HEREDITARY XEROCYTOSIS: CLINICAL AND BIOLOGICAL PRESENTATION AT DIAGNOSIS IN A RETROSPECTIVE SERIES OF 103 PATIENTS
(Abstract release date: 05/18/17)
EHA Library. garcon l. 06/24/17; 181740; S453
Dr. loic garcon
Contributions
Contributions
Abstract
Abstract: S453
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 12:00 - 12:15
Location: Room N109
Background
Dehydrated hereditary stomatocytosis, also called hereditary xerocytosis (HX), is a dominant non-spherocytic chronic hemolytic anemia characterized by an increased leak of monovalent cations through the red cell membrane leading to dehydration and a shortened red cell survival. HX is difficult to diagnose because of its rarity and the heterogeneity in its clinical presentation.
Aims
Our study aims to characterize the clinical and biological features at HX diagnosis in a retrospective multicentric series of 103 patients from 49 families.
Methods
HX diagnosis was based on the typical left-shifted curve of osmolar gradient ektacytometry performed at CHU Bicêtre from 1993 to 2016. All patients were from European origin. They were referred to our center for: chronic non-spherocytic hemolysis (30), thrombotic events after splenectomy (8), hyperferritinemia with hemolytic features (5), unexplained perinatal oedema (6) or family study (54) after diagnosis in a first-degree probands. PIEZO1 and KCNN4 were analyzed by Sanger sequencing of the exons and intron-exon junctions.
Results
Clinical features: Most of HX diagnosis was made in adults (median age 31.5 years, range 0-88), children less than 10 years representing only 21% of all cases. 71 patients (69%) were already followed for unexplained hemolysis. Hyperferritinemia and/or a chelation therapy were noticed for 26 patients among the 55 for whom this data was available (47%). 19 patients were treated for iron overload: phlebotomy (14) and/or Deferasirox (6) and/or Deferoxamine (6) and/or Deferiprone (1). A perinatal edema history was noted in 17 (16,5%) patients. A history of thrombotic complication was reported in 12 (11,6%) patients, corresponding to a total number of 17 thrombotic events including post-embolic pulmonary hypertension (2), arterial events (3), pulmonary embolism (4), portal thrombosis (4), splenic infarcts (2) and deep venous thrombosis (2). 10 among these 12 patients (83%) were splenectomized, confirming the very high risk of thrombosis after splenectomy in HX. Two patients underwent a thrombotic event without splenectomy: one cerebral stroke and one splenic infarct.
Biological features:The median hemoglobin level was in the normal range: 135 ±19 g/L (range 71-195) with a slight macrocytosis (median MCV: 99 ±8fL) and a marked reticulocytosis (median reticulocyte count: 252 ± 141G/L). Of note, 57 patients (55%) presented a totally compensated hemolysis with a hemoglobin level above 115 g/L. MCHC was in the normal range (median 35 ±1,3g/dL) but was above 36 g/dL for 28 (27,1%) patients. Stomatocytes were noticed on the blood smear in 42 patients over 70 available, numbered as rare (19%), few (60%) or numerous (21%). Genetics could be performed in 45 subjects from 22 distinct families. At least one PIEZO1 mutation was identified in very affected subjects. No KCNN4 mutations were found in these typical ektacytometric forms of HX.
Conclusion
This work represents the largest HX series and highlights the important heterogeneity in the clinical features at diagnosis. One important finding is that most patients were not anemic and presented a compensated hemolysis. In a significant percentage of cases, diagnosis was made in the exploration of extra hematological features including perinatal edema or hemochromatosis occurring despite the absence of any red blood cells transfusion. Moreover, we confirmed the very high risk of thrombotic events after splenectomy, underlining the absolute necessity of formally eliminating HX in any unexplained chronic hemolysis each time splenectomy is considered.
Session topic: 27. Enzymopathies, membranopathies and other anemias
Keyword(s): Red cell, Hemolytic anemia
Abstract: S453
Type: Oral Presentation
Presentation during EHA22: On Saturday, June 24, 2017 from 12:00 - 12:15
Location: Room N109
Background
Dehydrated hereditary stomatocytosis, also called hereditary xerocytosis (HX), is a dominant non-spherocytic chronic hemolytic anemia characterized by an increased leak of monovalent cations through the red cell membrane leading to dehydration and a shortened red cell survival. HX is difficult to diagnose because of its rarity and the heterogeneity in its clinical presentation.
Aims
Our study aims to characterize the clinical and biological features at HX diagnosis in a retrospective multicentric series of 103 patients from 49 families.
Methods
HX diagnosis was based on the typical left-shifted curve of osmolar gradient ektacytometry performed at CHU Bicêtre from 1993 to 2016. All patients were from European origin. They were referred to our center for: chronic non-spherocytic hemolysis (30), thrombotic events after splenectomy (8), hyperferritinemia with hemolytic features (5), unexplained perinatal oedema (6) or family study (54) after diagnosis in a first-degree probands. PIEZO1 and KCNN4 were analyzed by Sanger sequencing of the exons and intron-exon junctions.
Results
Clinical features: Most of HX diagnosis was made in adults (median age 31.5 years, range 0-88), children less than 10 years representing only 21% of all cases. 71 patients (69%) were already followed for unexplained hemolysis. Hyperferritinemia and/or a chelation therapy were noticed for 26 patients among the 55 for whom this data was available (47%). 19 patients were treated for iron overload: phlebotomy (14) and/or Deferasirox (6) and/or Deferoxamine (6) and/or Deferiprone (1). A perinatal edema history was noted in 17 (16,5%) patients. A history of thrombotic complication was reported in 12 (11,6%) patients, corresponding to a total number of 17 thrombotic events including post-embolic pulmonary hypertension (2), arterial events (3), pulmonary embolism (4), portal thrombosis (4), splenic infarcts (2) and deep venous thrombosis (2). 10 among these 12 patients (83%) were splenectomized, confirming the very high risk of thrombosis after splenectomy in HX. Two patients underwent a thrombotic event without splenectomy: one cerebral stroke and one splenic infarct.
Biological features:The median hemoglobin level was in the normal range: 135 ±19 g/L (range 71-195) with a slight macrocytosis (median MCV: 99 ±8fL) and a marked reticulocytosis (median reticulocyte count: 252 ± 141G/L). Of note, 57 patients (55%) presented a totally compensated hemolysis with a hemoglobin level above 115 g/L. MCHC was in the normal range (median 35 ±1,3g/dL) but was above 36 g/dL for 28 (27,1%) patients. Stomatocytes were noticed on the blood smear in 42 patients over 70 available, numbered as rare (19%), few (60%) or numerous (21%). Genetics could be performed in 45 subjects from 22 distinct families. At least one PIEZO1 mutation was identified in very affected subjects. No KCNN4 mutations were found in these typical ektacytometric forms of HX.
Conclusion
This work represents the largest HX series and highlights the important heterogeneity in the clinical features at diagnosis. One important finding is that most patients were not anemic and presented a compensated hemolysis. In a significant percentage of cases, diagnosis was made in the exploration of extra hematological features including perinatal edema or hemochromatosis occurring despite the absence of any red blood cells transfusion. Moreover, we confirmed the very high risk of thrombotic events after splenectomy, underlining the absolute necessity of formally eliminating HX in any unexplained chronic hemolysis each time splenectomy is considered.
Session topic: 27. Enzymopathies, membranopathies and other anemias
Keyword(s): Red cell, Hemolytic anemia
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