Assessment of splenic function A. P. N. A. Porto, A. J. J. Lammers, R. J. Bennink, I. J. M. Berge, P. Speelman, J. B. L. Hoekstra To cite this version: A. P. N. A. Porto, A. J. J. Lammers, R. J. Bennink, I. J. M. Berge, P. Speelman, et al.. Assessment of splenic function. European Journal of Clinical Microbiology and Infectious Diseases, Springer Verlag, 2010, 29 (12), pp.1465-1473. 10.1007/s10096-010-1049-1. hal-00624509 HAL Id: hal-00624509 https://hal.archives-ouvertes.fr/hal-00624509 Submitted on 19 Sep 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Manuscript Click here to download Manuscript: Review Assessment of Slenic Function.doc Click here to view linked References 1 2 3 4 Title-page. 5 6 7 8 Title: Assessment of splenic function 9 10 11 Authors: A.P.N.A. de Porto1, A.J.J. Lammers1, R.J. Bennink2, I.J.M. ten Berge3, P. Speelman1, 12 4 13 J.B.L. Hoekstra . 14 15 16 Affiliations 17 18 1: Department of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, 19 Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. 20 21 2: Department of Nuclear Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ, 22 Amsterdam, Netherlands. 23 24 25 3: Department of Internal Medicine, Nephrology Unit, Academic Medical Center, Meibergdreef 26 9, 1105AZ, Amsterdam, Netherlands. 27 28 29 4:Department of Internal Medicine, Academic Medical Center, Meibergdreef 9, 1105AZ, 30 Amsterdam, Netherlands 31 32 33 Corresponding author: 34 35 A.P.N.A. de Porto, Department of Infectious Diseases, Tropical Medicine and AIDS, G2-105, 36 Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, Netherlands. 37 e-mail: [email protected], telephone number: +31205662067, fax number: 38 6977192. 39 40 41 42 43 Keywords: Spleen function, Pitted erythrocytes, Howell Jolly Bodies, IgM Memory B cells, 44 45 46 Radionuclide Scintigraphy. 47 48 49 50 51 52 53 54 55 Wordcount: 3926 56 57 58 59 60 61 62 1 63 64 65 1 2 3 4 Abstract 5 6 7 Hyposplenic patients are at risk for Overwhelming Post Splenectomy Infection (OPSI), which 8 9 has a mortality of up to 70%. Therefore, preventive measures are warranted. However, patients 10 11 with diminished splenic function are difficult to identify. In this review we discuss (i) 12 13 14 immunological, (ii) haematological and (iii) scintigraphic parameters that can be used to measure 15 16 splenic function. 17 18 19 (i) IgM memory B cells are a potential parameter to assess splenic function, however more 20 21 studies are necessary for its validation. (ii) Detection of Howell Jolly bodies does not reflect 22 23 24 splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well 25 26 evaluated method and seems a good first line investigation to assess splenic function. (iii) When 27 28 99m 29 assessing spleen function, Tc labelled heat-altered autologous erythrocyte scintigraphy with a 30 31 multimodality Single Photon Emission Computed Tomography (SPECT)-CT technology is the 32 33 best approach, as all facets of splenic function are evaluated. 34 35 36 In conclusion, although scintigraphic methods are most reliable, they are not suitable for 37 38 screening large populations. We therefore recommend using the percentage of pitted 39 40 41 erythrocytes, albeit suboptimal, as a first line investigation and subsequently confirm abnormal 42 43 readings by means of scintigraphy. More studies evaluating the value of potentially new markers 44 45 46 are needed. 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 2 63 64 65 1 2 3 4 Introduction 5 6 7 The spleen is the largest lymphoid organ in the human body. Its rich and diverse population of 8 9 immune cells and its ingenious anatomy that enables optimal surveillance and phagocytosis of 10 11 circulating blood elements play an important role in the defence against pathogens. Table 1 12 13 14 summarizes the different aspects of splenic functions. After splenectomy, patients are at 15 16 increased risk for Overwhelming Post Splenectomy Infection (OPSI), see Box [1-4]. 17 18 19 Apart from patients with a status after splenectomy, there is a much larger group of patients with 20 21 diminished splenic function. Many diseases are associated with a dysfunctional spleen (Table 2) 22 23 24 and the degree of splenic dysfunction varies between patients [5]. For patients suspected to have 25 26 a diminished functioning spleen, it is important to quantify their splenic function in order to 27 28 29 assess the risk of developing OPSI. Subsequently, preventive measurements can be taken and, in 30 31 case of infection, therapy can be started without delay. In this review we evaluate the available 32 33 methods to measure splenic function. 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 3 63 64 65 1 2 3 4 5 After splenectomy, patients are at risk for overwhelming infection. This syndrome is called 6 7 overwhelming post-splenectomy infection (OPSI) or post-splenectomy sepsis (PSS). Patients 8 with functional asplenia are also at risk for this syndrome. 9 10 Symptoms: OPSI is characterized by a mild onset with flu-like symptoms such as low grade 11 12 fever, chills, muscle aches and nausea. However, a subsequent fast deterioration may occur in 13 hours rather than days leading to fulminant sepsis, disseminated intravascular coagulation and 14 multi-organ failure [6]. 15 16 Incidence: Incidence of OPSI is estimated to be low, 2-5 per 1000 asplenic patients per year [7]. 17 18 The lifetime risk for developing OPSI is estimated to be 5% [8]. Although more than half of 19 these infections occur within the first two years after splenectomy, the risk remains increased 20 lifelong [1,9]. 21 22 23 Mortality: Although incidence is low, mortality is high. Numbers in literature vary between 50 24 and 70% [1,3]. Notably, 68% of patients die in the first 24 hours, and 80% within 48 hours after 25 onset [3,10]. 26 27 Micro-organisms: Encapsulated bacteria are important causative organisms of OPSI. S. 28 29 pneumoniae causes 70% of bacteraemic episodes after splenectomy [3]. Other pathogens, 30 responsible for OPSI are H. influenzae, N. meningitidis, E. coli and Pseudomonas. 31 32 Guideline: To prevent OPSI several preventive measures should be taken, such as immunization 33 against the encapsulated bacteria S. pneumoniae, H. influenzae B and N. meningitidis C. 34 35 Furthermore, patients should use continuous prophylactic antibiotics during the first 2 years after 36 splenectomy and have on-demand antibiotics to use in case of (suspected) infection [11-13] 37 38 Box Overwhelming post-splenectomy infection. 39 40 41 42 43 Approaches to measure splenic function 44 45 46 Throughout the years, several methods have been developed to quantify the many different 47 48 functions of the spleen. These methods are based on haematological, immunological and 49 50 51 scintigraphic parameters. 52 53 54 55 Haematological parameters 56 57 58 Haematological methods reflect the capacity of the spleen to phagocytose deviant erythrocytes 59 60 and to facilitate an environment wherein erythrocytes rid themselves of solid waste material 61 62 4 63 64 65 1 2 3 4 [14,15]. In case of splenic dysfunction these capacities are impaired, which results in an increase 5 6 7 of abnormal circulating red blood cells. Furthermore, large amounts of thrombocytes and 8 9 leukocytes normally reside in the spleen. Circulating thrombocyte- and leukocyte counts can 10 11 either be increased or decreased indicative of hyposplenism in a patient with a dysfunctional 12 13 14 spleen (for example thrombocytosis in asplenia and thrombopenia associated with splenomegaly) 15 16 [5,16]. 17 18 19 One of the first methods available to evaluate splenic function was the detection of erythrocytes 20 21 containing Howell Jolly bodies, using a light microscope viewing a stained peripheral blood 22 23 24 smear [17,18]. Howell Jolly bodies are basophilic DNA remains from the nucleus of the 25 26 erythrocyte precursor cell. Normally, upon leaving the bone marrow, the erythrocyte precursor 27 28 29 cell expels its nucleus. In some erythrocytes however, a small portion of DNA remains. Normally 30 31 the spleen clears the erythrocyte of these nuclear remnants or removes the erythrocytes from the 32 33 circulation, but when the spleen is absent or has a decreased function these Howell Jolly body 34 35 36 containing erythrocytes remain in the circulation. A recently developed method uses flow 37 38 cytometry to quantify the amount of erythrocytes containing Howell Jolly bodies [19]. 39 40 41 Other abnormalities that can be seen on peripheral blood smears of patients with absent or 42 43 diminished splenic function are acanthocytes (spur cells), target cells (condocytes: erythrocytes 44 45 46 with a pattern of central staining, a ring of pallor and an outer ring of staining), haemoglobin 47 48 remnants (Heinz bodies), siderocytes and iron granulocytes (Pappenheimer bodies) [5,16] . 49 50 In individuals with a dysfunctional or absent spleen the membrane of erythrocytes appears to 51 52 53 contain so called “pits” when studied with interference phase microscopy [20].