Personalising care for patients: implementing a treatment summary folder following cytoreductive surgery.

BACKGROUND: A patient survey highlighted that patients treated with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) at one NHS trust lacked confidence with the transition of care between teams. A personalised folder of treatment information was designed and given to patients prior to discharge. AIMS: To obtain patient feedback on the implementation and content of the folder. METHODS: 30 consecutive patients were given the folder at discharge. Participants completed an online questionnaire to determine whether the information in the folder was appropriate, given at the right time in the pathway and enhanced confidence on discharge. FINDINGS: 90% response rate was achieved. Of the respondents, 96% strongly agreed/agreed that the folder was helpful, 4% disagreed; 92% strongly agreed/agreed that the amount of information was right, 8% preferred more information, none less; 74% agreed/strongly agreed that the folder was provided at the right time; 96% said that the content met their expectations. CONCLUSION: Patients treated with CRS and HIPEC have specific needs related to their treatment. Implementation of the patient information folder at discharge increases patient confidence.

The Role of Platelets in Venous Thromboembolism.

Multiple factors contribute to the risk of venous thromboembolism (VTE). Platelets have attracted much interest in arterial cardiovascular disease, whereas their role in VTE has received much less attention. Recent evidence suggests that platelets may play a more important role in VTE than previously anticipated. This review discusses the mechanisms that link platelets with venous thrombotic disease and their potential applications as novel risk factors for VTE. In addition, animal studies and randomized clinical trials that highlight the potential effect of antiplatelet therapy in venous thrombosis are evaluated to assess the role of platelets in VTE. The clinical significance of platelets for VTE risk assessment in specific patient cohorts and their role as a suitable therapeutic target for VTE prevention is acknowledged. The role of platelets in VTE is a promising field for future research.

Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study.

BACKGROUND: There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3-5 days after loading doses of aspirin. METHODS: Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3-5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). RESULTS: Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3-5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. CONCLUSIONS: Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3-5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing.

The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.

BACKGROUND: Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (d f )) ex-vivo, real-time clot formation time (T GP ) and blood clot strength (elasticity at the gel point (G'GP)). We aimed to evaluate these novel clotting biomarkers in ischaemic stroke and changes of clot structure following therapeutic intervention. METHODS: In a prospective cohort study clot microstructure was compared in ischaemic stroke patients and a control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours after therapeutic intervention in the stroke group to assess the effects of thrombolysis and anti-platelet therapy. RESULTS: 75 patients (mean age 72.8 years [SD 13.1]; 47 male, 28 female) with ischaemic stroke were recruited. Of the 75 patients, 32 were thrombolysed with t-PA and 43 were loaded with 300 mg aspirin. The following parameters were significantly different between patients with stroke and the 74 healthy subjects: d f (1.760 ± .053 versus 1.735 ± 0.048, p = 0.003), TGP (208 ± 67 versus 231 ± 75, p = 0.05), G'GP (0.056 ± 0.017 versus 0.045 ± 0.014, p < 0.0001) and fibrinogen (3.7 ± 0.8 versus 3.2 ± 0.5, p < 0.00001). There was a significant decrease in d f (p = 0.02), G'GP (p = 0.01) and fibrinogen (p = 0.01) following the administration of aspirin and for d f (p = 0.003) and fibrinogen (p < 0.001) following thrombolysis as compared to baseline values. CONCLUSION: Patients with ischaemic stroke have denser and stronger clot structure as detected by d f and G'GP. The effect of thrombolysis on clot microstructure (d f ) was more prominent than antiplatelet therapy. Further work is needed to assess the clinical and therapeutic implications of these novel biomarkers.

Prospective evaluation of blood coagulability and effect of treatment in patients with stroke using rotational thromboelastometry.

BACKGROUND: Stroke is the second largest cause of death worldwide. Abnormalities in hemostasis play an important role in the pathophysiology of ischemic stroke (IS). These hemostatic defects can be detected using rotational thromboelastometry (ROTEM) as a global method of measuring coagulation. This study assessed the effects of IS on blood hypercoagulability using ROTEM method, before and subsequent to therapeutic interventions. METHODS: In a prospective observational cohort study, whole blood coagulation using ROTEM, along with full blood count and standard coagulation tests, were compared between patients with IS and an age-matched control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours in the stroke group after therapy to assess the effects of therapeutic intervention. RESULTS: Seventy-two patients with IS were age-matched to 71 healthy subjects. Clotting time (CT) INTEM (P = .01) and maximum clot firmness (MCF) INTEM (P = .02) were significantly different between stroke patients at baseline and healthy subjects, but this difference disappeared when controlled for by smoking status. There was no association between ROTEM parameters and time from stroke symptom onset or stroke severity as reflected in The National Institute of Health Stroke Scale score. Significant but small changes in the values of MCF-EXTEM, clot formation time (CFT) EXTEM, and alpha-EXTEM CT were observed after therapeutic intervention (thrombolysis or aspirin treatment). CONCLUSIONS: ROTEM testing does not seem to detect a hypercoagulable state in patients with IS. Nonetheless, some ROTEM parameters had a small change after antiplatelet therapy or thrombolysis.

Fear of Cancer Recurrence in peritoneal malignancy patients following treatment: a cross-sectional study.

PURPOSE: To assess Fear of Cancer Recurrence (FCR)-its prevalence, trajectory, and relationship to several demographic and clinical characteristics, and quality of life-in a sample of peritoneal malignancy survivors, up to 5 years post-surgery. METHODS: The Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) and 36-Item Short-Form Health Survey (SF-36) were used to collect cross-sectional data from peritoneal malignancy survivors to assess their Fear of Cancer Recurrence and quality of life respectively as well as other demographic and clinical data. RESULTS: The results show that more than two-thirds of the participants (N = 301) experience severe/clinical FCR. FCR is relatively stable over time. Younger patients who are struggling with anxiety or depression or receiving professional mental health support at the time of the surgery are at a higher risk of FCR. FCR is associated with a worse quality of life. CONCLUSIONS: Peritoneal malignancy survivors are at a high risk of FCR, and it compromises their psychological, mental, and social well-being (quality of life). IMPLICATIONS FOR CANCER SURVIVORS: Raise awareness about the high risk of FCR in this population and the demographic and clinical factors that are associated with it. Encourage peritoneal malignancy services and health professionals to address FCR in this population by normalizing it and providing support for those struggling with it.

Differences in coagulation-relevant parameters: Comparing cryoprecipitate and a human fibrinogen concentrate.

BACKGROUND: Variable fibrinogen content within cryoprecipitate makes accurate dosing challenging in patients with coagulopathic bleeding, in addition to pathogen transmission risks associated with its administration. Purified and standardized human fibrinogen concentrates (HFCs) represent reliable alternatives. Full cryoprecipitate characterization is required to inform selection of an appropriate fibrinogen source for supplementation therapy. METHODS: Extended biochemical comparison of pooled cryoprecipitate and HFC (Fibryga, Octapharma) was performed using commercially available assays to determine levels of variability in cryoprecipitate and HFC. In addition to standard procoagulant factors, measurements included activities of platelet-derived microparticles (PMPs) and plasminogen, and levels of fibrin degradation products. RESULTS: Cryoprecipitate contains lower fibrinogen levels than HFC (4.83 vs.19.73 g/L; p<0.001), translating to approximately half the amount of fibrinogen per standard cryoprecipitate dose (two pools, pre-pooled from five donations each) vs. HFC (2.14 vs. 3.95 g; p<0.001). Factor XIII (FXIII) levels were also lower in cryoprecipitate vs. HFC (192.17 vs. 328.33 IU/dL; p = 0.002). Levels of procoagulants in cryoprecipitate, such as von Willebrand Factor (VWF) and factor VIII (FVIII), were highly variable, as was PMP activity. A standard cryoprecipitate dose contains significantly higher levels of measured plasminogen and D-dimer fragments than a standard HFC dose. CONCLUSION: The tested HFC is a more reliable fibrinogen and FXIII source for accurate dosing compared with cryoprecipitate. Cryoprecipitate appears considerably less predictable for bleeding management due to wide variation in pro- and anticoagulation factors, the presence of PMPs, and the potential to elevate VWF and FVIII to prothrombotic levels.

Comparison of coagulation parameters associated with fibrinogen concentrate and cryoprecipitate for treatment of bleeding in patients undergoing cytoreductive surgery for pseudomyxoma peritonei: Subanalysis from a randomized, controlled phase 2 study.

Background and Aims: The FORMA-05 study compared the efficacy and safety of human fibrinogen concentrate (HFC) versus cryoprecipitate for hemostasis in bleeding patients undergoing cytoreductive surgery for pseudomyxoma peritonei (PMP). This subanalysis explores coagulation parameters in the FORMA-05 patients, with a focus on the seven patients who developed thromboembolic events (TEEs). Methods: FORMA-05 was a prospective, randomized, controlled phase 2 study in which patients with predicted blood loss ≥2 L received HFC (4 g) or cryoprecipitate (two pools of five units), repeated as needed. Plasma fibrinogen, platelet count, factor (F) XIII, FVIII, von Willebrand Factor (VWF) antigen and ristocetin cofactor activity levels, EXTEM A20, FIBTEM A20, and endogenous thrombin potential (ETP) were measured perioperatively. Results: Fibrinogen, platelet count, EXTEM and FIBTEM A20, FXIII, FVIII, VWF levels, and ETP were maintained throughout surgery in both the HFC group (N = 21) and the cryoprecipitate group (N = 23). Seven TEEs were observed in the cryoprecipitate group. The two patients developing deep vein thromboses (DVT) appeared to have a procoagulant status preoperatively, with distinctively higher fibrinogen level, FIBTEM A20, and platelet levels, all of which persisted perioperatively. The five patients developing pulmonary embolism (PE) had slightly higher VWF levels preoperatively, with a disproportionate increase intraoperatively (postcryoprecipitate administration) and postoperatively. Conclusions: Patients treated with HFC versus cryoprecipitate showed broad overlaps in coagulation parameters. Patients with PE experienced a disproportionate VWF rise following cryoprecipitate administration, whereas patients developing DVT displayed a procoagulant status before and following surgery. Preoperative testing may allow these patients to be identified.

Pilot study to evaluate hypercoagulation and inflammation using rotational thromboelastometry and calprotectin in COVID-19 patients.

INTRODUCTION: Abnormal coagulation and inflammation are hallmarks of SARs-COV-19. Stratifying affected patients on admission to hospital may help identify those who at are risk of developing severe disease early on. Rotational Thromboelastometry (ROTEM) is a point of care test that can be used to measure abnormal coagulation and calprotectin is a measure of inflammation. AIM: Assess if ROTEM can measure hypercoagulability on admission and identify those who will develop severe disease early on. Assess if calprotectin can measure inflammation and if there is a correlation with ROTEM and calprotectin. METHODS: COVID-19 patients were recruited on admission and ROTEM testing was undertaken daily for a period of 7 days. Additionally inflammatory marker calprotectin was also tested for the same period. RESULTS: 33 patients were recruited to the study out of which 13 were admitted to ITU and 20 were treated on the ward. ROTEM detected a hypercoagulable state on admission but did not stratify between those admitted to a ward or escalated to ITU. Calprotectin levels were raised but there was no statistical difference (p = 0.73) between patients admitted to a ward or escalated to ITU. Significant correlations were observed between FIBA5 (r = 0.62; p<0.00), FIBCFT (r = -0.57; p<0.00), FIBMCF (r = 0.64; p<0.00) and INMCF (r = 0.57; p<0.00) and calprotectin. CONCLUSION: COVID-19 patients were hypercoagulable on admission. The correlations between ROTEM and calprotectin underline the interactions between inflammation and coagulation.

Fear of cancer recurrence in peritoneal malignancy patients following complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): an observational study protocol.

INTRODUCTION: Fear of cancer recurrence (FCR) is correlated with higher depression levels, worse quality of life and increased utilisation of healthcare services. There is no research on FCR in peritoneal malignancy (PM) patients-a rare type of abdominal cancer. This study aims to explore the prevalence, trajectory, demographic and clinical characteristics that are associated with FCR and its relationship with quality of life in PM patients. METHODS AND ANALYSIS: This is a cross-sectional study. Validated measures will be used to collect data on the levels of FCR (Fear of Cancer Recurrence Inventory-Short Form) and quality of life (36-Item Short-Form Health Survey) of PM patients who have had surgery in the last 5 years at the Peritoneal Malignancy Institute in Basingstoke Hospital (minimum N=260). Descriptive statistics, Pearson χ2 tests and correlational tests will be used to analyse the data. ETHICS AND DISSEMINATION: Ethical approval was obtained from the HRA and Health and Care Research Wales (HCRW). The results of this study will be shared with the participants of this study, presented at conferences and PM patients' days in the form of presentations or posters, and published in a scientific journal. DISCUSSION: The results of this exploratory study will be used to inform a multicentre observational study to explore the effect of FCR on PM patients' mental health (depression and anxiety), quality of life and healthcare utilisation which will inform a multicentre randomised controlled trial to assess the effectiveness of using evidenced-based interventions to lower FCR in PM patients.

Efficacy of fibrinogen concentrate in major abdominal surgery - A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei (PMP) is associated with excessive bleeding and acquired fibrinogen deficiency. Maintaining plasma fibrinogen may support hemostasis. OBJECTIVES: To compare hemostatic efficacy and safety of human fibrinogen concentrate (HFC) vs cryoprecipitate as fibrinogen sources for bleeding patients with acquired fibrinogen deficiency undergoing PMP CRS. METHODS: FORMA-05 was an off-label single-center, prospective, randomized, controlled phase 2 study. Patients undergoing PMP surgery with predicted intraoperative blood loss ≥2 L received human fibrinogen concentrate (HFC; 4 g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0-4.6 g fibrinogen), repeated as needed. The primary endpoint was a composite of intraoperative and postoperative efficacy, graded using objective 4-point scales and adjudicated by an independent committee. RESULTS: One hundred percent of patients receiving HFC (95% confidence interval: 83.9-100.0, n = 21) or cryoprecipitate (84.6-100.0, n = 22) achieved hemostatic success. HFC demonstrated noninferior efficacy (P = .0095; post hoc) and arrived in the operating room 46 minutes faster. There were significantly greater mean increases with HFC vs cryoprecipitate in plasma fibrinogen (0.78 vs 0.35 g/L; P < .0001) and FIBTEM A20 (3.33 vs 0.93 mm; P = .003). Factor XIII, factor VIII, and von Willebrand factor activity were maintained throughout surgery. Only red blood cells were transfused intraoperatively (median units: HFC group, 1.0; cryoprecipitate group, 0.5). Thromboembolic events were detected with cryoprecipitate only. Safety was otherwise comparable between groups. CONCLUSIONS: Human fibrinogen concentrate was hemostatically efficacious in patients undergoing major abdominal PMP surgery, with a favorable safety profile. These results are relevant to other surgical settings where bleeding and acquired fibrinogen deficiency occur.

Adenovirus-associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A.

BACKGROUND: Current treatment for severe hemophilia A is replacement of deficient factor. Although replacement therapy has improved life expectancy and quality, limitations include frequent infusions and high costs. Gene therapy is a potential alternative that utilizes an adeno-associated virus (AAV) vector containing the human genetic code for factor 8 (FVIII) that transduces the liver, enabling endogenous production of FVIII. Individuals with preexisting immunity to AAV serotypes may be less likely to benefit from this treatment. OBJECTIVES: This study measured seroprevalence of antibodies to AAV5 and 8 in an UK adult hemophilia A cohort. PATIENTS/METHODS: Patients were recruited from seven hemophilia centres in the UK. Citrated plasma samples from 100 patients were tested for preexisting activities against AAV5 and 8 using AAV transduction inhibition and total antibodies assays. RESULTS: Twent-one percent of patients had antibodies against AAV5 and 23% had antibodies against AAV8. Twenty-five percent and 38% of patients exhibited inhibitors of AAV5 or AAV8 cellular transduction respectively. Overall seroprevalence using either assay against AAV5 was 30% and against AAV8 was 40% in this cohort of hemophilia A patients. Seropositivity for both AAV5 and AAV8 was seen in 24% of participants. CONCLUSIONS: Screening for preexisting immunity may be important in identifying patients most likely to benefit from gene therapy. Clinical studies may be needed to evaluate the impact of preexisting immunity on the safety and efficacy of AAV mediated gene therapy.

Altered clot microstructure detected in obstructive sleep apnoea hypopnoea syndrome.

Abnormal clot microstructure plays a pivotal role in the pathophysiology of thromboembolic diseases. Assessing the viscoelastic properties of clot microstructure using novel parameters, Time to Gel Point (T GP ), Fractal Dimension (d f ) and clot elasticity (G׳ GP ) could explain the increased cardiovascular and thromboembolic events in patients with Obstructive Sleep Apnoea Hypopnea Syndrome (OSAHS). We wanted to compare T GP , d f , and G׳ GP and their diurnal variation in OSAHS and symptomatic comparators. thirty six patients attending a sleep disturbed breathing clinic with symptoms of OSAHS were recruited. T GP , d f and G׳ GP were measured alongside standard coagulation screening, thrombin generation assays, and platelet aggregometry at 16:00 h and immediately after an in-patient sleep study at 07:30 h. OSAHS group had significantly lower afternoon d f than comparators (1.705±0.033 vs. 1.731±0.031, p<0.05). d f showed diurnal variation and only in the OSAHS group, being significantly lower in the afternoon than morning (p<0.05). Diurnal changes in d f correlated with 4% DR, even after controlling for BMI (r=0.37, p=0.02). The lower d f in the afternoon in OSAHS suggests a partial compensatory change that may make up for other pro-clotting abnormalities/hypertension during the night. The change to the thrombotic tendency in the afternoon is biggest in severe OSAHS. d f Shows promise as a new microstructural indicator for abnormal haemostasis in OSAHS.

Anti-thrombotic therapy in patients with atrial fibrillation and intracranial hemorrhage.

Patients with atrial fibrillation have an increased risk of ischemic stroke that can be dramatically lowered by treatment with anticoagulants. The annual rate of major bleeds with warfarin averages about 2%. The rates of intracerebral and intracranial bleeds are significantly reduced with the use of the novel direct oral anticoagulants (DOACs) compared with warfarin. Treatment of anticoagulation-related intracerebral hemorrhage is based on the results of case series and small trials. Resumption of anticoagulation in patients with atrial fibrillation who had an intracerebral bleed depends on the etiology and location of the bleeding and the absolute rate of stroke in the absence of anticoagulation.