Contaminant in the recalled unfractionated heparin preparations: where is the problem?

In a recently held press conference, the USFDA (United States Food and Drug Administration) briefed the press that the potential contaminant in the recalled Baxter product is a heparin-like substance. The USFDA commented that heparin-like molecules have been identified using high-tech methods. No specifics regarding these contaminants were given. The manufacturing process of heparin is such that other heparin-like contaminants, such as the dermatan sulfate, heparan sulfate, and chondroitin sulfate are removed effectively. These represent the main contaminants in heparin. However, these contaminants are unlikely to produce any allergic effects, nor the reported adverse reactions, because some of the antithrombotic drugs contain significant amounts of these heparin-like substances. Because of the carbohydrate nature of the contaminants identified by a special method of nuclear magnetic resonance (NMR), it is quite disturbing to note that such contaminants may have inadvertently been added to the recalled heparin. Heparin-like materials have been isolated from the shellfish, marine plants, bones, or skin of mammalian origin for several therapeutic purposes. Although structurally similar, these heparin-like substances exhibit different biochemical and pharmacologic effects. There are also various protein contaminants that can be expected along with the carbohydrates. Thus, it is likely that besides the carbohydrate contaminants, some unknown protein contaminants may also be present in these products. The statement that a heparin-like material was identified using high-tech methods is ambiguous and misleading. Such statements should be specific and clear regarding the methods used and the nature In late January, Baxter Healthcare Corporation voluntarily recalled the following lots of heparin: 107054, 117085, 047056, 097081, 107024, 107064, 107066, 107074, and 107111. These products were labeled as heparin 1000 U/mL in 10 mL vials and heparin 1000 U/mL in 30 mL vials. The reason for this recall was the reported adverse reactions, which were associated with the use of these heparin batches. These included abdominal pain, hypotension, burning, chest pain, diarrhea, dizziness, dyspepsia, dyspnea, arrhythmia, flushing, headache, hyperthyroidism, hypoesthesia, increased lacrimation, loss of consciousness, malaise, nausea, pallor, palpitation, paresthesia, pharyngeal edema, restlessness, vomiting, stomach discomfort, tachycardia, thirst, trismus, unresponsiveness to stimuli, and drug ineffectiveness. These adverse reactions were reported in hundreds of patients treated with these heparins in the USA. Initially 19 deaths were linked with the use of the recalled heparins. However, this figure has now reached 81, and it is likely that it will go even higher. These multiple adverse reactions were later attributed to heparin manufactured by Baxter’s [Deerfield, IL] suppliers using Chinese raw material from SPL Changzhou, China. Subsequently, Baxter recalled all of the remaining lots and doses of its heparin sodium injection multidose, single dose vials, and Hep-lock heparin flush product.