On 8/4/97, a 200 pound female with a history of asthma developed difficulty breathing approximately 13 minutes after the start of a platelet donation using the cs-3000 plus blood cell separator. The donor first complained of a tickling in the throat and was given a piece of candy. The tickling sensation continued and progressed to subjective difficulty in breathing. The apheresis nurse elected to discontinue the donation procedure and return blood within the apheresis kit to the donor. Blood return was almost immediately halted (approx 35 ml returned) as the donor continued to complain of being unable to breathe. After the donor needles had been removed, the donor rose from the chair, said she was okay, but continued to indicate that she was having respiratory difficulty. The apheresis staff did not observe wheezing, gasping or other signs of respiratory difficulty such as exaggerated respiratory movements. There was no flushing, urticaria or other evidence of allergic reaction noted. The donor self-administered a single dose of proventil from an inhaler she carried. Subjective respiratory distress worsened, again without visible physical signs of dyspnea. The fire department rescue squad was called and responded within a few minutes, by which time the donor's condition had deteriorated significatly. Attempts to intubate the donor were unsuccessful and oxygen was administered via an oral airway as resuscitation efforts were initiated. Shortly thereafter a second group of emergency medical technicians arrived and transported the donor to the hosp where she was successfully intubated. Resuscitation efforts were said to have continued for approx one hour without success. Following death, the donor's husband indicated to the medical examiner that the donor had discontinued some of her asthma medication(theo-dur) approx two weeks previously. It was also learned that the donor had self-administered an unk amount of benadryl prior to the donation to prevent the effects of citrate. The donor had been participating in a regular platelet donation program for several years without significant complications other than occasional difficulty in establishing adequate venous access. The previous donation (on july 25, 1997) was noted from center records to have been terminated prematurely due to hyperventilation. No other details are available re: the hyperventilation episode which was noted in the donor record but considered to be of a non-serious nature.

Mfr investigation, customer feedback and follow up #1 investigation results & info: provided in full detail in the initial report of 8/8/1997 and follow up #1 dated 9/17/1997. Autopsy report on case. Report read in part: thirteen (13) glass microscopic slides were examined. All were stained with hematoxylin and eosin. They include lung (x7), heart (x3), kidney, brain, and liver. Seven lung sections are remarkable for few changes of typical bronchial asthma (smooth muscle hyperplasia, eosinophls, mucous plugging and goblet cell thrombi throughout, more peripherally. Hear was (x3) within normal histologic parameters. Liver within normal histologic parameters. Kidneys within normal histologic parameters. Specifically, there is no evidence of platelet or fibrin thrombi. Brain within normal histologic parameters. It is medical examiners opinion that donor died of anaphylaxis related to plasmapheresis. Manner of her death is accident. He stated it is interesting to note donors ante-mortem self-medication with benadryl (diphenhydramine hc1). Prior to her collapse & death, she stated she had done this to ameliorate her known citrate allergy. This form of allergic reaction is related to cellular calcium channel abnormalities and not to release of intracellular histamine typical in allergic reactions. Common causes of sudden collapse & arrest in this clinical setting of plasmapheresis have been explored. They include pulmonary thromboemboli, bacterial septic shock, myocardial abnormalities, and air embolus, to name few. All of these were examined for and none were found. Medical examiner report noted that: this case was reviewed intramurally with pathologist, and medical director. Given negative results of commonest causes of sudden collapse, medical examiner and doctors are in agreement that only two probable sources of donors initiating event remain anaphylaxis or bronchial asthma. This, despite toxicologic finding of subtherapautic level of theophyline in her system at time of her death and family's knowledge that she was not taking that medication as directed by her physician. Per medical examiner this case was also reviewed in consultation with 2 independent university physicians, and with another county medical examiner. Medical examiner's report reflected fact that they were in agreement with info offered in report. B. Manufacturer's medical director comments: cause of this donor's death remains puzzling based upon following observations: donor was known to have asthma and had discontinued long-acting asthma medication several days prior to donation. Donor's symptoms appeared to be limited to difficulty breathing. She described her problem as 'not my lungs, just my throat' which might appear more consistent with anaphylaxis than asthma. Other signs or symptoms which might be expected with anaphylaxis (flushing, hives, rash, abdominal distress, itching wheezing, sneezing, tearing) were not noted during episode.