BACKGROUND:

Hyperhemolysis syndrome is a serious transfusion reaction mostly reported in association with sickle cell disease, characterized by destruction of both donor and host red blood cells (RBCs) by an unknown mechanism.

CASE REPORT:

A 21-year-old man with sickle cell disease and multiple prior transfusions received two phenotype-matched, compatible RBC units during a brief admission for pain crisis. He developed rapid-onset progressive anemia and hemoglobinuria. Methylprednisolone, erythropoietin, and rituximab were administered. Fifteen days posttransfusion the hemoglobin (Hb) concentration decreased to 3.1 g/dL, with evidence of severe congestive heart failure. No new antibodies were identified. It was felt that his heart failure would not improve without increasing oxygen-carrying capacity. A combination of volume overload, anemia, and hemolysis prompted a novel isovolemic procedure to increase Hb level without removing his own RBCs or causing fluid overload. A cell separator was used operating on the plasma-exchange program, with three cross-match-compatible, washed RBC units as the replacement fluid. After the procedure, there was no evidence of hemolysis. Over the following 6 days, the congestive heart failure resolved, the Hb concentration increased to 7.5 g/dL, and the patient fully recovered. He had a similar event 3 years previously.

CONCLUSIONS:

Plasma-to-RBC replacement may be beneficial for selected patients with life-threatening anemia. This intervention provides immediate improvement in oxygen-carrying capacity, conserving the patient's own RBCs, while avoiding fluid overload. Although blood transfusion may precipitate further hemolysis, this case report describes successful plasma-to-RBC exchange transfusion with concurrent supportive care to offset hemolysis, including corticosteroid, intravenous immunoglobulin, and rituximab.

To analyze the clinical characteristics and risk factors on responses and survival of myelodysplastic syndromes (MDS) patients with paroxysmal nocturnal hemoglobinuria (PNH) clones.The clinical data of 31 MDS cases with PNH clones from October 2004 to June 2012 were retrospectively analyzed to reveal the influence of PNH clone size on responses and survival.①The chromosome karyotypes were analyzed in all patients, 23 patients with normal karyotype, 7 patients with abnormal karyotype [including 3 patients with +8, 2 -Y, 1 del(7q) and 1 Xp+] and 1 patient with no mitosis. 1 patient belonged to low-risk, 27 intermediate-1 risk, 2 intermediate-2 risk and 1 high-risk groups, respectively, according to IPSS. There were significantly statistical differences between responders and nonresponders in terms of infection, ANC, Reticulocyte count and IPSS (P values were 0.049, 0.006, 0.031 and 0.043, respectively). ②The overall responsive rate was 67.7%, no patients progressed to acute leukemia (AL) during median follow-up of 19 months after immunosuppressive therapy (IST). The 3-year and 5-year overall survival rates were 82.7% and 55.1%,respectively. ③According to univariate analysis,age, infection and ANC had significant influence on survival (P values were 0.050, 0.031 and 0.026, respectively). ④The PNH clone size had no significant influence on survival through univariate and COX analyses (P=0.393).MDS patients with PNH clone had less cytogenetic abnormalities, higher probability of response to IST and lower probability of progression to AL; Furthermore, the PNH clone size had no significant influence on response and survival.

Hematopoietic stem cell transplantation (HSCT) is a new window to therapy of many diseases. From March 1991 through April 2011, a total of 3237 HSCT were performed in the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. Here we report 20 years experience of HSCT.Our strategy and aim include the protraction of cytogenetic and molecular biological diagnostic tests, the expansion of the first Iranian Cord Blood Bank (ICBB) and development of the first Iranian Stem Cell Donor Program (ISCDP), and improvement the researches in new therapeutic fields.Totally, 3237 patients were undergone HSCT. Of these transplants, 2205 were allogeneic stem cell transplantation, 1016 autologous and 16 syngeneic. Among 2205 patients who were undergone allogenic-HSCT, 34 received cord blood stem cells as stem cell source for transplantation. It is important to point out that cord blood bank at our center provides reliable storage of cord blood stem cells for our patients. Stem cell transplantation was performed for treatment of various diseases such as acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, beta-thalassemia major, sickle- cell thalassemia, sickle- cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combined immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. Also, we had 220 cellular therapies for post-myocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, Diabetes Mellitus and GvHD treatment. 45 patients were undergone retransplantation in this center.About 78.2% of the patients (2530 of 3237) remained alive between one to 211 months after stem cell transplantation. Nearly, 21.8% (707) of our patients died after stem cell transplantation. The main causes of death were relapse, infection, hemorrhagic cystitis, graft-versus- host disease and etc.In Iran, HSCT has been successfully adapted in routine clinical care. Recently, new methods such as double cord blood and haploidentical transplantation have been used to treat many life-threatening diseases.

Drug-induced immune hemolytic anemia (DIIHA) is a relatively uncommon condition characterized by a sudden drop in hemoglobin, putatively following exposure to drugs. Severe forms of hemolysis characterized by rapidly falling hemoglobin levels and hemoglobinuria are extremely rare. Here we report the case of a patient who exhibited severe DIIHA due to puerarin. Direct antiglobulin testing and drug-dependent antibody testing indicated that the antibodies were drug-dependent and reacted only with RBCs in the presence of the drug. Puerarin is the major isoflavonoid derived from the Chinese medical herb Radix puerariae, and has not yet been widely reported as associated with DIIHA. These results suggest that puerarin may be a cause of severe hemolysis and should be used with caution.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired clonal disorder characterized by chronic complement-mediated hemolysis. The humanized anti-C5 antibody eculizumab binds to the C5 protein and suppresses hemolysis by inhibiting C5b-9 generation. Here, we report on a 27-year-old woman who was found to have PNH in 1997 (at 13 years of age), without subsequent transfusions, thrombosis, or renal disorder. She had been experiencing frequent malaise and fatigue and was sometimes unable to participate in social activities. She had also experienced repeated hemolytic episodes due to infection, and the hemoglobin level had decreased from 7.0 to 5.0 g/dL several times since February 2010. Red blood cell transfusion was necessary, and 6 months later, treatment with eculizumab was started. The hemoglobin level stabilized, and the patient became transfusion-independent. Furthermore, the patient showed significant improvements in fatigue scale scores and quality of life. Six months after the start of eculizumab therapy, the percentage of PNH-type red blood cells was found to have increased from 82.0% (1.95 × 10(12) cells/L) to 89.1% (2.78 × 10(12) cells/L). Furthermore, during treatment with eculizumab, intravascular hemolysis occurred due to a viral infection accompanied by a high fever. We also observed a persistent elevation in reticulocytes and total bilirubin levels, as well as a persistent reduction in haptoglobin levels. Extravascular hemolytic findings were also observed. Because treatment with eculizumab was started at a young age (27 years) and will be continued for many years, careful observation of the patient is required.

A 69-year-old man with advanced heart failure treated with a continuous-flow left ventricular assist device presented for evaluation of dark urine and severe dysphagia. Because of evidence of ongoing intravascular hemolysis with device dysfunction, there was a clinical suspicion for pump thrombosis. He had progressive end-organ dysfunction and was therefore treated with tissue plasminogen activator with prompt resolution in hemolysis and dysphagia. Although symptoms of smooth muscle dystonia could represent worsening heart failure in the setting of device failure, the observation may also be related to intravascular hemolysis as described in the prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria.

Aplastic anemia (AA), myelodysplastic syndrome (MDS), and paroxysmal nocturnal hemoglobinuria (PNH) are rare disorders of bone marrow failure. Once considered distinct entities, these three diseases are now believed to have overlapping pathophysiologies. The Aplastic Anemia and MDS International Foundation, a nonprofit organization that supports patients and families living with bone marrow failure disorders, sponsored a scientific symposium in Bethesda, MD, in March 2012. This report summarizes the symposium presentations by 30 of the world's leading AA, MDS, and PNH researchers on recent findings, current areas of controversy, and recommendations for basic and clinical research to advance the field.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by chronic, complement-mediated hemolysis, frequently leading to debilitating clinical symptoms and life-threatening complications such as thromboembolism (TE). A retrospective analysis was performed on 301 patients from the South Korean National PNH Registry to describe disease burden and identify TE-associated risk factors. TE was identified in 18 % of patients and was associated with increased risk for mortality [odds ratio (OR), 6.85; P < 0.001]. A multivariate analysis showed that PNH patients with elevated hemolysis [lactate dehydrogenase (LDH) levels ≥1.5 times the upper limit of normal (ULN)] at diagnosis were at significantly higher risk for TE than patients with LDH <1.5 × ULN (OR 7.0; P = 0.013). The combination of LDH ≥1.5 × ULN with the clinical symptoms of abdominal pain, chest pain, dyspnea, or hemoglobinuria was associated with a greater increased risk for TE than elevated hemolysis or clinical symptoms alone. Continuous monitoring of these risk factors is critical for identifying PNH patients at risk for morbidities and mortality and allowing early intervention. (clinicaltrials.gov identifier: NCT01224483).