The Most Important Factor in a Hemostatic Agent - Poll Results

The Question for this Poll........"The Most Important Factor in a Hemostatic Agent is?".

Bit of a landslide for Efficacy with 50%. Following up was Safety with 23%, which is interesting when compared to our previous poll .

Cost was voted at 12% the equal of Ease of Use also with 12%.

Cryolife - Bioglue Hits 500,000 Procedure Milestone

CryoLife, Inc., (NYSE: CRY) an implantable biological medical device and cardiovascular tissue processing company, today announced that, according to company data, CryoLife's BioGlue(R) Surgical Adhesive has been used in more than 500,000 surgical procedures throughout the world since its introduction into the international market in 1998 and in the United States in 2001. BioGlue is a leading surgical adhesive used in cardiovascular surgeries worldwide.

This link will give you the IFU for BioGlue® Surgical Adhesive (BioGlue).

FDA Approves Treatment for Rare Genetic Defect

RiaSTAP, a new drug for treatment for patients living with congenital fibrinogen deficiency, a condition that affects blood coagulation, has reportedly gained FDA approval.
According to FDA officials, the condition, which affects only 150-300 people in the U.S., can lead to potentially life-threatening bleeding without treatment and is usually diagnosed at birth.
An intravenous fibrinogen concentrate made from the plasma of healthy human blood donors, RiaSTAP is indicated for patients who have no fibrinogen or low levels of the substance. The FDA warns that RiaSTAP is not indicated for patients with dysfibrinogenemic (those who may have normal fibrinogen levels but defective fibrinogen function) as these individuals are at risk for both bleeding and clotting complications.
Fever and headache were the most common adverse reactions to the drug, the FDA reported.

A keratin biomaterial gel hemostat derived from human hair

Aboushwareb Tamer; Eberli Daniel; Ward Catherine; Broda Christopher; Holcomb John; Atala Anthony; Van Dyke Mark A keratin biomaterial gel hemostat derived from human hair: evaluation in a rabbit model of lethal liver injury. Journal of biomedical materials research. Part B, Applied biomaterials
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.

Phase II clinical trial for Fibrocaps

SEATTLE, Washington, and LEIDEN, The Netherlands, June 18 /PRNewswire/ -- ProFibrix B.V. today announced the start of the company's Phase II clinical trial for Fibrocaps(TM), the company's lead topical Hemostat product, with the successful treatment of the first patients for mild to moderate bleeding during liver surgery. ProFibrix expects to complete the study before the end of 2009.
Fibrocaps is based on a mixture of two essential blood clotting proteins, fibrinogen and thrombin, and is a unique dry powder topical tissue sealant that rapidly stops bleeding after or during surgery. Fibrocaps has major advantages over existing liquid tissue sealants: it is ready for immediate use, is stable at room temperature, highly effective and fast acting.
ProFibrix expects to submit an Investigational New Drug Application (IND) for Fibrocaps to the U.S. Food and Drug Administration in the first half of 2010, and conduct a combined phase II/III pivotal study in various surgical indications.
Jaap Koopman, PhD, Chief Executive Officer, said: "The successful treatment of the first patients with our lead product Fibrocaps is an important milestone for the company. With focus and dedication we have made enormous progress over the past two years, and we are on track to bring Fibrocaps to the point of market approval."
About ProFibrix
ProFibrix was founded in 2004 and is headquartered in Leiden, The Netherlands, with a subsidiary in Seattle, WA. The company leverages its expertise in fibrinogen technology to develop and market innovative products for the hemostasis and regenerative medicine markets. Human fibrinogen plays a pivotal role in blood clotting and tissue healing. ProFibrix is led by a team with extensive commercial, clinical and scientific experience in the hemostasis field.

Hemostasis Market - Review of Gelfoam, Surgicel, Avitene, Floseal, Bovine Thrombin

This post is to provide further commentary to a readily available 2005 article posted early last year from an online source. The source of the original article is linked below*.

So what do we want in a good hemostatic agent? First, the ideal hemostatic agent would of course be such that the agent itself is as well as any of its metabolic breakdown products would be safe to use within the body. Second, you want it to work and you want it to be efficacious.
The definition of efficacy can vary between the different uses, for example a vascular surgeon may want something that polymerizes very quickly in order to stop bleeding, but does not cause clot of the vessel that they spent all this time anastomosing, where as a reconstructive surgeon for example may want something that polymerizes very slowly to give them time to reposition their flaps or grafts.
Third is usability; you want something that is easy to use and that you can use in a variety of different circumstances. Fourth is affordability. This may be more relevant to a hospital administrator or pharmacist who actually does the purchasing, but it impacts the surgeon because that determines what you have available to you in the operating room. And finally, fifth, approvability. Any of these agents need to be approved by the FDA in order to be used in the US. So the different types of hemostatic agents, which I will be addressing in this talk are listed below and I am going to go through each one of these specifically.Gelatin sponge or Gelfoam®, which is also known as commercially as Surgifoam again was first introduced in the 1940s by Dr. Gray in the neurosurgical procedures. What it is is purified pork skin gelatin which you can kind think of like Jello®, as it is the same thing that Jello® is made out of.
It has a very amorphous form and has a lot of air spaces and it stains very eosinophilic on H&E stain. Basically the way it works is that its surface essentially acts in the intrinsic pathway causing contact activation and thus platelets. Since it works very proximally within this cascade, you have to have functioning cofactors or clotting factors in order for this to work in helping create clot. Of note, it does absorb approximately 45 times its weight in blood and can expand to approximately 200% of its initial volume. It is absorbed in approximately four to six weeks and on the nasal mucosa it liquifies within two to five days. In the case presentation, this child was initially packed with Gelfoam® approximately a week prior to the time she was seen in the ER and at that point there was no evidence of any Gelfoam left within her nasal cavity. Now the way Gelfoam® can be used, you can either apply dry, directly to the bleeding surface and hold pressure over it or you can wet it in saline and then squeeze out all the air bubbles and use it that way.
Oxidized regenerated cellulose is also known as Surgicel or Oxycel in its commercial forms. It is derived from alpha-cellulose that is actually plant-based. As you can see on microscopic view, Surgicel comes in knit formwhere as Oxycel comes in a microfibrillar form and on microscopic view Surgicel has these fibers which are knit together and they are solid fibers whereas Oxycel has the hollow fibers but they essentially work the same way. Surgicel is relatively acidic and is thought to cause some small vessel contraction. Like Gelfoam, it works at the same point in the intrinsic pathway of clotting causing contact activation. So again the same thing holds that functional clotting factors are needed in order for this to work. It is thought to berelatively bacteriostatic when compared to other hemostatic agents. The theory behind this is that because of its relatively low pH, it deactivates and denatures some of the bacterial proteins especially those related to antibiotic resistance, thus making them more susceptible to antibiotics. It needs to be applied dry and absorbs within four to eight weeks. Of note, on postop imaging Surgicel sometimes causes a ring-enhancing lesion as you can see here on postop imaging, which can be mistaken for an abscess cavity or tumor recurrence. That is something to keep in mind if you are imaging a patient within two months of having operated on them and Surgicel was used during the procedure. On microscopic view, you can see a giant cell reaction.
Our next agent is microfibrillar collagen commercially known as Avitene ®. It is most commonly used in a light flour form, but it does also come in a non-woven web form. This is collagen, which is derived from bovine skin. Under the microscope it is very eosinophilic and of note, under polarizing light it does have periodicity. It binds tightly to blood surfaces, so you do not actually need to achieve a relatively dry field in order to apply it. It causes minimal swelling especially when compared to Gelfoam ®. T he way it works is slightly different because in addition to being collagen and causing contact activation, it does somehow directly activate platelets. But again, it works very proximally within the intrinsic pathway. It is absorbed in three months and it needs to be applied dry.
Collagen sponges, these come in a wide variety of different commercial forms. Again it is similar to Avitene ® and it is derived from bovine Achilles tendon or bovine skin and it works in basically the exact same way as Avitene works and it absorbs in 8-10 weeks.
The next class of hemostatic agents is slightly different: topical thrombin. The idea of topical thrombin has been around since the early 1900s in order to try to achieve clot and in addition the idea of using topical thrombin plus other hemostatic agents such as Gelfoam ® has been around for quite a longtime. In 1999 a new agent was introduced called Floseal™ which basically consists of bovine thrombin plus cross-linked gelatin granules mixed together. So the way it works is your bovine thrombin directly activates fibrinogen and converts it into fibrin monomers. So you can see that this works in a completely different place within the clotting cascade. It works down here in the common pathway bypassing all of the other necessary clotting factors. You do however have to have functional fibrinogen in order for this to work. The product Floseal™ itself is a little bit different from just using topical thrombin plus Gelfoam ® because the gelatin granules have been cross linked in such a way that they do not swell to nearly the same extent. It is absorbed in approximately 6-8 weeks.
Fibrin sealants are the last class of the hemostatic agents that I am going to address. Commercially it comes in many forms including tisseal and crosseal and there are many variations on the idea of fibrin sealants. One of those basic ideas is that you take pure human fibrinogen and combine it with bovine thrombin and they usually throw in an antifibrinolyticagent into the mix as well. So the way this works is that we take the bovine thrombin, it then converts this exogenous human fibrinogen to fibrin monomers, but you do need intrinsic, you need the patient’s own factor XIII and calcium, which then converts it into fibrin polymer. In addition, they usually add an antifibrinolytic agent to the mix as well in order to stabilize the clot. So this does require functional factor XIII and calcium in order for these fibrin sealants to work. They are absorbed within 10-14 days and need a relatively dry field in order to work.
I am going to briefly mention some of the other classes of agents which are out there, but I am not going to address these in detail. There are some completely autologous fibrin sealants. The patient’s own serum is taken and the fibrinogen and thrombin are purified. This achieves essentially the same effect as the fibrin sealants previously mentioned. There are a target platelet gels where again you purify the platelet with plasma and the patient’s own serum combined with thrombin and you get similar agent to the fibrin sealants only there are some additional benefits: you do have some platelet direct growth factors involved which help with wound healing. There are some completely synthetic agents, which are made from polyethylene glycol gels that when you combine them make a completely synthetic hydrogel. Another product is bovine serum plus albumin plus glutaraldehyde, and poly N-acetyl glucosamine is something that the military is investigating as a hemostatic agent and it is a seaweed-based agent. This is just an idea of what is out there in addition to the agents I addressed previously.
Gelfoam ® and Surgicel, work here very proximally in the intrinsic coagulation pathway via contact activation. Collagen also works via contact activation, but also activates platelets. In a completely separate class we have agents that work in the common pathway, which includes Flowseal™, which is essentially topical thrombin and as well as fibrin glue and its variants.
Safety, three things to remember that Gelfoam® swells and it swells a lot. This has proven to be a problem when used within confined spaces such as the spinal foramina where in it can cause spinal cord nerve compression and brain compression. (Gelfoam adverse events HERE and HERE).
Surgicel, of note, even though it does have an antimicrobial effect relative to the other hemostatic agents, it is still a nidus for infection.( Links of interest HERE and Adverse events HERE and HERE and HERE ). Avitene®, and in fact all of these agents, do cause a certain amount of foreign body reaction and granulation formation. But Avitene® has been found to be the worst offender in this way. You can see in this particular slide, they have the Avitene® cavity here, and then a large amount of surrounding edema and a foreign body reaction with giant cells here surrounding the Avitene®. In this picture you can see the periodic nature of Avitene® under polarized light. In fact, the manufacturers recommend that you apply these agents, then hold pressure and wait a while for a clot to form and then you remove the agent afterwards so that you do not leave it within the cavity in order to try to prevent foreign body reaction as much as possible. In addition, Avitene® because it comes in a light fluffy form, has been known to occasionally cause arterial embolization and it had been reported that it is causing laryngospasm when used in tonsillectomy. Collagen sponge has many of the same side effects as any of the bovine derived agents because there are known allergic reactions to some of these bovine antigens, which are containing these agents. (Avitene adverse events HERE and HERE ).
Floseal™ again as I mentioned before has much less swelling than the Gelfoam so it can be used within some of the more enclosed spaces. Because it is Gelfoam beads it can cause arterial embolization if it is used near a larger vessel. In fact Gelfoam beads themselves have been used in order to embolize arterial malformation. Because it contains bovine antigens, it can have antibody formation, which I am going to talk about a little bit more in detail later. Some of the fibrin sealants use pooled human fibrinogen, in which there is always the potential for transmission of infectious agents. Also again, risks of arterial embolization and antibody formation. ( Floseal, Tisseel, CoSeal and Bioglue discussion HERE  and bioglue HERE).
Antithrombin antibodies: These are foreign antigens. A study of 200 patients showed 90% of those exposed to topical thrombin do have a transient elevation in IgG titers. Tadokoro et al in Japan also noted that you can have development of IgE antibodies. This can result in a prolonged thrombin time. Of note, thrombin time is actually a measure of fibrinogen count.
Thrombin time: the way this test was done, you add bovine thrombin to the patient’s fibrinogen and see how long it takes for it to form a monomer. Because you have development of antibodies to bovine thrombin, you can have elevation in your thrombin time. This antibovine thrombin antibody can cross-react with human thrombin, but interestingly enough, this rarely ever causes any sort of clinical bleeding.
The real problem is with antifactor V antibody, as most commercial form of thrombin is contaminated with a certain amount of other bovine antigens and most importantly bovine factor V. So if you can get these antibovine factor V antibodies, which then cross-react with human factor V this can lead to a very severe coagulopathy and because this antibody can act as an inhibitor of factor V. On laboratory tests you can find a very decreased factor V level, increased PT and PTT, which does not correct when you add FFP and vitamin K. When you mix the patient’s sera with a normal human sera, you do not get correction of the PT and PTT which suggest that it is not a cofactor deficiency, but it is actually an inhibitor causing the problem. So as you can see here the factor V is an activator of the conversion of prothrombin to thrombin and this is where you end up with problems. The same study noted that 50% of the 200 patients that they found that were exposed to topical thrombin did develop human factor V antibodies. The problem usually does not happen on the initial exposure, but it is when they are exposed again in the later point to the topical thrombin is when the potential for coagulopathy is exposed. Fortunately these IgG titers do fall off rapidly three to four weeks after the exposure and the treatment if you do encounter this is steroids, cyclophosphamides, IVIG plasmapheresis and platelet transfusion. Of note, I did not see actually any reports of this in the head and neck literature per se; most of the case reports of these events are in the cardiovascular and vascular literature. (Gelfoam or Thrombin adverse event HERE link of interest HERE . Of course we now have J&J human thrombin HERE and Zymogenetics recombinant HERE).
Another requirement of a good hemostatic agent is efficacy. Basically there have been lots of studies both in vitro and in vivo using various animal models as well as human studies comparing these various hemostatic agents. The general gist of them is that fibrin sealant work better than Floseal™ which is better than Avitene® and then the collagen sponge, Surgicel and Gelfoam® are essentially equivocal. They do work better than placebo but can barely differentiate efficacy between any of them. Of note, Floseal™ and Avitene® do cause more inflammatory reactions than the others.
Usability: Gelfoam®, Surgicel, Avitene® and these collagen sponge can be stored at the room temperature and are basically ready to use out of the box. Floseal™ does require two to five minute prep time, you combine the thrombin with calcium and combine that to the gelatin granules. Fibrin sealants on the other hand need to be kept in cold storage and thawed prior to usage; it depends on what company you are using and what type and the prep time can be anywhere up to 20-30 minutes. So it is something to keep in mind if you think you want to use fibrin sealant during your case you should be prepared ahead of time in order to do so.
Affordability: This is an average or sort of an idea of what the cost is for some of these agents. Gelfoam®, Surgicel, collagen sponges are relatively inexpensive in a $10-20 per individual piece, whereas Avitene®, Floseal™ and fibrin sealants are much more expensive.
Approvability: All of these agents are regulated through the FDA as a class III medical device, which means they are subjective to this medical device reporting systems so that the manufacturers are obligated to report to the FDA when an adverse event happens. In fact, in 2004 the FDA released notification to users about Gelfoam® and its swelling and use in neurosurgical procedures because of the potential for paralysis.
*The Full article is available HERE. Links have been added here regarding adverse events and are placed within parentheses.

There is a solution to many of the issues faced with Hemostat requirements with HaemoCer Plus.......read more HERE

Vascular Solutions to Participate in Jefferies 3rd Annual Healthcare Conference

Vascular Solutions, Inc. (Nasdaq:VASC) today announced that the Company is scheduled to participate in the Jefferies 3rd Annual Healthcare Conference being held this week in New York City. Howard Root, Chief Executive Officer of Vascular Solutions, will present on Wednesday, June 17th at 4:15pm (EDT). To hear the live audio webcast of the panel discussion, go to the investor relations page of the Company's web site http://www.vascularsolutions.com and click on the "IR Conferences" icon a few minutes prior to start time to download any necessary software.

Bovie Medical Corporation Announces FDA Submission Of Laparoscopic Device For Solid Organ Resection

Bovie Medical Corporation (the "Company") (NYSE-AMEX Symbol: BVX), a manufacturer and marketer of electrosurgical products, announced a 510K submission to the FDA seeking pre-market clearance for a laparoscopic SEER device for solid organ resection. The laparoscopic SEER is a line extension of the Saline Enhance Electrosurgical Resection (SEER) device that Bovie launched earlier this year and will address the growing market of minimally invasive liver resection.
The laparoscopic SEER allows the surgeon to dissect and achieve hemostasis with a single device resulting in less instrument utilization and fewer instrument changes in a minimally invasive approach. The laparoscopic SEER is the second developed product in a series of new products under development based on the sintered steel technology.
Andrew Makrides, president of Bovie, stated, "Surgeons response to the SEER has been very positive and this new device will allow us to address their requests for a laparoscopic version."

CPC Strengthens Foundation as a Closure Products Company with its Vertically Integrated Product Pipeline

 CPC of America, Inc. (OTC Bulletin Board: CPCF), announced today that its first patent filing of a synthetic sealant for its specific application to the MedClose(TM) Vascular Closure System (VCS) -- previously announced May 21, 2009 -- represents a much broader foundation and basis for its new strategic plan as a Closure Products Company. CPC is presently focused on the development and testing of the MedClose(TM) VCS, which is an internal puncture-closing system for use in percutaneous intravascular diagnostic and interventional procedures, and announced today it will alsi gueo design and develop new vascular closure applications based upon a broader range of French sizes (i.e., introducer sheath diameters). The MedClose(TM) VCS design has the capabilities to be rapidly adapted to not only focus on its core VCS application for vascular closure following diagnostic or interventional procedures (coronary, carotid, cerebral, peripheral) with 6-9 French (Fr) catheters but also for:

• 4-5Fr for applications such as vascular closure following catheterization procedures in pediatric populations, closure of central line access points for chemo-therapy patients, hemostasis after arteriovenous fistulae access and peripheral arterial and/or venous closure after diagnostic and interventional electrophysiology procedures.
• 10-12Fr for applications such as iliac and abdominal aortic aneurysm (AAA) stent/graft implants.
• 15-20Fr for applications such as existing designs for percutaneous aortic and mitral valve replacement, endovascular stent grafts.

Importantly, the synthetic sealant and its characteristics also have potential future applications such as internal and external bonding and coating of tissue and instruments, (e.g., temporary coatings for burn victims, grafting of artificial skin, adhesion prevention, coatings on polymers, or coatings on implant devices such as stents or grafts), biopsy sealing) with or without drug delivery (e.g., the delivery of glucosamine and chondroitin sulfate into the spine area or other body organs), stem cell or growth factor delivery (e.g., the delivery of stem cells and/or growth factors into the spine area or other body regions), tissue sealants/adhesives to control of bleeding or fluid leakage in body tissue (e.g., lung sealing or hemostasis, tissue, muscle, and bone growth and regeneration) and dermatology (e.g., collagen restoration/replacement, topical application or void-filling by injection to fill wrinkles).

We believe that our sealant offers some important potential advantages over other sealants in several respects. First, as a synthetic sealant, our product is free from the risk of blood-borne and other pathogens. Second, testing to date indicates excellent adhesive strengths when applied to wet areas of tissue which could offer a tremendous competitive advantage due to the fact that vascular closure sites are normally initially wet due to the presence of blood or body fluids. And finally, the synthetic sealant appears to perform independently with respect to the level of anti-coagulation present.

We believe the MedClose(TM) VCS System has the potential to represent multiple product lines in multiple market segments, enhancing the value to such intellectual property. We are no longer one dimensional but believe in the original vision we had with the acquisition in November 1999 of closure technology with broad applications as stated above. We continue to improve the MedClose(TM) VCS by strengthening the platform of regulatory, quality, manufacturing, etc. capabilities for new product development and sustaining engineering.

CSL Limited and Talecris Biotherapeutics Agree to Terminate Merger Agreement

CSL Limited (ASX: CSL) and Talecris Biotherapeutics, Inc. announced today that they have mutually agreed to terminate their merger agreement, announced on August 12, 2008, under which CSL agreed to acquire Talecris for US$3.1 billion in cash.

Dr. Brian McNamee, CEO and Managing Director of CSL Limited, said, "We are disappointed that the U.S. Federal Trade Commission (FTC) resolved to block the transaction. As we have previously stated we fundamentally disagree with the FTC case and matters included in their complaint. Although we continue to believe in the many customer benefits and significant financial synergies that supported the transaction, CSL's Board of Directors did not believe that entering into a protracted litigation process with the FTC, with its inherent risks, substantial costs, and lengthy distraction of CSL management and staff from planning and running our businesses would be in the best interests of our stakeholders."

Dr. McNamee continued, "While we regret that the transaction cannot be completed, CSL remains a well positioned global biopharmaceutical business and will continue to expand on its core strengths. We have consistently produced year-on-year growth for our shareholders and we are confident in the continued value and growth potential of our stand-alone business. We continue to have great respect for Talecris and wish them well in the future."

Lawrence D. Stern, Talecris' Chairman and Chief Executive Officer, said, "After discussions with CSL, we have mutually agreed that litigation regarding the antitrust issue was not the path forward. Based on a careful analysis of the situation and all alternatives available, we believe that termination of the merger agreement is in the best interest of all parties. We are disappointed that patients will not benefit from the efficiencies we saw in the proposed combination. Talecris continues to focus on its patient community and customers, and on building and realizing value for its employees and owners. Through the process, we developed an even greater appreciation for CSL's competencies, professionalism and integrity, and we wish Brian and his team well in their future endeavors."

Both parties will fulfill their obligations for termination contained in the merger agreement. As part of the agreement, CSL will pay Talecris a US$75 million break fee, and the plasma supply contract the parties entered into in connection with the merger agreement will remain in effect.

Poll Results - Will the Feb. '09 vCJD scare in the UK affect your consideration of using a human or bovine sourced hemostat or sealant?

We asked "Will the Feb. '09 vCJD scare in the UK affect your consideration of using a human or bovine sourced hemostat or sealant?"

50% said YES

20% said NO

13% said DEPENDS ON THE COUNTRY OF ORIGIN OF PRODUCT

16% said MAYBE

Obviously human and animal sourced products do exhibit some concerns for many.

Researchers Detect Blood-Clotting Mechanism

Ever wonder how your blood miraculously stops flowing and forms a scab after a cut? Researchers have now pinpointed the mechanism down to the molecular level.

"The human body has an incredible ability to heal from life's scrapes and bruises," study co-author Wesley P. Wong, a principal investigator at the Rowland Institute at Harvard University, said in a university news release.

"A central aspect of this response to damage is the ability to bring bleeding to an end, a process known as hemostasis," Wong said. "Yet regulating hemostasis is a complex balancing act."

If people have too much hemostatic activity, they can develop an excess of blood clots, resulting in thrombosis, which is a potentially deadly condition. On the other hand, if there is too little hemostatic activity, people could bleed to death, according to background information in the news release.

To achieve and maintain the right hemostatic balance, the body has a feedback system controlled by miniscule forces in the circulation system. The forces are applied to the highly-sensitive A2 domain of the blood-clotting protein called von Willebrand factor (VWF), which acts as a "force sensor," the researchers explained.

By manipulating single molecules, the researchers found that the tiniest force causes A2 molecules to unfold and lose much of their complex, three-dimensional organization. After the unfolding, the enzyme ADAMTS13 comes into play. The enzyme cuts the molecule, hence controlling the size of the blood clot, according to the study, in the June 5 issue ofScience.

"In the body, these cutting events decrease hemostatic potential and also enable blood clots to be trimmed in size," Wong said. "The system is so finely tuned that the A2 shear sensor is able to regulate the size of VWF within the bloodstream, maintaining the optimal size for responding properly to traumas."

To manipulate molecules, the researchers used "optical tweezers" developed in Wong's lab, which can apply miniscule forces to individual molecules while observing tiny changes in their length.

A better understanding of the mechanism of blot clotting could lead to new treatments for injuries or bleeding disorders, such as type 2A von Willebrand disease, the researchers noted.

Angiotech Enters License, Distribution and Supply Agreements for Fibrin and Thrombin Technologies with Haemacure Corporation

Angiotech, a specialty pharmaceutical and medical device company, announced today the completion of a collaboration transaction with Haemacure Corporation (TSX:HAE), a specialty bio-therapeutics company, relating to certain of Haemacure's proprietary fibrin and thrombin technologies, both of which are currently in development.

As part of this collaboration, Angiotech has agreed to provide to Haemacure a senior secured bridge financing facility in the amount of US$2.5 million, with the option for Angiotech to invest an additional US$1 million in the facility.

"Our new collaboration with Haemacure provides Angiotech with access to critically important technology for certain of our surgical product candidates currently in preclinical development," said Dr. William Hunter, President and CEO of Angiotech. "We believe we have assembled the majority of the key components necessary to deliver on the next generation of innovations, adding to our proprietary Quill SRS franchise for our surgical business, and we will provide additional details as we prepare certain of these product candidates for the clinical development and regulatory approval process.The collaboration will consist principally of the following three agreements:
- Fibrin Sealant Distribution Agreement. The parties have entered into a Distribution Agreement whereby Angiotech is granted non-exclusive,world-wide distribution rights to Haemacure's fibrin sealant product candidate in selected surgical indications. The distribution agreement has a term on a country-by-country and product-by-product basis of 10 years from the date Haemacure receives United States Food and Drug Administration (FDA) approval or similar regulatory approval in countries outside of the United States of its fibrin selant, and has an option for Angiotech to renew for an additional five years, subject to certain performance adjustments. Any fibrin sealant product would be marketed and distributed by Angiotech's surgical sales organization upon regulatory approval. Haemacure will be responsible for all clinical development and related costs with respect to fibrin sealant product candidates.
- Drug-Loaded Fibrin Sealant License and Development Agreement. The parties have entered into a License and Development Agreement whereby Haemacure and Angiotech have agreed to jointly develop and commercialize a next generation, drug-loaded fibrin sealant product candidate. Angiotech and Haemacure will collaborate to create novel fibrin sealant technologies that, in addition to the haemastatic properties offered by the fibrin sealant itself, may target the prevention of infection, pain, or delivery of stem cells using Haemacure's fibrin sealant as a carrier of such therapies. The companies will jointly conduct research and clinical development, with each party contributing key personnel, technology and intellectual property. Collaboration costs will be shared based on each company's contribution to the program, and eventual profits will be shared pro-rata based on each company's contribution to collaboration expenses. This term of the agreement will expire on a collaboration product-by-collaboration product basis upon the later of 15 years after the first commercial sale of such collaboration product, and the last-to-expire valid claim applicable to such collaboration product.
- Thrombin Supply Agreement. The parties have entered into an exclusive Supply Agreement whereby Haemacure will supply thrombin to Angiotech for the development of certain Angiotech preclinical product candidates that may require thrombin. The Supply Agreement has a term of 10 years from the first commercial sale of an approved Angiotech product containing thrombin procured from Haemacure, and has an option for Angiotech to renew for an additional five years. The senior secured bridge loan from Angiotech to Haemacure will provide US$2.5 million to Haemacure in multiple drawdowns. The loan will be senior to all of Haemacure's existing and future indebtedness, subject to certain exceptions; will bear interest at an annual rate of 10%, compounded quarterly and have a term of two years. Angiotech may, at its sole discretion, advance during a period of two years up to an additional US$1 million to Haemacure from time to time, in multiple draw-downs, for a total loan of US$3.5 million. The senior secured bridge loan also has certain equity conversion features and rights to board representation, as described in detail in Haemacure's press release dated May 22, 2009

Omrix founder Taub in LifeBond $8m funding round

Biosurgical products developer LifeBond Ltd. has raised $8 million in its second financing round. Pitango Venture Capital and Robert Taub led the round. 

Taub founded Omrix Biopharmaceuticals Ltd. and led the company until it was sold to Johnson & Johnson (NYSE: JNJ) for $438 million in 2008. Following the sale, Taub said that he would seek new investment opportunities, and the investment in LifeBond is the first. 

About Lifebond.

LifeBond is developing a series of next-generation biosurgical products which incorporate a proprietary adhesive platform that mimics the biochemical cross-linking cascade of late stage blood coagulation.  The adhesive formulation forms a network similar to the fibrin network of blood clots but has demonstrated adhesive strength even greater than that of blood-derived fibrin sealants.  LifeBond’s technology functions through the rapid and biocompatible in situ cross-linking of structural proteins.  As they cross-link, proteins in the physiological environment undergo a process of gelation to form an adhesive hydrogel matrix.  The properties of the cross-linking reaction and the hydrogel matrix can be controlled to fit a variety of applications.