Effect of splenectomy on destructive bone changes in children with chronic (Type I) Gaucher disease

Ashkenazi, Avraham; Zaizov, Rina; Matoth, Y

doi:10.1007/bf00441877

Cited by 56 publications

(20 citation statements)

References 4 publications

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“…In this large cohort of patients with Gaucher disease, D-dimer levels were significantly correlated with the presence of avascular necrosis but also with splenectomy, which itself has been associated with avascular necrosis, as removal of the spleen as the preferred site of lipid storage may induce infiltration in the bone [18].…”

Section: Discussionmentioning

confidence: 86%

D‐dimer assay in Gaucher disease: Correlation with severity of bone and lung involvement

et al. 2003

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The D-dimer assay as a marker of cross-linked fibrin may also be an indicator of active microvascular thrombosis, even in patients without overt hypercoagulation. In type I Gaucher disease, there is tremendous phenotypic variability that cannot be ascribed solely to different genotypes. Thus, there are no predictive tests to ascertain patients at risk for bone involvement, such as avascular necrosis, or lung disease, particularly pulmonary hypertension, which are two of the major causes of morbidity in Gaucher disease and which are slow to respond to enzyme replacement therapy. Previous studies to correlate these parameters with thrombophilic profiles have not been conclusive. Levels of D-dimers were assayed and compared to the presence of avascular necrosis and abnormally elevated TI gradient among other variables, in 118 unselected adult patients (52 males) with Gaucher disease. Of these, 19 patients had very mild Gaucher disease (Severity Score Index, SSI < 5) and 23 had severe disease (SSI > 15); 29 had avascular necrosis; 37 were splenectomized (due to massive splenomegaly and hypersplenism). As an indirect measure of pulmonary hypertension, TI gradient was used: 90 patients had normal TI gradients (<25 mmHg), and 12 patients had abnormal TI gradients (>30 mmHg). There were significant correlations between D-dimers and avascular necrosis, splenectomy, and elevated TI gradient. Thus, the D-dimer assay may be potentially predictive of bone and lung involvement in Gaucher disease. Am. J. Hematol. 73:236-239, 2003.

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Section: Discussionmentioning

confidence: 86%

D‐dimer assay in Gaucher disease: Correlation with severity of bone and lung involvement

et al. 2003

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“…Macrophage-targeted enzyme replacement therapy with imigucerase is safe and effective in reversing or preventing many manifestations of type 1 GD, including hepatosplenomegaly, marrow infiltration, cytopenias, bone crises and osteopenia [16]. ERT with imiglucerase has virtually eliminated the need for splenectomy, which has been associated with pulmonary hypertension, fatal sepsis, advanced liver disease, and rapid progression of bone disease [17][18][19][20][21][22]. However, ERT cannot reverse established avascular necrosis, advanced bone disease, or hepatic, splenic or marrow fibrosis, underscoring the importance of timely treatment before irreversible complications develop [23].…”

Section: Discussionmentioning

confidence: 99%

Consequences of diagnostic delays in type 1 Gaucher disease: The need for greater awareness among Hematologists–Oncologists and an opportunity for early diagnosis and intervention

et al. 2007

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Gaucher disease (GD) is a progressive macrophage lipidosis capable of causing disabling and life-threatening complications. Anecdotal experiences suggest that GD may go undiagnosed for many years, leading to severe complications that are preventable or reversible by enzyme replacement therapy (ERT) with imiglucerase. We conducted surveys of patients and Hematology-Oncology specialists to assess the frequency of diagnostic delays. Additionally, we report a series of patients who suffered diagnostic delays and as a result developed disabilities including potentially life-threatening manifestations of GD. Of 136 patients surveyed, the average time from first appearance of GD symptoms to final diagnosis was 48.7 ± 123.6 months. More than two-thirds were evaluated and managed by a Hematologist-Oncologist (Hem-Onc). A global survey of 406 Hem-Oncs found that only 20% considered GD in the differential diagnosis for all of its classic symptoms (cytopenia, hepatosplenomegaly, bone pain); the diagnosis considered most likely included leukemia, lymphoma, and multiple myeloma. To illustrate actual consequences of diagnostic delays, we describe 14 patients with GD who suffered from symptoms for up to 10 years before correct diagnosis. Diagnostic delays led to complications that are preventable or reversible with ERT (i.e., avascular necrosis, severe bleeding, chronic bone pain, life-threatening sepsis, pathologic fractures, growth failure, liver pathology). Patients homozygous for N370S mutation in this series were vulnerable to diagnostic delays. In conclusion, prolonged diagnostic delays occur in GD and may result in severe disease manifestations. Our findings suggest that physician education will increase the likelihood of prompt detection of GD and improve its management with ERT with imiglucerase when indicated. Am. J. Hematol. 82:697-701, 2007. V

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“…Consequently, these data do not support the use of splenectomy as an adjunct to lowering the enzyme dose required. In addition, the morbidity associated with splenectomy (19)(20)(21)(22)(23), per se, and in Gaucher disease, in particular (24,25), would indicate that reduction of splenic size by enzyme augmentation would be preferable to the surgical approach for the hematologic management of Gaucher disease patients. Importantly, extensive hepatic fibrosis (case 2) and cirrhosis (case 4) were present in severely involved patients who had splenectomies early in life.…”

Section: Discussionmentioning

confidence: 99%

Enzyme Augmentation in Moderate to Life-Threatening Gaucher Disease

et al. 1992

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ABSTRACT. Gaucher disease type 1 (GD type 1) is the most prevalent lysosomal storage disease and has its highest frequency in the Ashkenazi Jewish population. Deficiency of the enzyme, acid 8-glucosidase, results in the deposition of glucocerebroside primarily in macrophages. The accumulation of such "Gaucher cells" leads to visceromegaly, hepatic and bone marrow dysfunction, hypersplenism, and bony disease. Eleven GD type 1 patients, ages 4-52 y, with moderate to life-threatening manifestations, received 6-12 mo of enzyme augmentation with a macrophage-targeted acid 8-glucosidase preparation.Within 6 mo, substantial increases in Hb levels (mean = +30%) and platelet counts (mean = +39%) were observed. Hepatic and splenic volumes decreased by -20% (range = 3-35%) and -35% (20-52%), respectively. Hematologic and hepatic volume improvements were similar in the splenectomized (n = 4) and nonsplenectomized (n = 7) patient groups. In this patient population, no major differences were observed in the hematologic and visceral improvements with enzyme doses of 30, 50, or 60 IU/kg administered every 2 wk. Normal levels of acid 8-glucosidase activity were present in hepatic autopsy samples from one patient 11 d after enzyme infusion. In comparison, exogenous activity was absent from brain and lung specimens of the same patient. High levels (-10-fold normal) were present in bone marrow samples from two patients obtained at 1 and 11 d after infusions. These studies demonstrate biochemical and clinical improvements by targeted enzyme augmentation in GD type 1, even in far advanced, life-threatening involvement. These and previous studies indicate that earlier intervention in patients with more mild signs may be warranted to obviate the need to rescue extraordinarily ill patients with GD type 1. (Pediatr Res 31': 496-502, 1992) not absence, of the enzyme acid P-glucosidase and results from numerous point mutations at that locus (3

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Effect of splenectomy on destructive bone changes in children with chronic (Type I) Gaucher disease

Cited by 56 publications

References 4 publications

D‐dimer assay in Gaucher disease: Correlation with severity of bone and lung involvement

D‐dimer assay in Gaucher disease: Correlation with severity of bone and lung involvement

Consequences of diagnostic delays in type 1 Gaucher disease: The need for greater awareness among Hematologists–Oncologists and an opportunity for early diagnosis and intervention

Enzyme Augmentation in Moderate to Life-Threatening Gaucher Disease

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