Blood disease attacks body’s ability to stop bleeding

A 16-year-old Paducah boy and a 72-year-old Hickory woman share a condition that could leave them unable to stop bleeding from a major wound.

Dr. Danny Butler of Paducah said  Derek Willett and Phyllis Dublin suffer from idiopathic thrombocytopenic purpora. He described the disease as an assault by the body’s own immune system on blood platelets. Platelets are the component of the blood that gather at wound sites and form blood clots, stopping the body from bleeding to death. Different from hemophilia, the body suffers only from sudden acute drops in platelet levels, not in clotting factor.

“Common side effects are bruising, nosebleeds, a black spot in the mouth and bleeding into the gums,” Butler said. “We usually diagnose with a platelet count.”

Butler said the cause of the disease is unknown. Some patients, like Dublin, experience severe bleeding. Dublin bled into her lungs, which could have caused her to drown. The condition is treated by suppressing the entire immune system through anti-inflammatory steroids such as prednisone. Once treated, Dublin’s lungs re-absorbed the blood.

“We don’t know why some people choose to bleed from a certain location.” Butler said. “It could be life-threatening. We have to always look at the platelet levels. If it’s low, we would not like to operate and have to treat.”

If blood platelet levels are low or a patient has suffered severe bleeding, a blood transfusion remains an option. Butler warned that even with a transfusion, the body’s immune system could attack blood platelets. In severe cases, surgeons could remove a patient’s spleen. The spleen removes blood platelets attacked by antibodies.

“It’s a little more common in women than men and people 65 or older,” Butler said. “A lot can trigger the immune system. For every organ, we’re finding auto-immune disorders. We have a lot of work to do.”

Willett said his physician discovered the disease in a routine blood screening in 2009. The junior at St. Mary High School in Paducah said he was undergoing a physical for cross-country running when doctors noted his low platelet count. He’s reported no major episodes of bleeding, but monitors his platelet count closely.

“Doctors say I should avoid head and other serious trauma, but I’m not on steroids at this point,” Willett said. “They won’t do that unless my platelet count falls below 20,000 because steroids affect other organs in a bad way.”

Willett said he has conducted several fundraisers for Vanderbilt University Medical Center to research ITP. He’s raised $600 with a bake sale, selling bracelets and with a donation jar. For now, he is mindful of potential risks and hopes he grows out of his condition.

Dublin said she’s had no major episodes since August, but blames ITP for periods of weakness and fatigue earlier in the year.

“It was difficult to breathe, no worse than that,” Dublin said. She said the difficulty hit her one day about 11 a.m. “By 12:30, I was in the ER fighting for my life,” Dublin said.

Dublin said she stopped at the Mayfield Fire Department for oxygen. An ambulance took her to Western Baptist Hospital for treatment.

“I haven’t had any problems since, and the doctor started me on 90 mg of prednisone,” Dublin said. “He moved me from 90 to 60 to 40 and 10. Now I take 5 mg every other day. The thing is, this can affect anyone at any age, and comes on with no warning.”

Willett told teens and people of all ages to have complete blood count exam to determine if platelet levels are low.

Novo Nordisk presents positive clinical data on two investigational compounds within bleeding disorders

New data presented at American Society of Hematology annual meeting highlight promising treatments that may help patients with bleeding disorders to better manage their condition than today.
Orlando, US – (7 December 2010) – Novo Nordisk presented data from a phase 2 trial evaluating the safety, pharmacokinetics and efficacy of a recombinant factor VIIa (rFVIIa) analogue, designed to have a faster action profile than NovoSeven® (rFVIIa) in haemophilia patients with inhibitors (antibody formation against factor preparations). The company also presented data from a phase 3 trial investigating a recombinant compound in patients with congenital factor XIII deficiency, a rare, inherited bleeding disorder. The data were presented at the 52nd American Society of Hematology (ASH) Annual Meeting and Exposition.
rFVIIa analogue (NN1731)[1]: phase 2 results
Results were presented from a phase 2 trial, adept™1, in which haemophilia patients aged 12 years or older experiencing a joint bleed were randomised to  receive up to three doses of NN1731 or NovoSeven®. The trial showed that NN1731 was safe and no antibody formation against NN1731 was seen in the trial. Evaluation of patients who received NN1731at the two highest dose levels showed that 96% of the joint bleeds were well-controlled with the product; the efficacy of NovoSeven® was similar to that observed in previous clinical studies (efficacy in approximately 90% of bleeds).
In addition, the number of adverse events (AEs), including serious adverse events (SAEs), was lower in patients being treated with NN1731 compared to those in the control group. A total of 12 SAEs were reported and all occurred 16 days or longer after exposure to NN1731.
“There were no safety concerns observed in patients at any dose level of NN1731,” said Dr Erich de Paula, of the State University of Campinas in São Paulo, Brazil, who presented the trial during the meeting. “Additionally, the phase 2 trial results demonstrated the potential of the rFVIIa analogue to stop joint bleeds quickly and effectively. These results further support the distinct fast action profile of the rFVIIa analogue in treating bleeds in haemophilia patients with inhibitors.”
NovoSeven® was used as a control in the trial due to its proven efficacy and safety profile. NovoSeven®was specifically developed to treat people with haemophilia A or B with inhibitors to factor VIII or IX replacement.
rFXIII compound: phase 3 results
Results were presented from mentor™1[2], a phase 3 trial examining the efficacy and safety of a recombinant factor XIII (rFXIII) compound for the prevention of bleeds associated with congenital FXIII deficiency, a rare bleeding disorder with about 600–1,000 diagnosed patients worldwide.
In the trial, 41 patients were treated for one year, with rFXIII administered as a preventative, once-monthly replacement therapy for congenital FXIII deficiency. FXIII-deficient patients with no previous history of FXIII treatment were used as a control. Currently, the only treatment available is derived from human blood plasma, which carries an inherent risk of infections.[3]
The trial results demonstrated that treatment with monthly recombinant FXIII injections significantly decreased the number of bleeding episodes requiring treatment compared to the historic control group. Over the course of the treatment period, a total of five bleeding episodes were observed in four patients. All five events were associated with trauma, and were not related to low FXIII activity levels in patients. Additionally, no thromboembolic events or fatal adverse events were reported.
“These data show the potential for rFXIII to become a safe and effective treatment option for patients who would otherwise use treatments at risk for contamination,” said Prof Aida Inbal of the Hemostasis Unit and Hematology Clinic in the Institute of Hematology at Rabin Medical Center in Tel Aviv, Israel. “We think this is an extremely important milestone in the development of a treatment that is not sourced from human plasma for patients suffering from congenital FXIII deficiency.”
Novo Nordisk plans to file for US Food and Drug Administration approval of the rFXIII in the first half of 2011.

Appeals Court Stays Judgment in HemCon's Patent Infringement Case

PORTLAND, Ore.--(BUSINESS WIRE)--HemCon Medical Technologies, Inc., announced today that the U.S. Court of Appeals for the Federal Circuit granted HemCon's motion to stay the injunction and final judgment (including the damages award) obtained against it in a patent infringement case brought by Marine Polymer Technologies, Inc. The stay halts any enforcement of the lower court’s injunction and damages award while HemCon attempts to have both overturned on appeal, a process expected to take on the order of 12 to 18 months to complete. As a result, HemCon can continue selling its chitosan-based wound care products and will not be required to pay financial damages during this appeal process.
"HemCon is extremely pleased that the appellate court agreed that HemCon could continue selling its product line during the pendency of the appeal. We will urge on appeal that the lower court decision finding infringement was incorrect, in part because the Marine Polymer patent is invalid when properly interpreted," said John W. Morgan, HemCon's President and Chief Executive Officer. "The stay is a victory for HemCon's customers, including military personnel whose lives are being saved by HemCon products, and hospital patients who benefit from reduced infection risk and better hemostasis."
The stay is the most recent decision in the patent infringement action instituted by Marine Polymer Technologies, Inc. "In imposing the stay, the Court of Appeals concluded that HemCon had shown a strong likelihood of succeeding on appeal, or at least a substantial case on the merits and that any potential harm weighed in HemCon’s favor," Morgan explained. "We believe the appeals court will ultimately agree with our conclusion that our products do not infringe the Marine Polymer patent. We look forward to further presenting our case to the Court.”
HemCon Medical Technologies, Inc. (www.hemcon.com) founded in 2001, develops, manufactures, and markets innovative technologies to control bleeding and infection resulting from trauma or surgery. HemCon products are designed for use by military and civilian first responders as well as medical professionals in hospital, dental and clinical settings where rapid control of bleeding is of critical importance. HemCon is headquartered in Portland, Ore., with additional commercial operations in Ireland and the Czech Republic.

Baxter buying hemophilia business for up to $285M

Baxter International Inc. said Friday that it will pay as much as $285 million to buy a hemophilia drug candidate and other assets from privately held biotechnology company Archemix.Baxter currently sells the hemophilia drug Advate. The new deal gives the company all of Archemix's hemophilia assets, including an early-stage drug candidate called ARC19499. ARC19499 is a subcutaneous hemophilia therapy that is intended to improve blood clotting. An early clinical trial is being performed in the U.K.Baxter said the value of the deal could rise to $285 million including milestone payments. The drug and medical device maker said it will take a $30 million charge in the fourth quarter for the value of the hemophilia unit's research and development activities. Baxter expects the purchase to close by the end of 2010.

Ethicon Inc announces submission of BLA for Fibrin Pad

Ethicon Inc, a Johnson & Johnson (NYSE: JNJ) company, reported on Thursday the submission of a Biologic License Application (BLA) to the US Food and Drug Administration (FDA) for the Fibrin Pad to aid in stopping soft tissue bleeding during surgery.

The company's BLA submission includes efficacy and safety data from a randomised, controlled clinical study in which the Fibrin Pad was used as an adjunct to hemostasis in soft tissue bleeding. According to Ethicon the Fibrin Pad is a novel product candidate that combines two methods of action: biomaterials and plasma-derived biologics (Human Fibrinogen and Human Thrombin).The Fibrin Pad is intended for use by surgeons as an adjunct to hemostasis when surgical methods are ineffective or impractical to control bleeding.

ArterX™ Clinical Trial Results Announced at Veith Meeting

MOUNTAIN VIEW, Calif., Nov. 18, 2010 /PRNewswire/ -- US clinical trial results for Tenaxis' investigational vascular surgical sealant, ArterX, were presented today at the Veith Meeting in New York.  William M. Stone, MD of the Mayo Clinic, Scottsdale AZ reported a more than 20% margin of improvement for ArterX Surgical Sealant in the sealing of vascular suture lines compared with a control group featuring a commercially available gelatin foam/thrombin combination.
In a presentation titled "A Novel More Effective Glue-Sealant (ArterX) for Hemostasis at Vascular Suture Lines and Other Sites," Dr. Stone reported that ArterX Surgical Sealant achieved immediate hemostasis more than 60% of the time in a 217 patient clinical trial conducted at 11 different hospitals in the US.
President and CEO, David Smith, commented, "We are delighted with the preliminary results of our US clinical trial.  We were also able to show a statistically significant reduction in operating time of 36 minutes in the ArterX group, and ArterX patients were discharged from hospital after 4.1 days, an improvement of 1.3 days over the control group. If approved, we believe that ArterX Surgical Sealant will yield economic benefits for surgeons and hospitals that adopt it."
ArterX Surgical Sealant is currently under review by the FDA and is not available for sale in the USA.
ArterX is CE marked for the EU.

Blood-clotting drug given to wounded soldiers can cause heart attacks

A drug given to wounded soldiers in Iraq and Afghanistan may be putting their lives in further danger by causing heart attacks and strokes.
The treatment is used to stop serious bleeding in injured troops, but trials show the drug increases the risk of blood clots forming in arteries, which can kill or cause complications that result in amputation.
The dangerous side effects are all the more concerning because years of trials have yet to prove the drug is any better at saving the lives of injured soldiers than a placebo.
The drug, called NovoSeven, was licensed more than a decade ago to stop bleeding in haemophiliacs, but is used by military doctors and in civilian hospitals on an "off-label" basis to treat patients suffering from major blood loss due to trauma or surgery. The drug, also known as recombinant factor seven, costs several thousand pounds per patient but an effective alternative called tranexamic acid costs just £5 per patient.
A spokesman for the Ministry of Defence confirmed that NovoSeven was used by UK forces as "a medicine of last resort", when all other attempts to stem bleeding had failed. The US military also uses the drug.
Prof Ian Roberts, an expert in trauma care at the London School of Hygiene and Tropical Medicine, warned in 2006 that NovoSeven was being used off-label before trials had clarified whether or not it helped save lives.
"There are both civilian patients and wounded soldiers who will have been given this drug and the best evidence shows they would not have benefited, but would have experienced heart attacks, strokes and possible amputations," Roberts said.
By continuing to use the drug, the military and hospital surgeons were leaving themselves vulnerable to legal action, he added. "You cannot defend giving this treatment outside of a randomised controlled trial," he said.
He added that the US military, which has used NovoSeven for years, should explain why it embraced the drug. "What advice were they acting on? Was the advice they received truly independent, or were people compromised in any way? It is important to know," he said.
Dr Mads Krogsgaard Thomsen, chief science officer at Novo Nordisk, the Danish company that makes NovoSeven, said the drug posed very low risk when used under licence to stop bleeding in haemophiliacs and for certain rare blood clotting disorders. "We cannot encourage as a company, by any means, the off-label use of NovoSeven. This is not something we are promoting and it is not something we are responsible for."
Thomsen estimates that between 10% and 20% of NovoSeven is used off-label. "Every now and then, physicians do use it as a last resort in patients that are otherwise likely to die," he said.
Roberts believes the case for using NovoSeven is weakened further by the availability of a much cheaper alternative drug, tranexamic acid, which is known to save lives in bleeding patients without dangerous side effects. A trial of tranexamic acid, called Crash-2, was published in the Lancet in June.
Marcel Levi, professor of internal medicine at Amsterdam Medical Centre, published a review of NovoSeven trials in the New England Journal of Medicine last week that was funded by NovoNordisk. "If you look at whether the drug stops bleeding, or whether fewer transfusions are needed, then many studies are positive. If the only thing that matters is mortality, then it is much harder to prove that this is a useful drug," he said.
Beverley Hunt, a consultant haematologist who worked on the Crash 2 trial at Guy's and St Thomas's Hospital in London, said: "The issue around the use of factor seven in patients with massive blood loss is that there is a lack of evidence to show us how clinically efficacious it really is, what dose to use and when to use it. The problem with using an agent that alters blood clotting is that it is a tightrope walk in reducing the risk of bleeding without increasing the risk of blood clots.
"The recent data showing that its use is associated with a 5% risk of arterial thrombosis means we should not be using it early in the management of massive blood loss. If however despite normal good practice, somebody is bleeding to death and you have nothing left, are you willing to take a 5% risk of arterial thrombosis, and the answer is yes you are."

Patient Safety in Surgery

X-ray crystallography reveals structure of precursor to blood-clotting protein

ST. LOUIS — Using state-of-the-art robotic and x-ray crystallographic equipment, researchers at Saint Louis University have revealed for the first time the molecular structure of the zymogen, or inactive, form of a blood-clotting enzyme.
In an article published in Proceedings of the National Academy of Sciences, Enrico Di Cera, M.D., chair of the department of biochemistry and molecular biology at Saint Louis University School of Medicine and lead researcher of the study, said the NIH-funded research offers important information about the protein.
“This research is very basic and very important,” said Di Cera. “It provides a missing link between the inactive zymogen form of thrombin and the mature enzyme generated upon vascular injury.”
Before thrombin becomes active, it circulates throughout the blood in the inactive zymogen form. When the active enzyme is needed, for example after a vascular injury, the coagulation cascade is initiated and the zymogen is converted into an active enzyme that causes blood to clot.
Blood clotting performs the important function of stopping blood loss after an injury. However, when triggered in the wrong conditions, clotting can lead to debilitating or fatal conditions like heart attack, stroke and deep vein thrombosis.
In previous laboratory research, Di Cera re-engineered thrombin to act as an anticoagulant, stopping blood from clotting and opening the door to the development of new therapeutic strategies for the treatment of thrombosis, the presence of blood clots in blood vessels, which is responsible for nearly a third of all deaths in the U.S.
While researchers have an understanding of the structure of active thrombin, very little was known about its zymogen form. In order to learn more, researchers used x-ray crystallography to gather data about the molecular structure of the protein.
The process involves growing a crystal of the protein, shooting x-ray beams through the crystal and analyzing the diffraction patterngenerated on a detector plate in order to detail the three-dimensional structure of the protein.
The structure of the zymogen form of thrombin provides crucial details about the activation mechanism that sheds light on the way the mature enzyme works. Future research can capitalize on these new findings to define better strategies for therapeutic intervention.
“Until now, we’ve known nothing about the zymogen form of thrombin or any blood-clotting enzyme,” said Di Cera. “All the structural information has been limited to the active form.
“We now know that the zymogen form of thrombin is very different from the mature enzyme, in ways that open new opportunities for therapeutic intervention.”
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.

Hemostasis and Thrombosis