In vivo fluorescence molecular tomography of induced haemarthrosis in haemophilic mice: link between bleeding characteristics and development of bone pathology.

BACKGROUND: Haemophilic arthropathy is a chronic and debilitating joint disease caused by recurrent spontaneous joint bleeds in patients with haemophilia. Understanding how characteristics of individual joint bleeds relate to the subsequent development of arthropathy could improve management and prevention of this joint disease. Here, we aimed to explore relations between joint bleed characteristics and development of bone pathology in a mouse model of haemophilic arthropathy by using novel in vivo imaging methodology. METHODS: We characterised induced knee bleeds in a murine model of haemophilic arthropathy by quantitative in vivo fluorescence molecular tomography (FMT) and by measurements of changes in the diameter of the injured knee. Wild-type mice and non-injured haemophilic mice acted as controls. Development of arthropathy was characterised by post mortem evaluation of bone pathology by micro-CT 14 days after bleed-induction. In an in vitro study, we assessed the effect of blood on the quantification of fluorescent signal with FMT. RESULTS: In most injured haemophilic mice, we observed significant loss of trabecular bone, and half of the mice developed pathological bone remodelling. Development of pathological bone remodelling was associated with significantly increased fluorescent signal and diameter of the injured knee just 1 day after induction of the bleed. Further, a correlation between the fluorescent signal 1 day after induction of the bleed and loss of trabecular bone reached borderline significance. In the in vitro study, we found that high concentrations of blood significantly decreased the fluorescent signal. CONCLUSION: Our results add novel insights on the pathogenesis of haemophilic arthropathy and underline the importance of the acute phase of joint bleeds for the subsequent development of arthropathy.

Abrogating fibrinolysis does not improve bleeding or rFVIIa/rFVIII treatment in a non-mucosal venous injury model in haemophilic rodents.

Essentials The efficacy of systemic antifibrinolytics for hemophilic non-mucosal bleeding is undetermined. The effect of systemically inhibiting fibrinolysis in hemophilic mice and rats was explored. Neither bleeding nor the response to factor treatment was improved after inhibiting fibrinolysis. The non-mucosal bleeding phenotype in hemophilia A appears largely unaffected by fibrinolysis. SUMMARY: Background Fibrinolysis may exacerbate bleeding in patients with hemophilia A (HA). Accordingly, antifibrinolytics have been used to help maintain hemostatic control. Although antifibrinolytic drugs have been proven to be effective in the treatment of mucosal bleeds in the oral cavity, their efficacy in non-mucosal tissues remain an open question of significant clinical interest. Objective To determine whether inhibiting fibrinolysis improves the outcome in non-mucosal hemophilic tail vein transection (TVT) bleeding models, and to determine whether a standard ex vivo clotting/fibrinolysis assay can be used as a predictive surrogate for in vivo efficacy. Methods A highly sensitive TVT model was employed in hemophilic rodents with a suppressed fibrinolytic system to examine the effect of inhibiting fibrinolysis on bleeding in non-mucosal tissue. In mice, induced and congenital hemophilia models were combined with fibrinolytic attenuation achieved either genetically or pharmacologically (tranexamic acid [TXA]). In hemophilic rats, tail bleeding was followed by whole blood rotational thromboelastometry evaluation of the same animals to gauge the predictive value of such assays. Results The beneficial effect of systemic TXA therapy observed ex vivo could not be confirmed in vivo in hemophilic rats. Furthermore, neither intravenously administered TXA nor congenital knockout of the fibrinolytic genes encoding plasminogen or tissue-type plasminogen activator markedly improved the TVT bleeding phenotype or response to factor therapy in hemophilic mice. Conclusions The findings here suggest that inhibition of fibrinolysis is not effective in limiting the TVT bleeding phenotype of HA rodents in non-mucosal tissues.

Bone marrow transplantation: the battle for hope in the face of fear.

PURPOSE/OBJECTIVES: To describe patients' experience of having an autologous bone marrow transplantation (BMT). DESIGN: Hermeneutic phenomenologic, descriptive, and interpretive. SETTING: Outpatient treatment area of a comprehensive cancer center in the Southwest. SAMPLE: 20 adult survivors of autologous BMT, 15 women and 5 men, with a mean age of 46 years. METHODS: Content analysis of verbatim transcriptions of open-ended interviews using hermeneutic phenomenology, which combines descriptive and interpretive phenomenology. CONCLUSIONS: These patients illustrate that fear, a predominant reality when undergoing autologous BMT, is balanced with hope for survival. The overarching fear, fear of death, often was related to the unknown, including cancer recurrence. The fear of the unknown also came from being unprepared physically and emotionally. Losses were intertwined with these fears and included loss of both control and trust in one's body. Patients discussed fear of leaving the hospital and not having someone "constantly looking at you to make sure that the cancer isn't back." These fears and losses changed patients' view of life and led to a need for help in bringing closure to the experience. IMPLICATIONS FOR NURSING PRACTICE: Specific nursing actions to help allay fear include providing information about both feelings and procedures, giving opportunities to discuss fears and losses, arranging meetings with others who have had a BMT or suggesting an appropriate support group, and including family in all interventions, as appropriate. Reducing fears with these interventions helped patients maintain hope. By understanding the relationship between hope and fear, nurses caring for people having BMT can use specific strategies to decrease fear, hence increasing hope in patients. Nursing education can emphasize the need to adequately prepare patients. Further research is indicated to explore the effectiveness of interventions to prepare patients for BMT and the interplay between hope and fear.