scholarly journals Management of thrombosis in paroxysmal nocturnal hemoglobinuria: a clinician’s guide

2016 ◽  
Vol 8 (3) ◽  
pp. 119-126 ◽  
Author(s):  
Morag Griffin ◽  
Talha Munir
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Paroxysmal Nocturnal Haemoglobinuria ◽  
Orphan Disease ◽  
Life Threatening

Paroxysmal nocturnal haemoglobinuria (PNH), an ultra-orphan disease with a prevalence of 15.9 per million in Europe, is a life-threatening disorder, characterized by haemolysis, bone marrow failure and thrombosis. Patients with PNH prior to the availability of eculizumab had a median survival of between 10 and 22 years, with thrombosis accounting for 22–67% of deaths. 29–44% of patients had at least one thrombosis. This paper provides a clinician’s guide to the diagnosis, management and complications of PNH, with an emphasis on thrombosis.

scholarly journals The Management of Paroxysmal Nocturnal Hemoglobinuria—Recent Advances in Diagnosis and Treatment, and New Hope for Patients

2009 ◽  
Vol 02 ◽  
pp. 74
Author(s):  
Hubert Schrezenmeier ◽  
Britta Höchsmann ◽  
◽  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Complement Factor ◽  
Humanized Monoclonal Antibody ◽  
Life Threatening ◽  
Clinical Triad ◽  
Disease Modifying Treatment

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening and debilitating disorder of hematopoiesis. It is characterized by the clinical triad of Coombs-negative acquired extracorpuscular hemolytic anemia, thrombophilia, and bone marrow failure. The sequelae of intravascular hemolysis drastically affect the quality of life of patients. Cytopenia and in particular thrombophilia can cause life-threatening complications. Thromboembolic events are the major cause of death. The only curative treatment for PNH is allogeneic stem cell transplantation from a related or unrelated stem cell donor. Recent reports demonstrated favorable outcomes. Other treatments were generally supportive in nature. Recently, eculizumab, a humanized monoclonal antibody that inhibits complement factor C5, was approved. It is a targeted, disease-modifying treatment of PNH. This article will summarize major advances in the management of PNH during the last year, and in particular will discuss new results of eculizumab, treatment of thrombosis, and stem cell transplantation. Given the new advances there is hope for improved survival of these patients.

Anaemia, cytopenias, and thrombosis in palliative medicine

2015 ◽  
Author(s):  
Nancy Y. Zhu ◽  
Cynthia Wu
Keyword(s):  
Bone Marrow ◽  
End Of Life ◽  
End Of Life Care ◽  
Bone Marrow Failure ◽  
Nutritional Deficiencies ◽  
Adverse Side Effects ◽  
Care Plans ◽  
Life Threatening ◽  
Expected Benefits

Many haematological issues can complicate end-of-life care, including cytopenias and venous thromboembolism (VTE). Anaemia is very common and can significantly impact quality of life; causes include haemorrhage, iron deficiency, nutritional deficiencies, and bone marrow infiltration. Neutropenia from bone marrow failure as a result of disease infiltration or from chemotherapy effects can result in life-threatening infections. Finally, VTE is commonly seen in cancer patients as well as those who require prolonged hospitalization. Symptoms can cause discomfort, mortality is increased, and treatment is associated with major bleeding. Understanding the therapeutic options and their adverse side effects is essential in the management of these complex problems. Despite the presence of effective therapies, it is also important to realize that events such as febrile neutropenia and pulmonary embolism are often seen at the end of life and intervention may not always impact prognosis. The risks of intervention should be weighed against expected benefits when developing appropriate palliative care plans.

NKG2D-Mediated Marrow Injury in Paroxysmal Nocturnal Hemoglobinuria and Its Related Disorders.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3674-3674
Author(s):  
Nobuyoshi Hanaoka ◽  
Tatsuya Kawaguchi ◽  
Kentaro Horikawa ◽  
Shoichi Nagakura ◽  
Sonoko Ishihara ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Cells ◽  
Close Association ◽  
Bone Marrow Failure ◽  
Γδ T Cells ◽  
Refractory Anemia ◽  
Nkg2d Ligands ◽  
Marrow Cells

Abstract Immune mechanism is considered to exert in the pathogenesis of marrow failure in paroxysmal nocturnal hemoglobinuria (PNH), idiopathic aplastic anemia (AA) and myelodysplastic syndromes (MDS); however, the molecular events are unknown. We have currently reported the appearance of NKG2D ligands such as cytomegalovirus glycoprotein UL16 binding proteins (ULBPs) and MHC class I-related chains A and B (MICA/B) on granulocytes and CD34+ marrow cells of some patients with PNH and its related diseases (Hanaoka N, et al. Blood. 2006;107:1184–1191). ULBP and MICA/B are stress-inducible membrane proteins that appear in infection and transformation. The ligands share NKG2D receptor on lymphocytes such as NK, CD8+ T, and γδ T-cells and promote activation of the lymphocytes. Cells expressing the ligands are then deadly injured by NKG2D+ lymphocytes (Groh, PNAS 1996; Cosman, Immunity 2001). Indeed, cells expressing NKG2D ligands were killed in vitro by autologous NKG2D+ lymphocytes of our patients (Hanaoka N, et al. Blood. 2005;106:304a; Blood. 2006;108:295a). In further analysis, ligands were detected on granulocytes in 47 (53%) of 88 patients: 11 (58%) of 19 PNH, 28 (60%) of 47 AA, and 8 (36%) of 22 refractory anemia. Ligands were also detected on immature bone marrow cells in all 11 patients (3 PNH, 5 AA, and 3 refractory anemia) who permitted analysis of their marrow cells. In the patients, it is conceivable that blood cells were exposed to a certain stress to induce NKG2D ligands, leading to NKG2D-mediated marrow injury. We also observed a close association of the ligand expression with pancytopenia and favorable response to immunosuppressive therapy by prospective analysis of 5 patients (3 AA-PNH syndrome and 2 AA) for more than one year up to 5 years. Thus, we here propose that NKG2D-mediated immunity, which drives both NK and T-cells, is critically implicated in the pathogenesis of bone marrow failure of PNH and its related disorders.

Bone Marrow Histology in Patients with Paroxysmal Nocturnal Hemoglobinuria.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4215-4215
Author(s):  
Sandra van Bijnen ◽  
Konnie Hebeda ◽  
Petra Muus
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Aplastic Anemia ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Plasma Cells ◽  
Bone Marrow Failure ◽  
Clone Size ◽  
Immune Mediated ◽  
Lymphoid Nodules ◽  
Pnh Clone

Abstract Abstract 4215 Introduction Paroxysmal Nocturnal Hemoglobinuria (PNH) is a disease of the hematopoietic stem cell (HSC) resulting in a clone of hematopoietic cells deficient in glycosyl phosphatidyl inositol anchored proteins. The clinical spectrum of PNH is highly variable with classical hemolytic PNH at one end, and PNH in association with aplastic anemia (AA/PNH) or other bone marrow failure states at the other end. It is still largely unknown what is causing these highly variable clinical presentations. Immune-mediated marrow failure has been suggested to contribute to the development of a PNH clone by selective damage to normal HSC. However, in classic PNH patients with no or only mild cytopenias, a role for immune mediated marrow failure is less obvious. No series of trephine biopsies has been previously documented of patients with PNH and AA/PNH to investigate the similarities and differences in these patients. Methods We have reviewed a series of trephine biopsies of 41 PNH patients at the time the PNH clone was first detected. The histology was compared of 27 patients with aplastic anemia and a PNH clone was compared to that of 14 patients with classic PNH. Age related cellularity, the ratio between myeloid and erythroid cells (ME ratio), and the presence of inflammatory cells (mast cells, lymphoid nodules and plasma cells) were evaluated. The relation with clinical and other laboratory parameters of PNH was established. Results Classic PNH patients showed a normal or hypercellular marrow in 79% of patients, whereas all AA/PNH patients showed a hypocellular marrow. Interestingly, a decreased myelopoiesis was observed not only in AA/PNH patients but also in 93% of classic PNH patients, despite normal absolute neutrophil counts (ANC ≥ 1,5 × 109/l) in 79% of these patients. The number of megakaryocytes was decreased in 29% of classic PNH patients although thrombocytopenia (< 150 × 109/l) was only present in 14% of the patients. Median PNH granulocyte clone size was 70% (range 8-95%) in classic PNH patients, whereas in AA/PNH patients this was only 10% (range 0.5-90%). PNH clones below 5% were exclusively detected in the AA/PNH group. Clinical or laboratory evidence of hemolysis was present in all classical PNH patients and in 52% of AA/PNH patients and correlated with PNH granulocyte clone size. Bone marrow iron stores were decreased in 71% of classic PNH patients. In contrast, increased iron stores were present in 63% of AA/PNH patients, probably reflecting their transfusion history. AA/PNH patients showed increased plasma cells in 15% of patients and lymphoid nodules in 37%, versus 0% and 11% in classic PNH. Increased mast cells (>2/high power field) were three times more frequent in AA/PNH (67%) than in PNH (21%). Conclusion Classic PNH patients were characterized by a more cellular bone marrow, increased erythropoiesis, larger PNH clones and clinically by less pronounced or absent peripheral cytopenias and more overt hemolysis. Decreased myelopoiesis and/or megakaryopoiesis was observed in both AA/PNH and classic PNH patients, even in the presence of normal peripheral blood counts, suggesting a role for bone marrow failure in classic PNH as well. More prominent inflammatory infiltrates were observed in AA/PNH patients compared to classical PNH patients. Disclosures: No relevant conflicts of interest to declare.

Screening Patients with Myelodysplastic Syndrome and Aplastic Anemia for Paroxysmal Nocturnal Hemoglobinuria Clones: A Retrospective Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3426-3426 ◽  
Author(s):  
Andrew Shih ◽  
Ian H. Chin-Yee ◽  
Ben Hedley ◽  
Mike Keeney ◽  
Richard A. Wells ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retrospective Study ◽  
Aplastic Anemia ◽  
Board Of Directors ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Cell Surface Expression ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Pnh Clone

Abstract Abstract 3426 Introduction: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare disorder due to a somatic mutation in the hematopoietic stem cell. The introduction of highly sensitive flow cytometric and aerolysin testing have shown the presence of PNH clones in patients with a variety of other hematological disorders such as aplastic anemia (AA) and myelodysplasic syndrome (MDS). It is hypothesized that patients with these disorders and PNH clones may share an immunologic basis for marrow failure with relative protection of the PNH clone, due to their lack of cell surface expression of immune accessory proteins. This is supported by the literature showing responsiveness in AA and MDS to immunosuppressive treatments. Preliminary results from a recent multicenter trial, EXPLORE, notes that PNH clones can be seen in 70% of AA and 55% of MDS patients, and therefore there may be utility in the general screening of all patients with bone marrow failure (BMF) syndromes. Furthermore, it has been suggested that the presence of PNH cells in MDS is a predictive biomarker that is clinically important for response to immunosuppressive therapy. Methods: Our retrospective cohort study in a tertiary care center used a high sensitivity RBC and FLAER assay to detect PNH clones as small as 0.01%. Of all patients screened with this method, those with bone marrow biopsy and aspirate proven MDS, AA, or other BMF syndromes (defined as unexplained cytopenias) were analysed. Results from PNH assays were compared to other clinical and laboratory parameters such as LDH. Results: Overall, 102 patients were initially screened over a 12 month period at our center. 30 patients were excluded as they did not have biopsy or aspirate proven MDS, AA, or other BMF syndromes. Of the remaining 72 patients, four patients were found to have PNH clones, where 2/51 had MDS (both RCMD, IPSS 0) [3.92%] and 2/4 had AA [50%]. The PNH clone sizes of these four patients were 0.01%, 0.01%, 0.02%, and 1.7%. None of the MDS patients with known recurrent karyotypic abnormalities had PNH clones present. Only one of the four patients had a markedly increased serum LDH level. Conclusions: Our retrospective study indicates much lower incidence of PNH clones in MDS patients or any patients with BMF syndromes when compared to the preliminary data from the EXPLORE trial. There is also significant disagreement in other smaller cohorts in regards to the incidence of PNH in AA and MDS. Screening for PNH clones in patients with bone marrow failure needs further study before adoption of widespread use. Disclosures: Keeney: Alexion Pharmaceuticals Canada Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wells:Alexion Pharmaceuticals Canada Inc: Honoraria. Sutherland:Alexion Pharmaceuticals Canada Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Different clinical courses with the same findings: two cases of paroxysmal nocturnal hemoglobinuria presenting with thrombocytopenia

2021 ◽  
Vol 15 (3) ◽  
Author(s):  
Volkan Karakuş ◽  
Egemen Kaya ◽  
Yelda Dere ◽  
Fahri Şahin
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Clinical Findings ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Laboratory Findings

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal stem cell disease that manifests with chronic intravascular hemolysis, thrombosis, and bone marrow failure. Various degrees of cytopenias accompany the disease. Although laboratory and clinical findings are similar, the disease may show different courses and require different treatments. Herein, we report two different courses of PNH with similar clinical and laboratory findings.

Establishment of a flow cytometry assay for detecting paroxysmal nocturnal hemoglobinuria-type cells specific to patients with bone marrow failure

2018 ◽  
Vol 97 (12) ◽  
pp. 2289-2297
Author(s):  
Kohei Hosokawa ◽  
Chiharu Sugimori ◽  
Ken Ishiyama ◽  
Hiroyuki Takamatsu ◽  
Hideyoshi Noji ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Flow Cytometry Assay

scholarly journals Paroxysmal Nocturnal Hemoglobinuria: Diagnostic Challenges in Pediatric Patient

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Dharshana Krishnaprasadh ◽  
Inna Kaminecki ◽  
Anna Sechser Perl ◽  
Jonathan Teitelbaum
Keyword(s):  
Bone Marrow ◽  
Small Bowel ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Bone Marrow Failure ◽  
Exploratory Laparotomy ◽  
Recurrent Abdominal Pain ◽  
Histological Evaluation ◽  
Small Vessel Vasculitis ◽  
Wall Thickening ◽  
Erythroid Hyperplasia

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening hematologic stem cell disorder characterized by hemoglobinuria, thrombosis, and tendency for bone marrow failure. The rare incidence of PNH in children, its nonspecific clinical presentation, and occasional absence of hemoglobinuria make the diagnosis challenging. We present a case of a 17-year-old boy who was hospitalized with a history of recurrent abdominal pain, fever, and dark-colored urine. Laboratory tests revealed anemia, thrombocytopenia, and elevated inflammatory markers. Urinalysis was positive for protein and red blood cells, too many to be counted. Complement studies were within normal limits. Abdominal computed tomography showed a segment of the small bowel with wall thickening and signs of possible microperforation. Exploratory laparotomy revealed necrosis of the small bowel, and histological evaluation was suggestive of an autoimmune process with small vessel vasculitis. Bone marrow biopsy showed hypocellular marrow with a decreased number of myeloid cells, normal number of megakaryocytes, and signs of erythroid hyperplasia. Flow cytometry detected deficiency of CD59 leading to the diagnosis of PNH. The patient was treated with eculizumab infusions resulting in significant improvement. This case highlights the need for high clinical suspicion for rare entities such as PNH in patients presenting without hemoglobinuria.

Sign in / Sign up

Export Citation Format

Share Document