Rationale:Dengue fever is capable of inciting the formation of transient polyclonal antibodies directed at red blood cell antigens,resulting in complement-mediated hemolysis,leading to intravascular hemolysis and hemo...Rationale:Dengue fever is capable of inciting the formation of transient polyclonal antibodies directed at red blood cell antigens,resulting in complement-mediated hemolysis,leading to intravascular hemolysis and hemoglobinuria.Patient’s concern:A 12-year-old male patient who recovered from dengue fever a week ago had red blood cell agglutination,spherocytes,and engulfment of red blood cells(erythrophagocytosis)by monocytes and neutrophils on routine hematological peripheral blood smear.The unexpected blood smear results prompted the lab physicians to investigate autoimmune hemolytic anemia,which revealed a monospecific positive direct antiglobulin test for complement(C3d,C3b)and the presence of Donath-Landsteiner antibody.Diagnosis:Paroxysmal cold hemoglobinuria(PCH),secondary to dengue fever.Interventions:Oxygen supplements,antibiotics,intravenous immunoglobulins,steroid therapy,and packed cell transfusions were administered.Outcomes:The patient’s condition was improved following the therapy.Lessons:Post-dengue PCH is a rare complication that requires a thorough peripheral smear examination for erythrophagocytosis,as advanced hematology analyzers fail to detect such findings.展开更多
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemo-lytic disease in which there is a stem cell disorder of clonal nature. Previous studies have demonstrated that the numbers of burst-forming units-erythroid...Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemo-lytic disease in which there is a stem cell disorder of clonal nature. Previous studies have demonstrated that the numbers of burst-forming units-erythroid (BFU-E) and colony-forming units-granulocyte / macrophage (CFU-GM) from bone marrow of PNH patients growing in the medium containing PHA-LCM from the normai donors were more reduced than those of normai bone marrow. The purpose of present study was to investigate if PNH lymphocytes are defective in supporting hematopoiesis in vitro. PHA-LCM from PNH blood was added to the culture medium for the growth of PNH and normai BFU-E and CFU-GM. The numbers of PNH bone marrow BFU-E and CFU-GM in the medium containing PHA-LCM from PNH blood were less than those from normai blood; the numbers of normai bone marrow BFU-E and CFU-GM grown in the medium containing PHA-LCM from PNH blood were more decreased than those from normai blood. The results suggest that diminished numbers of PNH bone marrovv BFU-展开更多
BACKGROUND Idiopathic non-cirrhotic portal hypertension(INCPH)is mainly associated with thrombophilia in Western countries.Paroxysmal nocturnal hemoglobinuria(PNH)is a rare hematologic disease that manifests with hemo...BACKGROUND Idiopathic non-cirrhotic portal hypertension(INCPH)is mainly associated with thrombophilia in Western countries.Paroxysmal nocturnal hemoglobinuria(PNH)is a rare hematologic disease that manifests with hemolytic anemia,thrombosis,and peripheral blood cytopenias.Portal and hepatic venous thrombosis were reported in PNH.A rare case of INCPH complicating PNH is described.CASE SUMMARY A 63-year old woman with a 2-year past medical history of PNH without treatment was admitted because of jaundice and refractory ascites requiring large volume paracentesis.Liver histology revealed portal venopathy with portal fibrosis and sclerosis,nodular regenerative hyperplasia,parenchymal ischemic changes,and focal sinusoidal and perivenular fibrosis without bridging fibrosis or cirrhosis,all indicative of INCPH.The flow cytometry confirmed PNH diagnosis and eculizumab treatment was initiated.Her condition was improved gradually,bilirubin was normalized 6 months following initiation of eculizumab,and 1 year later diuretics were stopped.CONCLUSION Eculizumab improved intravascular hemolysis and reversed clinical manifestations of INCPH in a patient with paroxysmal nocturnal hemoglobinuria.展开更多
The molecular mechanism in the damage of erythrocyte membrane of the cows with hemoglobinuria was studied with the field cases and the group comparison.The field cases were devided into three groups:the hemoglobinuria...The molecular mechanism in the damage of erythrocyte membrane of the cows with hemoglobinuria was studied with the field cases and the group comparison.The field cases were devided into three groups:the hemoglobinuria group(HG),the low phosphorous group(LPG)and the control group(CG).The content of phospholipid constituents in the erythrocyte membrane and the protein constituents in membrane skeleton were determined molecularly and the shape of erythrocyte was examined with the scanning electron microscope.The result showed that:(1)the concentration of phosphatidylethanolamine(PE)in HG was lower significantly than that in LPG and CG;the concentration of sphingomyeline(SM) and phosphatidylcholine(PC)+phosphatidylserine(PS) in HG was significantly lower than that in the other groups;the content of PC+PS was lower and the concentration of SM was higher in LPG with comparing that in CG,the significant positive correlation was observed between the concentration of phosphorus in serum and the concentration of PE,respectively.The significant negative correlation was observed between the content of phosphorus in serum and the content of SM,respectively.(2)the difference of protein constituent in membrane skeleton between LPG and CG was not found,however,the concentration of spectin in band Ⅰ,Ⅱ and the content of protein in band Ⅳ 2 was lower and the concentration of protein in band Ⅲ significantly higher in HG than that in LPG and CG(P<0.01);(3)the form of erythrocyte observed with scanning electron microscope changed from discal to the spinal,to spheric form,to hemolysis ultimately following the reduction of the concentration of phosphorus in serum.It was concluded that the change of the constituent of phospholipid in erythrocyte membrane and protein in membrane skeleton and the form of erythrocyte is the most important factors in hemolysis for hypophosphatemia.展开更多
BACKGROUND Jaundice is a major manifestation of posthepatectomy liver failure,a feared complication after hepatic resection.Herein,we report a case of posthepatectomy jaundice that was not caused by liver failure but ...BACKGROUND Jaundice is a major manifestation of posthepatectomy liver failure,a feared complication after hepatic resection.Herein,we report a case of posthepatectomy jaundice that was not caused by liver failure but by paroxysmal nocturnal hemoglobinuria(PNH)-induced hemolysis.CASE SUMMARY A 56-year-old woman underwent right hepatectomy and biliary tract exploration surgery due to hepatic duct stones.Prior to surgery,the patient was mildly anemic.The direct antiglobulin test was negative.A bone marrow biopsy showed mild histiocyte hyperplasia.After surgery,the patient suffered a progressive increase in serum bilirubin.Meanwhile,the patient developed hemolytic symptoms after blood transfusion.She was ultimately diagnosed with PNH.PNH is a rare bone marrow failure disorder that manifests as complement-dependent intravascular hemolysis with varying severity.After steroid treatment,the patient’s jaundice gradually decreased,and the patient was discharged on the 35th postoperative day.CONCLUSION PNH-induced hemolysis is a rare cause of posthepatectomy jaundice.It should be suspected in patients having posthepatectomy hyperbilirubinemia without other signs of liver failure.Steroid therapy can be considered for the treatment of PNH in such cases.展开更多
BACKGROUND Thrombotic microangiopathy(TMA)is a group of disorders that converge on excessive platelet aggregation in the microvasculature,leading to consumptive thrombocytopenia,microangiopathic hemolysis and ischemic...BACKGROUND Thrombotic microangiopathy(TMA)is a group of disorders that converge on excessive platelet aggregation in the microvasculature,leading to consumptive thrombocytopenia,microangiopathic hemolysis and ischemic end-organ dysfunction.In predisposed patients,TMA can be triggered by many environmental factors.Glucocorticoids(GCs)can compromise the vascular endothelium.However,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of clinicians.Given the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal complication.CASE SUMMARY An elderly Chinese man had a 12-year history of aplastic anemia(AA)and a 3-year history of paroxysmal nocturnal hemoglobinuria(PNH).Three months earlier,methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated hemolysis.Following GC treatment,his platelet counts and hemoglobin levels rapidly decreased.After admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect.However,increasing the GC dose did not alleviate hemolysis,and his cytopenia worsened.Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia.Cluster of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes.In the following days,platelet transfusion was required due to severe thrombocytopenia.Observation of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored proteins.We examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target cells.Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels.The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.CONCLUSION GCs can drive TMA episodes.When thrombocytopenia occurs during GC treatment,TMA should be considered,and GCs should be discontinued.展开更多
BACKGROUND Patients with paroxysmal nocturnal hemoglobinuria(PNH)have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored(GPIanchored)proteins,most of the time resulting from a mutati...BACKGROUND Patients with paroxysmal nocturnal hemoglobinuria(PNH)have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored(GPIanchored)proteins,most of the time resulting from a mutation in the X-linked gene PIGA.We report a patient with PNH resulting from a rare biallelic PIGT mutation on chromosome 20.CASE SUMMARY A 47-year-old man was referred to our hospital for febrile pancytopenia.The patient reported a history of recurrent urticaria and arthralgia and he presented during 3 mo recurrent acute dermo-hypodermitis and aseptic meningitidis.Based on clinical cases published with PIGT-PNH,with clinically typical PNH and autoinflammatory symptoms,we treated our patients with repeated infusions of eculizumab to decrease autoinflammatory symptoms and then we performed an allogeneic stem cell transplantation(allo-SCT)with a mismatched unrelated donor.Our patient experienced no acute Graft vs Host disease(GvHD)and a moderate chronic GvHD and is now considered cured at 24 mo after allo-SCT.CONCLUSION This case report suggests that allo-SCT should be considered to cure PIGT-PNH patients.展开更多
Objective: To evaluate the risk factors for hemoglobinuria and acute kidney injury(AKI) after percutaneous mechanical thrombectomy(MT) with or without catheter-directed thrombolysis(CDT) for iliofemoral deep vein thro...Objective: To evaluate the risk factors for hemoglobinuria and acute kidney injury(AKI) after percutaneous mechanical thrombectomy(MT) with or without catheter-directed thrombolysis(CDT) for iliofemoral deep vein thrombosis(IFDVT).Methods: Patients with IFDVT who had MT with the Angio Jet catheter(group A), MT plus CDT(group B), or CDT alone(group C) from January 2016 to March 2020 were retrospectively evaluated. Hemoglobinuria was monitored throughout the treatment course, and postoperative AKI was assessed by comparing the preoperative(baseline) and postoperative serum creatinine(sCr) levels from the electronic medical records of all patients. AKI was defined as an elevation in the sCr level exceeding 26.5 μmol/L within 72 h after the operation according to the Kidney Disease Improving Global Outcomes criteria.Results: A total of 493 consecutive patients with IFDVT were reviewed, of which 382(mean age, 56 ± 11 years;41% of them were females;97 in group A, 128 in group B, and 157 in group C) were finally analyzed. Macroscopic hemoglobinuria was evident in 44.89% of the patients of the MT groups(101/225, 39 in group A, and 62 in group B), with no significant difference between the groups(P = 0.219), but not in the patients in group C. None of the patients developed AKI(mean sCr difference-2.76 ± 13.80 μmol/L, range =-80.20 to 20.60 μmol/L) within 72h after surgery.Conclusions: Rheolytic MT is an independent risk factor for hemoglobinuria. A proper aspiration strategy, hydration, and alkalization following thrombectomy are particularly favorable for preventing AKI.展开更多
Postpartum hemoglobinuria (PPH) is a sporadic noninfectious syndrome which normally seen in bovine around the world. PPH is most commonly affecting high-productive cows and buffaloes during </span><span style...Postpartum hemoglobinuria (PPH) is a sporadic noninfectious syndrome which normally seen in bovine around the world. PPH is most commonly affecting high-productive cows and buffaloes during </span><span style="font-family:"">the early</span><span style="font-family:""> pregnancy and early lactation period. PPH stand</span><span style="font-family:"">s</span><span style="font-family:""> as a serious threat to the dairy cattle and buffaloes in Afghanistan, Pakistan</span><span style="font-family:"">,</span><span style="font-family:""> and India, affecting </span><span style="font-family:"">a </span><span style="font-family:"">considerable number of animals every year. It is characterized by hemoglobinuria, intravenous <span>hemolysis, severe anemia</span></span><span style="font-family:"">,</span><span style="font-family:""> and death due to anemia and hypoxia. However,</span><span style="font-family:""> the exact mechanism of the mentioned illness is not completely understood. Lots of comprehensive studies have been done and/or still are in progress in order to find the exact causes of intravascular hemolysis that is responsible for hemoglobinuria in the mentioned disease. But, hypophosphatemia in the high productive milking cows during the early stage of milk production is widely confiden</span><span style="font-family:"">t</span><span style="font-family:""> to be associated with PPH. In different part</span><span style="font-family:"">s</span><span style="font-family:""> of the world, many risk factors had been reported to be associated with PPH. Decreasing the level of phosphorous in blood serum, interrupted the phospholipid layers of red blood cells resulting in hemoglobinuria,</span><span style="font-family:""> a</span><span style="font-family:""> decrease in milk production, anorexia</span><span style="font-family:"">,</span><span style="font-family:""> and </span><span style="font-family:"">the </span><span style="font-family:"">death of animals in the cause if remained untreated. Urinalysis and hematology findings are the most commonly suitable diagnostic tools for this disease. Lots of studies have been suggesting that injection of sodium acid phosphate along with important minerals and supportive therapy with an<span>ti-oxidants can be used as </span></span><span style="font-family:"">the </span><span style="font-family:"">therapeutic protocol for the management o</span><span style="font-family:"">f PPH.展开更多
BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution.In approximately 10%-1...BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution.In approximately 10%-15%of patients with severe aplastic anemia(SAA),the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy.In some of these patients,myeloid neoplasms appear during or shortly after immunosuppressive therapy.Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.CASE SUMMARY A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria(PNH).With aggravation of systemic inflammatory symptoms,severe pancytopenia developed,and her hemoglobinuria disappeared.Laboratory findings in cytological,immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for“SAA.”Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches.Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment,and complete hematological remission was achieved within 4 mo of treatment.Frustratingly,the hematological response lasted for only 3 mo,and pancytopenia reemerged.At this time,cytological findings(increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0%of all nucleated hematopoietic cells),immunological findings(increased percentage of cluster of differentiation 34+cells that accounted for 12.28%of all nucleated hematopoietic cells)and molecular biological findings(identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes)revealed that“SAA”had transformed into acute myeloid leukemia with mutated nucleophosmin-1.The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages,as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo.Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis,and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis.The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.CONCLUSION Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis,and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.展开更多
PNH is a rare acquired clonal hematopoietic stem cell disorder characterized by abnormal sensitivity of red blood cells to lysis by complement. It is caused by genetic mutation resulting in deficiency of glycosyl phos...PNH is a rare acquired clonal hematopoietic stem cell disorder characterized by abnormal sensitivity of red blood cells to lysis by complement. It is caused by genetic mutation resulting in deficiency of glycosyl phosphatidylinositol anchor (GPA) for cell membrane proteins including complement regulating proteins CD55 and CD59. PNH tends to be associated with Aplastic Anemia (anemia due to failure of the bone marrow to produce red and white blood cells as well as platelets), Myelodysplastic Syndrome (a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells) or rarely Acute Myeloid Leukemia (AML) (also known as acute nonlymphocytic leukemia, representing a group of clonal hematopoietic stem cell disorders in which both a block in differentiation and unchecked proliferation result in the accumulation of myeloblasts at the expense of normal hematopoietic precursors). Here we report a case and assume possible evolution of PNH into CML (a myeloproliferative malignant clonal disease characterized by presence of fusion BCR/ABL fusion oncogene).展开更多
Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the ne...Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the network.Methods:In this research,the PNH and AA-related genes were screened through Online Mendelian Inheritance in Man(OMIM).The plugins and Cytoscape were used to search literature and build a protein-protein interaction network.Results:The protein-protein interaction network contains two molecular complexes that are five higher than the correlation integral values.The target genes of this study were obtained:CD59,STAT3,TERC,TNF,AKT1,C5AR1,EPO,IL6,IL10 and so on.We also found that many factors regulate biological behaviors:neutrophils,macrophages,vascular endothelial growth factor,immunoglobulin,interleukin,cytokine receptor,interleukin-6 receptor,tumor necrosis factor,and so on.This research provides a bioinformatics foundation for further explaining the mechanism of common development of both.Conclusion:This indicates that the PNH and AA is a complex process regulated by many cellular pathways and multiple genes.展开更多
Objective To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria(PNH)and evaluate their association with clinical manifestations.Methods This study enro...Objective To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria(PNH)and evaluate their association with clinical manifestations.Methods This study enrolled patients with PNH,who had not been treated with complement inhibitors and appeared at Peking Union Medical College Hospital from February 2021 to February 2023.The clinical information of participants was retrospectively recorded,and peripheral blood samples were collected.Gender-and age-matched normal controls(NC)were recruited accordingly.展开更多
Paroxysmal nocturnal hemoglobinuria(PNH)is a clonal proliferative disease of hematopoietic stem cells that is clinically characterized by he-molysis,thrombosis,and bone marrow failure.In recent years,significant progr...Paroxysmal nocturnal hemoglobinuria(PNH)is a clonal proliferative disease of hematopoietic stem cells that is clinically characterized by he-molysis,thrombosis,and bone marrow failure.In recent years,significant progress has been made in the complement inhibitor-based treatment of PNH,but the only curative treatment is still hematopoietic stem cell transplantation(HSCT).This article reviews the research progress on al-logeneic HSCT for PNH,systematically summarizes the overview,indica-tions,influencing factors,and treatment outcomes of allogeneic HSCT for PNH,and provides an analysis of HSCT for PNH.展开更多
OBJECTIVE: To learn more about the clinical and laboratory features of patients with paroxysmal nocturnal hemoglobinuria (PNH) diagnosed in the past ten years. METHODS: Clinical and laboratory data for 78 cases of PNH...OBJECTIVE: To learn more about the clinical and laboratory features of patients with paroxysmal nocturnal hemoglobinuria (PNH) diagnosed in the past ten years. METHODS: Clinical and laboratory data for 78 cases of PNH diagnosed from January 1990 to November 1999 in our hospital were analyzed retrospectively. RESULTS: In comparison with PNH cases reported in the 1980s, the newly diagnosed PNH cases showed the following features: (1) older age of disease onset (from 27 to 34 years); more female cases (from 18.5% to 38.5%); more cases without hemoglobinuria (from 24.2% to 38.5%). (2) No positive family hereditary history. (3) Bone marrow dysplasia, abnormal karyotype and negative sister chromatid differentiation were found in 19.2%, 12.2% and 8.9% of the PNH patients, respectively. 12.3% of the patients had bone marrow hypoplasia, and most of them had no hemoglobinuria. Ham's tests were negative in about 34.2% of the cases. CD55 and CD59 on peripheral blood cells were deficient in 100.0% of the cases, suggesting that CD55 and CD59 tests can improve the diagnosis of PNH. (4) Adrenocortical hormone was effective in 83.8% of the patients, 54.2% of whom relapsed within one year. Eight refractory and relapsed patients were treated with low dose chemotherapy (MP therapy: Melphalan 2 - 6 mg x d(-1); Prednisone 0.5 mg x kg(-1) x d(-1)). Five (62.5%) of them showed positive responses. Bone marrow failure and other side effects were not serious in this group of patients. CONCLUSIONS: PNH, an acquired blood disease seen more often among adult males, can be diagnosed more sensitively by hemocyte member CD55 and CD59 tests and treated more effectively with adrenocortical hormone or low dose chemotherapy.展开更多
OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METH...OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.展开更多
OBJECTIVE: To determine whether affected reticulocytes could be a reliable marker for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), we analyzed CD59-antigen expression on the membranes of reticulocytes a...OBJECTIVE: To determine whether affected reticulocytes could be a reliable marker for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), we analyzed CD59-antigen expression on the membranes of reticulocytes and erythrocytes. METHODS: We studied 10 PNH patients and 5 healthy volunteers by two-color flow cytometry with a membrane permeable fluorescent dye, thiazole orange (TO), and anti-CD59 monoclonal antibodies (MoAb). TO was introduced to gate reticulocytes and anti-CD59 MoAb were used to identify glycosylphosphatidylinositol (GPI)-deficient cells. RESULTS: Cells from healthy individuals were only CD59 positive. However, in all PNH patients, CD59-antigen expression could be divided into 3 types: type I cells (CD59 normally positive), type II cells (CD59 partly positive) and type III cells (CD59 negative). The majority of reticulocytes belonged to type III cells, GPI-deficient cells (61.0%). In addition, the percentage of affected reticulocytes was higher than that of erythrocytes. CONCLUSIONS: Analyzing PNH reticulocytes was important, because most patients had elevated numbers of reticulocytes, which represent more closely the recent erythroid output of BM. However, circulating mature erythrocytes were subject to complement-mediated intravascular lysis. Therefore, the percentage of abnormal erythrocytes may not accurately reflect the proliferation rate of normal and abnormal erythroid progenitor cells. Thus, affected reticulocytes could be a more reliable indicator for the diagnosis of PNH than mature erythrocytes.展开更多
文摘Rationale:Dengue fever is capable of inciting the formation of transient polyclonal antibodies directed at red blood cell antigens,resulting in complement-mediated hemolysis,leading to intravascular hemolysis and hemoglobinuria.Patient’s concern:A 12-year-old male patient who recovered from dengue fever a week ago had red blood cell agglutination,spherocytes,and engulfment of red blood cells(erythrophagocytosis)by monocytes and neutrophils on routine hematological peripheral blood smear.The unexpected blood smear results prompted the lab physicians to investigate autoimmune hemolytic anemia,which revealed a monospecific positive direct antiglobulin test for complement(C3d,C3b)and the presence of Donath-Landsteiner antibody.Diagnosis:Paroxysmal cold hemoglobinuria(PCH),secondary to dengue fever.Interventions:Oxygen supplements,antibiotics,intravenous immunoglobulins,steroid therapy,and packed cell transfusions were administered.Outcomes:The patient’s condition was improved following the therapy.Lessons:Post-dengue PCH is a rare complication that requires a thorough peripheral smear examination for erythrophagocytosis,as advanced hematology analyzers fail to detect such findings.
文摘Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemo-lytic disease in which there is a stem cell disorder of clonal nature. Previous studies have demonstrated that the numbers of burst-forming units-erythroid (BFU-E) and colony-forming units-granulocyte / macrophage (CFU-GM) from bone marrow of PNH patients growing in the medium containing PHA-LCM from the normai donors were more reduced than those of normai bone marrow. The purpose of present study was to investigate if PNH lymphocytes are defective in supporting hematopoiesis in vitro. PHA-LCM from PNH blood was added to the culture medium for the growth of PNH and normai BFU-E and CFU-GM. The numbers of PNH bone marrow BFU-E and CFU-GM in the medium containing PHA-LCM from PNH blood were less than those from normai blood; the numbers of normai bone marrow BFU-E and CFU-GM grown in the medium containing PHA-LCM from PNH blood were more decreased than those from normai blood. The results suggest that diminished numbers of PNH bone marrovv BFU-
文摘BACKGROUND Idiopathic non-cirrhotic portal hypertension(INCPH)is mainly associated with thrombophilia in Western countries.Paroxysmal nocturnal hemoglobinuria(PNH)is a rare hematologic disease that manifests with hemolytic anemia,thrombosis,and peripheral blood cytopenias.Portal and hepatic venous thrombosis were reported in PNH.A rare case of INCPH complicating PNH is described.CASE SUMMARY A 63-year old woman with a 2-year past medical history of PNH without treatment was admitted because of jaundice and refractory ascites requiring large volume paracentesis.Liver histology revealed portal venopathy with portal fibrosis and sclerosis,nodular regenerative hyperplasia,parenchymal ischemic changes,and focal sinusoidal and perivenular fibrosis without bridging fibrosis or cirrhosis,all indicative of INCPH.The flow cytometry confirmed PNH diagnosis and eculizumab treatment was initiated.Her condition was improved gradually,bilirubin was normalized 6 months following initiation of eculizumab,and 1 year later diuretics were stopped.CONCLUSION Eculizumab improved intravascular hemolysis and reversed clinical manifestations of INCPH in a patient with paroxysmal nocturnal hemoglobinuria.
文摘The molecular mechanism in the damage of erythrocyte membrane of the cows with hemoglobinuria was studied with the field cases and the group comparison.The field cases were devided into three groups:the hemoglobinuria group(HG),the low phosphorous group(LPG)and the control group(CG).The content of phospholipid constituents in the erythrocyte membrane and the protein constituents in membrane skeleton were determined molecularly and the shape of erythrocyte was examined with the scanning electron microscope.The result showed that:(1)the concentration of phosphatidylethanolamine(PE)in HG was lower significantly than that in LPG and CG;the concentration of sphingomyeline(SM) and phosphatidylcholine(PC)+phosphatidylserine(PS) in HG was significantly lower than that in the other groups;the content of PC+PS was lower and the concentration of SM was higher in LPG with comparing that in CG,the significant positive correlation was observed between the concentration of phosphorus in serum and the concentration of PE,respectively.The significant negative correlation was observed between the content of phosphorus in serum and the content of SM,respectively.(2)the difference of protein constituent in membrane skeleton between LPG and CG was not found,however,the concentration of spectin in band Ⅰ,Ⅱ and the content of protein in band Ⅳ 2 was lower and the concentration of protein in band Ⅲ significantly higher in HG than that in LPG and CG(P<0.01);(3)the form of erythrocyte observed with scanning electron microscope changed from discal to the spinal,to spheric form,to hemolysis ultimately following the reduction of the concentration of phosphorus in serum.It was concluded that the change of the constituent of phospholipid in erythrocyte membrane and protein in membrane skeleton and the form of erythrocyte is the most important factors in hemolysis for hypophosphatemia.
文摘BACKGROUND Jaundice is a major manifestation of posthepatectomy liver failure,a feared complication after hepatic resection.Herein,we report a case of posthepatectomy jaundice that was not caused by liver failure but by paroxysmal nocturnal hemoglobinuria(PNH)-induced hemolysis.CASE SUMMARY A 56-year-old woman underwent right hepatectomy and biliary tract exploration surgery due to hepatic duct stones.Prior to surgery,the patient was mildly anemic.The direct antiglobulin test was negative.A bone marrow biopsy showed mild histiocyte hyperplasia.After surgery,the patient suffered a progressive increase in serum bilirubin.Meanwhile,the patient developed hemolytic symptoms after blood transfusion.She was ultimately diagnosed with PNH.PNH is a rare bone marrow failure disorder that manifests as complement-dependent intravascular hemolysis with varying severity.After steroid treatment,the patient’s jaundice gradually decreased,and the patient was discharged on the 35th postoperative day.CONCLUSION PNH-induced hemolysis is a rare cause of posthepatectomy jaundice.It should be suspected in patients having posthepatectomy hyperbilirubinemia without other signs of liver failure.Steroid therapy can be considered for the treatment of PNH in such cases.
基金Supported by Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University,No.YLJT20201002.
文摘BACKGROUND Thrombotic microangiopathy(TMA)is a group of disorders that converge on excessive platelet aggregation in the microvasculature,leading to consumptive thrombocytopenia,microangiopathic hemolysis and ischemic end-organ dysfunction.In predisposed patients,TMA can be triggered by many environmental factors.Glucocorticoids(GCs)can compromise the vascular endothelium.However,GC-associated TMA has rarely been reported,which may be due to the lack of awareness of clinicians.Given the high frequency of thrombocytopenia during GC treatment,particular attention should be given to this potentially fatal complication.CASE SUMMARY An elderly Chinese man had a 12-year history of aplastic anemia(AA)and a 3-year history of paroxysmal nocturnal hemoglobinuria(PNH).Three months earlier,methylprednisolone treatment was initiated at 8 mg/d and increased to 20 mg/d to alleviate complement-mediated hemolysis.Following GC treatment,his platelet counts and hemoglobin levels rapidly decreased.After admission to our hospital,the dose of methylprednisolone was increased to 60 mg/d in an attempt to enhance the suppressive effect.However,increasing the GC dose did not alleviate hemolysis,and his cytopenia worsened.Morphological evaluation of the marrow smears revealed increased cellularity with an increased percentage of erythroid progenitors without evident dysplasia.Cluster of differentiation(CD)55 and CD59 expression was significantly decreased on erythrocytes and granulocytes.In the following days,platelet transfusion was required due to severe thrombocytopenia.Observation of platelet transfusion refractoriness indicated that the exacerbated cytopenia may have been caused by the development of TMA due to GC treatment because the transfused platelet concentrates had no defects in glycosylphosphatidylinositol-anchored proteins.We examined blood smears and found a small number of schistocytes,dacryocytes,acanthocytes and target cells.Discontinuation of GC treatment resulted in rapidly increased platelet counts and steady increases in hemoglobin levels.The patient’s platelet counts and hemoglobin levels returned to the levels prior to GC treatment 4 weeks after GC discontinuation.CONCLUSION GCs can drive TMA episodes.When thrombocytopenia occurs during GC treatment,TMA should be considered,and GCs should be discontinued.
文摘BACKGROUND Patients with paroxysmal nocturnal hemoglobinuria(PNH)have a clonal population of blood cells deficient in glycosylphosphatidylinositol-anchored(GPIanchored)proteins,most of the time resulting from a mutation in the X-linked gene PIGA.We report a patient with PNH resulting from a rare biallelic PIGT mutation on chromosome 20.CASE SUMMARY A 47-year-old man was referred to our hospital for febrile pancytopenia.The patient reported a history of recurrent urticaria and arthralgia and he presented during 3 mo recurrent acute dermo-hypodermitis and aseptic meningitidis.Based on clinical cases published with PIGT-PNH,with clinically typical PNH and autoinflammatory symptoms,we treated our patients with repeated infusions of eculizumab to decrease autoinflammatory symptoms and then we performed an allogeneic stem cell transplantation(allo-SCT)with a mismatched unrelated donor.Our patient experienced no acute Graft vs Host disease(GvHD)and a moderate chronic GvHD and is now considered cured at 24 mo after allo-SCT.CONCLUSION This case report suggests that allo-SCT should be considered to cure PIGT-PNH patients.
基金supported by the Medical and Health Science and Technology Development Plan of Shandong Province, China (Grant No.2017WS688)。
文摘Objective: To evaluate the risk factors for hemoglobinuria and acute kidney injury(AKI) after percutaneous mechanical thrombectomy(MT) with or without catheter-directed thrombolysis(CDT) for iliofemoral deep vein thrombosis(IFDVT).Methods: Patients with IFDVT who had MT with the Angio Jet catheter(group A), MT plus CDT(group B), or CDT alone(group C) from January 2016 to March 2020 were retrospectively evaluated. Hemoglobinuria was monitored throughout the treatment course, and postoperative AKI was assessed by comparing the preoperative(baseline) and postoperative serum creatinine(sCr) levels from the electronic medical records of all patients. AKI was defined as an elevation in the sCr level exceeding 26.5 μmol/L within 72 h after the operation according to the Kidney Disease Improving Global Outcomes criteria.Results: A total of 493 consecutive patients with IFDVT were reviewed, of which 382(mean age, 56 ± 11 years;41% of them were females;97 in group A, 128 in group B, and 157 in group C) were finally analyzed. Macroscopic hemoglobinuria was evident in 44.89% of the patients of the MT groups(101/225, 39 in group A, and 62 in group B), with no significant difference between the groups(P = 0.219), but not in the patients in group C. None of the patients developed AKI(mean sCr difference-2.76 ± 13.80 μmol/L, range =-80.20 to 20.60 μmol/L) within 72h after surgery.Conclusions: Rheolytic MT is an independent risk factor for hemoglobinuria. A proper aspiration strategy, hydration, and alkalization following thrombectomy are particularly favorable for preventing AKI.
文摘Postpartum hemoglobinuria (PPH) is a sporadic noninfectious syndrome which normally seen in bovine around the world. PPH is most commonly affecting high-productive cows and buffaloes during </span><span style="font-family:"">the early</span><span style="font-family:""> pregnancy and early lactation period. PPH stand</span><span style="font-family:"">s</span><span style="font-family:""> as a serious threat to the dairy cattle and buffaloes in Afghanistan, Pakistan</span><span style="font-family:"">,</span><span style="font-family:""> and India, affecting </span><span style="font-family:"">a </span><span style="font-family:"">considerable number of animals every year. It is characterized by hemoglobinuria, intravenous <span>hemolysis, severe anemia</span></span><span style="font-family:"">,</span><span style="font-family:""> and death due to anemia and hypoxia. However,</span><span style="font-family:""> the exact mechanism of the mentioned illness is not completely understood. Lots of comprehensive studies have been done and/or still are in progress in order to find the exact causes of intravascular hemolysis that is responsible for hemoglobinuria in the mentioned disease. But, hypophosphatemia in the high productive milking cows during the early stage of milk production is widely confiden</span><span style="font-family:"">t</span><span style="font-family:""> to be associated with PPH. In different part</span><span style="font-family:"">s</span><span style="font-family:""> of the world, many risk factors had been reported to be associated with PPH. Decreasing the level of phosphorous in blood serum, interrupted the phospholipid layers of red blood cells resulting in hemoglobinuria,</span><span style="font-family:""> a</span><span style="font-family:""> decrease in milk production, anorexia</span><span style="font-family:"">,</span><span style="font-family:""> and </span><span style="font-family:"">the </span><span style="font-family:"">death of animals in the cause if remained untreated. Urinalysis and hematology findings are the most commonly suitable diagnostic tools for this disease. Lots of studies have been suggesting that injection of sodium acid phosphate along with important minerals and supportive therapy with an<span>ti-oxidants can be used as </span></span><span style="font-family:"">the </span><span style="font-family:"">therapeutic protocol for the management o</span><span style="font-family:"">f PPH.
文摘BACKGROUND Accumulating evidence demonstrates that autoimmune hematopoietic failure and myeloid neoplasms have an intrinsic relationship with regard to clonal hematopoiesis and disease evolution.In approximately 10%-15%of patients with severe aplastic anemia(SAA),the disease phenotype is transformed into myeloid neoplasms following antithymocyte globulin plus cyclosporine-based immunosuppressive therapy.In some of these patients,myeloid neoplasms appear during or shortly after immunosuppressive therapy.Leukemic transformation in SAA patients during anti-tuberculosis treatment has not been reported.CASE SUMMARY A middle-aged Chinese female had a 6-year history of non-SAA and a 2-year history of paroxysmal nocturnal hemoglobinuria(PNH).With aggravation of systemic inflammatory symptoms,severe pancytopenia developed,and her hemoglobinuria disappeared.Laboratory findings in cytological,immunological and cytogenetic analyses of bone marrow samples met the diagnostic criteria for“SAA.”Definitive diagnosis of disseminated tuberculosis was made in the search for infectious niches.Remarkable improvement in hematological parameters was achieved within 1 mo of anti-tuberculosis treatment,and complete hematological remission was achieved within 4 mo of treatment.Frustratingly,the hematological response lasted for only 3 mo,and pancytopenia reemerged.At this time,cytological findings(increased bone marrow cellularity and an increased percentage of myeloblasts that accounted for 16.0%of all nucleated hematopoietic cells),immunological findings(increased percentage of cluster of differentiation 34+cells that accounted for 12.28%of all nucleated hematopoietic cells)and molecular biological findings(identification of somatic mutations in nucleophosmin-1 and casitas B-lineage lymphoma genes)revealed that“SAA”had transformed into acute myeloid leukemia with mutated nucleophosmin-1.The transformation process suggested that the leukemic clones were preexistent but were suppressed in the PNH and SAA stages,as development of symptomatic myeloid neoplasm through acquisition and accumulation of novel oncogenic mutations is unlikely in an interval of only 7 mo.Aggravation of inflammatory stressors due to disseminated tuberculosis likely contributed to the repression of normal and leukemic hematopoiesis,and the relief of inflammatory stressors due to anti-tuberculosis treatment contributed to penetration of neoplastic hematopoiesis.The concealed leukemic clones in the SAA and PNH stages raise the possibility of an inflammatory stress-fueled antileukemic mechanism.CONCLUSION Aggravated inflammatory stressors can repress normal and leukemic hematopoiesis,and relieved inflammatory stressors can facilitate penetration of neoplastic hematopoiesis.
文摘PNH is a rare acquired clonal hematopoietic stem cell disorder characterized by abnormal sensitivity of red blood cells to lysis by complement. It is caused by genetic mutation resulting in deficiency of glycosyl phosphatidylinositol anchor (GPA) for cell membrane proteins including complement regulating proteins CD55 and CD59. PNH tends to be associated with Aplastic Anemia (anemia due to failure of the bone marrow to produce red and white blood cells as well as platelets), Myelodysplastic Syndrome (a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells) or rarely Acute Myeloid Leukemia (AML) (also known as acute nonlymphocytic leukemia, representing a group of clonal hematopoietic stem cell disorders in which both a block in differentiation and unchecked proliferation result in the accumulation of myeloblasts at the expense of normal hematopoietic precursors). Here we report a case and assume possible evolution of PNH into CML (a myeloproliferative malignant clonal disease characterized by presence of fusion BCR/ABL fusion oncogene).
文摘Background:To develop a protein-protein interaction network of Paroxysmal nocturnal hemoglobinuria(PNH)and Aplastic anemia(AA)based on genetic genes and to predict pathways underlying the molecular complexes in the network.Methods:In this research,the PNH and AA-related genes were screened through Online Mendelian Inheritance in Man(OMIM).The plugins and Cytoscape were used to search literature and build a protein-protein interaction network.Results:The protein-protein interaction network contains two molecular complexes that are five higher than the correlation integral values.The target genes of this study were obtained:CD59,STAT3,TERC,TNF,AKT1,C5AR1,EPO,IL6,IL10 and so on.We also found that many factors regulate biological behaviors:neutrophils,macrophages,vascular endothelial growth factor,immunoglobulin,interleukin,cytokine receptor,interleukin-6 receptor,tumor necrosis factor,and so on.This research provides a bioinformatics foundation for further explaining the mechanism of common development of both.Conclusion:This indicates that the PNH and AA is a complex process regulated by many cellular pathways and multiple genes.
文摘Objective To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria(PNH)and evaluate their association with clinical manifestations.Methods This study enrolled patients with PNH,who had not been treated with complement inhibitors and appeared at Peking Union Medical College Hospital from February 2021 to February 2023.The clinical information of participants was retrospectively recorded,and peripheral blood samples were collected.Gender-and age-matched normal controls(NC)were recruited accordingly.
基金supported by the National Key Research and Development Program of China(N2023YFC2507803)Key Program of National Natural Science Foundation of China(82230004 and 82430006)+1 种基金Capital Health Development and Research of Special(2022-1-4082)Beijing Natural Science Foundation(7242154 and 7232188).
文摘Paroxysmal nocturnal hemoglobinuria(PNH)is a clonal proliferative disease of hematopoietic stem cells that is clinically characterized by he-molysis,thrombosis,and bone marrow failure.In recent years,significant progress has been made in the complement inhibitor-based treatment of PNH,but the only curative treatment is still hematopoietic stem cell transplantation(HSCT).This article reviews the research progress on al-logeneic HSCT for PNH,systematically summarizes the overview,indica-tions,influencing factors,and treatment outcomes of allogeneic HSCT for PNH,and provides an analysis of HSCT for PNH.
文摘OBJECTIVE: To learn more about the clinical and laboratory features of patients with paroxysmal nocturnal hemoglobinuria (PNH) diagnosed in the past ten years. METHODS: Clinical and laboratory data for 78 cases of PNH diagnosed from January 1990 to November 1999 in our hospital were analyzed retrospectively. RESULTS: In comparison with PNH cases reported in the 1980s, the newly diagnosed PNH cases showed the following features: (1) older age of disease onset (from 27 to 34 years); more female cases (from 18.5% to 38.5%); more cases without hemoglobinuria (from 24.2% to 38.5%). (2) No positive family hereditary history. (3) Bone marrow dysplasia, abnormal karyotype and negative sister chromatid differentiation were found in 19.2%, 12.2% and 8.9% of the PNH patients, respectively. 12.3% of the patients had bone marrow hypoplasia, and most of them had no hemoglobinuria. Ham's tests were negative in about 34.2% of the cases. CD55 and CD59 on peripheral blood cells were deficient in 100.0% of the cases, suggesting that CD55 and CD59 tests can improve the diagnosis of PNH. (4) Adrenocortical hormone was effective in 83.8% of the patients, 54.2% of whom relapsed within one year. Eight refractory and relapsed patients were treated with low dose chemotherapy (MP therapy: Melphalan 2 - 6 mg x d(-1); Prednisone 0.5 mg x kg(-1) x d(-1)). Five (62.5%) of them showed positive responses. Bone marrow failure and other side effects were not serious in this group of patients. CONCLUSIONS: PNH, an acquired blood disease seen more often among adult males, can be diagnosed more sensitively by hemocyte member CD55 and CD59 tests and treated more effectively with adrenocortical hormone or low dose chemotherapy.
文摘OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.
文摘OBJECTIVE: To determine whether affected reticulocytes could be a reliable marker for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), we analyzed CD59-antigen expression on the membranes of reticulocytes and erythrocytes. METHODS: We studied 10 PNH patients and 5 healthy volunteers by two-color flow cytometry with a membrane permeable fluorescent dye, thiazole orange (TO), and anti-CD59 monoclonal antibodies (MoAb). TO was introduced to gate reticulocytes and anti-CD59 MoAb were used to identify glycosylphosphatidylinositol (GPI)-deficient cells. RESULTS: Cells from healthy individuals were only CD59 positive. However, in all PNH patients, CD59-antigen expression could be divided into 3 types: type I cells (CD59 normally positive), type II cells (CD59 partly positive) and type III cells (CD59 negative). The majority of reticulocytes belonged to type III cells, GPI-deficient cells (61.0%). In addition, the percentage of affected reticulocytes was higher than that of erythrocytes. CONCLUSIONS: Analyzing PNH reticulocytes was important, because most patients had elevated numbers of reticulocytes, which represent more closely the recent erythroid output of BM. However, circulating mature erythrocytes were subject to complement-mediated intravascular lysis. Therefore, the percentage of abnormal erythrocytes may not accurately reflect the proliferation rate of normal and abnormal erythroid progenitor cells. Thus, affected reticulocytes could be a more reliable indicator for the diagnosis of PNH than mature erythrocytes.
