Earlier in 2008, the FDA said contaminated Heparin from facilities in China was linked to 81 deaths in the U.S. and hundreds of allergic reactions. Baxter International Inc. is the largest supplier of Heparin. The FDA later said it received reports of 11 deaths and other adverse events associated with medical devices that contain Heparin.

Once again heparin is back in the new and there is new evidence that the Chinese government didn’t pursue an investigation into contaminated heparin sent to the U.S. in 2007 and 2008, despite repeated requests from the U.S. for help, according to a congressional probe, according to a recent New York Times news report.

Two House Republicans said Food and Drug Administration officials recently told them that the agency has been “severely hampered” by the lack of cooperation from China in finding those responsible. Contamination in the widely used blood-thinner was linked to at least 81 deaths in the U.S.

The probe by Reps. Joe Barton and Michael Burgess, both of Texas, comes as FDA Commissioner Margaret Hamburg prepares for her first trip to China since assuming her post last year.

“It is shocking to find out two years after Chinese-made heparin was killing Americans, the Chinese government still has done no investigating to find out why,” said Mr. Barton, the top Republican on the House Energy and Commerce Committee. He called on Ms. Hamburg to air the issue with Chinese officials.

Yan Jiangying, spokeswoman for China’s State Food and Drug Administration, said the congressmen’s accusations are “not true.”

Ms. Yan said her agency “did a very thorough investigation, including very detailed inspection and testing, and surveys of enterprises as well. We signed an agreement with the FDA on drug safety in the end of 2007, and strengthened the monitoring of heparin.”

A spokeswoman for the FDA said Wednesday that “there are serious limitations on what the FDA can do to pursue civil and criminal investigations in foreign countries, especially without the cooperation of the foreign government.”

In a June 16 letter to the congressmen, the FDA wrote that it was “denied full access” to manufacturers of raw heparin in China.

Mr. Barton and Mr. Burgess said the FDA told members of Congress that China hasn’t had any breakthroughs in the investigation, which they said left the “misleading impression” that “there was some kind of open investigation.”

In fact, Chinese security authorities told a U.S. official in Beijing on June 18, 2008, that China wasn’t investigating the heparin issue as either a criminal or administrative matter, according to the congressmen.

The FDA requested new manufacturing standards for the blood thinner in 2008 after the problems were linked to tainted ingredients from China. Baxter which at the time supplied about 50 percent of the blood thinner and anticoagulant used in the United States began a voluntary recall after its monitors noticed an increase in reports of allergic reactions to injections of the drug.

The company began a full recall after determining that other drug makers would be able to ensure an adequate national supply, according to Gardiner.

A key ingredient in heparin is made in China from pig intestines, the company said in a May 2008 statement. “The decision to source from China is based solely on supply the majority of the world’s supply of crude heparin comes from China, due to the large number of pigs required,” Baxter said then.

The complaints accuse Baxter and the supplier, Scientific Protein Laboratories LLC, of negligence, alleging their products were unsafe for their intended use. The suits seek money damages for those who were injured and for survivors of those who died.

Researchers examined 320 people who were given heparin injections at a German hospital. Of those, 7.5% developed skin lesions as a result of the treatment. That’s higher than the 2% rate the researchers had anticipated.

“During the study, we were surprised by the high number of patients with heparin-induced skin lesions,” the study authors wrote. “For most patients, the diagnosis was made because of our study.”

The researchers found that in most cases, the lesions resulted from an allergic reaction. Women were more likely to have the reaction, and three factors: pregnancy, obesity and long-term heparin use resulted in a higher likelihood of the condition, the study found.

The authors suggested that doctors be aware that skin lesions might occur and realize that they need to figure out the cause. The lesions could be a sign, they said, of a serious condition called “heparin-induced thrombocytopenia,” in which the number of platelets in the blood decreases.

The study results appear in the September 28, 2009 Canadian Medical Association Journal.

One patient was transferred by air ambulance to Christiana Care Health System and two patients were flown to the University of Maryland Hospital. Additional patients are being closely monitored at Beebe.

Officials said they have informed the manufacturer, the FDA and the Delaware Health Care Operations Center. Wally Hudson, vice president of Beebe’s corporate affairs, said the three patients suffered internal bleeding, but tests on two other patients with similar symptoms ruled out internal bleeding.

“The patients affected experienced internal bleeding,” he said. “We started to see it overnight, and because of the nature of the bleeding, we (needed to transport the patients to other facilities).”

Hudson said hospital officials have received no updates from other medical centers regarding patient conditions. Contents of the bags have been sent off for testing.

“I’m not saying these were tainted bags of medicine,” he said. “What I am saying is we’ve had some unusual patient outcomes and (the heparin seems to be) the common denominator.”

Hudson said an investigation will be conducted as to what caused the patients’ reactions.

Rehoboth Beach resident Walter Brittingham said in most cases Beebe gives “excellent service.”

“Have I or my family encountered problems as a patient or patients at Beebe, yes,” he said. “But all in all, I think they offer good care.”

A spokeswoman for Baxter said the company has not received similar reports from any other institutions and was working with Beebe to establish what happened. The spokeswoman also said that premixed bags such as those involved in the incident were not part of last year’s heparin product recall, which was made after increased reports of adverse reactions.

Barton, the ranking member on the House Energy and Commerce Committee, wants the FDA to turn over any databases that show heparin was contaminated, according to a letter sent to Acting FDA Commissioner Joshua Sharfstein.

In early 2008, the FDA began investigating heparin, essential for procedures such as cardiac surgery, after receiving hundreds of reports of allergic reactions and dozens of deaths in patients who had taken the blood thinner.

The FDA has said the raw heparin came from factories in China and was purposefully contaminated, for economic reasons, with a man-made chemical called over-sulfated chondroitin sulfate, or OSCS. Chinese drug officials have disagreed with the FDA, saying OSCS may not be responsible.

The FDA’s handling of the issue has drawn scrutiny, especially from Barton. He has asked the investigative arm of Congress, the Government Accountability Office, to investigate the FDA’s response to the heparin affair. The GAO said it recently began its investigation but couldn’t provide a time frame for when it would be finished.

Barton wants to know if the FDA tracked the origins of the contamination and whether the agency has sought assistance from the Chinese government. He also wants to know what actions, if any, the Chinese government has taken related to the contamination.

A Republican staffer for the Energy and Commerce Committee said Barton is trying to determine whether anyone in China has been held responsible for contaminating heparin that ultimately sickened and killed U.S. citizens.

“We don’t seem to be any further along a year later from understanding” this issue, said the staffer, who asked not to be named. “What are they doing about it? Is this an acceptable practice in China?”

The heparin issue doesn’t seem to be going away. Last month, the FDA publicized documents showing two Chinese-based companies shipped contaminated heparin to the U.S. between 2007 and 2008 and one lied to federal health regulators about their role in the matter. It was the first public disclosure of the firms involvement in the heparin matter.

On May 1, 2009, the agency held a public hearing to better understand how to prevent people from contaminating products for economic reasons.

Barton wants the FDA to respond to his letter within two weeks.

Nurses at the hospital mistakenly gave twins Thomas Boone and Zoe Grace 1,000 times the recommended dose of the blood thinner heparin, leaving them vulnerable to uncontrolled bleeding and leaving them, for a time, in critical condition.

Cedars-Sinai Medical Center was not sued, though the hospital was described in a court filing as a “potential defendant.”

Hospital officials have cited at least three safety lapses that led to the overdoses.

The couple has a pending lawsuit against Baxter Healthcare Corp., alleging that the labeling and design of heparin led to the massive overdose. The suit alleges that the company knew other infants had died as a result of errors involving the drug but failed to recall the high-concentration vials.

U.S. Marshals seized the Heparin at the request of the FDA, according to a press release. The FDA said the products from Cincinnati-based Celsus Laboratories Inc. were contaminated with over-sulfated chondroitin sulfate, a substance that mimics heparin’s blood-thinning activity. The company’s products were made from material imported from China.

Earlier this year, the FDA said contaminated Heparin from facilities in China was linked to 81 deaths in the U.S. and hundreds of allergic reactions. Baxter International Inc. is the largest supplier of Heparin. The FDA later said it received reports of 11 deaths and other adverse events associated with medical devices that contain Heparin.

The FDA’s handling of the contamination scandal has drawn criticism and sparked congressional inquiry. The agency has been working to prevent contaminated forms of the blood-thinner from getting to patients.

“This action will help prevent this contaminated heparin from finding its way into the marketplace,” said Mike Chappell, acting associate commissioner for regulatory affairs, in a statement.

The agency has initiated 13 recalls of contaminated products that contain Heparin.

In April and May, the agency alerted Celsus Laboratories that it wasn’t effectively recalling the contaminated Heparin, and that’s why it asked U.S. Marshals to seize the company’s products.

The FDA said companies who may have purchased Heparin from Celsus should contact the company to determine whether the heparin they purchased was from the seized lots. The FDA has notified Japanese, Canadian, Australian, European Union and other international authorities of shipments of contaminated heparin from Celsus.

The recalled drug Heparin was found 94 times in inspections of all 533 hospitals in California, and at least 16 hospitals administered the drug to patients, according to the state Board of Pharmacy. Fines range from $2,500 to $5,000.

“This was really an alert that the recall system doesn’t work,” Virginia Herold, head of the state’s pharmacy board, told The Associated Press.

Regulators have not released the full list of hospitals involved. However, documents obtained by the Daily Journal show newborns were allegedly given heparin at the University of California San Francisco Medical Center and Children’s Hospital of Central California in Madera. Both hospitals are appealing the charges.

Heparin, which is often used in premature children to prevent blood clots, has come under scrutiny because of accidental life-threatening overdoses given to babies, including actor Dennis Quaid’s newborn twins at a Los Angeles hospital last November. Fourteen other babies received accidental heparin overdoses in July at a hospital in Corpus Christi, Texas.

The FDA issued a drug recall in February because “a higher than usual number” of patients reported adverse effects to heparin, which include chest pain, dizziness and headache.

The state’s Department of Public Health has also launched an investigation to determine whether recalled Heparin, Digitex and Procrit caused harm to any patients.

No link has been found, though a state health official said the state will try to ensure recalled drugs are taken out of hospitals.

“Our actions are to act as both a partner and an enforcer to look at what kinds of system breakdowns are taking place, to make sure we don’t have a reoccurrence of this in the future,” Kathleen Billingsley, deputy director of the state’s Center for Healthcare Quality, told the AP.

In March, the state Board of Pharmacy voted 12-0 to give drug makers, wholesalers and pharmacies until Jan. 1, 2011, to start electronically tracking drugs from factory to patient. The electronic tracking system has been delayed a number of times since 2004, when a recall of 175,000 bottles of fake Lipitor, the cholesterol drug, led state regulators to require tracking.

Herold said although it’s unclear whether the tracking system would have prevented this incident, it will give pharmacists a better idea of what is on their shelves.

Additionally, the Oakbrook Terrace, Ill.-based Joint Commission, an independent, not-for-profit organization health quality group, issued a safety alert asking hospitals nationwide to adopt stricter measures to prevent errors involving blood thinners, including Heparin.

The Joint Commission issued a safety alert saying hospitals need to adopt prevention measures that could include bar-coding technology for medicines or computerized drug orders. It advised hospitals to more closely monitor patients on these drugs and make sure that adult-strength Heparin is stored nowhere near children’s units.

The alert said 28 deaths are among 32 reports of drug errors involving blood thinners that it received between 1997 and last year.

“We know that there are many more (deaths) and that’s the reason for issuing this alert,” said Dr. Mark Chassin, president of the Oakbrook Terrace, Illinois based commission.

Recent errors include accidental life-threatening Heparin overdoses given to actor Dennis Quaid’s newborn twins at a Los Angeles hospital last November. In July, 14 babies received accidental Heparin overdoses at a hospital in Corpus Christi, Texas.

Commission investigators will make unannounced visits to make sure hospitals are adopting strict measures to prevent blood thinner errors, and those who fail to do so could see their accreditation revoked, Chassin said.

The commission is a private group that sets hospital standards and accredits most of the nation’s hospitals. Accreditation brings prestige and federal dollars.

A total of 59,316 medication errors involving blood thinners were reported between 2001 and 2006 to a database run by U.S. Pharmacopeia, a group that sets drug standards, the alert said. Nearly 3 percent, or roughly 1,700, resulted in patient harm or death, the commission said.

Blood thinners are particularly tricky to use because too much can cause hard-to-control bleeding internally and from everybody opening; too little can result in life-threatening blood clots, Chassin said.

Heparin is usually given intravenously. Warfarin, another blood thinner cited in the alert, is available in pills patients can take at home but can cause bad reactions when mixed with other medicines.

The recommendations “absolutely” will make a difference and hospitals will pay attention, said James Conway, senior vice president of the nonprofit Institute for Healthcare Improvement in Cambridge, Massachusetts.

He said state and federal agencies including the Texas Department of Health Services and the FDA have been notified.

It’s still unclear what role, if any, the heparin played in the infant’s death, because the child already was seriously ill and being cared for in the neonatal intensive care unit before dying on the morning of July 8, 2008, said Dr. Richard Davis, the hospital’s chief medical officer.

Officials did not say when the autopsy on the deceased infant would be conducted.

The infant was among at least 17 babies given an overdose of the pediatric version of heparin. Heparin routinely is used in the hospital’s neonatal intensive care unit to flush intravenous lines and prevent blood clots from forming.

A preliminary investigation indicates that the error happened during a process in which pharmacy personnel mixed it with other solutions, including saline.

The heparin first was administered in the neonatal intensive care unit. It’s unclear how many of the children were dosed, because there were syringes from a different drug batch in medical cabinets in the unit, Davis said.

Nurses discovered the dosing error during routine blood work, Christus Spohn Health System spokeswoman Sherri Carr-Deer said.

They discontinued the drug’s use immediately and gave newborns that needed it medications to counter its effects.

One infant remains in critical condition in the unit, and was in that condition for several days before the heparin dosages, Davis said. Three infants have been discharged and 12 are stable and remain in intensive care.

Emily Palmer, a spokeswoman with the Texas Department of Health Services, said the agency is aware of the situation, but said she could not disclose whether there is a complaint or investigation because of confidentiality rules.

The Joint Commission on Accreditation of Healthcare Organizations, an independent, nonprofit agency that accredits and certifies more than 15,000 hospitals in the U.S. including those in the Spohn system, was notified, officials said.

During the past 18 months, there have been roughly 250 medical errors nationwide involving heparin and children a year or younger, according to U.S. Pharmacopeia, the public standards-setting authority for all prescription and over-the-counter medicines, dietary supplements and other health-care products manufactured and sold in the United States.