Systematic review of hemostatic agents used in vascular surgery.

BACKGROUND: Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of comparative research studies have left surgeons with the option of choosing hemostatic agents based on their personal experience. The present review has highlighted the efficacy and safety of hemostatic agents and categorized them according to their primary mechanism of action and cost. METHODS: A systematic search strategy encompassing hemostatic agent products was deployed in the PubMed database. Single-center and multicenter, randomized, controlled trials with >10 patients were included in the present study. RESULTS: We reviewed 12 studies on the efficacy and safety of hemostatic agents compared with manual compression or other hemostatic agents. Using the time to hemostasis as the primary end point, all studies had found hemostatic agents to be significantly more efficient than manual compression. Likewise, adhesives (high pressure sealants) and dual agents (containing biologically active and absorbable components) were found to be more efficient, but costlier, than agents with either biologically active or absorbable components only. Agents with porcine or bovine constituents were found to trigger anaphylactic reactions in rare cases. Additionally, the absence of fibrin stabilizing factor XIII in a brand of fibrin sealant was speculated to reduce the affinity of the fibrin sealant for the expanded polytetrafluoroethylene graft. The cost of agents varied greatly depending on their active ingredient. CONCLUSIONS: Hemostatic agents appear to be highly effective at decreasing the risk of bleeding during surgical procedures. Although some hemostatic agents were demonstrated to achieve hemostasis faster than others, most are able to control bleeding within <10 minutes. Based on the limited data, the least expensive agents might suffice for limited suture lines used in routine procedures.

Antithrombotic and hemostatic stewardship: evaluation of clinical outcomes and adverse events of recombinant factor VIIa (Novoseven®) utilization at a large academic medical center.

BACKGROUND: Recombinant factor VIIa (rFVIIa) (Novoseven®) is utilized for the reversal of anticoagulation-associated bleeding and refractory bleeding in cardiac surgery. In August 2015, rFVIIa was transferred from the blood bank to the pharmacy at New York University (NYU) Langone Health. Concordantly, an off-label dosing guideline was developed. The objective of this study was to describe utilization and cost of rFVIIa and assess compliance to our dosing guideline. METHODS: We performed a retrospective, observational review of rFVIIa administrations post-implementation of an off-label dosing guideline. All patients who received rFVIIa between September 2015 and June 2017 were evaluated. For each rFVIIa administration, anticoagulation and laboratory values, indications for use, dosing, ordering and administration times, concomitant blood products, and adverse events were collected. Adverse events included venous thromboembolism, stroke, myocardial infarction, and death due to systemic embolism and mortality. The primary endpoint was the utilization of rFVIIa in accordance with the off-label dosing guideline. Secondary endpoints included hemostatic efficacy of rFVIIa, adverse events, blood products administered, and cost-effectiveness of rFVIIa transition to pharmacy. RESULTS: A total of 63 patients [pediatric (n = 6), adult (n = 57)] received rFVIIa, with the majority of use for refractory bleeding after cardiac surgery. The utilization of rVIIa decreased after development of the off-label dosing guideline and transition from blood bank to pharmacy. The total incidence of thromboembolic events within 30 days was 19.6%; 17.6% arterial and 2% venous; 70% of patients with an adverse event were over 70 years of age. Use of rFVIIa reduced the median number of units of blood products administered. CONCLUSION: Administration of rFVIIa for cardiac surgery appears to be effective for hemostasis. Transitioning rFVIIa from the blood bank to pharmacy and implementation of a dosing guideline appears to have reduced utilization. Patients receiving rFVIIa should be monitored for thromboembolic events. Elderly patients may be at higher risk for thromboembolic events.

Topical Hemostatic Agents in Gynecologic Surgery for Benign Indications.

Since a variety of procoagulant products, collectively called hemostatic agents, became available to surgeons in the mid-20th century, their use has increased across multiple specialties, including gynecology. Congruent with past research on the causes of regional variation in the practice of medicine, available evidence suggests that a central predictor for use of these products is physician preference rather than documented clinical necessity. Use of these products adds risks and avoidable cost. This article seeks to highlight specific gynecologic circumstances in which evidence and surgical judgment supports hemostatic agent use and other settings in which use should be reconsidered.

Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients With Antiplatelet-Associated Intracranial Hemorrhage.

OBJECTIVE: Current international guidelines offer a conditional recommendation to consider a single dose of IV desmopressin (DDAVP) for antiplatelet-associated intracranial hemorrhage based on low-quality evidence. We provide the first comparative assessment analyzing DDAVP effectiveness and safety in antiplatelet-associated intracranial hemorrhage. DESIGN: Retrospective chart review. SETTING: Single tertiary care academic medical center. PATIENTS: Adult patients taking at least one antiplatelet agent based on presenting history and documented evidence of intracranial hemorrhage on cerebral CT scan were included. Patients were excluded for the following reasons: repeat cerebral CT scan not performed within the first 24 hours, noncomparative repeat cerebral CT scan, chronic anticoagulation, administration of fibrinolytic medications, concurrent ischemic stroke, and neurosurgical intervention. In total, 124 patients were included, 55 received DDAVP and 69 did not. INTERVENTIONS: DDAVP treatment at recognition of antiplatelet-associated intracranial hemorrhage versus nontreatment. MEASUREMENTS AND MAIN RESULTS: Primary effectiveness outcome was intracranial hemorrhage expansion greater than or equal to 3 mL during the first 24 hospital hours. Primary safety outcomes were the largest absolute decrease from baseline serum sodium during the first 3 treatment days and new-onset thrombotic events during the first 7 days. DDAVP was associated with 88% decreased likelihood of intracranial hemorrhage expansion during the first 24 hours ([+] DDAVP, 10.9% vs [-] DDAVP, 36.2%; p = 0.002; odds ratio [95% CI], 0.22 [0.08-0.57]). Largest median absolute decrease from baseline serum sodium ([+] DDAVP, 0 mEq/L [0-5 mEq/L] vs [-] DDAVP, 0 mEq/L [0-2 mEq/L]; p = 0.089) and thrombotic events ([+] DDAVP, 7.3% vs [-] DDAVP, 1.4%; p = 0.170; odds ratio [95% CI], 5.33 [0.58-49.16]) were similar between groups. CONCLUSIONS: DDAVP was associated with a decreased likelihood of intracranial hemorrhage expansion during the first 24 hours. DDAVP administration did not significantly affect serum sodium and thrombotic events during the study period.

Effect of late prophylaxis in hemophilia on joint status: a randomized trial.

Essentials High-quality data are lacking on use of prophylaxis in adults with hemophilia and arthropathy. SPINART was a 3-year randomized clinical trial of late/tertiary prophylaxis vs on-demand therapy. Prophylaxis improved function, quality of life, activity and pain but not joint structure by MRI. Prophylaxis improves function but must start before joint bleeding onset to prevent arthropathy. SUMMARY: Background Limited data exist on the impact of prophylaxis on adults with severe hemophilia A and pre-existing joint disease. Objectives To describe 3-year bleeding, joint health and structure, health-related quality-of-life (HRQoL) and other outcomes from the open-label, randomized, multinational SPINART study. Patients/Methods Males aged 12-50 years with severe hemophilia A, ≥ 150 factor VIII exposure days, no inhibitors and no prophylaxis for > 12 consecutive months in the past 5 years were randomized to sucrose-formulated recombinant FVIII prophylaxis or on-demand therapy (OD). Data collected included total and joint bleeding events (BEs), joint structure (magnetic resonance imaging [MRI]), joint health (Colorado Adult Joint Assessment Scale [CAJAS]), HRQoL, pain, healthcare resource utilization (HRU), activity, and treatment satisfaction. Results Following 3 years of prophylaxis, adults maintained excellent adherence, with a 94% reduction in BEs despite severe pre-existing arthropathy; 35.7% and 76.2% of prophylaxis participants were bleed-free or had fewer than two BEs per year, respectively. As compared with OD, prophylaxis was associated with improved CAJAS scores (least squares [LS] mean, - 0.31 [n = 42] versus + 0.63 [n = 42]) and HAEMO-QoL-A scores (LS mean, + 3.98 [n = 41] versus - 6.00 [n = 42]), less chronic pain (50% decrease), and approximately two-fold less HRU; activity, Euro QoL-5D-3L (EQ-5D-3L) scores and satisfaction scores also favored prophylaxis. However, MRI score changes were not different for prophylaxis versus OD (LS mean, + 0.79 [n = 41] versus + 0.96 [n = 38]). Conclusions Over a period of 3 years, prophylaxis versus OD in adults with severe hemophilia A and arthropathy led to decreased bleeding, pain, and HRU, better joint health, activity, satisfaction, and HRQoL, but no reduction in structural arthropathy progression, suggesting that pre-existing joint arthropathy may be irreversible.

Assessment and validation of a defined fluid restriction protocol in the use of subcutaneous desmopressin for children with inherited bleeding disorders.

INTRODUCTION: Despite the availability of subcutaneous desmopressin (1-deamino-8-d-arginine vasopressin, SC-DDAVP) as a haemostatic agent for children with mild bleeding disorders, few publications specifically address the safety or efficacy of this mode of administration. AIM: Our aim was to assess whether a defined fluid restriction protocol was effective in preventing hyponatremia in children receiving perioperative SC-DDAVP, and to document adequate biological and clinical response in this setting. METHODS: We retrospectively analysed a cohort of children with mild bleeding disorders prescribed SC-DDAVP over a 5-year period following institution of a 'two-thirds maintenance' fluid restriction protocol. RESULTS: Sixty-nine patients received SC-DDAVP following this protocol, including 15 with mild haemophilia A, 49 with von Willebrand disease (VWD) and five with platelet storage pool disorder. In patients who underwent formal preoperative assessment a complete or partial response was observed in 28/29 with type 1 VWD and 14/15 with mild haemophilia A. Perioperative SC-DDAVP provided excellent haemostasis in all patients, with no requirement for factor concentrate or blood products. Mild asymptomatic hyponatremia was detected in seven children who received multiple doses of DDAVP (lowest sodium 129 mmol L(-1) ); however, adherence to the prescribed fluid restriction protocol was questionable in six of these cases. Symptomatic hyponatremia was not observed. CONCLUSION: Subcutaneous desmopressin was well-tolerated, with no serious side-effects observed, and good biological responses in preoperative trials. A two-thirds maintenance fluid regimen was effective at preventing symptomatic hyponatremia in our cohort, and is now the standard protocol for fluid restriction post-DDAVP administration in our centre.

Determination of the efficacy of EVICEL™ on blood loss in orthopaedic surgery after total knee replacement: study protocol for a randomised controlled trial.

BACKGROUND: After total knee replacement, overall blood loss is often underestimated, although it exceeds the visible blood loss caused by bleeding into the tissues or into the joint. The use of fibrin sealants during surgery has been suggested to reduce perioperative blood loss and transfusion rates and may be beneficial for patient recovery and the postoperative function of the joint. METHODS/DESIGN: This will be a single-centre, single-blinded, randomised controlled trial with a parallel design, for which 68 patients undergoing total knee replacement will be recruited and followed up at 3, 6 and 12 months; 34 will be control patients who will receive the standard orthopaedic surgery treatment (electrocoagulation), and the other 34 will receive the same treatment plus 5 ml EVICEL™ applied during surgery and used according to the manufacturer's instructions. The primary objective is to test the null hypothesis that the effect of EVICEL™ for controlling haemostasis and reducing postoperative blood loss in patients undergoing total knee replacement is not superior to the use of electrocoagulation alone. The secondary objective is to show that EVICEL™ reduces the need for transfusion, increases range of motion, improves clinical outcome and wound healing, and reduces the need for analgesics. The tertiary objective is to show that EVICEL™ reduces the costs of total knee replacement treatment. DISCUSSION: So far, studies on the effect of fibrin sealants in total knee replacement have delivered inconsistent and ambivalent results, indicating that there is still a need for high-evidence studies as proposed in the presented study protocol. TRIAL REGISTRATION: German registration number DRKS00007564; date of registration: 26 November 2014.

Observational evaluation of outcomes and resource utilization from hemostatic matrices in spine surgery.

OBJECTIVE: Studies have indicated that outcomes may differ by choice of flowable hemostat, but there is limited evidence in spine surgery. The objective of this study was to conduct a comparison of outcomes following use of advanced flowable hemostatic matrices in a large spine surgery population. METHODS: This is an observational retrospective cohort analysis using Premier's US Perspective Hospital Database. Two commonly-used hemostatic matrices (Floseal and Surgiflo kitted with thrombin) were compared in cases categorized as either major or severe spine surgery. Outcomes included complications, blood product administration, hospital length of stay (LOS), surgery time, and amount of matrix used in surgery. RESULTS: Major spine surgery patients treated with Surgiflo were associated with increased risk of blood product transfusion (OR = 2.56, 95% CI = 1.79-3.65, p < 0.001), longer surgery time (+8.84 min, p < 0.0001), and increased product usage (+3.34 mL, p < 0.001), compared to Floseal; however, risk of complications and LOS did not differ by choice of matrix in this patient group. Severe spine surgery patients treated with Surgiflo were associated with longer surgical time (+26.9 min, p < 0.001) and increased product usage (+1.52 mL, p < 0.01), compared to Floseal; however, risk of complications, transfusion and LOS did not differ by choice of matrix in this patient group. LIMITATIONS: Inherent to limitations associated with database analysis, this study did not evaluate potential physician differences such as skill and experience, assess long-term outcomes, nor include cases with missing data. CONCLUSION: The results from this analysis indicated that surgery time, risk of blood transfusion, and amount of matrix used are greater with Surgiflo patients, compared to Floseal patients. Choice of matrix did not appear to impact hospital LOS or risk of surgical complications. Future research should evaluate the cost consequences of increased clinical and resource utilization by choice of hemostatic matrix in spine surgery.

Evaluation of safety and effectiveness of factor VIII treatment in haemophilia A patients with low titre inhibitors or a personal history of inhibitor. Patient Data Meta-analysis of rAFH-PFM Post-Authorization Safety Studies.

There is no prospective evidence on inhibitor recurrence among haemophilia A patients with low titre inhibitors or history of inhibitors, and whether or how therapeutic choices affect the risk of recurrence. The aims of this study were to synthesise safety data in patients with moderate-severe haemophilia A and with low titre inhibitors or inhibitor history enrolled in the rAHF PFM (ADVATE) - Post-Authorization Safety Studies (ADVATE-PASS) international programme. The study was conducted in clinics participating to the ADVATE PASS programme. The patient population consisted of patients entering the studies with low titre (≤ 5 BU) inhibitors or a positive personal history of inhibitors. Patients on Immune Tolerance Induction at study entry were excluded. Primary outcome was new or recurrent inhibitor titre > 5 BU. Secondary outcomes were any increase of inhibitor titre not reaching 5 BU; any unexplained change in treatment regimen. Primary analysis was done by two-stage random effects meta-analysis. Secondary analysis was done by a hierarchical Bayesian random effects logistic model. A total of 219 patients from seven studies were included. Of these 214 (97.7 %) patients had been previously treated for more than 50 exposure days. Two hundred ten patients had positive history for inhibitors, nine a baseline measurable titre. No patient presented a primary outcome event (95 % confidence interval [CI] 0-1.6 %). Six patients with previous history developed a low titre recurrence (overall rate 2.2, 95 %CI 0-4.8 %). When any increase of inhibitor titre or any treatment change was accounted for, overall 3.7 % (95 % CI 0 %-8.0 %) of patients experienced the outcome. In conclusion, the observed rate of events does not support the definition of this population as at high risk for inhibitor development.

Benefits of prophylaxis versus on-demand treatment in adolescents and adults with severe haemophilia A: the POTTER study.

Rigorous evidence is lacking on long-term outcomes of factor VIII (FVIII) prophylaxis initiated in adolescent or adult patients with severe haemophilia A. The prospective, open-label Prophylaxis versus On-demand Therapy Through Economic Report (POTTER) study (ClinicalTrials.gov NCT01159587) compared long-term late secondary prophylaxis (recombinant FVIII-FS 20-30 IU/kg thrice weekly) with on-demand treatment in patients aged 12 to 55 years with severe haemophilia A. The annual number of joint bleeding episodes (primary endpoint), total bleeding episodes, orthopaedic and radiologic (Pettersson) scores, health-related quality of life (HRQoL), pharmacoeconomic impact, and safety were evaluated over a > 5-year period (2004-2010). Fifty-eight patients were enrolled at 11 centres in Italy; 53 (27 prophylaxis, 26 on demand) were evaluated and stratified into 2 age subgroups (12-25 and 26-55 years). Patients receiving prophylaxis experienced a significantly lower number of joint bleeding episodes vs the on-demand group (annualised bleeding rate, 1.97 vs 16.80 and 2.46 vs 16.71 in younger and older patients, respectively; p=0.0043). Results were similar for total bleeding episodes. Prophylaxis was associated with significantly fewer target joints (p< 0.001), better orthopaedic (p=0.0019) and Pettersson (p=0.0177) scores, better HRQoL, and fewer days of everyday activities lost (p< 0.0001) but required significantly higher FVIII product consumption. The POTTER study is the first prospective, controlled trial documenting long-term benefits of late secondary prophylaxis in adolescents and adults with severe haemophilia A. The benefits of reduced bleeding frequency, improved joint status, and HRQoL may offset the higher FVIII consumption and costs.

Assessment of relative bioavailability of two presentations of moroctocog alfa (AF-CC) in subjects with moderately severe or severe hemophilia A.

UNLABELLED: An open-label, single-dose, randomized, two-period, cross-over study comparing the pharmacokinetics of factor VIII activity in plasma ( FVIII: C) after administration of a new presentation of moroctocog alfa containing 3,000 IU in a dual-chamber syringe and the combined contents of approved 1,000 and 2,000 IU vials was conducted in 16 male subjects who had moderately severe or severe hemophilia A (FVIII:C ≤2 IU/dL). Blood samples were collected for 72 hours after administration of the dose. FVIII: C were assayed using a chromogenic substrate assay in a central laboratory. The FVIII: C pharmacokinetic parameters were calculated using noncompartmental analysis. The dual-chamber syringe would be bioequivalent to the combined contents of the vials if the 90% confidence limits of the ratio of the geometric mean values of AUCinf , and Cmax fell within the interval of 80-125%. The bioequivalence criteria were met. A total of seven treatment related adverse events were observed in a total of five subjects. All were mild and none was determined to be related to administration of study medication.

Comparative analysis of Cutanplast and Spongostan nasal packing after endoscopic sinus surgery: a prospective, randomized, multicenter study.

Commercial gelatin-based packing materials are available under different names and compositions to be used after endoscopic sinus surgery (ESS). The purpose of this study was to investigate the efficacy of Spongostan and Cutanplast nasal packing on patients' subjective symptoms, hemostasis, and wound healing following ESS. One hundred adult patients with chronic sinusitis requiring the same extent of ESS were included. Following surgery, one nasal cavity was packed with Cutanplast and the other one with Spongostan. Patients' subjective symptoms while the packing was in situ, hemostatic properties, degree of remaining amount of packing materials, postoperative wound healing, and the cost of the pack were evaluated. Cutanplast and Spongostan are equally effective in the control of postoperative bleeding following ESS. However, Cutanplast packing was significantly more comfortable than Spongostan for nasal obstruction, postnasal drip, rhinorrhea, and headache. Furthermore, the Cutanplast packing was significantly less painful at all time points. The remaining amount of the pack was significantly lower in the Cutanplast than Spongostan packing. Spongostan packing appears to impair wound healing within the sinus cavities up to 3 months postoperatively. Cutanplast was less expensive than Spongostan as used in this study. Cutanplast may be more useful gelatin-based packing material than Spongostan in terms of efficacy and cost-benefit after ESS.

Use of topical hemostatic agents in gynecologic surgery.

Sutures, hemoclips, and electrocautery are the primary mechanisms used to achieve hemostasis during gynecologic surgery, but in situations in which these are inadequate or not feasible, an array of hemostatic agents are available to help achieve hemostasis. These agents include physical agents such as cellulose, collagen, or gelatin products as well as biologic agents such as thrombin and fibrin products. Limited data are available on many of these agents, although their use is increasing, sometimes at high costs. In gynecologic surgery, hemostatic agents are likely most effective when used in areas of oozing or slow bleeding and as an adjunct to conventional surgical methods of hemostasis.

The use fibrinogen/thrombin-coated equine collagen patch in children requiring reoperations for congenital heart disease. A single center clinical experience.

AIM: The aim of this study was to evaluate the efficacy and cost-effectiveness of fibrinogen/thrombin-coated collagen patch (FTCCP)(TachoSil®) during intraoperative hemostasis in patients with congenital heart disease, who required a reoperation during childhood. METHODS: We reviewed data on the intraoperative blood product requirements and hospital costs of children (age <16 years) who underwent a reoperation for treating their congenital heart disease between January 2009 and December 2011. RESULTS: One-hundred and seventeen patients were included. Median age at surgery was 2.1 years (range 3 days-14.1 years). Main causes of intraoperative bleeding were: 1) reinforcement of suture lines (106 patients, 90.6%); 2) lung lesions (5 patients, 4.2%); 3) epicardial lesions (3 patients, 2.6%); and 4) chest wall lesions (3 patients, 2.6%). At logistic regression the amount of packed red blood cells (PRBC) requirement was significantly higher in patients with preoperative cyanosis (P=0.008, OR=3.85) and in patients who required the use of cardiopulmonary bypass (P=0.005, OR=21.19). The use of FTCCP (N.=90 patients) as first line treatment was significantly associated with a lower PRBC requirement (P=0.0003, OR=0.1) which in addition to the avoidance of other hemostatic/sealant agents, leads to lower hospital cost. CONCLUSION: FTCCP is an effective hemostatic agent which can be safely used during the hemostasis of children requiring reoperations for their congenital heart malformations. When used as first line treatment, with specific indications, FTCCP limited the intraoperative PRBC requirement and the use of other hemostatic/sealant agents thus reducing hospital costs.

[Indications and use of prothrombin complex in cardiac surgery]. / Indicaciones y usos del complejo protrombínico en cirugía cardiaca.

On of the most common, and serious, complications in cardiac surgery is postoperative bleeding. According to the majority of studies, between 10% and 92% of patients subjected to elective surgery require transfusions of blood products and blood derivatives. Transfusions and reinterventions are associated with longer stays in critical care units and a decrease in survival rates. There have been some important changes in the treatment of changes in haemostasis and post-surgical bleeding in the last few years, particularly with the introduction into clinical practice of working procedures backed up by clinical guidelines, as well as the appearance of new drugs. The aim of this work is to describe the main characteristics and update the use of prothrombin complexes that are currently available in Spain, with special emphasis on their use in cardiac surgery.

No evidence or no alternative? Taking responsibility for off-label prescribing.

Recombinant activated factor VII (rFVIIa) is registered for patients with rare haematological disorders, but is used 'off-label' in many other situations, including intracranial haemorrhage, cardiac surgery, trauma, transplantation and prostatectomy. Lack of systematic evidence to support these off-label uses has not slowed the growth of off-label prescribing of rFVIIa. We use the case of rFVIIa to illustrate the issues raised by off-label prescribing, and the kind of impasse that can arise when views about evidence, expertise and clinical necessity are in conflict. We argue that clinicians, hospital drug committees and regulators all need to acknowledge the complexity of prescribing decisions, and ensure that decisions to prescribe off-label are sufficiently justified.

Administration of recombinant activated factor VII in the intensive care unit after complex cardiovascular surgery: clinical and economic outcomes.

OBJECTIVE: Refractory bleeding after complex cardiovascular surgery often leads to increased length of stay, cost, morbidity, and mortality. Recombinant activated factor VII administered in the intensive care unit can reduce bleeding, transfusion, and surgical re-exploration. We retrospectively compared factor VII administration in the intensive care unit with reoperation for refractory bleeding after complex cardiovascular surgery. METHODS: From 1501 patients who underwent cardiovascular procedures between December 2003 and September 2007, 415 high-risk patients were identified. From this cohort, 24 patients were divided into 2 groups based on whether they either received factor VII in the intensive care unit (n = 12) or underwent reoperation (n = 12) for refractory bleeding. Preoperative and postoperative data were collected to compare efficacy, safety, and economic outcomes. RESULTS: In-hospital survival for both groups was 100%. Factor VII was comparable with reoperation in achieving hemostasis, with both groups demonstrating decreases in chest tube output and need for blood products. Freedom from reoperation was achieved in 75% of patients receiving factor VII, whereas reoperation was effective in achieving hemostasis alone in 83.3% of patients. Prothrombin time, international normalized ratio, and median operating room time were significantly less (P < .05) in patients who received factor VII. Both groups had no statistically significant differences in other efficacy, safety, or economic outcomes. CONCLUSIONS: Factor VII administration in the intensive care unit appears comparable with reoperation for refractory bleeding after complex cardiovascular surgical procedures and might represent an alternative to reoperation in selected patients. Future prospective, randomized controlled trials might further define its role.

Clinical assessment of Optivate®, a high-purity concentrate of factor VIII with von Willebrand factor, in the management of patients with haemophilia A.

Factor VIII (FVIII) concentrates have revolutionized the treatment of patients with haemophilia A. Concerns over the transmission of viral infections through these products have been addressed through stringent, donor-screening procedures and robust antiviral manufacturing steps. Bio Products Laboratory has developed a high-purity FVIII product with von Willebrand factor, Optivate(®). Its safety, tolerability and efficacy as prophylaxis and treatment of bleeds have been established in long-term studies. Seventy previously treated patients with severe haemophilia A, with ≥ 20 exposure days, were recruited into two long-term, multicentre, open-label studies. The protocols were virtually identical. Patients received Optivate(®) either prophylactically or on-demand. A mean of 159.0 EDs were experienced over 11,320 infusions. Under both conditions, Optivate(®) was well tolerated. Only 10% of patients experienced a treatment-related adverse event; the most commonly reported were headache (4% of patients) and dizziness (3% of patients). The mean number of bleeds/patient over the 2 year treatment period was 23.5 during prophylactic use and 70.4 during on-demand use. In patients treated prophylactically, clinical responses to breakthrough bleeds were rated by physicians as excellent or good and as very helpful or helpful by patients in 95% of bleeds. Clinical responses for on-demand patients were rated as excellent or good by physicians and helpful or very helpful by the patients for 91% of bleeds. There were no viral transmissions or inhibitors. The studies confirm the clinical efficacy and safety of Optivate(®) in both prophylactic and on-demand management of patients with haemophilia A.

Clinical assessment of efficacy and safety of DDAVP.

UNLABELLED: The efficacy of DDAVP (1-deamino-8-D-arginine-vasopressin, desmopressin) in mild haemophilia A and von Willebrand disease (VWD) has been established and the use of this well tolerated drug has become clinical routine. In case of increased fluid intake and based on very rarely occurring hyponatraemia, the indication of administration of DDAVP intravenously (i. v.) has to be performed diligently in elderly patients and in children below the age of five years. Aim, patients: Due to clinical practice we were interested in finding prospective parameter potentially correlating with adverse reactions of DDAVP and initiated this study. From 2007 to 2008, we included 49 patients suspicious to suffer from mild haemophilia A (n = 1) or VWD (n = 48) and investigated efficacy and safety of DDAVP after intravenous administration (mean: 0.29±0.032 μg/kg body weight). They underwent clinical and laboratory investigation and were questioned with regard to potential adverse reactions immediately and three days after administration of DDAVP. RESULTS, CONCLUSION: Most adverse reactions were mild and no serious adverse drug reactions were either observed or reported by the subjects. We identified significant changes of heart rate, blood pressure and leucocytes after conduct of the DDAVP test. The value of these findings has to be investigated in later prospective randomized studies. Further research on identification of prospective parameter is currently ongoing.