamin K-responsive coagulopathy.

Factores asociados a coagulopatías adquiridas en una unidad de cuidados intensivos / Factors Associated with Acquired Coagulopathies in an Intensive Care Unit

Introducción: en los pacientes críticos existe un desequilibrio entre las actividades procoagulantes y las anticoagulantes, por ello las alteraciones de la coagulación o coagulopatías son una complicación frecuente que se asocia con una elevada morbilidad y mortalidad. Objetivos: identificar factores de riesgo asociados con coagulopatías adquiridas en pacientes ingresados y analizar la relación entre coagulopatía y mortalidad. Métodos: se realizó un estudio longitudinal prospectivo, donde se revisaron complementarios e historias clínicas de 29 pacientes ingresados en la unidad de cuidados intensivos del hospital Hermanos Ameijeiras, desde abril hasta junio de 2011. Se identificaron factores de riesgo asociados a las coagulopatías y se analizó su relación con la mortalidad. Resultados: se identificó la presencia de coagulopatías al ingreso en 58,62 por ciento, entre las 48-72 h 44,82 por ciento y en la última evaluación 51,73 por ciento. Predominó la coagulopatía por deficiencia de factores dependientes de vitamina K. Dentro de la unidad, el uso de hemocomponentes y la administración de aminoglucósidos resultaron estadísticamente significativos. Fallecieron 21 de los pacientes y en 13 de ellos se detectó la presencia de coagulopatía representando 44,8 por ciento. Conclusiones: se detectó que es dos veces más probable que a la persona que le administren hemocomponentes desarrolle algún tipo de coagulopatía y 5 veces más probable si se le administran aminoglucósidos. No se encontró relación significativa entre la presencia de coagulopatía y mortalidad, ni relación significativa entre la presencia de sangramiento y mortalidad(AU)

Introduction: There is an imbalance between procoagulant activities and anticoagulants in critical patients, so coagulation disorders or coagulopathies are a frequent complication associated with high morbidity and mortality. Objectives: To identify risk factors associated with acquired coagulopathies in hospitalized patients and to analyze the relationship between coagulopathy and mortality. Methods: A prospective longitudinal study was carried out. Complementary and clinical histories of 29 patients were reviewed. These patients had been admitted to the intensive care unit at Hermanos Ameijeiras hospital from April to June 2011. Risk factors associated with coagulopathies were identified. Mortality relationship was analyzed. Results: The presence of coagulopathies on admission was identified in 58.62 percent, 44.82 percent in 48-72 h and 51.73 percent in last assessment. Coagulopathy was predominant due to deficiency of vitamin K dependent factors. The use of blood components and the administration of aminoglycosides were statistically significant in the unit. Twenty one (21) patients died and thirteen (13) coagulopathy was detected, (44.8 percent). Conclusions: It was detected that it is twice as likely that the person receiving hemocomponents will develop some type of coagulopathy and five times more likely if they are administered aminoglycosides. No significant relationship was found between the presence of coagulopathy and mortality, nor significant relationship between the presence of bleeding and mortality(AU)

Factores asociados a coagulopatías adquiridas en una unidad de cuidados intensivos / Factors Associated with Acquired Coagulopathies in an Intensive Care Unit

Introducción: en los pacientes críticos existe un desequilibrio entre las actividades procoagulantes y las anticoagulantes, por ello las alteraciones de la coagulación o coagulopatías son una complicación frecuente que se asocia con una elevada morbilidad y mortalidad. Objetivos: identificar factores de riesgo asociados con coagulopatías adquiridas en pacientes ingresados y analizar la relación entre coagulopatía y mortalidad. Métodos: se realizó un estudio longitudinal prospectivo, donde se revisaron complementarios e historias clínicas de 29 pacientes ingresados en la unidad de cuidados intensivos del hospital Hermanos Ameijeiras, desde abril hasta junio de 2011. Se identificaron factores de riesgo asociados a las coagulopatías y se analizó su relación con la mortalidad. Resultados: se identificó la presencia de coagulopatías al ingreso en 58,62 por ciento, entre las 48-72 h 44,82 por ciento y en la última evaluación 51,73 por ciento. Predominó la coagulopatía por deficiencia de factores dependientes de vitamina K. Dentro de la unidad, el uso de hemocomponentes y la administración de aminoglucósidos resultaron estadísticamente significativos. Fallecieron 21 de los pacientes y en 13 de ellos se detectó la presencia de coagulopatía representando 44,8 por ciento. Conclusiones: se detectó que es dos veces más probable que a la persona que le administren hemocomponentes desarrolle algún tipo de coagulopatía y 5 veces más probable si se le administran aminoglucósidos. No se encontró relación significativa entre la presencia de coagulopatía y mortalidad, ni relación significativa entre la presencia de sangramiento y mortalidad(AU)

Introduction: There is an imbalance between procoagulant activities and anticoagulants in critical patients, so coagulation disorders or coagulopathies are a frequent complication associated with high morbidity and mortality. Objectives: To identify risk factors associated with acquired coagulopathies in hospitalized patients and to analyze the relationship between coagulopathy and mortality. Methods: A prospective longitudinal study was carried out. Complementary and clinical histories of 29 patients were reviewed. These patients had been admitted to the intensive care unit at Hermanos Ameijeiras hospital from April to June 2011. Risk factors associated with coagulopathies were identified. Mortality relationship was analyzed. Results: The presence of coagulopathies on admission was identified in 58.62 percent, 44.82 percent in 48-72 h and 51.73 percent in last assessment. Coagulopathy was predominant due to deficiency of vitamin K dependent factors. The use of blood components and the administration of aminoglycosides were statistically significant in the unit. Twenty one (21) patients died and thirteen (13) coagulopathy was detected, (44.8 percent). Conclusions: It was detected that it is twice as likely that the person receiving hemocomponents will develop some type of coagulopathy and five times more likely if they are administered aminoglycosides. No significant relationship was found between the presence of coagulopathy and mortality, nor significant relationship between the presence of bleeding and mortality(AU)

How I treat poisoning with vitamin K antagonists.

Severe deficiency of vitamin K-dependent proteins in patients not maintained on vitamin K antagonists is most commonly associated with poisoning by or surreptitious ingestion of warfarin, warfarin-like anticoagulants, or potent rodenticides ("superwarfarins"), such as brodifacoum. Serious bleeding manifestations are common. Superwarfarins are 2 orders of magnitude more potent than warfarin and have a half-life measured in weeks. These rodenticides are readily available household environmental hazards and are sometimes consumed accidentally or as manifestations of psychiatric disease. Immediate diagnosis and proper therapy is critically important to minimize morbidity and mortality because this condition, affecting thousands of patients annually, is reversible. Treatment with large doses of oral vitamin K1, often over months to years, to maintain a near-normal prothrombin time can reverse the coagulopathy associated with superwarfarins. Although these patients initially present to various medical specialties, the hematologist is often consulted to offer the definitive diagnosis and proper therapy.

Spinal haematoma after removal of a thoracic epidural catheter in a patient with coagulopathy resulting from unexpected vitamin K deficiency.

Postoperative epidural analgesia is effective and widely utilised after major abdominal surgery. Spinal haematoma is a rare and devastating complication after epidural analgesia. Well-established risk factors for the development of spinal haematoma after neuraxial procedures have been documented. We present the case of a patient with normal pre-operative coagulation parameters who developed a spinal haematoma more than 24 h after removal of an epidural catheter; she had been without oral intake for only 4 days during which time she developed vitamin K-deficient coagulopathy. Clinicians should consider pre-operative screening of coagulation (International Normalised Ratio), or giving vitamin K supplementation, before performing neuraxial procedures in patients who are at risk of developing vitamin K deficiency or coagulopathy in the peri-operative period.

Energy metabolism disorder and myocardial injury in chronic myocardial ischemia with Qi deficiency and blood stasis syndrome based on 2-DE proteomics.

OBJECTIVE: To inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis (2-DE) map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome. METHODS: Ameroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome. RESULTS: The preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDITOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 (NAD+) alpha, NADH dehydrogenase (NAD) Fe-S protein 1, chain A (crystal structure of aldose reductase by binding domain reveals a new Nadph), heat shock protein 27 (HSP27), oxidoreductase (NAD-binding protein), antioxidant protein isoform, cardiac troponin T (cTnT), myosin (myosin light polypeptide), cardiac alpha tropomyosin, apolipoprotein A-I and albumin. CONCLUSION: Down-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker(s) for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine.

Sangre y Cirugía. EStrategia de Ahorro en cirugía cardiaca / Blood and Surgery. Strategic saving in cardiac surgery

El incremento de intervenciones quirúrgicas y su mayor complejidad y agresividad, especialmente en cirugía cardiovascular y trasplantes, junto con el envejecimiento de la población ha supuesto un considerable aumento de la demanda de transfusión sanguínea y derivados hemáticos. Los riesgos médicos inherentes al uso de sangre homóloga, el rechazo por motivaciones personales, éticas o creencias religiosas y una insuficiente disponibilidad de hemoderivados consecuencia de la escasezde donaciones, ha condicionado la necesidad del desarrollo de procesos de ahorro de sangre en cirugía y la búsqueda de técnicas alternativas a la transfusión. Problemática que alcanza su máxima expresión en cirugía cardiaca bajo circulación extracorpórea, como consecuencia del alto consumo de sangre de los enfermos cardiológicos intervenidos. Con la experiencia que aporta un promedio de quinientas cirugías anuales de corazón se realiza una revisión sobre las diferentes medidas y procedimientos asociados al ahorro de sangre en cirugía, especialmente en cirugía cardiovascular (AU)

The increase in the number of operations and their greater complexity and aggressiveness, especially in cardiovascular surgery and transplants, together with the aging of the population, has entailed an increase in the demand for transfusion and haematological derivates. The inherent medical risks of homolog blood usage, rejection for personal motivations, ethical and religious beliefs and insufficient availability of haematological derivates as a consequence of the shortage of donations, have conditioned the necessity for the development of processes for saving blood during surgery and the search for alternative techniques to transfusion. This is a problem which has its highest repercussions in cardiac surgery with cardio-pulmonary by-pass because of the high consumption of blood of patients undergoing cardiac surgery. With the experience of approximately 500 operations per year a review of the different measures and procedures associated with saving blood in surgery has been carried out, especially with regard to cardiovascular surgery (AU)

Blood management in pediatric spinal deformity surgery: review of a 2-year experience.

BACKGROUND: Pediatric scoliosis surgery is associated with considerable blood loss and allogenic transfusions. Transfusions contribute to morbidities and cost. A perioperative pediatric blood management program was implemented at our institution. Patients received preoperative evaluation, cell salvage, topical hemostasis, antifibrinolytics, and hypotensive anesthesia. STUDY DESIGN AND METHODS: The study was a 2-year retrospective cohort review of the program's population from September 2007 through August 2009. RESULTS: A total of 110 scoliosis surgeries were performed with only 34 and 12% of the patients requiring preoperative oral iron and erythropoietin, respectively. Neuromuscular scoliosis patients had more repaired segments and a larger transfusion rate than idiopathic scoliosis patients (36% vs. 1.7%, p = 0.001). Transfused patients had more blood loss relative to their blood volume (p = 0.001) and blood loss was associated with higher Cobb angles (p = 0.04). Logistic regression revealed that blood loss (p = 0.001), number of segments fused (p = 0.004), and lower patient weight (p = 0.007) are associated with increased odds for transfusion. Twelve patients (10.9%) were identified with low von Willebrand activity with a trend toward higher blood losses (p = 0.07) with lower activity levels. CONCLUSION: Transfusion requirements in scoliosis patients are dependent on blood loss as determined by Cobb angles and number of segments fused relative to the patients' blood volume as determined by weight. Implementation of a blood management protocol resulted in a low transfusion rate and unexpectedly led to the preoperative diagnosis of a number of patients with low levels of von Willebrand activity.

Recombinant factor VIIa reduces bleeding after blunt liver injury in coagulopathic, hypofibrinogenaemic pigs.

BACKGROUND: Recombinant factor VIIa (rFVIIa) has been successfully used in various clinical conditions to treat severe coagulopathy, but its efficacy may be affected by the underlying conditions. We therefore investigated the efficacy of rFVIIa treatment under conditions of hypofibrinogenaemia in a pig model of blunt liver injury. METHODS: Severe haemodilution was instigated in four groups of seven anaesthetized pigs. Before inflicting liver injury, animals were assigned to receive either 70 mg kg(-1) fibrinogen (fibrinogen group) or placebo (control group). Thirty seconds after injury, rFVIIa (180 µg kg(-1)) (rFVIIa and fibrinogen+rFVIIa groups) or vehicle (control and fibrinogen groups) was administered. Haemodynamic variables, coagulation parameters, and blood loss were monitored for 2 h. Histology was examined to evaluate the presence of thrombi and the consistency of liver injury. RESULTS: At the end of the observation period, total blood loss [median (range)] decreased in all intervention groups [fibrinogen: 1275 (1221-1439) ml, P=0.036; rFVIIa: 966 (923-1136) ml, P=0.008; fibrinogen+rFVIIa: 678 (475-756) ml, P=0.008] when compared with control animals [blood loss: 1752 (1735-2221) ml]. The mortality rate in the control group was 100%, whereas only 42% of fibrinogen-substituted animals died (P=0.023). All animals treated with rFVIIa or fibrinogen+rFVIIa (P<0.001) survived and no signs of thromboembolism were observed. CONCLUSIONS: rFVIIa under conditions of hypofibrinogenaemia exhibited a positive impact on coagulation parameters and a reduction in blood loss. These effects were significantly improved after prior substitution with fibrinogen.

Differential gene expression profiles in coronary heart disease patients of blood stasis syndrome in traditional Chinese medicine and clinical role of target gene.

OBJECTIVE: To investigate the differential gene expression profiles in coronary heart disease (CHD) patients of blood-stasis syndrome (BSS) by oligonucleotide microarray technique, and the clinical significance of target gene. METHODS: Subjects were assigned to CHD patients with BSS (n=8), CHD patients without BSS (n=8), and BSS patients without CHD (n=8) based on coronary angiography and the diagnostic criteria of BSS. The sex- and age-matched healthy volunteers (n=8) were enrolled as the control group. Venous blood samples were collected for RNA extraction; Test-3 chip was employed to examine the quality of samples. Then, the samples were hybridized with Affymetrix U133 Plus 2.0 array to compare the gene expression profiles among the four groups. Gene-array scanner and gene chip operating software were applied to screen out hybridization signals and analyze gene expression, respectively. Based on the comparison of the samples of the four groups, the differential genes related with CHD and BSS were analyzed with Gene Ontology (GO) and pathway, and target genes selected were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR). Thirty CHD patients with BSS were selected according to the former criteria and 40 healthy as controls. The serum concentration of interleukin-8 (IL-8) was determined by double-antibody sandwich avidin-biotin peroxidase complex enzyme-linked (ABC-ELISA). RESULTS: A total of 107 differential genes were found being associated with CHD, including 48 up-regulated genes and 59 down-regulated genes. Among these 107 differential genes, 14 genes (13.1%) were found related to inflammatory reaction and immune response through GO analysis. In the pathway analysis, 4 of 15 conspicuous pathways were referred to the inflammation and immune response. Among 48 differential genes related to BSS, 26 genes were up-regulated, and 22 were down-regulated. Five of the 48 genes (10.4%) and 5 of 10 significant pathways were involved in inflammation and immunity. The results of real-time RT-PCR proved the accuracy of the gene chip. The patients have markedly higher level of serum IL-8 compared to the controls (P<0.05). CONCLUSION: The correlation of inflammatory- and immune-related genes with CHD patients of BSS was revealed at the level of nucleic acid, and the target gene IL-8 may play a role in the pathobiology of CHD with BSS.

Inflammatory bowel disease: a paradigm for the link between coagulation and inflammation.

Inflammatory bowel diseases (IBDs) are associated with platelet activation and an increased risk for thromboembolism. While the mechanisms that underlie the altered platelet function and hypercoagulable state in IBD remain poorly understood, emerging evidence indicates that inflammation and coagulation are interdependent processes that can initiate a vicious cycle wherein each process propagates and intensifies the other. This review addresses the mechanisms that may account for the mutual activation of coagulation and inflammation during inflammation and summarizes evidence that implicates a role for platelets and the coagulation system in the pathogenesis of human and experimental IBD. The proposed link between inflammation and coagulation raises the possibility of targeting the inflammation-coagulation interface to reduce the morbidity and mortality associated with IBD.