Presence Of Howell-Jolly Bodies Research Articles

Are accessory spleen screening and resection in refractory immune cytopenia an effective strategy or a waste of resources?

Splenectomy remains an effective treatment for refractory immune cytopenia (RIC), which encompasses immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Accessory spleens (AS) have been described without identifying specific risk factors. We retrospectively analyzed patients with RIC after splenectomy who underwent splenic scintigraphy (SS) at our institution. Seventy-one patients were included. Sixty-two patients had ITP, five had AIHA, and four had Evans syndrome. Seventy-five percent (n = 53) were women. Eleven patients (15.5%) had an AS detected by SS. A complete response (CR) to first-line steroids (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.37-24.14, p = 0.017) and the absence of Howell-Jolly bodies (HJB) in peripheral blood smear (PBS) (OR 11.37, 95% CI 2.70-47.85, p = 0.001) were found to be risk factors. Patients with both elements had a higher rate of AS (83.3%) when compared to those with one or no factors (p < 0.001). Eight patients (73%) underwent an accessory splenectomy: seven (87.5%) achieved a CR, and none had perioperative complications. The presence of HJB in PBS changed from 25 to 87.5% after accessory splenectomy. We recommend the search for an AS via SS in patients with RIC due to ITP, who had a CR to corticosteroids and the absence of HJB in PBS. Accessory splenectomy is a safe and effective procedure.

S112: COMPARATIVE SCORE OF HOWELL-JOLLY BODIES IN SICKLE CELL DISEASE PATIENTS ACCORDING TO GENOTYPE, AGE, SPLENECTOMY OR STEM CELL TRANSPLANTATION HISTORY

Background: Presence of Howell-Jolly bodies is associated with splenic dysfunction which progressively appears during aging or after splenectomy in patients with sickle cell disease. Improvement of splenic function has been found in several transplanted patients for SCD (Ferster 1993, Bernaudin 2007) encouraging our team to propose partial splenectomy to patients with hypersplenism and available matched-sibling donor. Aims: The goal of the present study was to evaluate the outcome of the splenic function from birth to adult age and the impact of splenectomy (partial or total) in SCD patients transplanted or not. Patients and Methods: In the pediatric Créteil SCD-cohort, including 907 SCD patients (111 SC, 47 Sb+, 725 SS, 21 Sb0 and 3 SDPunjab), Howell-Jolly bodies score (from 0 to 4) was prospectively assessed and recorded at each annual check-up. This study included 5013 annual check-ups (637 in SC/Sb+ and 4376 in SS/Sb0 patients) from Jan 1991 to July 2019. Results: Howell-Jolly bodies mean score increased during aging in SCD patients but was significantly lower in SC/Sb+ than in SS/Sb0 patients at each age of assessment (Figure 1). During the 2nd year of life, mean (SD Howell-Jolly bodies score was 0.34 (0.61) in SC/Sb+ vs 0.69 (0.82) in SS/Sb0 (P=0.01) while during the 18th year it was 0.61 (0.61) in SC/Sb+ vs 1.33 (1.1) in SS/Sb0 children (P<0.001). Among 749 SCA children, 86 were splenectomized at mean (SD) age of 6.4 years (3.9). As expected, mean (SD) Howell-Jolly bodies score was significantly higher at check-up in splenectomized than in non-splenectomized SCA-patients: 1.73 (1.2) vs 1.1 (1.0), p<0.001. However, the difference between both populations decreased during aging because of the progressive functional splenic dysfunction in non-splenectomized patients (Figure 2) Among SCA-children, 138 were transplanted with matched sibling donor at mean (SD) age of 9.0 years (4.9y). At each age of assessment, Howell-Jolly bodies score was strongly significantly (p<0.001) lower in transplanted than in non-transplanted children (Figure 3). At check-up performed during the 18th year of life, mean (SD) Howell-Jolly bodies score was 1.57 (1.0) in 241 non transplanted vs 0.54 (0.9) in 70 transplanted children (p<0.001) and the score in transplanted children was significantly positively correlated with the age at transplant (r=0.335, p=0.002). Seven children with splenic sequestration history or hypersplenism and available MSD-donor had partial splenectomy before transplant in order to try to preserve splenic function. Mean (SD) Howell-Jolly bodies score was 1.83 (1.2) before and was nul after transplant in all seven children.Conclusion: This cohort study clearly shows that splenic dysfunction increases during aging in SCA children and that stem cell transplantation allows to preserve splenic function especially since the transplant is performed early. In children with indication of splenectomy for recurrent splenic sequestrations or hypersplenism who have an available matched sibling donor, the present study encourages to propose partial vs total splenectomy just before stem cell transplantation in order to preserve splenic function.

Search for and Extraction of Accessory Spleen in Refractory Immune Cytopenias. Effective or a Waste in Resources?

Background: Splenectomy is an effective second line therapy for patients with immune cytopenias. Fifteen percent of patients are going to relapse after splenectomy. These patients are categorized as refractory and their treatment is challenging. The incidence of an accessory spleen diagnosed by gammagraphy is estimated to be 8-20% in this scenario. Current treatment guidelines do not address the issue of searching for an accessory spleen or performing accessory splenectomy as a treatment strategy for these patients. The aim of this study was to identify risk factors for the presence of accessory spleen diagnosed by gammagraphy in patients with refractory immune cytopenias and analyze the response rate of its removal. Methods: It is a case control, single center, retrospective study. We included adult patients with refractory immune cytopenias who underwent gammagraphy to search for an accessory spleen, from 1996 to 2016. Cases were patients with a positive gammagraphy, controls were those with a negative gammagraphy. Patients who failed to have at least one year of follow-up after splenectomy or accessory splenectomy, were excluded. A logistic regression was performed to determine factors associated with the presence of an accessory spleen. Results: We analyzed 71 refractory patients with a gammagraphy performed searching for an accessory spleen, 87.3% with a diagnosis of immune thrombocytopenia (IT), 7% autoimmune hemolytic anemia (AHA) and 5.6% Evans Syndrome. Fourteen percent of the patients had secondary immune cytopenias all of them due to autoimmune diseases. There was a predominance of women with 74.6% of the subjects studied. Patients received a median of 2 (0-4) lines of treatment before the splenectomy. The majority of patients (98.6%) had received, as first line of treatment corticosteroids, with an overall response rate (ORR) of 84% and a complete response (CR) rate of 38.6%. Of the 71 patients, splenectomy achieved an ORR of 83.1% with CR in 80.3%. The incidence of accessory spleen diagnosed by gammagraphy at their relapse was 15.5% (11 patients). In the multivariate analysis, we found two factors associated with positivity of the gammagraphy: CR to corticosteroids pre-splenectomy with an OR of 5.2 (CI 95% 1.24-21.78; p=0.021) and the presence of Howell Jolly bodies (HJb) with an OR of 0.088 (CI95% 0.02-0.37; p=0.001) as a protective factor. We developed a risk score consisting of: 0 risk factors, 1 risk factor (CR to corticosterois pre-splenectomy or abscense of HJb) and 2 risk factors. The percentage of patients who were positive by gammagraphy using this score was 83.3%, 25.6% and 3% for 2, 1 and no risk factors respectively (p&amp;lt;0.001) (Figure1). Eight patients underwent accesory splenectomy, all of them achieved responses with CR of 87.5%, and none experienced complications associated with the procedure. Seven patients acquired the presence of HJb after accesory splenectomy (Table 1). With a median follow-up of 60.2 months (1.54-194.56), 62.5% mantained the response obtained with the accesory splenectomy. One patient didn´t acquire HJb post accesory splenectomy, he relapsed and was diagnosed with a new accesory spleen. He underwent a second accesory splenectomy and is now in CR with the presence of HJb in the blood smear. Conclusions: The search for an accesory spleen in patients with refractory immune cytopenias with risk factors (absence of Howell Jolly bodies and or complete response to steroids as first line therapy) is usefull. Accesory splenectomy is a safe and effective therapeutic strategy in the treatment of these patients. Disclosures No relevant conflicts of interest to declare.

Howell-Jolly bodies and liver-spleen scanning for assessment of splenic filtrative function yields discordant results in renal transplant recipients.

Given discrepancies between methods for diagnosing hyposplenism, the purpose of this study was to evaluate the effect of the spleen size on the correlation between the methods, and to propose a model for improving the interpretation. Patients with renal allografts were included, in whom the spleen was assessed using Doppler ultrasound, scintiscan, and the presence of Howell-Jolly bodies (HJBs) in peripheral smears. In 35 subjects, scintiscan and HJBs were normal (Group 0); 20 had an abnormal result in both methods (Group 1); 34 had discordant results with HJBs present (Group 2); and 14 had discordant results with decreased spleen uptake (Group 3). There was no association between HJBs and scintiscan. The patients of Groups 1 and 2 had smaller spleens. The patients with smaller spleen had more hematological evidence of hyposplenism and exhibit smaller discrepancies between the methods than patients with larger spleen. The spleen can tip the balance from a normal to impaired function provided that the spleen size is below the critical mass required to maintain splenic function. A mild impairment of phagocytic function and slight dyserythropoiesis along with a small spleen would result in decreased take up of radiocolloid or the appearance of HJBs in blood smears.

Antibody response to a T-cell-independent antigen is preserved after splenic artery embolization for trauma.

Splenic artery embolization (SAE) is increasingly being used as a nonoperative management strategy for patients with blunt splenic injury following trauma. The aim of this study was to assess the splenic function of patients who were embolized. A clinical study was performed, with splenic function assessed by examining the antibody response to polysaccharide antigens (pneumococcal 23-valent polysaccharide vaccine), B-cell subsets, and the presence of Howell-Jolly bodies (HJB). The data were compared to those obtained from splenectomized patients and healthy controls (HC) who had been included in a previously conducted study. A total of 30 patients were studied: 5 who had proximal SAE, 7 who had distal SAE, 8 who had a splenectomy, and 10 HC. The median vaccine-specific antibody response of the SAE patients (fold increase, 3.97) did not differ significantly from that of the HC (5.29; P = 0.90); however, the median response of the splenectomized patients (2.30) did differ (P = 0.003). In 2 of the proximally embolized patients and none of the distally embolized patients, the ratio of the IgG antibody level postvaccination compared to that prevaccination was <2. There were no significant differences in the absolute numbers of lymphocytes or B-cell subsets between the SAE patients and the HC. HJB were not observed in the SAE patients. The splenic immune function of embolized patients was preserved, and therefore routine vaccination appears not to be indicated. Although the median antibody responses did not differ between the patients who underwent proximal SAE and those who underwent distal SAE, 2 of the 5 proximally embolized patients had insufficient responses to vaccination, whereas none of the distally embolized patients exhibited an insufficient response. Further research should be done to confirm this finding.

Functional hyposplenism is an important and underdiagnosed immunodeficiency condition in children.

Few studies have focused on paediatric hyposplenism/asplenism, in which splenic phagocytic activity is diminished or absent in an anatomically present spleen. This study aimed to evaluate clinical findings, laboratory tests and prognosis of children with functional hyposplenism/asplenism. The study group comprised 74 children who had liver/spleen technetium-99m sulphur colloid scintigraphy from 2002 to 2008. Information collected included demographic features, background diseases, blood smear findings, indications for scintigraphy and outcome. Children with functional hyposplenism were followed until 2012. We found that 34 patients had functional hyposplenism/asplenism. The main indications for scintigraphy in the hyposplenic patients were persistent thrombocytosis and recurrent infections. Associated conditions included immunodeficiencies, autoimmune diseases, malignancies and genetic disorders. Main infections were sinopulmonary infections, bacteraemia and sepsis. The major pathogens were Streptococcus pneumoniae and Haemophilus influenza group A. There was no correlation between the presence of Howell-Jolly bodies in blood smear with clinical disease severity or scintigraphic findings. Repeated scintigraphy showed spontaneous normalisation in 40% of patients. Functional hyposplenism is an important and underdiagnosed immunodeficiency condition in children, associated with various clinical conditions including prolonged unexplained thrombocytosis, immune deficiency and autoimmunity. Technetium-99m sulphur colloid scintigraphy is the method of choice for evaluating splenic function.

Abstract No. 311 - Coil embolization of the splenic artery: long-term impact on splenic volume

Purpose Maintenance of splenic function is often a concern when choosing the appropriate treatment for splenic and splenic arterial pathology. Splenic artery embolization is less morbid than splenectomy, but devascularization of the spleen has the potential to have a similar end-result. The purpose of this study is to determine whether coil embolization of the splenic artery results in a significant degree of splenic volume loss based on long-term CT follow-up data. Materials and Methods Between 1/2004 and 1/2012, a total of 148 patients underwent splenic artery embolization at our institution. Of these, 24 patients (13 males, 11 females, mean age 52) had follow-up contrast-enhanced CT imaging greater than 6 months post-procedure. Embolization was performed using coils anywhere from the splenic artery origin to the splenic hilum. The mean time between embolization and last follow up CT was 27.1 months. Pre- and postembolization splenic volumes were calculated with the use of volume rendering software and compared using the paired t-test. Inter-group comparisons were performed using the unpaired t-test. The presence of Howell-Jolly bodies were ascertained on lab tests. Results Splenic artery embolization resulted in a mean splenic volume loss of 15% (p=0.09). Two patients had a splenic volume loss of greater than 50%: one with 67% loss and one with 88% volume loss. The 9 patients with a grade 3-4 splenic laceration demonstrated a 22% mean volume loss compared to 8% in the 15 patients without trauma (p=NS). Patients that underwent distal splenic artery embolization (n=13) demonstrated a 21% volume reduction while patients with proximal embolization (n=11) demonstrated a 4% reduction (p=NS). No patients had Howell-Jolly bodies on most recent lab tests. No splenic abscesses requiring drainage occurred. No patients required repeat embolization or splenectomy. Conclusion Based on CT volumetric analysis, coil embolization of the main splenic artery resulted in only a mild degree of splenic volume loss over the long term, with a mean of 15% decrease in volume.

Prevalence of Howell-Jolly Bodies Caused by Partial Splenic Embolization for Portal Hypertension

Postsplenectomy sepsis (PSS) and overwhelming postsplenectomy infection (OPSI) following splenectomy or the development of hyposplenism are associated with a high mortality rate. The presence of Howell-Jolly bodies (HJBs) in peripheral erythrocytes is attracting attention as a parameter of hyposplenism. To date, whether HJBs appear following partial splenic embolization (PSE) has not been investigated. Therefore, we examined the prevalence of HJBs in patients who have undergone PSE. Whether HJBs were present in 95 patients who underwent PSE between November 2007 and August 2012 was assessed. No serious complications occurred due to PSE; however, 17 of the 95 patients (17.89%) exhibited HJBs during the follow-up. The residual spleen volume and splenic infarction rate did not differ significantly compared to those observed in the HJB-negative group. With the recent increase in the use of autoanalyzers, the opportunities to perform microscopic examinations have been decreasing. Therefore, the presence of HJBs, which can only be confirmed visually, may be overlooked, and the clinical significance of these bodies tends to be disregarded. However, the presence of HJBs is associated with a risk of PSS and OPSI due to hyposplenism. Because HJBs are common in the peripheral erythrocytes of patients who have undergone PSE, irrespective of the residual spleen volume or splenic infarction rate, the presence or absence of HJBs should be assessed visually. In HJB-positive patients, preventing serious infections, for example, by administering the pneumococcal vaccine, is important.

Hyposplenism: Comparison of different methods for determining splenic function

Asplenic patients are at risk for pneumococcal sepsis. Patients with hyposplenic function, such as associated with sickle cell disease (SCD), are also at risk. However, tests to assess splenic function are either unavailable or lacking standardization. The aim of this study was to compare different methods for determining splenic function. Eighteen patients with SCD (i.e., 10 heterozygous (SC) and 8 homozygous (SS) SCD patients), and eight splenectomized patients were compared to 10 controls. All subjects underwent spleen scintigraphy, after which functional splenic volumes (FSV) were calculated. FSV was compared to immunological function and B cell-subsets, as well as phagocytic function represented by the presence of Howell Jolly bodies (HJB) and percentages of pitted red cells (PIT). Heterozygous SCD (SC) patients had increased splenic volumes, but diminished FSV, homozygous SCD (SS) patients were asplenic. Splenectomized and SS patients had a strongly reduced phagocytic and immunological function. SC patients had reduced anti-polysaccharide responses without an increase in PIT. FSV correlated significantly with phagocytic and immunological function. HJB were indicative of splenic dysfunction, HJB absence was not indicative of normal functioning splenic tissue. Although visualizing HJB is methodologically advantageous to PIT, both are valid biomarkers of splenic dysfunction. The amount of non-switched memory B cells is strongly correlated to FSV.

Isolated Congenital Asplenia: A French Nationwide Retrospective Survey of 20 Cases

To better describe the natural history, mode of inheritance, and the epidemiological and clinical features of isolated congenital asplenia, a rare and poorly understood primary immunodeficiency. A French national retrospective survey was conducted in hospital pediatric departments. A definitive diagnosis of ICA was based on the presence of Howell-Jolly bodies, a lack of detectable spleen, and no detectable cardiovascular malformation. The study included 20 patients (12 males and 8 females) from 10 kindreds neither related to each other nor consanguineous. The diagnosis of ICA was certain in 13 cases (65%) and probable in 7 cases (35%). Ten index cases led to diagnosis of 10 additional cases in relatives. Five cases were sporadic and 15 were familial, suggesting autosomal dominant inheritance. Median age was 12 months at first infection (range, 2-516 months), 11 months at diagnosis of asplenia (range, 0-510 months), and 9.9 years at last follow-up (range, 0.7-52 years). Fifteen patients sustained 18 episodes of invasive bacterial infection, caused mainly by Streptococcus pneumoniae (61%). Outcomes were poor, with 9 patients (45%) dying from fulminant infection. ICA is more common than was previously thought, with an autosomal dominant inheritance in at least some kindreds. Relatives of cases of ICA should be evaluated for ICA, as should children and young adults with invasive infection.

Accessory Splenectomy for Relapsed Idiopathic Thrombocytopenic Purpura.

Background: Patients with ITP will frequently relapse following splenectomy. The search for and subsequent removal of accessory spleens remains a common therapeutic option in these patients. Conflicting data limit the interpretation of the current literature regarding the effectiveness of this treatment. We present a single institution study of the outcomes and clinical correlates of response in patients with ITP who underwent an accessory splenectomy (AS)Patients & Methods: The study cohort consisted of a consecutive group of splenectomized patients (pts) with ITP evaluated at the Mayo Clinic between 1960 and 2006 who underwent AS for relapsed disease. Only those patients who met ASH guidelines for diagnosis of ITP were included. Criteria for response after AS at 1 month and at last follow-up were defined as a Complete Response (CR, platelets ≥ 150 x 109/L), a Partial Response (PR, platelets ≥ 30 but < than 150 x 109/L) and No Response (NR, platelets < 30 x 109/L).Results:i.Baseline Patient Characteristics: A total of 14 pts were identified that underwent AS for relapsed ITP -- 4 pediatric pts with a median age at diagnosis of 10 years (range 7–14) and 10 adult pts with a median age at diagnosis of ITP of 41 years (range 20–63). In all cases the accessory spleen was detected by radionuclide imaging. Among pediatric and adults pts, the mean number of therapies attempted prior to AS other than splenectomy was 2.3 (1–5) and 2.4 (1–7); platelet count at AS was 17 x 109/L (11–88), and 16 x 109/L (6–112), and median time from diagnosis to AS was 99.5 mos. (48–288) and 139 mos. (1–269) and respectivelyii.Response to AS in Pediatric pts: All 4 pts had open laparotomy with 1 post-operative complication. Among these pediatric patients 50% (2/4) pts achieved a CR, one a PR and 1 did not respond at 1 month follow up. With a median follow up of 63.5 mos. (16–137), two responders subsequently relapsed (one PR and one CR) at 14 and 6 mos. respectively.iii.Response to AS in Adults: Eight of 10 patients underwent open laparotomy, 3 of whom experienced significant post-operative complications, one resulting in death. The other 2 had laparoscopic AS. A median number of 1 (1–4) splenules was removed. Evidence of a splenectomized state (defined as the presence of Howell-Jolly bodies (HJB) on blood smear) was present in 66% (6/10) of pts pre-operatively and 100% (10/10) post operatively. Overall, 50% (5/10) of pts responded to AS: Two pts achieved a CR, 3 pts had a PR and 5 pts had NR at the initial evaluation period of 1 month. With a median follow-up period of 11 mos. (range 1–265), 3 pts remain in continued remission and two pts have relapsed at 1.6 and 45 mos., respectively and required additional therapy.iv.Clinical Determinants of Response in Adults: Clinical factors suggestive of correlation with response to AS included: female gender (4/5 vs 1/5 in males), favorable response to prednisone at first exposure (5/7 vs 0/3) and absence of HJB prior to AS (3/3 vs 2/6).There was no evidence of correlation between age at diagnosis of ITP or AS, prior response to splenectomy, number of prior therapies, nor volume of splenules.Conclusions : Laparoscopic accessory splenectomy remains a viable treatment option for pts with relapsed ITP following splenectomy, especially in those without HJB on the peripheral smear. However, given the evolving role for novel therapeutic agents, the potential morbidity of this invasive surgical procedure must be weighed against its effectiveness.

Spleen scanning with 99Tcm-labelled red blood cells after splenectomy

In order to correlate the haematological changes which occur after splenectomy, with the presence or absence of residual splenic tissue, spleen scans using 99Tcm-labelled red blood cells were performed in 36 patients who had had a splenectomy. Positive spleen scans were found in 44 per cent (8 out of 18) of patients who had undergone splenectomy for trauma and in 17 per cent (3 out of 18) of patients who had undergone elective splenectomy. No relationship was found between the presence of Howell-Jolly bodies, platelet counts, the levels of IgG, IgM and IgA and the scan result. It is concluded that these findings are due to the presence of splenunculi, whose incidence is more common than the 12 per cent usually quoted.

Persistence of Natural Killer (NK) cell lymphocytosis with hyposplenism without development of leukaemia

BackgroundNatural killer (NK) cell lymphocytosis usually has an indolent course and can progress into massive lymphocytosis with development of cytopenias and neoplastic diseases. NK-cells usually express one or more "NK-associated" antigens (CD16, CD56, CD57). Reactive expansions are seen in autoimmune diseases, viral infections, solid tumours and non-Hodgkin's lymphoma.Case presentationWe report a lady with a benign clinical course over 10 years and persistent CD8+/CD3-/CD57+/CD16+ LGL proliferation with presence of Howell-Jolly bodies (functional hyposplenism), an association not previously described.ConclusionWe discuss the possible causes of clonal expansion and conclude that this may be part of the spectrum of immune dysregulation associated with NK-cell lymphocytosis.

Hyposplenism in alcoholic cirrhosis, facts or artifacts? A comparative analysis with non‐alcoholic cirrhosis and extrahepatic portal venous obstruction

Hyposplenism has been described in patients with alcoholic cirrhosis (AC). However, no data are available regarding hyposplenism in patients with non-alcoholic cirrhosis (NAC) and other forms of portal hypertension such as extrahepatic portal venous obstruction (EHPVO). The aim is to study the splenic functions in patients with AC, NAC, and EHPVO. Splenic functions were assessed consecutively in 22 patients with AC, 21 with NAC, and 23 with EHPVO. The tests included pitted red blood cells (RBC; %) and Howell-Jolly bodies in the peripheral smear. Pitted RBCs > 2% with or without the presence of Howell-Jolly bodies were taken as indicators of hyposplenism. The splenic function in each group was compared with age-matched controls. Hyposplenism was found in 10 (45.45%) patients with AC, six (28.57%) with NAC and one (4.34%) with EHPVO. The mean pitted RBCs were significantly increased in patients with AC (mean 4.93 +/- 1.36% vs control 1.22 +/- 0.17%, P < 0.05), but not so with NAC (2.01 +/- 0.69%) and EHPVO (mean 0.99 +/- 0.1% vs control 0.66 +/- 0.1%, P > 0.05). Howell-Jolly bodies were seen in only four patients. The mean pitted RBCs were significantly higher among patients who were actively consuming alcohol (9.14 +/- 3.35%) compared to those who abstained at least for more than 24 weeks (2.0 +/- 1.3%, P < 0.05). Hyposplenism is more common in AC patients, particularly those who are actively consuming alcohol compared with those who abstain. Patients with NAC have a lower incidence of hyposplenism, while in EHPVO patients, it is uncommon.

Progressive varicella presenting with pain and minimal skin involvement in children with acute lymphoblastic leukemia.

Here we report the experience at the Children's Hospital of Pittsburgh (CHP) with varicella zoster virus (VZV) in children with acute lymphoblastic leukemia (ALL). This record review was prompted by a patient with ALL who died suddenly of varicella hepatitis within 24 hours of presentation with a single skin lesion. We reviewed the medical records of children diagnosed with ALL at the CHP from January 1984 through December 1993, who subsequently developed VZV infection. Of 294 patients aged 0 to 15 years, 41 (14%) were identified as having had 42 episodes of VZV infection. Twenty patients (49%) had received prophylaxis with varicella zoster immunoglobulin (VZIG), and all 39 patients in whom the diagnosis was made premortem were treated with acyclovir. Twenty-nine of the 42 cases (70%) had disease limited to the skin. Thirteen cases (30%) had extracutaneous involvement, and five of these episodes (12% of all cases) ended in death. Risk factors for progressive varicella included age greater than 6 years and intensive immunosuppressive therapy at the time of exposure. Six of eight patients with progressive varicella, including two who died, had received VZIG. The clinical presentation in 10 of 13 patients with progressive disease and in four of five patients who died was dominated by severe abdominal and/or back pain. In seven cases, these symptoms preceded the development of skin lesions by several days, and in six patients were associated with extensive involvement of the spleen by varicella, as demonstrated histopathologically by the presence of Howell-Jolly bodies on peripheral-blood smear or radiographically. No patient with uncomplicated varicella was reported to have had premonitory pain. Recognition of these prodromes and suspicion of varicella even in the absence of skin lesions and even in children with a history of prior disease or VZIG administration should prompt early diagnostic and therapeutic measures.

Evaluation of Automated Reticulocyte Counts and Their Reliability in the Presence of Howell-Jolly Bodies

An automated reticulocyte procedure using a flow cytometer and the fluorescent dye thiazole orange was evaluated for clinical use. The mean reticulocyte count on 118 hematologically healthy adults was 1.56% (standard deviation [SD] 0.54), with virtually no difference in percentage between women and men. The mean absolute values were 68.4 x 10(9)/L (SD 24.6) and 75.7 x 10(9)/L (SD 27.2), respectively. When compared with the standard microscopic technique, the automated method showed excellent correlation (r = 0.98) and greatly improved precision (coefficient of variation [CV] 4.1%) over the manual method (CV 22.8%). Preanalytic storage of blood samples at 4 degrees C for up to 48 hours did not significantly affect results, nor did varying the incubation time of diluted samples from 1/2 to 2 hours. In a group of patients with appreciable numbers of Howell-Jolly bodies, automated reticulocyte counts were spuriously elevated. The difference between the manual and automated counts on these patients approximated the percentage of Howell-Jolly bodies observed on their Wright-Giemsa stained blood smears.

Hepatic amyloidosis (Primary [AL], immunoglobulin light chain): The natural history in 80 patients

Purpose: We wished to study patients with a premortem diagnosis of primary hepatic amyloidosis to determine what clinical and laboratory features might assist in recognizing the disease and assessing prognosis. Patients and methods: A group of 80 patients with liver biopsy proven primary hepatic amyloidosis was followed from diagnosis to death. Results: At presentation, 77 percent of the group had an associated nephrotic syndrome, congestive heart failure, peripheral neuropathy, or orthostatic hypotension. Certain clues suggested the diagnosis of hepatic amyloidosis in patients with liver disease, including the following: (1) proteinuria (88 percent); (2) abnormal serum protein electrophoresis (monoclonal protein or hypogammaglobulinemia, 64 percent); (3) hyposplenism on the peripheral blood smear (62 percent), defined by the presence of Howell-Jolly bodies; and (4) hepatomegaly disproportional to the liver enzyme abnormalities. Liver function tests were not sensitive or specific. Hepatomegaly from amyloid was frequently seen, with normal levels of alkaline phosphatase, aspartate aminotransferase, and bilirubin (32 percent). Myeloma was diagnosed in 11 patients but had no effect on the clinical course. In vitro coagulation abnormalities were common, bleeding was infrequent, and liver biopsy carried a slightly increased risk. The median survival of the entire group was nine months, and projected five- and 10-year survival rates were 13 and 1 percent, respectively. Conclusion: Because survival is poor and no clinical features permit prospective recognition of those patients in whom the disease is likely to have an indolent course, a trial of therapy is warranted in all patients.

Scintigraphic assessment of ectopic splenic tissue localization and function following splenectomy for trauma.

Twenty-three subjects who had a splenectomy as a result of trauma underwent scintigraphic evaluation with a sensitive heat-denatured 99mTc-labeled red blood cells (DRBC). This method enabled detection of ectopic splenic tissue foci (ESTF) as small as 1 X 1 cm in diameter. ESTF splenosis or accessory spleen was detected in 15 cases (65%), a higher incidence than previously reported. The size of the ESTF ranged from 1 X 1 to 5 X 10 cm (0.8-40 cm2), and 53% were less than 2 X 2 cma (3 cm2). A new multiparametric scintigraphic evaluating technique is described, which estimates the quantity of ESTF and its grade of activity, relative to that of the liver. The technique is a highly efficient assessor of ESTF function. Good correlation was found between the size and activity of the ESTF and the presence of Howell-Jolly bodies (HJB), but with a low sensitivity for detecting small ESTF. Correlation was low between residual splenic tissue and concentrations of IgM, IgA and IgG immunoglobulins. The 99mTc-DRBC method described is recommended for verification of ESTF existence, localization, and function.

Howell-Jolly Bodies and Splenectomy

To the Editor.— Concerning the question and the reply to determine residual spleen tissue after traumatic splenectomy (1982;247:2037), the presence of Howell-Jolly bodies in peripheral blood erythrocytes strongly supports the absence of spleen. In the absence of Howell-Jolly bodies, there must be some splenic tissue.

Sickle cell disease in Saudi Arabs in early childhood.

Haemoglobin electrophoresis screening of 2341 infants from the oases of eastern Saudi Arabia, performed in an attempt to detect cases early and then to follow up and give better management to patients with sickle cell disease, showed 20% with S-trait and 43 with sickle cell disease (37 HbSS and 6 S-beta(0) thalassaemia). On follow-up from birth (or from 3 months) for a mean of 3 1/2 years there was more morbidity and mortality than in matched Saudi Arab controls, but these rates were lower than for affected black infants in the US or Jamaica. Serial haemoglobin levels were l g/dl lower than for controls; height and weight increases were the same. Mean fetal haemoglobin level was 32% at 4-5 years. Half of a subsample of 23 cases had evidence of coexistent alpha-thalassaemia which appeared to protect against functional asplenia, judged by the presence of Howell-Jolly bodies; however there was no difference in degree of anaemia or clinical course. Early screening is recommended for infants at risk for sickle cell disease, and comprehensive care should be given even if the infant has the less severe type.