The application of a haemorrhage assessment tool in evaluating control of bleeding in a pilot trauma haemorrhage trial.

OBJECTIVES: To determine whether it was feasible to use a haemorrhage assessment tool (HAT) within a trauma trial and whether the data obtained could differentiate patients who had achieved haemostasis. BACKGROUND: Major haemorrhage is one of the leading causes of death worldwide, affecting 40% of trauma patients. Clinical trials evaluating haemostatic interventions often use transfusion outcomes as a primary endpoint. Transfusion is highly dependent on local practice, limiting its reliability as a robust, transferable endpoint. METHODS: A five-point HAT questionnaire was applied to participants enrolled into the EFIT-1 trial. This RCT evaluated the feasibility of administering a 6 g fibrinogen concentrate to patients with severe trauma haemorrhage. RESULTS: Of participants, 98% completed a HAT; 75% participants had 'achieved haemostasis' at the time of tool completion, as determined by clinical acumen alone. HAT scores were able to differentiate which participants required transfusion after 3 h. Of participants, 56% were transfused red blood cells when they scored 0-2, compared to 17% with HAT scores between 3 and 5. CONCLUSION: This study has confirmed the feasibility of using a HAT during the emergency care of patients suffering trauma haemorrhage, and future studies should be conducted to determine its value as an endpoint in haemostasis studies.

Mortality from trauma haemorrhage and opportunities for improvement in transfusion practice.

BACKGROUND: The aim of this study was to describe the prevalence, patterns of blood use and outcomes of major haemorrhage in trauma. METHODS: This was a prospective observational study from 22 hospitals in the UK, including both major trauma centres and smaller trauma units. Eligible patients received at least 4 units of packed red blood cells (PRBCs) in the first 24 h of admission with activation of the massive haemorrhage protocol. Case notes, transfusion charts, blood bank records and copies of prescription/theatre charts were accessed and reviewed centrally. Study outcomes were: use of blood components, critical care during hospital stay, and mortality at 24 h, 30 days and 1 year. Data were used to estimate the national trauma haemorrhage incidence. RESULTS: A total of 442 patients were identified during a median enrolment interval of 20 (range 7-24) months. Based on this, the national incidence of trauma haemorrhage was estimated to be 83 per million. The median age of patients in the study cohort was 38 years and 73·8 per cent were men. The incidence of major haemorrhage increased markedly in patients aged over 65 years. Thirty-six deaths within 24 h of admission occurred within the first 3 h. At 24 h, 79 patients (17·9 per cent) had died, but mortality continued to rise even after discharge. Patients who received a cumulative ratio of fresh frozen plasma to PRBCs of at least 1 : 2 had lower rates of death than those who received a lower ratio. There were delays in administration of blood. Platelets and cryoprecipitate were either not given, or transfused well after initial resuscitation. CONCLUSION: There is a high burden of trauma haemorrhage that affects all age groups. Research is required to understand the reasons for death after the first 24 h and barriers to timely transfusion support.

Usefulness of standard plasma coagulation tests in the management of perioperative coagulopathic bleeding: is there any evidence?

Standard laboratory coagulation tests (SLTs) such as prothrombin time/international normalized ratio or partial thromboplastin time are frequently used to assess coagulopathy and to guide haemostatic interventions. However, this has been challenged by numerous reports, including the current European guidelines for perioperative bleeding management, which question the utility and reliability of SLTs in this setting. Furthermore, the arbitrary definition of coagulopathy (i.e. SLTs are prolonged by more than 1.5-fold) has been questioned. The present study aims to review the evidence for the usefulness of SLTs to assess coagulopathy and to guide bleeding management in the perioperative and massive bleeding setting. Medline was searched for investigations using results of SLTs as a means to determine coagulopathy or to guide bleeding management, and the outcomes (i.e. blood loss, transfusion requirements, mortality) were reported. A total of 11 guidelines for management of massive bleeding or perioperative bleeding and 64 studies investigating the usefulness of SLTs in this setting were identified and were included for final data synthesis. Referenced evidence for the usefulness of SLTs was found in only three prospective trials, investigating a total of 108 patients (whereby microvascular bleeding was a rare finding). Furthermore, no data from randomized controlled trials support the use of SLTs. In contrast, numerous investigations have challenged the reliability of SLTs to assess coagulopathy or guide bleeding management. There is actually no sound evidence from well-designed studies that confirm the usefulness of SLTs for diagnosis of coagulopathy or to guide haemostatic therapy.

Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial.

BACKGROUND: Low fibrinogen (Fg) concentrations in trauma haemorrhage are associated with poorer outcomes. Cryoprecipitate is the standard source for Fg administration in the UK and USA and is often given in the later stages of transfusion therapy. It is not known whether early cryoprecipitate therapy improves clinical outcomes. The primary aim of this feasibility study was to determine whether it was possible to administer cryoprecipitate, within 90 min of admission to hospital. Secondary aims were to evaluate laboratory measures of Fg and clinical outcomes including thrombotic events, organ failure, length of hospital stay and mortality. METHODS: This was an unblinded RCT, conducted at two civilian UK major trauma centres of adult trauma patients (age ≥16 yrs), with active bleeding and requiring activation of the major haemorrhage protocol. Participants were randomised to standard major haemorrhage therapy (STANDARD) (n=22), or to standard haemorrhage therapy plus two early pools of cryoprecipitate (CRYO) (n=21). RESULTS: 85% (95% CI: 69-100%) CRYO participants received cryoprecipitate within 90 min, median time 60 min (IQR: 57-76) compared with 108 min (67-147), CRYO and STANDARD arms respectively (P=0.002). Fg concentrations were higher in the CRYO arm and were maintained above 1.8 g litre(-1) at all time-points during active haemorrhage. All-cause mortality at 28 days was not significantly different (P=0.14). CONCLUSIONS: Early Fg supplementation using cryoprecipitate is feasible in trauma patients. This study supports the need for a definitive RCT to determine the effect of early Fg supplementation on mortality and other clinical outcomes. TRIAL REGISTRY NUMBER: ISRCTN55509212.

Simulation training improves clinical knowledge of major haemorrhage management in foundation year doctors.

OBJECTIVES: (i) To develop a major haemorrhage simulation training programme. (ii) To design an assessment tool to measure the effectiveness of this programme. (iii) To use simulation training to create more effective protocols. BACKGROUND: Major haemorrhage is a time-critical medical emergency that can be faced by every Foundation Year (FY) doctor. Standard methods of teaching provide limited opportunity for junior doctors to improve their knowledge and practical skills for major haemorrhage situations. Simulation is increasingly used in medical training but has not been used as a means both to facilitate learning and refine hospital major haemorrhage policy. METHODS: The effect of major haemorrhage simulation on attendees' learning was compared to a comparator group not exposed to simulation. Questionnaire pre-simulation and 3 months post-simulation training assessed knowledge of the Trust Major Haemorrhage Protocol (MHP). RESULTS: Sixteen FY1 doctors attended simulation training. The comparator group included 47 FY1 doctors. No significant difference was found between simulation and comparator groups on baseline questionnaire scores. The simulation group showed significant improvement (total score, mean standard deviation (SD) pre-test 27.15 (4.02), post-test 39.13 (3.91), p < 0.001). The comparator group showed no significant change (total score, pre-test 25.06 (5.70), post-test 23.54 (6.85), p = 0.33) (19 lost to follow up). The study resulted in the production of a new MHP. CONCLUSION: This study has demonstrated that simulation training improved doctors' knowledge in major haemorrhage management and that the experience of observing the simulation training allowed senior staff to undertake analysis and improvement of an existing MHP.

Plasma exchange and intravenous immunoglobulin for the peri-operative management of type 2 heparin-induced thrombocytopaenia in a patient requiring urgent surgery for critical limb ischaemia.

We report the case of a 61-year-old female who developed heparin-induced thrombocytopaenia following treatment of a submassive pulmonary embolism, and who then required an above knee amputation for critical limb ischaemia. Heparin-induced thrombocytopaenia is a rare, immune-mediated complication associated with an in-hospital mortality rate of 10%. It is more common in surgical patients, with patients undergoing orthopaedic surgery more likely to develop it than patients undergoing cardiac surgery, but heparin-dependent immunoglobulin G antibodies are more likely to be formed in the latter. Peri-operative management remains a challenge. Ideally, it is preferable to wait for the platelet count to improve; but in certain cases, surgery cannot be delayed. Heparin-induced thrombocytopaenia is usually managed with direct thrombin inhibitors, such as argatroban and bivalirudin. Newer therapeutic modalities, such as plasmapheresis and intravenous immunoglobulin, as used in this case, can rapidly remove antibodies, but the certainty of evidence is low. Our case adds to the literature regarding the use of these modalities and highlights the multidisciplinary team approach required to manage such complex cases.

Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial.

PURPOSE: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76-1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54-1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84-5.34). CONCLUSION: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

Acquired factor V inhibitor in a critically ill patient.

Acquired inhibitor of factor V is a rare condition with a variety of clinical manifestations, from extremely mild to life threatening haemorrhage. We present a case from our intensive care unit as a reminder of the less common causes of elevated prothombin and activated partial thromboplastin times, and how knowledge of the variable presentation may aid management.

Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery.

Essentials Recombinant von Willebrand factor (rVWF) is effective in von Willebrand disease (VWD). A phase 3 study of rVWF, with/without recombinant factor VIII (rFVIII) before surgery in VWD. Overall rVWF's efficacy was rated excellent/good; rVWF was administered alone in most patients. rVWF was well-tolerated and hemostasis was achieved in patients with severe VWD undergoing surgery. SUMMARY: Background Recombinant von Willebrand factor (rVWF) has demonstrated efficacy for on-demand treatment of bleeding in severe von Willebrand disease (VWD), warranting evaluation in the surgical setting. Objectives This study (NCT02283268) evaluated the hemostatic efficacy/safety profile of rVWF, with/without recombinant factor VIII (rFVIII), in patients with severe VWD undergoing surgery. Patients/Methods Patients received rVWF 40-60 IU kg-1 , VWF ristocetin cofactor activity was measured 12-24 h before surgery. If endogenous FVIII activity (FVIII:C) target levels were achieved 3 h before surgery, rVWF was administered alone 1 h before surgery; rVWF was co-administered with rFVIII if target endogenous FVIII levels were not achieved. rVWF was infused postoperatively to maintain target trough levels. Overall and intraoperative hemostatic efficacy, the pharmacodynamics of rVWF administration and the incidence of adverse events (AEs) were assessed. Results All patients treated with rVWF for major (n = 10), minor (n = 4) and oral (n = 1) surgery had overall and intraoperative hemostatic efficacy ratings of excellent (73.3% and 86.7%) or good (26.7% and 13.3%). Most rVWF infusions (89.4%) were administered alone, resulting in hemostatically effective levels of endogenous FVIII within 6 h, which were sustained for 72-96 h; 70% (n = 7/10) of major surgeries were performed without rFVIII co-administration. Six patients reported 12 treatment-emergent AEs. Two patients each had one serious AE: diverticulitis (not treatment related) and deep vein thrombosis (sponsor-assessed as possibly treatment related). No severe allergic reactions or inhibitory antibodies were reported. Conclusions These data support the efficacy and safety profile of rVWF in patients with severe VWD undergoing elective surgery.

Plasma androgen responce to hCG stimulation in prepubertal boys with hypospadias and cryptorchidism.

Serum levels of testosterone, androstenedione and dehydroepiandrosterone were measured before and after 5 days of treatment with hCG (2000 IU/d) in 36 prepubertal boys with cryptorchidism and 11 with hypospadias in order to determine whether a defect in androgen synthesis could be a common cause for these disorders. Baseline and stimulated levels of testosterone, androstenedione and dehydroepiandrosterone were similar in patients with unilateral cryptorchidism, monorchism and hypospadias; baseline and stimulated levels of testosterone were lower in boys with bilateral cryptorchidism. Testosterone levels did not correlate with either the anatomical location of the testis in patients with unilateral cryptorchidism or with the site of the urethra in boys with hypospadias. Seven of 36 patients with cryptorchidism had a positive family history of a similar disorder; testosterone levels were similar in patients with and without a family history. It is concluded: 1) in all patients studied, the gonadotropin dependent phase of testosterone production is present; 2) hCG stimulation cannot detect unilateral Leydig cell dysfunction; and 3) in familial cases of cryptorchidism, some factor other than an abnormality in androgen synthesis may be responsible for the hereditary tendency.

An evaluation of the effectiveness of CT vs. other imaging modalities in the diagnosis of atypical renal masses.

A retrospective review of 34 patients undergoing nephrectomy for suspected renal malignancy was undertaken to evaluate the effectiveness of computed tomography (CT), ultrasound, arteriography, and cyst puncture in providing a definitive preoperative diagnosis of benign vs. malignant renal abnormality. The predictive value of a test suggesting malignancy was 88% for angiography, 86% for ultrasound, 71% for cyst puncture, and 80% for CT. The predictive value of a test suggesting no malignancy for non-CT imaging modalities was poor. The predictive value of renal CT increased to 96%, when three or more characteristics are present which suggest the lesion is not a simple, benign renal cyst. Using these criteria all malignancies were identified, and all but one benign lesion excluded. Unusual lesions that have equivocal or indeterminate diagnostic studies and only one or two noncystic CT features should undergo selective exploration rather than radical nephrectomy.

Isolated lymphoma of genitourinary tract and adrenals.

With the routine use of computed tomographic imaging, intrinsic involvement of the genitourinary tract in newly diagnosed non-Hodgkin's lymphoma is seen in as many as 10 percent of patients. Incidental discovery of an extranodal, extra-lymphatic lesion in the genitourinary tract without clinical or radiographic evidence of disease elsewhere, however, is an uncommon occurrence. The clinical presentation and imaging findings in 4 patients with initial manifestation of lymphoma isolated to the kidney, ureter, bladder, and adrenals, respectively, are presented. These patients had no evidence of lymphoma elsewhere, and imaging studies mimicked the more common neoplasms affecting these organs.

Radiologic evaluation of small and indeterminant renal masses.

A common problem in radiologic and urologic practice today is what to do with the small or indeterminant renal mass. Whether found incidentally or sought after because of patient symptomatology, these lesions present a challenge in diagnosis and management. This article outlines the scope of the problem, illustrates representative lesions, suggests imaging and management strategies culled from personal experience, and provides a review of available literature.

Complications of nasoenteric feeding tubes.

Small-bore, silicone nasoenteric feeding tubes are increasingly utilized in the critically ill patient to provide nutritional support. The metallic-weighted tips and stiffening introducing stylets create the potential for misplacement with potentially serious consequences. We have reported our experience with 14 patients who had inadvertent tube misplacement, resulting in complications that included pneumothorax, hydrothorax, empyema, mediastinitis, pneumonia, and esophageal perforation. The incidence of radiographically detected abnormal tube position was 1.3 percent. The presence of cuffed tracheostomy or endotracheal tubes did not prevent this occurrence. The institution of enteral feedings should, therefore, be performed according to strict guidelines which include radiographic confirmation of desired position before feedings are initiated, limited and supervised use of stylets, and a need for special precautions in patients who are obtunded or receiving intubated respiratory assistance.