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Risk for Hospital Contact With Infection in Patients With Splenectomy: A Population-Based Cohort Study

Reimar W. Thomsen, MD, PhD; W. Marieke Schoonen, MSc, PhD; Dóra K. Farkas, MSc; Anders Riis, MSc; Jacob Jacobsen, MSc; Jon P. Fryzek, PhD; and Henrik Toft Sørensen, MD, DMSc
[+] Article, Author, and Disclosure Information

From Aarhus University Hospital, Aalborg, Denmark, and Amgen, Uxbridge, Middlesex, United Kingdom, and Thousand Oaks, California.

Grant Support: By Amgen, the Clinical Epidemiological Research Foundation at Aarhus University, and the Karen Elise Jensens Foundation.

Potential Conflicts of Interest:Employment: W.M. Schoonen (Amgen), J.P. Fryzek (Amgen). Stock ownership or options (other than mutual funds): W.M. Schoonen (Amgen), J.P. Fryzek (Amgen).

Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Sørensen (e-mail, hts@dce.au.dk). Data set: The Danish Data Protection Agency does not allow transferral of the project data to external research institutions. Most of the source data are stored with Statistics Denmark and can be made available for analysis from www.dst.dk/research.

Requests for Single Reprints: Reimar W. Thomsen, MD, PhD, Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg Hospital Science and Innovation Center, Søndre Skovvej 15, DK-9000 Aalborg, Denmark; e-mail, r.thomsen@rn.dk.

Current Author Addresses: Dr. Thomsen: Department of Clinical Epidemiology, Aarhus University Hospital, Aalborg Hospital Science and Innovation Centre, Søndre Skovvej 15, DK-9000 Aalborg, Denmark.

Dr. Schoonen: Amgen, 1 Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex UB8 1DH, United Kingdom.

Ms. Farkas, Mr. Riis, Mr. Jacobsen, and Dr. Sørensen: Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Alle 43-45, DK-8200 Århus Nord, Denmark.

Dr. Fryzek: Amgen, One Amgen Center Drive, Thousand Oaks, CA 91360.

Author Contributions: Conception and design: D.K. Farkas, J. Jacobsen, R.W. Thomsen, W.M. Schoonen, A. Riis, J.P. Fryzek, H.T. Sørensen.

Analysis and interpretation of the data: R.W. Thomsen, W.M. Schoonen, D.K. Farkas, A. Riis, J. Jacobsen, J.P. Fryzek, H.T. Sørensen.

Drafting of the article: R.W. Thomsen, W.M. Schoonen, J.P. Fryzek.

Critical revision of the article for important intellectual content: D.K. Farkas, J. Jacobsen, R.W. Thomsen, W.M. Schoonen, J.P. Fryzek, H.T. Sørensen.

Final approval of the article: R.W. Thomsen, W.M. Schoonen, D.K. Farkas, A. Riis, J. Jacobsen, J.P. Fryzek, H.T. Sørensen.

Administrative, technical, or logistic support: D.K. Farkas, J. Jacobsen.

Statistical expertise: W.M. Schoonen, D.K. Farkas, A. Riis, J. Jacobsen, J.P. Fryzek.

Collection and assembly of data: A. Riis.

Ann Intern Med. 2009;151(8):546-555. doi:10.7326/0003-4819-151-8-200910200-00008
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Our large nationwide, population-based study provides strong evidence of an increased risk for pneumonia and other infections, in particular early bacteremia, among patients undergoing splenectomy. This excess risk was most pronounced during the first 90 days after splenectomy, persisted for more than 365 days, and was seen regardless of the medical indication for splenectomy.

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Adjusted relative risk for any infection involving hospital contact among splenectomized patients compared with general population, appendectomized, and matched-indication cohorts.

Relative risk is estimated as the odds ratio of infection within 90 days and as the hazard ratio of infection within 91 to 365 days and more than 365 days after splenectomy. Estimates are adjusted by age, sex, and presence of comorbid condition at the time of splenectomy.

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Submit a Comment/Letter
Impact of Splenectomy on Subsequent Infections
Posted on November 9, 2009
Tetsuji Fujita
Jikei University School of Medicine
Conflict of Interest: None Declared

TO THE EDITOR: Linking the national hospital discharge records to the civil registration system in 3812 splenectomized patients, 38120 general population members, 16962 appendectomized patients and 8310 matched patients with hematologic disorder, Dr Thomsen and colleagues (1) clarified the clinical impact of splenectomy on subsequent infections. Compared with the general population, the odds ratio of infection was 18.1 in the first 90 days after splenectomy, and the hazard ratio was 4.6 from 91 to 365 days, and 2.5 more than 365 days after splenectomy. Surprisingly, in a subcohort for which detailed data on bacterial infections were available, the 90-day odds ratio for bacteremia was 138.2 compared to the general population cohort. These results may compel the patients to receive pneumococcal vaccines or antibiotic prophylaxis to reduce infection rates. However, I suppose that a markedly increased infection rate in the first study period does not necessarily reflect the role of the spleen in the elimination of bacteria. The removal of a huge spleen is a challenging operation, and is not rarely associated with infectious complications such as wound infection, catheter sepsis, subphrenic abscess, and pneumonia. In a study of 135 patients undergoing splenectomy for hematologic malignancies, overall morbidity and mortality rates were 52 % and 9 % (2). Even for patients with immune thrombocytopenic purpura, splenectomy was associated with a morbidity of 40 % if they had received medical therapy for a long time (3). In the current study, among the infections within 90 days after splenectomy, a substantial portion is thought to be attributable to operative insult, but not to immune deficit resulting from splenectomy

Besides increased susceptibility to infection, another concern about splenectomy is whether it can affect long-term survival rates, particularly for patients with abdominal cancer or hematologic malignancy. In a recent cohort study using the Scottish hospital records and death registration system in 1648 splenectomized patients with a mean follow-up of 4.45 years, 739 patients (45 %) died during the study period (4). Unfortunately, in that study, how many deaths were related to severe infections or how many patients died of the progression of the disease is not known. In the study by Thomsen et al, it appears that about 18 % of patients died within 1 year after splenectomy, and about 27 % of splenectomized patients died during a median follow-up of 2,2 years, whereas about 15 % of the matched patients with hematologic disorder died within 1year and about 28 % of these died during a median follow-up of 2.1 years, as shown in Table 3 of the article. Defining whether splenectomy contributed to the death of patients with abdominal or hematologic malignancies would be clinically important.


1. Thomsen RW, Schoonen WM, Farkas DK, Riis A, Jacobsen J, Fryzek JP, et al. Risk for hospital contact with infection in patients with splenectomy. Ann Intern Med. 2009; 151: 546-55.

2. Horowitz J, Smith JL, Weber TK, Rodriguez-Bigas MA, Petrelli NJ. Postoperative complications after splenectomy for hematologic malignancies. Ann Surg 1996; 223: 290-6.

3. Gibson M, Sehon JK, White S, Zibari GB, Johnson LW. Splenectomy for idiopathic thrombocytopenic purpura: a five-year retrospective review. Am Surg 2000; 66: 952-5.

4. Kyaw MH, Holmes EM, Toolis F, Wayne B, Chalmers J, Jones IG, et al. Evaluation of severe infection and survival after splenectomy. Am J Med 2006; 119: 276.e1-e7.

Conflict of Interest:

None declared

Submit a Comment/Letter

Summary for Patients

Risk for Hospitalization for Infection in Patients Who Have Had Splenectomy

The summary below is from the full report titled “Risk for Hospital Contact With Infection in Patients With Splenectomy. A Population-Based Cohort Study.” It is in the 20 October 2009 issue of Annals of Internal Medicine (volume 151, pages 546-555). The authors are R.W. Thomsen, W.M. Schoonen, D.K. Farkas, A. Riis, J. Jacobsen, J.P. Fryzek, and H.T. Sørensen.


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