Course Of Paroxysmal Nocturnal Hemoglobinuria Research Articles

COVID-19 vaccination prevents a more severe course and treatment with complement inhibitors reduce worsening hemolysis during the Omicron pandemic in patients with PNH: a single-center study

Objective Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disease characterized by chronic complement-mediated hemolysis. The concentrated outbreak of coronavirus disease 2019 (COVID-19) in China after 6 December 2022, provided an opportunity to observe the disease course of PNH during an active Omicron infection epidemic. Patients and method Patients diagnosed with PNH at Peking Union Medical College Hospital (PUMCH) before 6 December 2022, were followed up until 10 April 2023. Clinical data related to coronavirus infection and hemolysis were recorded. Factors influencing the infection and severity rate of Omicron, as well as hemolysis provocation, were analyzed. Results In total, 131 patients with PNH were included in this retrospective analysis; 87.8% were infected with Omicron. Among them, 15.7% met the criteria for severity, and 1 patient died (0.87%). No protective factors were identified against Omicron infections. However, patients with severe Omicron infection (n = 18) had a lower vaccination rate than those with non-severe infection (n = 97; p = 0.015). Among those infected (n = 115) with Omicron, there was a significant increase in lactate dehydrogenase (LDH) levels compared with those in the uninfected group (n = 16, p = 0.000). Patients with severe infections (n = 18) had even higher LDH increase rates than those without severe infections (n = 97; p = 0.002). 10 (37.0%) patients treated with complement inhibitors developed breakthrough hemolysis (BTH). Patients treated with complement inhibitors (n = 27) exhibited less severe hemolysis than treatment-naïve patients (n = 104; p = 0.003). Conclusions Omicron infection exacerbates hemolytic attacks in patients with PNH. Vaccination helps mitigate the severity of Omicron infection, and using complement inhibitors reduces hemolysis exacerbation.

The Features of COVID-19's Course and the Efficacy of the Gam-COVID-Vac Vaccine in Patients with Paroxysmal Nocturnal Hemoglobinuria.

COVID-19 and other infectious diseases can exacerbate the course of paroxysmal nocturnal hemoglobinuria (PNH). The efficacy and safety of the Gam-COVID-Vac vaccine in patients with PNH has not been adequately studied. A retrospective, observational, cohort, non-comparative study was performed to assess the course of COVID-19 as well as the safety and efficacy of the Gam-COVID-Vac (Sputnik V) vaccine in patients with paroxysmal nocturnal hemoglobinuria (PNH). The study included data from 52 patients with PNH aged 18 to 75 years, 38 of whom received background therapy with eculizumab (Elizaria®) between March 2020 and January 2022. COVID-19 was diagnosed according to the results of PCR testing. The patients were divided into two groups for comparison of the incidence of COVID-19. Group 1 included non-vaccinated patients with PNH, and Group 2 included patients vaccinated prior to the onset of COVID-19. According to vaccination, patients were subdivided into non-vaccinated and vaccinated groups without signs of previous COVID-19 at the beginning of the analyzed period, and patients vaccinated half a year or more after recovery from COVID-19. Testing for anti-SARS-CoV-2 IgG levels was carried out in patients with PNH in the year after their COVID-19. Tests for anti-SARS-CoV-2 RBD IgG levels were performed on vaccinated patients. In total, 28 (53.8%) of the enrolled patients had COVID-19, including asymptomatic forms in 7 (25%) and mild forms in 16 (57%) patients. A total of 22 (42.3%) patients were fully vaccinated with Gam-COVID-Vac, of which 13 (25%) patients were vaccinated without the signs of previous SARS-CoV-2infection, and 9 (17.3%) patients were vaccinated after COVID-19. The number of patients who had COVID-19 was about two times higher in Group 1 (non-vaccinated; 24) (61.5%), whereas in Group 2 (vaccinated), the number of patients with COVID-19 was only 4 (30.8%). The proportion and number of patients who did not have COVID-19 was higher in the group of vaccinated patients (9; 69.2%) than in the group of non-vaccinated patients (15; 38.5%) (p = 0.054). In patients who had been infected with COVID-19, maximum concentrations of anti-SARS-CoV-2 IgG were observed 2-3 months after the acute infection phase, followed by a gradual decline by month 9-10. The mean RBD IgG concentration was higher in the group of patients who had been infected by COVID-19 than in the group of patients without COVID-19 (p = 0.047). Therapy type, including eculizumab, did not have a significant impact on RBD IgG titers (p > 0.05). Hospitalization was required in five (18%) patients, all of whom had breakthrough hemolysis and severe lung damage on CT scans. After the first dose, adverse events (AEs) were reported in 41% of the patients (body temperature increased in 18%; headache in 13.6%; and pain in joints in 4.5%; colitis exacerbation was observed in 4.5%). After the second dose, no AEs were reported. The performed study suggests the possible efficacy and demonstrates the safety of Gam-COVID-Vac (Sputnik V) for the prophylaxis of COVID-19 in patients with PNH who experience immunosuppression due to target therapy.

Comparison of Baseline Clinical Characteristics between Asian Vs. Non-Asian Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) from International PNH Registry

Background: PNH is clinically characterized by intravascular haemolysis, bone marrow failure and thrombosis. Thrombosis and bleeding/serious infections have been reported as major causes of death in PNH. The difference in clinical manifestations of PNH among different races has also been suggested; however, it has not been clearly demonstrated due to rarity of the disease. Objectives: The aim of this study was to clarify whether the racial background of patients with PNH affects their clinical characteristics. Methods: As of June 5, 2017, 4,928 patients were enrolled in the International PNH Registry. After excluding patients with missing data for race, birth date, sex, enrollment date, and/or treatment status with eculizumab, 1,793 patients, who were eculizumab naïve at enrollment and had ≥1% GPI-deficient granulocytes or erythrocytes, were selected for analysis. The study population was divided into two cohorts according to their racial background. The “Asian cohort” consisted of patients with Asian or mixed Asian race (N=246), and the non-Asian cohort consisted of patients with White/Caucasian, Black/African descent and other racial background (N=1547). “Asian cohort” was further divided into “Asians in Asia cohort” (N=202) where the patients were enrolled in the registry from Japan (N=22), South Korea (N=122), Taiwan (N=25), and other Asian countries (N=33), and “Asians in non-Asia cohort” where Asian patients were enrolled from countries outside Asia (N=44). Baseline was defined as enrollment in the registry for all patients. Results: Median (Q1, Q3) disease duration (time from disease start to enrollment) was 1.6 years (0.3, 6.1) for Asian cohort and 1.2 years (0.4, 5.0) for non-Asian cohort. There was no significant difference in sex ratio, median age, and the proportion of patients with a history of bone marrow disorder, aplastic anemia, or myelodysplastic syndrome between the two cohorts. The mean platelet counts at baseline also did not differ significantly between two cohorts. However, Asian cohort had higher LDH value (Median LDH Ratio (Q1, Q3), 2.0 (1.1, 5.6) in the Asian cohort and 1.6 (1.0, 3.8) in the non-Asian cohort; p<0.0001) and mean percent GPI-deficient granulocyte clone (50% vs 43%; p=0.0041) compared with non-Asian cohort. In comparison between Asian in Asia cohort and Asian in non-Asia cohort, the difference in mean percent GPI-deficient granulocyte clone remained significant (53% vs 39%; p=0.036). The proportion of patients with a history of major adverse vascular events (MAVE) at baseline was significantly higher in non-Asian cohort than in Asian-cohort (p=0.0005). The significant differences were also observed in all thrombotic events (TE), venous TE, and non-TE MAVE (Fig. 1). However, the proportion of patients with a history of arterial TE was not significantly different between two cohorts, or in comparison between Asians in Asia cohort and Asians in non-Asia cohort (Fig. 2). The proportion of patients with a history of MAVE/TE at baseline did not differ significantly among Japan, Taiwan, and Korea. Regarding the treatment, Asian cohort had more patients with a history of RBC transfusion (67% vs 52%; p=<0.0001) and corticosteroid therapy (47% vs 34%; p=0.0003) than non-Asian cohort, but less patients with a history of anticoagulant therapy such as heparin or warfarin (9% vs 16%; p=0.002) and cyclosporine/ATG (29% vs 42%; p<0.0001). The difference remained significant in the comparison between Asians in Asia and Asians in non-Asia except for the history of cyclosporine/ATG. Regarding the history of physician-reported symptoms, the proportion of patients with easy bruise/bleeding was higher in non-Asian cohort than Asian cohort (38% vs 20%; p<0.0001). The same difference was also observed between Asians in Asia cohort and Asians in non-Asia cohort (15% vs 41%; p=0.0004). Conclusions: This study with large-scale data base strongly suggested that history of MAVE/TE is higher in non-Asian patients with PNH compared with Asian patients. The comparison between Asians in non-Asia and Asians in Asia cohorts suggested that genetic factors rather than life style and diet play a role in developing MAVE/TE in PNH patients. This study also highlighted that the registry data serve as a valuable resources to understand the clinical course of PNH and thus contribute to establish optimal therapeutic approaches according to patient's racial background. [Display omitted] DisclosuresOkamoto:Chugai Pharmaceutical Co.: Research Funding; Novartis: Research Funding; Bristol-Myers K.K: Research Funding; Pfizer: Research Funding; Bristol-Myers K.K: Honoraria; Astellas: Honoraria; Pfizer Japan: Speakers Bureau; Alexion Pharma G.K.: Honoraria. Sakurai:Alexion: Honoraria. Wilson:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Nishimura:Alexion Pharma GK: Honoraria, Research Funding. Kanakura:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding; Nippon Shinyaku: Research Funding; Pfizer: Research Funding; Kyowa Hakko Kirin: Research Funding; Astellas: Research Funding; Eisai: Research Funding; Shionogi: Research Funding; Bristol Myers: Research Funding; Toyama Chemical: Research Funding; Chugai Pharmaceutical: Research Funding; Fujimotoseiyaku: Research Funding.

The Value of Population Based Data to Study Rare Diseases: An Example Using the Department of Defense Healthcare System

The Value of Population Based Data to Study Rare Diseases: An Example Using the Department of Defense Healthcare System

Eculizumab in pregnancy: a narrative overview.

Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. However, data on the safety of eculizumab in pregnancy are scarce. In this narrative overview, we summarize current evidence on the use of eculizumab during pregnancy in women with PNH, aHUS and HELLP syndrome. Eculizumab is not present in breast milk, and the levels observed in umbilical cord blood samples are not sufficient to affect the concentrations of complement in newborns. Therefore, eculizumab may be regarded as safe in pregnancy. Nonetheless, given that data on eculizumab in pregnancy are limited, it is not possible to completely exclude risks for both mother and fetus in treating PNH, aHUS and HELLP syndrome.

Allo-HCT from MUD/MRD for Paroxysmal Nocturnal Hemoglobinuria - 12 Years of Experience

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal abnormality of hematopoietic stem cell leading to lack of phosphatidylinositol glycoproteins, sensitizing cells to complement-mediated lysis. Despite the efficient symptomatic treatment of hemolytic PNH with eculizumab, allo-HCT is the only curative treatment for the disease, although outcomes presented in the past were controversial.Material and methods: We report 41 allo-HCTs: 37 from MUD and 4 from MRD performed for PNH in 2004-2016. Median age of recipients was 29(20-62) years and donors 30(19-53), median time from diagnosis to allo-HCT was 16(2-307) months. Median size of PNH clone was 80% granulocytes (0.5%-100%). Indication for allo-HCT was PNH with aplastic/hypoplastic bone marrow (19 pts), MDS (2 pts), overlapping MDS/aplasia (3 pts), severe course of PNH with hemolytic crises and transfusion-dependency without access to eculizumab (17 pts). Additional risk factors were Budd-Chiari syndrome and hepatosplenomegaly (1 pt), history of renal insufficiency requiring hemodialyses (2 pts), chronic hepatitis B (1 pt) and C (1 pt). The preparative regimen consisted of treosulfan 3x14 g/m2 plus fludarabine 5x30 mg/m2 (31 pts) or treosulfan 2x10 g/m2 plus cyclophosphamide 4x40 mg/kg (10 pts). Standard GVHD prophylaxis consisted of cyclosporine-A, methotrexate and pre-transplant ATG in MUD-HCT. 2 pts instead of cyclosporine-A received mycophenolate mofetil and tacrolimus. Source of cells was bone marrow (13 pts) or peripheral blood (28 pts) with median 6.3x108NC/kg, 5.7x106CD34+cells/kg, 24.7x107CD3+cells/kg. Myeloablation was complete in all pts with median 9(1-20) days of absolute agranulocytosis <0.1 G/l. Median number of transfused RBC and platelets units was 9(0-16) and 8(2-18).Results: All pts engrafted, median counts of granulocytes 0.5 G/l, platelets 50 G/l and Hb 10 g/dl were achieved on days 17.5(10-33), 16(9-39) and 19.5(11-34). Acute GVHD grade I,II and III was present in 16, 7 and 3 pt, limited and extensive chronic GVHD respectively in 11 and 3 pts. LDH decreased by 73%(5%-91%) in first 30 days indicating disappearance of hemolysis. 100% donor chimerism was achieved in all pts. In 1 patient donor chimerism decreased to 81% what was treated with donor lymphocytes infusion (DLI). 3 patients died, 1 previously hemodialysed pt died on day +102 due to nephrotoxicity complicating adenoviral/CMV hemorrhagic cystitis, two other SAA patients with PNH clone<10% died on days +56 due to severe pulmonary infection and +114 due to aGvHD-III and multi organ failure. Complications in survivors were FUO (10 pts), CMV reactivation (13), VOD (1), neurotoxicity (1), venal thrombosis (1), hemorrhagic cystitis (4) and mucositis (8). 38 pts (92.7%) are alive 4.2 (0.4-12) years post-transplant and are doing well without treatment. Complete disappearance of PNH clone was confirmed by flow cytometry in all surviving pts.Conclusions: Allo-HCT with treosulfan-based conditioning is effective and well tolerated curative therapy for PNH. DisclosuresNo relevant conflicts of interest to declare.

Allo-HSCT from MUD/MRD As a Curative Treatment in Paroxysmal Nocturnal Hemoglobinuria

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal abnormality of the hematopoietic stem cell caused by somatic mutation in the phosphatidylinositol glycan-class A (PIG-A) gene located on the short arm of the X chromosome. Cells with lack phosphatidylinositol glycoproteins are more sensitive to complement-mediated lysis. Despite the efficient symptomatic treatment of hemolytic PNH with eculizumab, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment of the disease, although outcomes presented in the past were controversial.Material and methods: We report 32 allo-HSCTs: 31 from MUD and 1 from MRD performed for PNH in 2004-2014. Median age of recipients was 28 years (range 20-55) and donors 33(19-53), median time from diagnosis to allo-HSCT was 18(2-307) months. Median size of PNH clone was 80% granulocytes (0.41%-98%). Indication for allo-HSCT was aplastic/hypoplastic bone marrow (15 pts), overlapping MDS (2 pts), severe course of PNH with hemolytic crises and transfusion-dependency without access to eculizumab (15 pts). Additional risk factors were Budd-Chiari syndrome and hepatosplenomegaly (1 pt), history of renal insufficiency requiring hemodialyses (2 pts) and chronic hepatitis B (1 pt). The preparative regimen consisted of treosulfan 3x14 g/m2 plus fludarabine 5x30 mg/m2 (25 pts) or treosulfan 2x10 g/m2 plus cyclophosphamide 4x40 mg/kg (7 pts). Standard GVHD prophylaxis consisted of cyclosporine-A, methotrexate and pre-transplant ATG or thymoglobulin in MUD-HSCT. 2 pts instead cyclosporine-A received mycophenolate mofetil and tacrolimus. Source of cells was bone marrow (12 pts) or peripheral blood (20 pts) with median 7.7x10(8)NC/kg, 5.3x10(6)CD34+cells/kg, 24.2x10(6)CD3+cells/kg. Myeloablation was complete in all pts with median 9 days (6-13) of absolute agranulocytosis <0.1 G/l. Median number of transfused RBC and platelets units was 8.5(1-16) and 8(3-18).Results All pts engrafted, median counts of granulocytes 0.5 G/l, platelets 50 G/l and Hb 10 g/dl were achieved on days 17.5(13-33), 17.5(11-39) and 19.5(11-34). Acute GVHD grade I,II and III was present in 14, 6 and 1 pt, limited chronic GVHD in 11 pts. LDH decreased by 77%(5%-91%) in first 30 days indicating disappearance of hemolysis. 100% donor chimerism was achieved in all pts. In 1 patient donor chimerism decreased to 83% what was treated with donor lymphocytes infusion (DLI). 2 patients died, 1 previously hemodialysed pt died on day +102 in a consequence of nephrotoxicity complicating adenoviral/CMV hemorrhagic cystitis and second on day +56 because of severe pulmonary infection. Complications in survivors were FUO (7 pts), CMV reactivation (8), VOD (1), neurotoxicity (1), venal thrombosis (1), hemorrhagic cystitis (1) and mucositis (8). 30 pts (93.7%) are alive 42 months (1-85) post-transplant and are doing well without treatment. Complete disappearance of PNH clone was confirmed by flow cytometry in all surviving pts.Conclusions: Our results indicate, that allo-HSCT with treosulfan-based conditioning is effective and well tolerated curative therapy in PNH. DisclosuresNo relevant conflicts of interest to declare.

Perforation of Ileum Due to Thrombosis in the Course of Paroxysmal Nocturnal Hemoglobinuria: A Case Report

Perforation of Ileum Due to Thrombosis in the Course of Paroxysmal Nocturnal Hemoglobinuria: A Case Report

Fanconi syndrome and chronic kidney disease in paroxysmal nocturnal hemoglobinuria: effect of eculizumab therapy

The association of Fanconi syndrome (FS) and chronic kidney disease (CKD) has been rarely described during the course of paroxysmal nocturnal hemoglobinuria (PNH). We report 2 patients with PNH and CKD associated with proximal tubule dysfunction, which manifested as full-blown FS in one case. In both patients, abnormal iron load within the kidneys was demonstrated by magnetic resonance imaging, which correlated with diffuse and numerous hemosiderin inclusions within proximal tubular cells. After 12 months, eculizumab treatment resulted in significant decrease in the kidney iron load in both cases. Glomerular filtration rate improved in one case and was stabilized in the other, in whom pretreatment kidney biopsy had shown severe extensive interstitial fibrosis. However, symptoms of proximal tubular dysfunction persisted in both patients. These data suggest that hemosiderin deposition in proximal tubules is probably an important mechanism involved in the development of FS, an under recognized and early manifestation of CKD in PNH. Prolonged treatment with eculizumab may improve long-term renal function in PNH patients with CKD.

A Case Presenting with Acute Kidney Injury and Paroxysmal Nocturnal Hemoglobinuria

There may be different clinical presentations of kidney involvement in the course of paroxysmal nocturnal hemoglobinuria, within a spectrum of acute kidney injury, generally due to hemolysis, to chronic kidney disease. Herein we discuss a case of PNH with recurrent hematuria and acute kidney

Strategy for bone marrow transplantation in eculizumab-treated paroxysmal nocturnal hemoglobinuria

Although the recent introduction of eculizumab has had a significant impact on the management of paroxysmal nocturnal hemoglobinuria (PNH), bone marrow transplantation (BMT) remains the only therapeutic option for patients who develop severe aplasia in the clinical course of PNH. However, information regarding BMT for eculizumab-treated PNH patients is scarce, and two major points-the optimal duration of eculizumab therapy, and the optimal BMT conditioning regimen-remain unclear. Here, we describe the clinical course of a PNH patient who was successfully treated with unrelated reduced-intensity BMT. Eculizumab was discontinued 2weeks prior to the initiation of the conditioning regimen, which consisted of fludarabine 180mg/m(2), cyclophosphamide 100mg/kg, rabbit anti-thymocyte globulin 2mg/kg, and TBI 3Gy. Complete donor chimerism was rapidly achieved in association with a rapid decrease in the proportion of PNH erythrocytes. The patient became transfusion-free immediately after BMT, and had no recurrence of hemolysis. The present case suggests that discontinuation of eculizumab before BMT and the use of a highly lymphoablative conditioning regimen may act as a successful treatment strategy in BMT for PNH. Further studies are warranted to evaluate the efficacy and safety of this treatment strategy.

The Favorable Outcome of Allo-HCT from MUD Following Treosulfan-Based Conditioning in Paroxysmal Nocturnal Hemoglobinuria

Although allo-HCT has a potential to cure patients with paroxysmal nocturnal hemoglobinuria (PNH), experience with allo-HCT from matched unrelated donors (MUD) is limited and favorable conditioning treatment for PNH has not been established. We report results of 8 allo-HCTs from MUD (matched in HLA-A,B,C,DR,DQ alleles) performed for PNH with treosulfan-based conditioning in years 2004–2008 in Katowice, Poland. Median age of recipients was 27 years (range 20–35) and donors 33(28–43), median time from diagnosis to transplantation was 20(15–36) months. Median size of PNH clone was 90% granulocytes (range 4%–95%), 4 donors were female and their recipients were male, AB0 incompatibility was minor in 5 pairs, major in 1 and bi-directional in 1 pair. Indication for transplantation despite severe refractory hemolysis with transfusion-dependency (observed in 6 pts) was aplastic or hypoplastic bone marrow and pancytopenia (5 pts), MDS (1 pt), severe course of PNH exacerbating with hemolytic crises (1 pt). Additional risk factors included thrombotic history with Budd-Chiari syndrome and hepatosplenomegaly (1 pt), history of renal insufficiency requiring hemodialyses (1 pt) and additional serological risk factors for hemolysis (1 pt). The preparative regimen consisted of treosulfan 3×14 g/m2 plus fludarabine 5×30 mg/m2 (7 pts) and treosulfan 2×10 g/m2 plus cyclophosphamide 4×40 mg/kg (1 pt). GVHD prophylaxis consisted of thymoglobuline 3×2 mg/kg pretransplant, cyclosporine-A 3 mg/kg/d since day -1 and methotrexate on days 1,3,6,(11). Transplanted cells were harvested from bone marrow (5 donors) and peripheral blood (3 donors) with median numbers 3.0 and 10.9 ×10(8)NC/kg, 3.0 and 6.9 ×10(6)CD34+ cells/kg, 27.5 and 427.7 ×10(6)CD3+ cells/kg, respectively. Myeloablation was complete in all pts with median 10 days (5–14) of absolute agranulocytosis <0.1 G/l. Median number of transfused RBC units was 7 (1–12) and of single-donor platelets units 9 (3–15). All pts engrafted, median granulocyte count of 1.0 G/l was achieved on day 17 (12–22), platelets 50 G/l on day 21 (9–30) and Hb 10 g/dl on day 30 (16–50). No serious acute GVHD was observed, grade I was transiently present in 4 pts and grade II in 3 pts. Transient limited chronic GVHD was observed in 2 pts. Hemolysis gradually decreased. 100% donor chimerism was present in the bone marrow on day +100 at latest in all pts. 1 previously hemodialysed pt died on day 102 in a consequence of nephrotoxicity complicating adenoviral/CMV haemorrhagic cystitis. Complications in survivors included FUO (2 pts), CMV reactivation (2), VOD (1), neurotoxicity (1), venal thrombosis (1), hemorrhagic cystitis (1) and mucositis (1). 7 pts (87.5%) are alive and are currently doing well under ambulatory control with no signs of hemolysis and without need for further hematological treatment, median follow-up is 23 months (2–44). Complete disappearance of PNH clone was confirmed by flow cytometry in all surviving pts. We conclude that MUD allo-HCT with treosulfan-based conditioning can be effectively and relatively safely used in PNH patients and thus it should be considered as a valuable therapeutic option in PNH.

Impact of Magnetic Resonance Imaging on the Diagnosis of Abdominal Complications of Paroxysmal Nocturnal Hemoglobinuria

Magnetic resonance (MR) imaging is a method of choice for assessing vascular patency and parenchymal iron overload. During the course of paroxysmal nocturnal hemoglobinuria (PNH), it is clinically relevant to differentiate abdominal vein thrombosis from hemolytic attacks. Furthermore, the study of the parenchymal MR signal intensity adds informations about the iron storage in kidneys, liver, and spleen. Twelve PNH patients had 14 MR examinations of the abdomen with spin-echo T1- and T2-weighted images and flow-sensitive gradient echo images. Vessels patency and parenchymal signal abnormalities--either focal or diffuse--were assessed. MR imaging showed acute complications including hepatic vein obstruction in five patients, portal vein thrombosis in two patients, splenic infarct in one patient. In one patient treated with androgens, hepatocellular adenomas were shown. Parenchymal iron overload was present in the renal cortex of eleven patients with previous hemolytic attacks. On the first MR study of the remaining patient with an acute abdominal pain showing PNH, no iron overload was present in the renal cortex. Follow-up MR imaging showed the onset of renal cortex iron overload related to multiple hemolytic attacks. Despite the fact that all our patients were transfused, normal signal intensity of both liver and spleen was observed in three of them. MR imaging is particularly helpful for the diagnosis of abdominal complications of PNH.

Visual perseveration following temporal lobe surgery Case report

A 26-year-old man with the diagnosis of paroxysmal nocturnal hemoglobinuria presented with papilledema due to increased intracranial pressure without localizing neurological signs. It is concluded that papilledema and benign intracranial hypertension could result from a cerebral vein thrombosis which can complicate the course of paroxysmal nocturnal hemoglobinuria. This has not been a well-recognized feature of the disease.

Paroxysmal nocturnal hemoglobinuria terminating as erythroleukemia

A case of a patient who developed erythroleukemia 3 years into the course of paroxysmal nocturnal hemoglobinuria (PNH) is presented. A case of erythroleukemia with a positive sucrose lysis test has been reported, but our case appears to be the first with a long clinical course of PNH evolving into erythroleukemia. The association between these two diseases, their possible clonal origin, and how they fit into the myelodysplastic syndromes are discussed.