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Ann Thorac Surg 2002;73:1098-1100
© 2002 The Society of Thoracic Surgeons

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Original article: general thoracic

Frequency of transmission of human parvovirus B19 infection by fibrin sealant used during thoracic surgery

^a Division of General Thoracic Surgery, Keio University Hospital, Tokyo, Japan

Accepted for publication January 4, 2002.

* Address reprint requests to Dr Kawamura, Division of General Thoracic Surgery, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
e-mail: kawamura{at}sc.itc.keio.ac.jp

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. Fibrin sealant is used in many kinds of surgical procedures. Although pasteurization is insufficient to remove human parvovirus (HPV) B19 from this plasma-derived product, the frequency of HPV B19 infection transmitted by its use has never been known.

Methods. Blood samples of 85 patients more than 20 years of age who had undergone pulmonary resection with fibrin sealant were obtained before and 12, 24, and 48 weeks after surgery. Anti-HPV B19 antibody IgG (HPV B19 IgG) and HPV B19 DNA were detected with these samples.

Results. In 56 (65.9%) of 85 patients, blood samples obtained before operation were positive for HPV B19 IgG. In these 56 patients, blood samples obtained 12 to 48 weeks after surgery were all negative for HPV B19 DNA by polymerase chain reaction (PCR). In 6 (20.7%) of 29 patients whose blood samples were negative for HPV B19 IgG before surgery, blood samples obtained 12 to 48 weeks after surgery were positive for HPV B19 DNA by PCR and also positive for HPV B19 IgG. In 5 of these 6 patients reticulocyte counts decreased to less than 10 x 10⁹/l 12 to 20 days after surgery.

Conclusions. Epidemiologic evidence suggests that more than 20% uninfected persons were subsequently infected with HPV B19 by use of fibrin sealant during surgery.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Fibrin sealant is used in various surgical procedures to stop bleeding, air leak, or cerebral fluid leak. As this material is produced from a donated blood pool that may be contaminated by many types of viruses, pasteurization is necessary 60°C for 10 hours for their removal. However, it has been pointed out that by this type of pasteurization, human parvovirus (HPV) B19 cannot be removed from plasma derived products such as factor VIII, albumin or fibrin sealant [1]. Clinical syndromes commonly associated with HPV B19 are usually not as severe as erythema infectiosum, fever, and arthralgia. A decrease in reticulocyte count is quite common 10 to 14 days after infection (Fig 1). More than half of adults persons have experienced this infection. It is reported that 51% of teenagers have already experienced a parvovirus infection and obtained protective antibodies, and this ratio rises to 78% for persons more than 50 years of age [2]. However, the infection sometimes leads to severe conditions such as transient aplastic crisis in patients with shortened red cell survival, including sickle cell anemia, chronic bone marrow failure in immunocompromised hosts, or fetal death after intrauterine infection. Moreover, it has been reported that acute hepatitis and central nervous system disorders were associated with HPV B19 infection in healthy children [3, 4]. Nevertheless, warnings against transmission of HPV B19 infection by use of plasma products have been insufficient. Therefore, the current study aimed to establish the frequency of infection of HPV B19 transmitted by the use of fibrin sealant during surgery.

View larger version (21K): [in this window] [in a new window]   Fig 1. Postinoculation laboratory data and symptoms. (Anti-HPV ab = anti-human parvovirus antibody.)

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

The 85 patients included 66 men and 19 women aged 24 to 82 years. Chest surgeries had been performed for primary lung cancer in 62 patients, metastatic lung tumor in 13, inflammatory lung disease in 4, pneumothorax in 2, benign lung tumor in 2, and mediastinal tumor invading lung in 2.

Blood samples were taken before and 12, 24, and 48 weeks after surgery. Anti-HPV B19 antibody IgG (HPV B19 IgG) was detected by use of enzyme immunoassay for the blood samples obtained before surgery in all cases and samples obtained 12 to 48 weeks after surgery in only those cases without antibodies before surgery. Detection of HPV B19 DNA in the blood samples obtained before and after surgery was performed using the polymerase chain reaction (PCR) technique. The primer of HPV B19 for PCR had the following: 5'-GTA CGC CCA TCC CCG GGA CCA GTT CAG G-3' and 5'-CAG GTA AAC CCC TTA CAC CGT CCC ACA C-3' [5]. The level of HPV B19 DNA to be detected with this assay was set at more than 4 x 10⁴ copies/mL.

As a control group, the clinical records (especially reticulocyte counts) of 72 patients who had undergone pulmonary resection without fibrin glue during the same period were evaluated.

The relationship between reticulocytepenia and use of fibrin glue was analyzed by the ² test for independence, as well as the relationship between HPV B19 infection and reticulocytepenia in the patients who underwent pulmonary resection with fibrin. Statistical difference was set at p < 0.05.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
A total of 56 blood samples (65.9%) of 85 samples obtained before operation were positive for HPV B19 IgG. The 56 blood samples obtained 12 to 48 weeks after surgery from the same patients all were negative for HPV B19 DNA by PCR. Six (20.7%) of 29 samples obtained 12 to 48 weeks after surgery from patients whose blood samples before surgery were negative for HPV B19 IgG were positive for HPV B19 DNA by PCR and also positive for HPV B19 IgG (Table 1). The other 23 samples obtained 12 to 48 weeks after surgery from patients whose blood samples before surgery were negative for HPV B19 IgG, were negative for both HPV B19 IgG and HPV B19 DNA.

Excluding the 6 patients with HPV DNA, reticulocyte counts were available in 35 of the remaining 79 cases. The lowest reticulocyte counts of those cases were more than 20.0 x 10⁹/l between postoperative day (POD) 10 and 20, indicating the absence of patients with reticulocyte decrease. Among these 41 patients who underwent pulmonary resection with fibrin glue and whose postoperative reticulocyte counts were available, reticulocytepenia statistically related to HPV B19 infection by the ² test for independence (p < 0.0001).

In the control group of 72 patients operated without fibrin glue, there were no patients whose postoperative reticulocyte count decreased to less 4.0 x 10⁹/l. Between the patients operated on with fibrin glue and those without, the frequency of reticulocytepenia after surgery was significantly higher in the fibrin group (p = 0.0365).

Lot numbers of fibrin sealant used in 2 of 6 patients whose blood samples after surgery were shown to be positive for B19 DNA by PCR were revealed by hospital records. However, these stocks of the manufacturer had already been lost because of the expiration of the stock period.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
It has been reported that parvovirus B19, a nonenveloped virus consisting of a single-stranded linear molecule of 5,596 nucleotides, is stable under the pasteurization for plasma-derived products such as fibrin sealant [6]. It has also been reported that HPV B19 DNA was detected by PCR in 64 samples of 75 (85%) donated plasma pools, in three of 12 albumin samples, in seven of seven factor VIII samples, and in six of 19 immunoglobulin samples [6]. Although such a detection has not been performed in fibrinogen samples, fibrinogen are extracted from the plasma pool in the fraction close to factor VIII; therefore, fibrinogen is supposed to be possibly contaminated with HPV B19. In Japan, the warning of HPV B19 transmission by use of fibrin sealant is printed in the explanatory notes included in the fibrin sealant set. However, the frequency of B19 infection associated with the use of fibrin sealant during surgery has been unknown. Only case reports are available to predict the possibility of B19 infection associated with the use of fibrin sealant [7, 8]. In this clinical study, after the use of fibrin sealant during chest surgery, B19 DNA was detected in only those patients whose blood samples were negative for HPV B19 IgG before surgery, and its frequency was more than over 20% in this group. Unfortunately, because of the loss of the same-lot stocks as used for HPV B19 DNA-positive patients, identification of B19 virus type by use of DNA sequence was not available. However, no patient who underwent pulmonary resection with fibrin glue but whose HPV B19 DNA were negative after surgery showed reticulocytepenia, and the correlation of reticulocytepenia and HPV B19 infection was shown statistically. On the other hand, no patient who underwent chest surgery without fibrin glue in the same period as these HPV B19-infected patients also showed reticulocytepenia. If we presume that infection was due to an epidemic or a nosocomial infection, the absence of reticulocytepenia among the patients who were hospitalized in the same wards during the same time and who underwent chest surgery without fibrin sealant becomes inexplicable. Therefore, according to these clinical data, we suspect that HPV B19 infections in 6 patients (20.7% of HPV IgG-negative patients) were transmitted by the use of fibrin sealant during chest surgery.

All 6 patients were discharged uneventfully, and during the 2 years of the follow-up period, no complicated events supposed to be associated with HPV B19 infection were observed. Clinical syndromes commonly associated with HPV B19 are usually not as severe as erythema infectiosum fever, and arthralgia. In cases of acute infection with HPV B19, it was reported that 61% to 79% of patients had arthritis [9, 10]. None of these 6 patients complained of arthralgia, possibly because of the analgesics that were given to all the patients for more than 4 weeks after chest surgery.

It has been reported that a large number of HPV B19 are detected in nasal fluid 7 to 10 days after inoculation of this virus to healthy volunteers, and that HPV B19 is highly infectious during this period [11]. Based on our investigation, reticulocytepenia was not detected among the patients who were admitted to the same wards at the same time as the HPV B19-infected patients. This means that a nosocomial infection of HPV B19 is not usual; however, the possibility of a nosocomial infection is undeniable, as the prevalence of HPV B19 infection is periodically observed.

Although fibrin sealant is a useful biomaterial for surgery, its use should be limited to healthy adults in whom it is inevitably required, until an HPV-B19 free product becomes clinically available.

	References

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawamura, M. Articles by Kobayashi, K. Search for Related Content PubMed PubMed Citation Articles by Kawamura, M. Articles by Kobayashi, K. Related Collections Lung - other