Extravascular factor IX pool fed by prophylaxis is a true hemostatic barrier against bleeding.

BACKGROUND: Factor (F)IX can bind to type IV collagen in the endothelial basement membrane and diffuse into extravascular spaces. Previous studies in rodents have reported a large biodistribution of FIX. OBJECTIVES: The aim of the study was to evaluate the potential hemostatic activity of extravascular FIX and its role in protecting against joint bleeds. METHODS: The capacity of 4 different FIX molecules (plasma-derived and recombinant) to bind type I and type IV collagen was studied here. FIX molecules were also administered intravenously at doses of 50 to 3000 IU/kg in FIX knockout mice. RESULTS: A specific FIX signal was detected in immunohistochemistry in the liver as well as in muscles and knee joints with recombinant FIX molecules injected at 1000 and 3000 IU/kg but not at the usual clinical doses of 50 to 100 IU/kg, while plasma-derived FIX generated a FIX signal at all doses, including 50 IU/kg. Such a signal was also detected after five 100 IU/kg daily infusions of recombinant FIX, suggesting that FIX can accumulate in the extravascular space during prophylaxis. The extravascular procoagulant activity of FIX, assessed in saphenous vein bleeding assays, was significantly higher in hemophilia B mice after these 5 days of prophylaxis compared to a single infusion of 100 IU/kg of FIX and assessment of FIX activity 7 days later. CONCLUSION: Taken together, these results show that in individuals with severe hemophilia B receiving regular prophylaxis with FIX, extravascular accumulation of FIX over time may have a significant impact on the coagulation capacity and protection toward bleeding.

Shear Forces Induced Platelet Clearance Is a New Mechanism of Thrombocytopenia.

BACKGROUND: Thrombocytopenia has been consistently described in patients with extracorporeal membrane oxygenation (ECMO) and associated with poor outcome. However, the prevalence and underlying mechanisms remain largely unknown, and a device-related role of ECMO in thrombocytopenia has been hypothesized. This study aims to investigate the mechanisms underlying thrombocytopenia in ECMO patients. METHODS: In a prospective cohort of 107 ECMO patients, we investigated platelet count, functions, and glycoprotein shedding. In an ex vivo mock circulatory ECMO loop, we assessed platelet responses and VWF (von Willebrand factor)-GP Ibα (glycoprotein Ibα) interactions at low- and high-flow rates, in the presence or absence of red blood cells. The clearance of human platelets subjected or not to ex vivo perfusion was studied using an in vivo transfusion model in NOD/SCID (nonobese diabetic/severe combined Immunodeficient) mice. RESULTS: In ECMO patients, we observed a time-dependent decrease in platelet count starting 1 hour after device onset, with a mean drop of 7%, 35%, and 41% at 1, 24, and 48 hours post-ECMO initiation (P=0.00013, P<0.0001, and P<0.0001, respectively), regardless of the type of ECMO. This drop in platelet count was associated with a decrease in platelet GP Ibα expression (before: 47.8±9.1 versus 24 hours post-ECMO: 42.3±8.9 mean fluorescence intensity; P=0.002) and an increase in soluble GP Ibα plasma levels (before: 5.6±3.3 versus 24 hours post-ECMO: 10.8±4.1 µg/mL; P<0.0001). GP Ibα shedding was also observed ex vivo and was unaffected by (1) red blood cells, (2) the coagulation potential, (3) an antibody blocking VWF-GP Ibα interaction, (4) an antibody limiting VWF degradation, and (5) supraphysiological VWF plasma concentrations. In contrast, GP Ibα shedding was dependent on rheological conditions, with a 2.8-fold increase at high- versus low-flow rates. Platelets perfused at high-flow rates before being transfused to immunodeficient mice were eliminated faster in vivo with an accelerated clearance of GP Ibα-negative versus GP Ibα-positive platelets. CONCLUSIONS: ECMO-associated shear forces induce GP Ibα shedding and thrombocytopenia due to faster clearance of GP Ibα-negative platelets. Inhibiting GP Ibα shedding could represent an approach to reduce thrombocytopenia during ECMO.

Colon cancer surgery in von Willebrand disease type 3 setting triggering vascular abnormalities on bowel anastomosis.

Background: von Willebrand disease (VWD) is associated with vascular malformations in the gastrointestinal tract. This complication, more frequent in VWD types 2A and 3, may be due to abnormal angiogenesis, but the precise mechanism is still unclear. Angiogenesis and inflammation are closely linked and can potentiate each other. Key Clinical Question: Can colon inflammation in the setting of cancer surgery potentiate angiogenesis in the VWD setting? Clinical Approach: A woman with VWD type 3 underwent partial colectomy twice for an adenocarcinoma. After managing the first surgery with a plasma-derived von Willebrand factor (VWF) concentrate (Wilfactin; LFB), refractory gastrointestinal bleeding occurred from neovessels on bowel anastomosis. After a multidisciplinary discussion, a second surgery was undertaken with a recombinant VWF concentrate (Veyvondi; Takeda Pharmaceuticals). Pathologic neovessels were again observed on the new anastomosis. Conclusion: Colectomy was complicated twice by pathologic neovessels on bowel anastomosis in 2 distinct procedures managed either with plasma-derived VWF or with recombinant VWF.

Suicide Prevention.

Suicide prevention begins with understanding depression and mental health protection.

Resistant Hypertension: Novel Insights.

Hypertension is the most common chronic disease and the leading risk factor for disability and premature deaths in the world, accounting for more than 9 million deaths annually. Resistant hypertension is a particularly severe form of hypertension. It was described 50 years ago and since then has been a very active field of research. This review aims at summarizing the most recent findings on resistant hypertension. The recent concepts of apparent- and true-resistant hypertension have stimulated a more precise definition of resistant hypertension taking into account not only the accuracy of blood pressure measurement and pharmacological class of prescribed drugs but also patient adherence to drugs and life-style recommendations. Recent epidemiological studies have reported a 10% prevalence of resistant hypertension among hypertensive subjects and demonstrated the high cardiovascular risk of these patients. In addition, these studies identified subgroups of patients with even higher morbidity and mortality risk, probably requiring a more aggressive medical management. In the meantime, guidelines provided more standardized clinical work-up to identify potentially reversible causes for resistant hypertension such as secondary hypertension. The debate is however still ongoing on which would be the optimal method(s) to screen for non-adherence to hypertension therapy, recognized as the major cause for (pseudo)-resistance to treatment. Recent randomized clinical trials have demonstrated the strong benefit of anti-aldosterone drugs (mostly spironolocatone) as fourth-line therapies in resistant hypertension whereas clinical trials with device-based therapies displayed contrasting results. New trials with improved devices and more carefully selected patients with resistant hypertension are ongoing.

Black southern rural adolescents' HIV stigma, denial, and misconceptions and implications for HIV prevention.

The HIV/AIDS epidemic is becoming increasingly concentrated among African Americans who live in the rural South. HIV denial, stigma, and misconceptions have been identified as helping spread the virus among adults. However, little is known about these psychosocial factors among African American rural adolescents. This article presents findings from a study aimed at exploring the role HIV denial, stigma, and misconceptions play in the disproportionate impact of HIV/AIDS on African American adolescents in the rural South. A mixed-method study, which included questionnaires and focus group discussions, was used. Results indicated that the majority of participants had average HIV knowledge levels and that HIV denial, stigma, and misconceptions played a role in the current HIV/AIDS epidemic among rural African American adolescents. Nurses and health care professionals can play a key role in understanding and addressing HIV stigma, denial, and misconceptions among African American adolescents in the rural South to reduce HIV/AIDS health disparities among this population.

Intimate partner violence: how clinicians can be an asset to their patients.

Intimate partner violence (IPV) has emerged as a public health concern. It does not consist of physical violence alone, but includes psychological and emotional issues as well. IPV cuts across all cultures, age groups, and socioeconomic classes and necessitates numerous health care visits. It is often difficult to identify those who are affected by IPV when assessing during health care services. This difficulty may be overcome as health care providers become aware of the need to integrate screening as part of the initial assessment. Although it can be difficult to measure the impact of IPV, several organizations have been able to determine that the economic cost to society is significantly increased when IPV is present. Because nurses are the largest class of health care providers, their ability to perform screening activities is paramount to early detection and management of IPV.