Study: Closure devices cut complications after cardiac procedure (VIDEO)

The use of vascular closure devices significantly reduced complications and the need for transfusions in obese and overweight patients undergoing transfemoral percutaneous coronary intervention (PCI), but the benefit over manual closure was not seen in lean and normal-weight patients or in those treated with a glycoprotein IIb/IIIa inhibitor, researchers reported.

The benefit was also counterbalanced by a small increase in risk of retroperitoneal bleeding, Hitinder S. Gurm, MD, of the University of Michigan Cardiovascular Center in Ann Arbor, and colleagues, wrote online in the Annals of Internal Medicine.

Vascular closure devices (VCDs) are designed to prevent arterial bleeding, especially after PCI performed by the transfemoral route, which is still the most common route in the U.S.

The devices permit closure of the arteriotomy site using sutures, plugs, or metallic clips, but the role of these devices in preventing vascular complications remains controversial, the researchers noted.

"Most randomized trials evaluating VCDs have been small and underpowered, and the largest meta-analysis on the subject raised concerns that these devices may be associated with an increase in vascular complications," they wrote. "These devices are commonly used in clinical practice, and a recent large observational study suggested that they may be associated with a reduction in bleeding complications."

The newly published study is among the first to compare the efficacy of VCDs to manual closure in the real-world PCI practice setting, with the focus on specific subgroups with the highest risk for complications.

Researchers collected data on 92,000 patients who had PCI procedures at 32 Michigan hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) between 2007 and 2009.

Of the 85,048 PCIs that met study inclusion criteria, 28,528 (37%) used VCDs.

A main study endpoint was vascular complications, including acute thrombosis, loss of limb, retroperitoneal bleeding, need for surgical repair, pseudoaneurysm, or hematoma requiring transfusion or arteriovenous fistula. Other endpoints included transfusion or in-hospital death.

Using propensity score-matched analysis, the use of VCDs was found to be associated with reductions in vascular complications (OR 0.78, 95% CI 0.67-0.90, P=0.001) and post-procedure transfusions (OR 0.85 CI 0.74-0.96, P=0.011).

"These findings were consistent across many prespecified subgroups except for patients with a BMI less than 25 kg/m2 and those treated with platelet glycoprotein IIb/IIIa inhibitors, in whom the benefit of VCDs over manual closure was attenuated," the researchers wrote.

When specific subtypes of vascular complications were evaluated, VCDs were associated with fewer hematomas (OR 0.69 CI 0.58-0.83, P<0 .001="" 0.38-0.76="" 0.54="" 1.12-2.20="" 1.57="" also="" an="" associated="" bleeding="" but="" ci="" in="" increase="" odds="" of="" or="" p="0.009).</span" pseudoaneurysms="" retroperitoneal="" the="" they="" were="" with="">

"Our sudy supports the conclusion that VCDs are associated with reduced vascular complications and transfusions," Gurm and colleagues wrote, adding that the benefit of these devices was evident only in obese and overweight patients in whom manual control of access site is usually difficult.

The study also confirmed that VCD use is particularly beneficial in patients treated with bivalirudin and that its use was associated with a significantly increased risk for retroperitoneal bleeding, which negated any benefit in patients who received GP IIb/IIIa.

"Our data suggest that physicians contemplating VCD use should carefully weigh this increased risk for retroperitoneal bleeding against the expected reduction in pseudoaneurysms and hematomas," the researchers wrote. "The decision to use these devices needs to be individualized for each patient."

Clinical Papers - Fibrin Sealants, BioGlue, Perclot, HaemoCer, Thrombin

Clinical Papers - Bonewax, Oxidized Cellulose, Surgicel,

Clinical Papers Hemostats Reviewed - Oxi Cell, Gelatin, Collagen, Thrombin, Polysaccharide Powders

A lot of our earlier embedded  document links have gone since our previous embedding agency sold (these things happen in 5 years of blogging). Now Google have this facility I am happy to provide you clinical data for your interest in the links below. 

Childhood Coagulation Marker Levels Distinct From Adulthood

Levels of key coagulation markers significantly vary with age in children, research reveals, potentially affecting the diagnosis and treatment of pediatric thrombotic and hemorrhagic disease.

Young children have significantly lower levels of fibrinogen and factor (F)II, IX, XI, and XII than older children, the researchers report in the Journal of Thrombosis and Haemostasis.

Younger age was also associated with significantly lower levels of Protein C and Protein S, but higher concentrations of D-dimer.

Von Willebrand factor (vWF) levels were also elevated in the first year of life, but there was no associated increase in FVIII levels, expected due to the known impact of vWF on FVIII half life.

vWF levels fell to a nadir at 1 year and then gradually increased to adult levels, but this trend was dependent on blood group type. Blood group O carriers showed only a slight increase from a median of 66% to 88% of adult levels, versus a median 106% in non-O blood group carriers.

The researchers believe this may be due to the increased susceptibility of vWF of blood group O to the proteolytic activity ofADAMTS13 compared with non-O blood groups. In the first months of childhood, when A, B, and H antigens of vWF are low, there may be less pronounced blood group differences in vWF levels.

"Our results underline the need for age-specific reference ranges," write Inge Appel and co-workers, from Erasmus Medical Centre - Sophia Children's Hospital in Rotterdam, the Netherlands.

The greatest variation was between infants in the first year of life versus adults, but inter-individual variability in coagulation factors was highest in the youngest children. The researchers therefore recommend: "In neonates and infants multiple reference samples are required to define the normal range in coagulation proteins for age more precisely."

The team examined blood samples from 218 healthy children aged 1-6 months (n=29), 7-12 months (n=25), 1-5 years (n=57), 6-10 years (n=57), 11-18 years (n=50), and over 19 years (n=52) using two different analyzers; the Behring Coagulation System (Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany) and the CA-1500 system (Sysmex, Kobe, Japan).

There was good correlation between the two systems for all coagulation markers, except prothrombin and activated partial thromboplastin time.

Symphogen Publishes Final Rozrolimupab (SYM001) Phase 2 Trial Results in ITP in BLOOD Journal

COPENHAGEN, DENMARK — The hematology journal BLOOD published today a full-length article describing final Phase 2 data for Symphogen’s rozrolimupab, a novel human recombinant mixture of 25 antibodies which all are manufactured simultaneously from a single batch. The data demonstrates rozrolimupab’s favorable safety profile and its induction of a rapid increase in platelet counts in patients with Primary Immune Thrombocytopenia Purpura (ITP). Professor Tadeusz Robak, MD, University of Lodz, Poland, is the first author of the article entitled “Rozrolimupab, A Mixture of 25 Recombinant Human Monoclonal RhD Antibodies, in the treatment of Primary Immune Thrombocytopenia” which has been prepublished in First Edition of Blood and can be viewed on Blood Online at http://bloodjournal.hematologylibrary.org/content/early/recent.

The Phase 2 study was an open-label, multi-center clinical trial evaluating the efficacy, safety, and tolerability of rozrolimupab (SYM001) in adult, RhD positive, non-splenectomized ITP patients. A total of 61 patients were treated with single doses from 75µg/kg to 300µg/kg as single i.v. infusions of 15-20 minutes’ duration. The trial demonstrated that at 300µg/kg, 8 of 13 (62%) of patients responded at day 7. Already within 5 to 8 hours after rozrolimupab administration, 23% of the patients achieved platelet responses (≥ 30×10⁹/L and increase in platelet count by > 20×10⁹/L from baseline). Median time to response was 59 hours (approximately 2.5 days) and the median duration of response was 14 days.

The most common adverse events observed, were headache (20%), mostly mild or moderate, pyrexia (13%), chills (10%), and fatigue (8%). Four serious adverse events considered related to study drug were reported: decreased hemoglobin, extravascular hemolysis/dizziness and two cases of transient rise in D-dimer values without clinical symptoms.

According to Professor Robak, “These Phase 2 results suggest an efficacy and safety profile similar to that seen with plasma derived immunoglobulin products. It seems promising that rozrolimupab rapidly yields platelet responses. This unique recombinant human monoclonal antibody mixture, rozrolimupab can be produced indefinitely and may represent a novel and convenient replacement for blood-derived immunoglobulins with more limited supply.”

Kirsten Drejer, Symphogen chief executive officer, added, “Symphogen has reached an important milestone by generating clinical proof of concept for a product consisting of a mixture of 25 monoclonal antibodies. The multicenter study included involvement of the regulatory authorities of the USA, Europe and Asia, and we are confident that antibody mixtures represent a viable new class of antibody therapeutics offering well-characterized and potentially more efficacious alternatives to existing treatments.”

New Study Reveals Wide Variation In Blood Transfusion Practices During Surgery

 According to a new study in the July 2012 print edition of Anesthesiology, blood transfusion, the most common procedure performed in U.S. hospitals¹, has wide variation in frequency by surgical procedure and physician as well as wide variation in the hemoglobin trigger used to help decide whether to transfuse.² The study also showed a significant number of transfusion decisions are made without laboratory hemoglobin measurements. The research adds to the growing clinical evidence highlighting the need for improved blood-management strategies. It also underscores the opportunity for noninvasive and continuous total hemoglobin (SpHb^®) monitoring from Masimo (NASDAQ:MASI) to facilitate optimal transfusion decision making to improve patient safety and reduce costs.

In the study, conducted at Johns Hopkins Hospital in Baltimore, Maryland, researchers collected data on 48,086 surgical patients over 18 months and evaluated blood transfusion frequency and hemoglobin triggers by surgical procedure and physician. A total of 2,981 patients (6.2%) received an intra-operative red blood cell transfusion, with two-thirds of those patients receiving two or more units. Transfusion rates varied up to threefold between different physicians performing the same procedure (p<0.05). The average transfusion hemoglobin trigger used to determine need for blood transfusion varied widely with both surgeons (7.2 g/dL to 9.8 g/dL, p=0.001 and anesthesiologists (7.2 g/dL to 9.6 g/dL, p=0.001). The ending hemoglobin values after the last recorded transfusion also varied widely for both surgeons (8.8 g/dL to 11.8 g/dL, p=0.001) and anesthesiologists (9.0 g/dL to 11.7 g/dL, p=0.0004). A recent laboratory hemoglobin measurement was not available when 31% of transfusion decisions were made.

Blood transfusions carry risks. In a previous meta-analysis of 45 studies evaluating the risks of blood transfusion, 42 studies showed a significant link to mortality, infection, or adult respiratory distress syndrome.³ In contrast to the historical belief that withholding transfusions harms patients, multiple randomized controlled trials have now proven that restrictive transfusion practice is safe.^4,5,6 This has led recent transfusion guidelines to focus transfusion decisions on the overall patient condition and to suggest hemoglobin transfusion triggers of 6-7 g/dL for most patients and above 7 g/dL only in select, high-risk patients.^7,8,9

Blood transfusions are also one of the largest cost centers in hospitals. While the material cost of blood ranges from $200 to $300 per unit, the additional costs from storage, labor, and waste result in an actual cost per unit between $522 and $1,183.¹⁰ In addition to the cost of blood itself, each unit of blood transfused increases the cost of care, with even higher costs incurred when patients are transfused at higher hemoglobin levels.¹¹

A recent systematic evaluation of 494 studies concluded that 59% of transfusions were “inappropriate” based on their impact on patient outcomes.¹² The risks and costs of blood transfusion paired with unnecessary transfusions led the Joint Commission in 2011 to introduce new patient blood management measures that hospitals are being encouraged to adopt as a quality indicator.¹³ The new measures include recording the clinical indication for transfusion along with the hemoglobin value of the patient prior to each unit transfused. With the need to stem rising health care expenditures, the Joint Commission and the American Medical Association have targeted blood transfusion procedures as one of the top procedures to reduce in a “National Summit on Overuse” scheduled for September 2012.¹⁴

There is no doubt that clinicians desire the best care for their patients without unnecessary costs, but they are also limited in their precise ability to determine need for transfusion with existing tools. Estimates of blood loss in the operating room can be inaccurate. Researchers at Duke University recently reported estimated surgical blood loss exceeded measured blood loss by more than 40% (860mL vs. 611 mL, p< 0.0001).¹⁵ The likely reason for this discrepancy is the inability to accurately estimate blood loss based on visual inspection of blood and fluid in suction canisters and surgical sponges. While estimating blood loss is challenging and laboratory hemoglobin results are only availably intermittently and are often delayed, transfusion decisions are made in real time. Acknowledging these challenges, the Duke Researchers stated: “Use of bedside hemoglobin concentration devices and continuous, noninvasive hemoglobin monitors may improve transfusion decisions.”

Masimo’s breakthrough SpHb measurement allows clinicians to noninvasively and continuously monitor hemoglobin. Results of an earlier randomized controlled trial conducted by researchers at Massachusetts General Hospital and Harvard Medical School showed that SpHb helped anesthesiologists reduce the frequency of blood transfusion by 87% (from 4.5% to 0.6%, p=0.03) and quantity of blood by 90% (from 0.1 to 0.01 units per patient, p<0 .0001=".0001" 327="327" in="in" orthopedic="orthopedic" patients="patients" sup="sup" surgery.="surgery." undergoing="undergoing">16

Dr. Aryeh Shander, Executive Medical Director at the Institute for Patient Blood Management & Bloodless Medicine Surgery and Chief of Anesthesiology and Critical Care Medicine at Englewood Hospital & Medical Center in New Jersey, stated: “The ability of Masimo’s noninvasive hemoglobin technology to continuously monitor hemoglobin during surgeries can offer earlier, real-time information that can result in diagnosis leading to interventions other than transfusion. And fewer unnecessary transfusions can mean improved patient outcomes.”

This year Masimo launched the Blood Transfusion Related Cost Reduction guarantee program (BTR-CR, “Better Care”) to help hospitals improve patient care and reduce costs. BTR-CR guarantees that a hospital’s blood transfusion-related cost reductions will be greater than the cost of SpHb monitoring. 

1 AHRQ, Center for Delivery, Organization, and Markets, Healthcare Cost and Utilization Project, Nationwide Inpatient Sample, 1997 and 2007.

2 Steven M. Frank, M.D., Will J. Savage, M.D., Jim A. Rothschild, M.D., Richard J. Rivers, M.D., Paul M. Ness, M.D., Sharon L. Paul, B.S., M.S., John  A. Ulatowski, M.D., Ph.D., M.B.A. “Variability in Blood and Blood Component Utilization as Assessed by an Aesthesia Information Management System.” Anesthesiology, July 2012 – Volume 117 – Issue 1 – p 99–106 doi: 10.1097/ALN.0b013e318255e550

3 Marik, P. E. and H. L. Corwin (2008). “Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature.” Crit Care Med 36(9): 2667-74.

4 Carson, J. L., M. L. Terrin, et al. (2011). “Liberal or restrictive transfusion in high-risk patients after hip surgery.” N Engl J Med 365(26): 2453-62.

5 Hebert, P. C., G. Wells, et al. (1999). “A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.” N Engl J Med 340(6): 409-17.

6 Hajjar, L. A., J.-L. Vincent, et al. (2010). “Transfusion Requirements After Cardiac Surgery: The TRACS Randomized Controlled Trial.” JAMA 304(14): 1559-1567.

7 American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies: Practice Guidelines for Perioperative Blood Transfusion and Adjuvant Therapies: An updated report by the American Society of Anesthesiologists Task Force on Perioperative Blood Transfusion and Adjuvant Therapies. Anesthesiology 2006; 105:198 –208

8 Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA, Hebert PC, Anderson GL, Bard MR, Bromberg W, Chiu WC, Cipolle MD, Clancy KD, Diebel L, Hoff WS, Hughes KM, Munshi I, Nayduch D, Sandhu R, Yelon JA, American College of Critical Care Medicine of the Society of Critical Care Medicine, Eastern Association for the Surgery of Trauma Practice Management Workgroup: Clinical practice guideline: Red blood cell transfusion in adult trauma and critical care. Crit Care Med 2009; 37:3124 –57

9 Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER, Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion, Shore-Lesserson LJ, Goodnough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J, International Consortium for Evidence Based Perfusion, Baker RA, Dickinson TA, FitzGerald DJ, Likosky DS, Shann KG: 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg 2011; 91:944 – 82

10 Shander, A.,A. Hofmann, et al. “Activity-based costs of blood transfusions in surgical patients at four hospitals.” Transfusion 50(4): 753-65.

11 Murphy, G. J., B. C. Reeves, et al. (2007). “Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery.” Circulation 116(22): 2544-52.

12 Shander, A., A. Fink, et al. (2011). “Appropriateness of allogeneic red blood cell transfusion: the international consensus conference on transfusion outcomes.”Transfus Med Rev 25(3): 232-246 e53.

13 Gammon HM, Waters JH, Watt A, Loeb JM, Donini-Lenhoff A: Developing performance measures for patient blood management.  Transfusion 2011; 51:2500 –9.

14 Joint Commission Perspectives.  The Joint Commission Continues to Study Overuse Issues.  Volume 32, Number 5, 2012 : 4-8(5).

15 Hill, S., Broomer, B Stover, J,  White, W. (2011). Accuracy of estimated blood loss in spine surgery. American Society of Anesthesiologists Annual Conference, San Diego, CA

16 Ehrenfeld JM, Henneman JP, Sandberg WS. “Impact of Continuous and Noninvasive Hemoglobin Monitoring on Intraoperative Blood Transfusions.” American Society Anesthesiologists. 2010;LB05

The incredible value of blood saving....

Click to enlarge.... Bloodless surgery in US Jehovah's Witnesses results in Heart benefits.

TRALI - further evidence to minimize transfusion

TRALI 

Transfusion-Related Acute Lung Injury (TRALI) is a syndrome characterized by acute respiratory distress following transfusion. All plasma-containing blood products have been implicated including rare reports of IVIG and cryoprecipitate. It is a rare complication of allogeneic blood transfusion but the incidence has not been well established due to difficulty in defining the syndrome and to variable reporting mechanisms worldwide. Various studies have estimated the overall frequency of TRALI to be between 1/1,120 and 1/57,810 units transfused. However, there is wide discrepancy in the literature with the reported frequency is as low as 1/557,000 RBC units and as high as 1/432 platelet units.

TRALI is associated with a high morbidity with the majority of patients requiring ventilatory support. However, the lung injury is generally transient with PO2 levels returning to pretransfusion levels within 48 -96 hours and CXR returning to normal within 96 hours. TRALI is associated with a significant mortality rate, often approximated at 5 to 10%. Given the gains in safety made within the blood component production industry, particularly with respect to transmission of infectious diseases, TRALI is now among the three leading causes of transfusion related fatalities along with ABO incompatibility and bacterial contamination.

Transfusion-related acute lung injury and pulmonary edema in critically ill patients: a retrospective study.

Rana R, Fernández-Pérez ER, Khan SA, Rana S, Winters JL, Lesnick TG, Moore SB, Gajic O.

Source

Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Abstract

BACKGROUND:

Using the recent Consensus Panel recommendations, we sought to describe the incidence of transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) in critically ill patients.

STUDY DESIGN AND METHODS:

Consecutive patients at four intensive care units (ICUs) who did not require respiratory support at the time of transfusion were identified with custom electronic surveillance system that prospectively tracks the time of transfusion and onset of respiratory support. Respiratory failure was defined as the onset of noninvasive or invasive ventilator support within 6 hours of transfusion. Experts blinded to specific transfusion factors categorized the cases of pulmonary edema as permeability edema (suspected or possible TRALI) or hydrostatic edema (TACO) according to predefined algorithm. In a nested case-control design, transfusion variables and lung injury risk factors were compared between the TRALI cases and controls matched by age, sex, and admission diagnosis.

RESULTS:

There were 8902 units transfused in 1351 patients of whom 94 required new respiratory support within 6 hours of transfusion. Among 49 patients with confirmed acute pulmonary edema, experts identified 7 cases with suspected TRALI, 17 patients with possible TRALI, and 25 cases with TACO. The incidence of suspected TRALI was 1 in 1271 units transfused; possible TRALI, 1 in 534 per unit transfused; and TACO, 1 in 356 per unit transfused. When adjusted for sepsis and fluid balance in a stepwise conditional logistic regression analysis, patients who developed acute lung injury (suspected or possible TRALI) received larger amount of plasma (odds ratio 3.4, 95% confidence interval 1.2-10.2, for each liter infused; p = 0.023).

CONCLUSION:

In the ICU, pulmonary edema frequently occurs after blood transfusion. The association between infusion of plasma and the development of suspected or possible TRALI may have important implications with regards to etiology and prevention of this syndrome.

Link: http://www.ncbi.nlm.nih.gov/pubmed/16965572

CRY Q3 10Q, FDA Disapproves Perclot IDE.....Perclot China Trial underway......

10Q - PerClot and HemoStase
Revenues from the sale of hemostats, consisting of PerClot and HemoStase, decreased 71% for the three months ended September 30, 2011 as compared to the three months ended September 30, 2010. Revenues from the sale of PerClot and HemoStase decreased 40% for the nine months ended September 30, 2011 as compared to the nine months ended September 30, 2010. The revenue decreases in the three and nine months ended September 30, 2011 were primarily due to a decrease in hemostat sales volume in domestic markets, partially offset by an increase in sales volume in international markets. The revenue decrease in the nine months ended September 30, 2011 was also impacted by a decrease in average selling prices, which decreased revenues by 6%.
International hemostat revenues increased 24% for the three months ended September 30, 2011 and 55% for the nine months ended September 30, 2011 as compared to the three and nine months ended September 30, 2010, respectively. This increase is primarily due to an increase in international sales of PerClot in the 2011 periods over the international sales of HemoStase in the corresponding 2010 periods. Management believes that international PerClot revenues have been favorably impacted by the Company’s ability to market PerClot for all surgical specialties, expanding the direct European sales force into Austria, and PerClot’s product performance when compared to other hemostatic agents.
The decrease in domestic sales volume for the three and nine months ended September 30, 2011 was due to the Company’s planned discontinuation of sales of HemoStase in late March 2011. The Company recognized no domestic hemostat sales in the second or third quarters of 2011, subsequent to the discontinuance of HemoStase sales, as PerClot is not yet approved for commercial distribution in domestic markets. The Company anticipates this loss of domestic hemostat sales to result in a decrease in total hemostat sales for the remainder of 2011 when compared to the corresponding 2010 periods.


The Company will not be able to sell PerClot in the U.S. in future years until U.S. Food and Drug Administration (“FDA”) approval is granted. On March 31, 2011 CryoLife filed an Investigational Device Exemption (“IDE”) with the FDA seeking approval to begin clinical trials for the purpose of obtaining Premarket Approval to distribute PerClot in the U.S. On April 29, 2011 the FDA disapproved CryoLife’s IDE filing with numerous comments and questions. CryoLife is currently addressing those comments and questions and anticipates refiling its IDE for PerClot in the fourth quarter of 2011.


Q3 Report - Brackets have been added-
Ashley Lee...

We experienced some delays in getting PerClot approved in certain international markets and some competitive issues in the EU, which leaves us to slightly lower our guidance.

Worldwide BioGlue revenues were up 10% for the third quarter and up 5% for the nine month period. These increases were predominantly driven by volume increases, particularly in Japan, due to the recent launch of the product. This was the largest year-over-year quarterly increase for BioGlue revenues, since third quarter of 2008, and we continue to remain enthusiastic about the opportunity in Japan.

Total sales in the third quarter in Japan were $651,000 and year-to-date in Japan were approximately $1.2 million. To-date, approximately 250 surgeons have been trained and over 160 accounts have ordered product. We expect another large order from Japan before the end of the year.

PerClot sales for the third quarter were $620,000 and were $1.9 million year-to-date. We experienced some delays in getting PerClot approved in certain international markets and some competitive issues in the EU, which leaves us to slightly lower our guidance. However, despite these delays, our international revenues from the sale of powdered hemostats in the third quarter still increased 24% compared to the prior year, and 55% for the nine month period compared to the prior year.

Steve Anderson...As Ashley has discussed earlier in third quarter of 2010, we announced our first technology acquisition and that we have signed a worldwide manufacturing and distribution agreement for a unique powered hemostatic agent PerClot with Starch Medical of San Jose (Shanghai), California (China).
(Chinese) PerClot is an ideal replacement for the hemostatic powder that we had been distributing worldwide. The primary difference is that PerClot’s gross margin will be 80%.....we filed our IDE for PerClot with the FDA in March of this year. The FDA had questions about our submission that we have been addressing. We will be reaching our IDE to the FDA in mid November. We expect to begin the clinical trial for PerClot (Link to current trial Xijing Hospital of Digestive Diseases, Xi'an, Shaanxi, China) during the second quarter of next year. The clinical trial will probably involve about 300 patients, 150 PerClot patients and 150 control patients. We expect that with six months enrollment and three months follow-up of these patients that we will file our PMA in the second quarter of 2013.

• In which circumstances does the FDA disapprove or withdraw an IDE?
  FDA may disapprove or withdraw approval of an IDE application if FDA finds that:
• 1. The sponsor has not complied with applicable requirements of the IDE Regulation, any other applicable regulations or statutes, or any condition of approval imposed by an IRB or FDA.
  2. The application or a report contains untrue statements or omits required material information.
  3. The sponsor fails to respond to a request for additional information within the time prescribed by FDA.
  4. There is reason to believe that the risks to the human subjects are not outweighed by the anticipated benefits to the subjects or the importance of the knowledge to be gained, that informed consent is inadequate, that the investigation is scientifically unsound, or that the device as used is ineffective.
  5. It is unreasonable to begin or to continue the investigation due to the way in which the device is used or the inadequacy of:
     (i) the report of prior investigations or the investigational plan; (ii) the methods, facilities, and controls used for the manufacturing, processing, packaging, storage, and, where appropriate, installation of the device; or (iii) the monitoring and review of the investigation.

Q & A...

Matt Dolan - Roth Capital Partners

Great. First question on the guidance, just looking at the revenue at this point it implies maybe around 10% sequential uptick in Q4. So how far below $122 million should we expect or what gets you to that type of sequential uptick, meaning, is there a category that improves something on the macro level that rebounds?

Ashley Lee

We think that the upside is in the Cardiogenesis product line and the PerClot product line as well as potentially BioGlue in Japan.

Matt Dolan - Roth Capital Partners

Okay. But given your guidance on those categories it still requires a pretty big sequential uptick?

Ashley Lee

Yeah well the possibility exists again that we could do better and then we expect to do better in Cardiogenesis, PerClot, and BioGlue in Japan. And that -- we think that that’s, we have more upside in those three areas than the rest of the business.

Matt Dolan - Roth Capital Partners

Okay. And then on the earnings guidance just to clarify, I think the delta between adjusted and GAAP last quarter was $0.05 as supposed to an $0.08 differential at mid year. So I wanted to make sure that that’s the reason for the increase in the earnings guidance? And secondly the implied guidance for Q4 cuts EPS basically in half. So I’m just trying to understand why that would be?

Ashley Lee

The primary driver in non-GAAP, the increase in non-GAAP EPS as compared to the end of the second quarter is primarily due to the shifting of some R&D expenses due to some delays and getting some studies started, as those will be shifting out of 2011 into 2012. As it relates to the fourth quarter we provided for some additional expenses in the fourth quarter this year to account for the ongoing discovery and the acceleration of the discovery in our litigation with Medafor.

Raymond Myers - Benchmark

And that was going to be my next question. So let’s get right to that. Roughly how much Medafor litigation expense should we expect?

Ashley Lee

If you go through the end of the third quarter we had spent about $1.4 million and we’re expecting a similar amount in the fourth quarter of this year about $1.4 million.....

A keratin biomaterial gel hemostat derived from human hair: evaluation in a rabbit model of lethal liver injury.

Abstract

Effective hemostatic dressings that are compatible with tissues are needed. Keratins are a class of biomaterials that can be derived by extraction of proteins from human hair. We have recently discovered that keratin biomaterials have hemostatic characteristics and hypothesize that a keratin hydrogel having the ability to absorb fluid and bind cells may be an effective hemostat. The goal of this study was to test a keratin hydrogel and evaluate it compared to current hemostats. Thirty-two New Zealand white rabbits received a lethal liver injury. Eight animals each were assigned to negative control, QuickClot, HemCon bandage, and keratin treatment groups. Vital stats and other data were recorded during surgery and all surviving animals were sacrificed after 72 h. Histology was conducted on all surviving animals. Twenty-four-hour survival rates were 0%, 62.5%, 62.5%, and 75% for the negative control, QuickClot, HemCon, and keratin groups, respectively. Other outcomes included blood loss, mean arterial pressure, heart rate, shock index, and liver histology. All of the hemostats were statistically better than the negative control group at late operative time points. The keratin group consistently performed as well as, or better than, the commercial hemostats. Histology showed an interesting healing response at the hemostat-liver interface in the keratin group.

Fibrinogen and Hemostasis: A Primary Hemostatic Target for the Management of Acquired Bleeding

Jerrold H. Levy, MD, FAHA,
Fania Szlam, MMSc,
Kenichi A. Tanaka, MDand
Roman M. Sniecienski, MD

+Author Affiliations
From the Department of Anesthesiology, Emory University School of Medicine, Cardiothoracic Anesthesiology and Critical Care, Emory Healthcare, Atlanta, Georgia.
Address correspondence to Jerrold H. Levy, MD, FAHA, Department of Anesthesiology, Emory University School of Medicine, Cardiothoracic Anesthesiology and Critical Care, Emory Healthcare, Atlanta, GA.

Abstract

Fibrinogen plays several key roles in the maintenance of hemostasis. Its cleavage by thrombin and subsequent polymerization to form fibrin strands provides the structural network required for effective clot formation. During cases of acute blood loss, attempts to maintain circulating volume and tissue perfusion often involve the infusion of crystalloids, colloids, and red blood cells. Intravascular volume resuscitation, although vital, frequently results in dilution of the remaining clotting factors and onset of dilutional coagulopathy. In such cases, fibrinogen is the first coagulation factor to decrease to critically low levels. There currently is a lack of awareness among physicians regarding the significance of fibrinogen during acute bleeding and, at many centers, fibrinogen is not monitored routinely during treatment. We reviewed current studies that demonstrate the importance of considering fibrinogen replacement during the treatment of acquired bleeding across clinical settings. If depleted, the supplementation of fibrinogen is key for the rescue and maintenance of hemostatic function; however, the threshold at which such intervention should be triggered is currently poorly defined. Although traditionally performed via administration of fresh frozen plasma or cryoprecipitate, the use of lyophilized fibrinogen (concentrate) is becoming more prevalent in some countries. Recent reports relating to the efficacy of fibrinogen concentrate suggest that it is a viable alternative to traditional hemostatic approaches, which should be considered. The prospective study of fibrinogen supplementation in acquired bleeding is needed to accurately assess the range of clinical settings in which this management strategy is appropriate, the most effective method of supplementation and a comprehensive safety profile of fibrinogen concentrate used for such an approach.
Accepted July 11, 2011.

Late wound healing problems after use of BioGlue® for apical hemostasis during transapical aortic valve implantation

Some Interesting Reading.....click on the thumbnails to read

Preoperative Fibrinogen Plasma Concentration Is Associated With Perioperative Bleeding and Transfusion Requirements in Scoliosis Surgery

Study Design. Prospective observational study.

Objective. To investigate the potential association between fibrinogen, bleeding, and transfusion requirements after scoliosis surgery.

Summary of Background Data. Bleeding complications during and after orthopedic surgery are associated with increased morbidity and mortality. Early identification of patients with increased risk of excessive bleeding offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade, and thus a potential biomarker for bleeding risk.

Methods. A total of 82 otherwise healthy patients (mean age: 15 ± 3 years, 85% girls) undergoing surgery for adolescent idiopathic scoliosis were included in the study. Patient variables (age, gender, operation time, and thrombosis prophylaxis), preoperative laboratory variables (hemoglobin, platelet count, activated partial thromboplastin time [aPTT], prothrombin time [PT], and fibrinogen), peroperative and postoperative bleeding volume, and transfusions were registered. Correlations between laboratory variables and bleeding volume were calculated with Pearson test. Patient variables and laboratory variables were compared with Student t test between patients with bleeding volume in the upper quartile (“bleeders”) and the remaining patients, and between patients with extensive transfusion (defined as >2 U of packed red cells) and no or limited transfusions (≤2 U).

Results. Mean fibrinogen concentration was 3.0 ± 0.7 g/L (range, 1.3– 4.9). Mean total perioperative bleeding volume was 1552 ± 1019 mL (range, 100–5800 mL). Total bleeding volume correlated significantly with preoperative fibrinogen concentration (r = −0.31, P = 0.005) but neither with platelet count, aPTT, nor PT (P = 0.61, 0.46, and 0.57, respectively). Bleeders had significantly lower preoperative fibrinogen plasma concentration (2.6 ± 0.6 vs. 3.1 ± 0.6 g/L, P = 0.002). Of total, 16% (13/82) of the patients were transfused with >2 U of packed red cells. Patients with extensive transfusions had significantly lower preoperative fibrinogen plasma concentration (2.5 ± 0.7 vs. 3.1 ± 0.6 g/L, P = 0.002), while preoperative platelet count, aPTT, and PT did not differ.

Conclusion. The results indicate that preoperative fibrinogen concentration is a limiting factor for postoperative hemostasis during and after scoliosis surgery. Preoperative measurement of fibrinogen concentration provides more information about bleeding volume and transfusion requirements than standard screening tests.

Cryolife Q4 - Upbeat news for shareholders 10 people in the EU until 2013 to carry Medafor Divorce, Perclot-China marriage and Bioglue EU IP

Product revenues which consists primarily of BioGlue and HemoStase increased 4% in the fourth quarter and full year of 2010 compared to the corresponding periods in 2009. For the three month and full year periods HemoStase revenue increased partially offset by a slight decrease in BioGlue revenues. Fourth quarter of 2010 also included $264,000 of PerClot revenue as we began to roll out PerClot in international markets.

Total gross margins were 60% for the fourth quarter of 2010 compared to 61% for the fourth quarter of 2009. Total gross margins excluding the write off of $1.6 million for the HemoStase inventory were 60% for the full year of 2010 compared to 62% in the full year of 2009. Preservation services gross margins for the fourth quarters of 2010 and 2009 were 39% for each period and 40% in the full year of 2010 compared to 42% in the full year of 2009.

Product gross margins for the fourth quarter of 2010 were 80% compared to 82% in the corresponding period in 2009. Product gross margins excluding the write down of $1.6 million of HemoStase inventory were 81% in the full year of 2010 compared to 83% in the full year of 2009. General administrative and marketing expenses for the fourth quarter of 2010 were $12.2 million compared to $12.6 million for the fourth quarter of 2009. These expenses for the fourth quarter of 2010 included approximately $474,000 in costs related to business development activities and $268,000 in costs related to our litigation with Medafor.

General administrative and marketing expenses for the full year of 2010 were $49.1 million compared to $50 million for the full year of 2009. The full year of 2010 included a charge of approximately $1.4 million in costs related to our litigation with Medafor $1 million related to business development activities and $729,000 related to the write off of capitalized legal expenses associated with our BioGlue intellectual property rights in Germany.....

Raymond Myers – The Benchmark Company

Okay. Good. When were you targeting PerClot approval and launch?

Product revenues which consists primarily of BioGlue and HemoStase increased 4% in the fourth quarter and full year of 2010 compared to the corresponding periods in 2009. For the three month and full year periods HemoStase revenue increased partially offset by a slight decrease in BioGlue revenues. Fourth quarter of 2010 also included $264,000 of PerClot revenue as we began to roll out PerClot in international markets.

Total gross margins were 60% for the fourth quarter of 2010 compared to 61% for the fourth quarter of 2009. Total gross margins excluding the write off of $1.6 million for the HemoStase inventory were 60% for the full year of 2010 compared to 62% in the full year of 2009. Preservation services gross margins for the fourth quarters of 2010 and 2009 were 39% for each period and 40% in the full year of 2010 compared to 42% in the full year of 2009.

Product gross margins for the fourth quarter of 2010 were 80% compared to 82% in the corresponding period in 2009. Product gross margins excluding the write down of $1.6 million of HemoStase inventory were 81% in the full year of 2010 compared to 83% in the full year of 2009. General administrative and marketing expenses for the fourth quarter of 2010 were $12.2 million compared to $12.6 million for the fourth quarter of 2009. These expenses for the fourth quarter of 2010 included approximately $474,000 in costs related to business development activities and $268,000 in costs related to our litigation with Medafor.

General administrative and marketing expenses for the full year of 2010 were $49.1 million compared to $50 million for the full year of 2009. The full year of 2010 included a charge of approximately $1.4 million in costs related to our litigation with Medafor $1 million related to business development activities and $729,000 related to the write off of capitalized legal expenses associated with our BioGlue intellectual property rights in Germany.....

Raymond Myers – The Benchmark Company

Okay. Good. When were you targeting PerClot approval and launch?

Steve Anderson

I think that PerClot’s approval will be sometime towards the end of 2012 or early 2013 the clinical study that we are going to run is includes about 300 patients and will be across a number of different specialties for a number of different indications. But I would say the soonest we could get it done at the end of 2012 probably a more timely expectation is early 2013.

Raymond Myers – The Benchmark Company

And that’s for approval or for finishing this study.

Steve Anderson

That’s approval.

Raymond Myers – The Benchmark Company

And so well let’s start with the study through this to finish the 300 patient study if you would follow your IDE at the end of March when do you think you can finish the study.

Steve Anderson

It will go pretty quickly but I don’t think that we would be finished with the 300 patient enrollment until fourth quarter of 2011.

Raymond Myers – The Benchmark Company

And that leaves about a year for FDA is that your thought?

Steve Anderson

Yeah.

Raymond Myers – The Benchmark Company

Great, your HemoStase revenue was quite strong in the fourth quarter is that related to winding down the sales and a desirable push out the last of your inventory before you can’t sell it anymore or does that more represent underlying strength in the market.

Ashley Lee

I think it represents both you know I mean you know this full area of powdered hemostatic agents is rolling and that’s why we’ve made the commitment to be in it long-term with the acquisition of the PerClot distribution rights and at the same time you know as you mentioned we do have some inventory that we are trying to sell prior to our discontinuing distributing HemoStase which is going to be in late March so it’s a combination of both.

Raymond Myers – The Benchmark Company

So should we expect similar sales on Q1 as if we saw in Q4.

Ashley Lee

For HemoStase.

Raymond Myers – The Benchmark Company

Yeah.

Ashley Lee

No.

Raymond Myers – The Benchmark Company

Lower, higher?

Ashley Lee

That would be lower than the fourth quarter of 2010 and I think that our guidance for again for the full year for all powdered hemostats is between $4 million and $6 million.

Raymond Myers – The Benchmark Company

Okay, and is some of the HemoStase that you might be selling in Q1 product that is already written off?

Ashley Lee

Potentially.

Raymond Myers – The Benchmark Company

So there could be a potential of a reversal of the prior charges?

Ashley Lee

I wouldn’t say a reversal of the prior charges we could be recognizing some revenue for which there is no associated – costs associated with the revenues so not by that finish in reversal but we could have some revenue with very high gross margin on it.

Raymond Myers – The Benchmark Company

Do you expect that to be potentially meaningful to earnings in the quarter.

Ashley Lee

I wouldn’t expect it to be meaningful to earnings in the quarter.

Raymond Myers – The Benchmark Company

Okay well.

Ashley Lee

It might be meaningful to cash flow though.

Raymond Myers – The Benchmark Company

Nice your cash flow is already very good. You’ve had a share buyback consistently through 2010 do you intend to continue that in 2011?

Ashley Lee

The buyback has continued into the first couple of months of 2011 and just to give you an idea of where we are we have purchased roughly about 1.3 million to 1.4 million stock in the first two months 2011 at an average price of you know somewhere around 5.25 [ph] that’s a guess.

Raymond Myers – The Benchmark Company

So you’ve purchased $1.3 million or shares?

Ashley Lee

Dollars.

Raymond Myers – The Benchmark Company

Dollars.....

Raymond Myers – The Benchmark Company

Yeah, thank you I’m here. Ashley and Steve could you maybe start with reminding us how many sales people do you have now and what are your plans to expand that.

Steve Anderson

In round numbers we have about 50 in the field in United States and we are direct in the UK, Germany and Austria with approximately 10 people in the field over there.


Steve Anderson

I think that PerClot’s approval will be sometime towards the end of 2012 or early 2013 the clinical study that we are going to run is includes about 300 patients and will be across a number of different specialties for a number of different indications. But I would say the soonest we could get it done at the end of 2012 probably a more timely expectation is early 2013.

FYI BioGlue paper, click on thumbnail.

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