Comparison of the effect of dabigatran and dalteparin on thrombus stability in a murine model of venous thromboembolism.

UNLABELLED: ESSENTIALS: Does thrombus stability alter the presentation of venous thromboembolism and do anticoagulants alter this? In a murine model, we imaged a femoral vein thrombus and quantified emboli in the pulmonary arteries. Dabigatran decreases thrombus stability via factor XIII increasing embolization and pulmonary emboli. This cautions against the unapproved use of dabigatran for acute initial treatment of deep vein thrombosis. BACKGROUND: Venous thromboembolism (VTE) is a collective term for deep vein thrombosis (DVT) and pulmonary embolism (PE). Thrombus instability possibly contributes to progression of DVT to PE, and direct thrombin inhibitors (DTIs) may alter this. AIM: To develop a model to assess thrombus stability and its link to PE burden, and identify whether DTIs, in contrast to low-molecular-weight heparin (LMWH), alter this correlation. METHODS: Twelve minutes after ferric chloride-induced thrombus formation in the femoral vein of female mice, saline, dalteparin (LMWH) or dabigatran (DTI) was administered. Thrombus size and embolic events breaking off from the thrombus were quantified before treatment and at 10-min intervals after treatment for 2 h using intravital videomicroscopy. Lungs were stained for the presence of PE. RESULTS: Thrombus size was similar over time and between treatment groups. Total and large embolic events and pulmonary emboli were highest after treatment with dabigatran. Variations in amounts of pulmonary embolic events were not attributed to variations in thrombus size. Large embolic events correlated with the number of emboli per lung slice independent of treatment. Embolization in factor XIII deficient (FXIII(-/-) ) saline-treated mice was greater than that in wild-type (WT) saline-treated mice, but was similar to WT dabigatran-treated mice. CONCLUSION: We have developed a mouse model of VTE that can quantify emboli and correlate this with PE burden. Consistent with clinical data, dabigatran, a DTI, acutely decreases thrombus stability and increases PE burden compared with LMWH or saline, which is a FXIII-dependent effect.

Comparison of the effect of coagulation and platelet function impairments on various mouse bleeding models.

Haemostatic impairments are studied in vivo using one of several murine bleeding models. However it is not known whether these models are equally appropriate for assessing coagulation or platelet function defects. It was our study objective to assess the performance of arterial, venous and combined arterial and venous murine bleeding models towards impaired coagulation or platelet function. Unfractionated heparin (UFH) or αIIbß3inhibitory antibody (Leo.H4) were administered to mice, and their effects on bleeding in saphenous vein, artery, and tail tip transection models were quantified and correlated with their effects on plasma clotting and ADP-induced platelet aggregation, respectively. All models exhibited similar sensitivity with UFH (EC50 dose = 0.19, 0.13 and 0.07 U/g, respectively) (95% CI = 0.14 - 0.27, 0.08 - 0.20, and 0.03 - 0.16 U/g, respectively). Maximal inhibition of ex vivo plasma clotting could be achieved with UFH doses as low as 0.03 U/g. In contrast, the saphenous vein bleeding model was less sensitive to αIIbß3 inhibition (EC50 = 6.9 µg/ml) than tail transection or saphenous artery bleeding models (EC50 = 0.12 and 0.37 µg/ml, respectively) (95% CI = 2.4 - 20, 0.05 - 0.33, and 0.06 - 2.2 µg/ml, respectively). The EC50 of Leo.H4 for ADP-induced platelet aggregation in vitro (8.0 µg/ml) was at least 20-fold higher than that of the tail and arterial, but not the venous bleeding model. In conclusion, venous, arterial and tail bleeding models are similarly affected by impaired coagulation, while platelet function defects have a greater influence in models incorporating arterial injury.

Identification of child maltreatment in Iranian children with the parent-child conflict tactics scale.

BACKGROUND: Child abuse and neglect is a worldwide problem and varies across many sociodemographic characteristics. AIM: The aim of this study was to examine the prevalence of different types of child maltreatment in Iranian kids according to the reports of their caregivers. SUBJECTS AND METHODS: In this cross-sectional study, 562 mothers with the last child aged between 1 and 12 years were recruited based on purposeful sampling method in one pediatric referent Mazandaran province, Iran. Child maltreatment among eligible participants was assessed by a validated version of conflict tactics scale for parent and child. Data were analyzed using Pearson Correlation coefficient and one-way ANOVA. RESULTS: Prevalence of emotional assault, physical assault, and child neglect were respectively 90.6% (509/562), 82.9% (466/562) and 78.8% (443/562), which were more frequent in preschool age children. Furthermore, different kinds of child maltreatments were correlated with each other (P < 0.001). CONCLUSION: Assessment of all forms of child maltreatment should be an important focus of evaluation in cases with one kind of child maltreatment. This is an important issue in preschool age children. Furthermore, this paper has some implications for health care providers in order to check some simple items to identify child abuse.

Diannexin, an annexin A5 homodimer, binds phosphatidylserine with high affinity and is a potent inhibitor of platelet-mediated events during thrombus formation.

BACKGROUND: Shielding of procoagulant phosphatidylserine (PS) with annexin A5 attenuates thrombosis, but annexin A5 (35.7 kDa) is rapidly cleared from the circulation. In contrast, Diannexin, a 73.1 kDa homodimer of annexin A5, has an extended half-life. OBJECTIVES: To quantify the affinity of Diannexin for PS, examine its interaction with activated platelets and determine its effects on platelet-mediated events during thrombus formation. METHODS: The affinities of Diannexin and annexin A5 for PS-containing lipid bilayers were compared using surface plasmon resonance, and binding to activated platelets was assessed by flow cytometry. Calibrated automated thrombography and thromboelastography were employed to study the effects of Diannexin on thrombin generation and platelet-fibrin clot formation, respectively, whereas intravital videomicroscopy was used to examine its effect on platelet accumulation and activation after laser-induced injury to murine cremaster arterioles, and a tail tip bleeding model was used to explore its effects on hemostasis. RESULTS: Diannexin and annexin A5 bind PS with K(D) values of 0.6 and 5 nm, respectively, and both bind to the same subpopulation of PS-exposing platelets. Diannexin inhibited thrombin generation and platelet-fibrin clot formation in vitro at 10 nm (P<0.05-0.001 compared with control), and reduced platelet accumulation at 1 µg g(-1) (P<0.05) and activation at 0.25 µg g(-1) (P<0.001) in experimentally induced arterial thrombi in mice while increasing blood loss at 1 µg g(-1) (P<0.01). CONCLUSIONS: Diannexin binds to PS with high affinity and is a potent inhibitor of platelet-mediated events during thrombus formation.

Changes in functional status and functional capacity following coronary artery bypass surgery.

The aim of the present study was to compare changes in health related-quality of life (H-RQOL) on physical functioning and mental health domains, changes in functional capacity before and 18 months after CABG surgery. Comprehensive data on 187 patients who underwent CABG surgery were prospectively collected, including preoperative factors and postoperative morbidity. Assessing functional status, the change in physical functioning score and change in mental health score were obtained using the physical functioning and mental health subscales out of the eight total subscales of the (SF-36) questionnaire. Also, functional capacity was estimated according to New York Heart Association (NYHA) class. The results showed 18 months after CABG surgery survival rates were (95.7%). Significant improvements in functional status were seen in physical functioning (p < 0.001), mental health (p < 0.000). However, there were no significant changes in the mean of functional status scores among patients in three age groups. Other significant improvement was found in functional capacity and NYHA class before and the 18 months after CABG. Functional status markedly and significantly improved after CABG surgery, particularly in physical functioning. However, the functional status among survivors of CABG surgery is worse than that of the general population. It seems further research is needed to identify factors explaining the change in H-RQOL to develop interventions to support patients.

Seroprevalence of hepatitis C infection and associated risk factors among addicted prisoners in Sari-Iran.

The aim of this study was to determine the seroprevalence of hepatitis C infection and associated risk factors among addicted prisoners in Sari-Iran. This is a simple random sampling cross sectional study that was performed on 312 addicted prisoner men at Khazarabad addicts' prison in Sari/Iran in September 2001. Their blood samples were examined through third generation enzyme immunoassay. Data were collected through questionnaires and interview. Associated risk factors were compared in 82 hepatitis C antibody positive addicts (the affected group) and 148 hepatitis C antibody negative addicts (the unaffected group). Out of 312 addicted prisoners, 96 were hepatitis C anti body positive. The seroprevalence of hepatitis C infection was found to be 30.8%. Major associated risk factors in the affected group were as follows: duration of addiction, duration of imprisonment (mean 48 months), route of drug administration, length of alcohol consumption, tattooing, shared usage of needles and razors, multiple sexual partners and type of drugs (p < 0.05). On multivariate logistic regression analysis these factors were found to be significant independent risk factors for HCV infection: tattooing (OR 100, 95% CI), multiple sexual partners (OR 4.97, 95% CI) and history of surgery (OR 6.23, 95% CI). It is concluded that hepatitis C infection had a considerable prevalence in addicted prisoners. High risk and unsafe behaviors were found to be the main factors of contamination.

Influence of short-chain fatty acids on iron absorption by proximal colon.

BACKGROUND: Short-chain fatty acids produced by bacterial fermentation in the colon enhance the local absorption of cations, such as calcium, that could be used to improve the bioavailability of iron if a significant colonic absorption of iron were to occur. METHODS: Iron (iron gluconate, 100 microM) absorption by the caecum of the rat was compared with that in proximal sites of the small bowel using the Ussing chamber model; the influence of probiotic bacteria (Propionibacterium freudenreichii) on iron absorption was assessed and compared with that of two of their fermentation products (acetic and propionic acids) using the Ussing chamber and the ligated colon with gamma emitting iron as experimental models. RESULTS: The caecum absorbed less iron than the duodenum, but significantly more than the jejunum and ileum. This occurred mainly through an enhanced mucosal transfer of iron uptake. Propionibacteria enhanced iron absorption from the proximal colon; the same effect was observed in the presence of viable bacteria, or the culture medium free of viable bacteria, or acetate and propionate or propionate alone. CONCLUSIONS: The proximal colon could be a significant site available for iron absorption; this absorption can be enhanced by local production of short-chain fatty acids such as propionate.