Showing papers in "Journal of hematology in 2016"
TL;DR: A case of severe intravascular hemolysis due to cold agglutinin syndrome that was treated successfully using proximal complement inhibition with commercial C1 esterase inhibitor is presented.
Abstract: Intravascular hemolysis related to cold agglutinin syndrome results from the activation of the classical complement pathway by red blood cell (RBC) surface I/i antigen bound autoantibodies. Despite built-in mechanisms that limit continued downstream complement activation, some patients may develop life-threatening intravascular hemolysis due to the formation of membrane attack complexes. We present a case of severe intravascular hemolysis due to cold agglutinin syndrome that was treated successfully using proximal complement inhibition with commercial C1 esterase inhibitor. The role of complement inhibition in controlling the intravascular hemolysis and resolving the immune dysfunction that leads to the syndrome is discussed. J Hematol. 2016;5(1):30-33 doi: http://dx.doi.org/10.14740/jh242w
16 citations
TL;DR: It is suggested that TLR-7 may play a role in the immune escape from acute leukemia which suggests a potential role for TLR -7 agonists in immunotherapy.
Abstract: Background: Toll-like receptors (TLRs) are agents of innate and adaptive immunity, involved in tumor activation. The expression and functionality of TLR on leukemic cells have seldom been investigated. The aims of the study were to throw some light on the quantitative expression of TLR-7 and TLR-9 on leukemic cells and to compare it with their expression on mononuclear cells of healthy volunteers. Methods: Ninety subjects were included: 30 acute leukemia, 30 chronic leukemia, and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and the expressions of TLR-7 and 9 were detected by real-time PCR. Results: Expression of TLR-7 in acute leukemia was significantly higher than normal controls, while TLR-9 did not show significant difference. TLR-7 and TLR-9 expression in chronic myeloid leukemia (CML) was significantly lower than normal controls. Expression of TLR-7 and TLR-9 in chronic lymphocytic leukemia (CLL) was significantly higher than normal controls. Conclusion: Although TLR-7 and TLR-9 could be expressed in acute leukemia cells, only TLR-7 shows significantly different expression with controls, indicating that TLR-7 may play a role in the immune escape from acute leukemia which suggests a potential role for TLR-7 agonists in immunotherapy. The mRNA expressions of TLR-7 and TLR-9 are significantly reduced in CML patients, which may be the main reason of function defects of PBMCs. The mRNA expressions of TLR-7 and TLR-9 are significantly increased in CLL. This might prove relevant for elucidating the immune mechanisms underlying CLL and define subgroups of patients who might benefit from treatment with specific TLR-7 and TLR-9 ligands. J Hematol. 2016;5(1):17-24 doi: http://dx.doi.org/10.14740/jh249w
7 citations
TL;DR: This case has shown that ET is an effective treatment of pediatric SCIC and should be introduced early on the onset of this severe complication.
Abstract: Pediatric acute liver sickle crisis, also known as sickle cell intrahepatic cholestasis (SCIC), is an uncommon but fatal complication of sickle cell disease observed mainly in patients with homozygous sickle cell anemia. Herein we describe a case of pediatric SCIC treated successfully with manual exchange transfusion (ET). The patient was admitted for jaundice, enlarged liver and signs of hepatic failure, such as hyperbilirubinemia and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. We performed a session of ET in order to reduce the percentage of Hb S to level inferior to 30% which was successfully accomplished. The patient had complete recovery of hepatic function. This case has shown that ET is an effective treatment of pediatric SCIC and should be introduced early on the onset of this severe complication. J Hematol. 2016;5(4):138-141 doi: https://doi.org/10.14740/jh304w
5 citations
TL;DR: After excluding other serious causes of severe new-onset TCP at term, management should be oriented towards securing hemostasis in preparation for delivery without wasting precious time and resources trying to discern between GT and ITP.
Abstract: Thrombocytopenia (TCP) is a common medical finding in obstetric population at term. The majority of new-onset TCP cases are mild, asymptomatic and diagnosed accidentally on routine antenatal screening. The most common causes at term are gestational thrombocytopenia (GT), preeclampsia/HELLP syndrome and immune-mediated thrombocytopenia (ITP). Preeclampsia/HELLP syndrome is accompanied with well-defined clinical characteristics and specific laboratory findings, while the other two are usually asymptomatic and are impossible to distinguish from one another. We encountered a case of new-onset TCP at 40 weeks gestation with negative history and a platelet count of 33 × 10 9 /L, yet, who had a fast spontaneous postpartum recovery. Her second pregnancy was also complicated by TCP of 77 × 10 9 /L at 37 weeks gestation. The newborn platelet count was normal in both instances. She was considered to have GT after a lapse of 4 years, being consistently healthy with normal platelet counts. After excluding other serious causes of severe new-onset TCP at term, management should be oriented towards securing hemostasis in preparation for delivery without wasting precious time and resources trying to discern between GT and ITP. J Hematol. 2016;5(4):142-150 doi: https://doi.org/10.14740/jh308w
4 citations
TL;DR: Analysis of the collected data showed that splenomegaly is of robust clinical and hematologic significance in patients with SAs, and prognostic significance and assume etiopathogenesis of splenomesgaly in SAs are assumed.
Abstract: Background: Sideropenic anemias (SAs) are a group of hypoproliferative anemias characterized by hyposideremia. Although they run an insidiously started slowly progressive course, they are a pointer for an underlying serious disease. Fortunately, in most cases, management of SAs is available, effective and relatively inexpensive. Splenomegaly was reported in patients with SAs with variation in Hacckett's grading and hematological profile. Etiopathogenesis of splenomegaly in SAs was mainly explained as related to the underlying pathologic process of anemia or as a component of the rarely occurring Paterson-Kelly syndrome. Apart from these, etiopathogenesis of splenomegaly in SAs is still a fruitful point for current research. The aim of the present study was to assess splenomegaly in patients with SAs in terms of frequency, clinical and hematological profile of splenomegaly in SAs. Another aim was to assess prognostic significance and assume etiopathogenesis of splenomegaly in SAs. Methods: A prospective study was conducted on 83 patients with SAs and 25 normal sex- and age-matched healthy controls. Patients’ demographic, clinical and hematologic data were collected through thorough history and clinical examination. Splenomegaly was assessed with clinical examination of the study subjects, graded with Hachett’s clinical grading, and then confirmed with ultrasonographic examination. Patients were treated as per the published guidelines for treatment of SAs. Those with splenomegaly were subjected to a strict follow-up plan. Results and conclusion: Analysis of the collected data showed that splenomegaly is of robust clinical and hematologic significance in patients with SAs. J Hematol. 2016;5(3):83-93 doi: http://dx.doi.org/10.14740/jh286w Â
4 citations
TL;DR: Outpatient management of AML patients receiving post-induction chemotherapy was feasible in this group of carefully selected individuals, liberating limited and costly inpatient resources for more appropriate patients.
Abstract: Background: In January 2012, our center developed an ambulatory model for acute myeloid leukemia (AML) patients receiving post-induction chemotherapy. The purpose of this study was to evaluate the feasibility and safety of the outpatient leukemia program at our center. Methods: A retrospective review of all consecutive AML patients receiving a first cycle of consolidation chemotherapy in the outpatient program in 2012 was compared to similarly managed patients primarily in the inpatient setting in 2010. Results: The 2012 cohort spent more days as outpatients in comparison to the 2010 cohort (median (range): 15.5 (0 - 27) vs. 0 (0 - 10), days, P = 0.002). There was no difference between the two cohorts in terms of median overall observation time (time from start of chemotherapy until discharged to clinic), transfusion requirements, days spent neutropenic or days spent febrile. There were no documented episodes of Clostridium difficile , clinically significant bleeding, venous thromboembolism, or death in either cohort. Conclusions: Outpatient management of AML patients receiving post-induction chemotherapy was feasible in this group of carefully selected individuals, liberating limited and costly inpatient resources for more appropriate patients. J Hematol. 2016;5(1):1-7 doi: http://dx.doi.org/10.14740/jh235w
3 citations
TL;DR: To prevent the birth of first thalassemic child by screening pregnant women before 17 weeks of gestation and offering prenatal diagnosis if needed and to increase the awareness among general population about prevention of birth of genetically abnormal child.
Abstract: Background: Hemoglobinopathies are group of diseases characterized by abnormalities both quantitative and qualitative in the production of hemoglobin. In India, major concerned hemoglobinopathic disorders are sickle cell anemia and beta-thalassemia. The aim of the study was to prevent the birth of first thalassemic child by screening pregnant women before 17 weeks of gestation and offering prenatal diagnosis if needed and to increase the awareness among general population about prevention of birth of genetically abnormal child. Methods: Blood samples were tested for complete blood count and hemoglobin electrophoresis. Results: During the study period, a total of 1,083 women were screened; among them 50 women who carried abnormal pattern (beta-thalassemia) were detected. The prevalence of carriers was 4.61%. Apart from I²-thalassemia and hemoglobin E carrier (1.10%), two additional variants were encountered. Conclusion: The data regarding prevalence and distribution can be useful in prevention and management of various hemoglobinopathies. J Hematol. 2016;5(3):99-102 doi: http://dx.doi.org/10.14740/jh297w Â
3 citations
TL;DR: The diverse effects of metformin of relevant therapeutic significance in SCA are deduced, including enhancement of nitric oxide bioavailability, induction of fetal hemoglobin synthesis, attenuation of the inflammatory phenotype and beneficial effects in ischemia/reperfusion injury.
Abstract: Sickle cell anemia (SCA) is one of the most important genetic disorders known to mankind. Even with the impressive advances in medical science, effective treatment and cure remain challenging. Currently available treatments including hydroxyurea, which is the only FDA approved drug for SCA, and hemopoietic stem cell transplantation all have significant limitations, so the search for new therapeutic options continues. Metformin, the traditional antidiabetic drug has recently gained novel attention from accumulating molecular evidence suggesting its pleiotropic effects and new potential applications. Our study of these new understandings of the pharmacodynamics and pleiotropic effects leads us to propose that the drug may be of potential therapeutic benefit in SCA. Our arguments are premised on a logical correlation of the interconnected pathophysiologic mechanisms in SCA with current information on the molecular pharmacodynamics of metformin. We reviewed existing evidence and deduced the diverse effects of metformin of relevant therapeutic significance in SCA, including enhancement of nitric oxide bioavailability, induction of fetal hemoglobin synthesis, attenuation of the inflammatory phenotype and beneficial effects in ischemia/reperfusion injury. Collectively, these considerations lead us to infer that there is reasonable evidence to support potential therapeutic adaptation of metformin in SCA. J Hematol. 2016;5(2):41-48 doi: http://dx.doi.org/10.14740/jh275w
3 citations
TL;DR: The findings indicated that the accuracy of the relative values was always much higher compared to the absolute values and this finding can be explained by “combined errors” which affect absolute cell counts and which are directed for all cell counts of one run into the same direction.
Abstract: Background: For many years, relative values based on 100 quantified cells have been used to assess blood counts in the field of hematology. However, modern blood counting machines have recently made it possible to determine absolute counts. Thus, the current study assessed whether the determination of relative values, based on 100 cells counted, or the determination of absolute values is more accurate in hematology. Methods: To calculate the errors of absolute counts and of quotients, we used two independent methods to determine the errors. For the error calculation, we first performed a Gaussian error calculation. Second we identified the errors using daily control checks and examined the high limit of the actual errors (precision) on the Sysmex XE5000 hematological analyzer. Results: Our findings indicated that the accuracy of the relative values was always much higher compared to the absolute values. Conclusion: This finding can be explained by "combined errors" which affect absolute cell counts and which are directed for all cell counts of one run into the same direction. These types of errors are reduced by quotient formation as shown here for the basophils. The accuracy of the absolute values obtained from the hematology machines of the latest generation was acceptable due to the very high number of cells quantified. J Hematol. 2016;5(2):49-53 doi: http://dx.doi.org/10.14740/jh265w
2 citations
TL;DR: It is suggested that MBL can be identified through routine hospital investigations among elderly subjects and that monoclonal proliferation of B lymphocytes can be detected in an increasing number depending on the progressive improvements in the flow cytometric techniques.
Abstract: Background: Monoclonal B-cell lymphocytosis (MBL) is a benign expansion of clonal B lymphocytes that can be found in the blood of healthy adults, and it has the potential for evolution to chronic lymphocytic leukemia (CLL). MBL is commonly found among elderly population. We aimed to study the frequency among 200 healthy elderly adults who were chosen from general practice, ophthalmology, gynecology, cardiology, dermatology, and orthopedic preoperative patients. The selected individuals had normal hematologic parameters with no evident history of malignant disease. Methods: Blood samples were collected on EDTA, the leukocytes were stained by CD5/CD19 and kappa/lambda/CD19, and then MBL cells were searched for using flow cytometry to detect CD19-positive B-cell population with abnormal kappa/lambda immunoglobulin light chain ratio (> 3 or < 0.3) or disease-specific immunophenotype (IPT), i.e., co-expression of CD5/CD19. Results: The frequency of MBL among the studied samples was 5.5% without significant difference between males and females. The detected frequency found may be related to the sensitivity of the method used. Higher frequencies may be detected if more colors were used to detect more antigens. Conclusion: The study suggested that MBL can be identified through routine hospital investigations among elderly subjects and that monoclonal proliferation of B lymphocytes can be detected in an increasing number depending on the progressive improvements in the flow cytometric techniques. J Hematol. 2016;5(2):54-59 doi: http://dx.doi.org/10.14740/jh269w
2 citations
TL;DR: A 74-year-old female with a previous history of colonic adenocarcinoma presented to a local hospital with a complaint of diarrhea, and responded well to 4 weeks of oral prednisone, with no further hemolysis after discontinuation of prednis one therapy.
Abstract: Delayed hemolytic transfusion reaction (DHTR) is a well-known complication of red blood transfusion. Occasionally, native red cell hemolysis can complicate transfused red cell hemolysis, resulting in a lower post-transfusion hemoglobin. This condition is known as hyperhemolysis syndrome, and is more common after a blood transfusion among patients with sickle cell disease and thalasemia. The occurrence of this syndrome in patients without underlying hemoglobinopathies is rare. A 74-year-old female with a previous history of colonic adenocarcinoma presented to a local hospital with a complaint of diarrhea. She was found to be anemic with hemoglobin of 8.4 g/dL. Her blood was group A, Rh-negative and she received two units of compatible packed red blood cells, after a negative antibody screen was documented. She returned to the hospital 12 days later with complaints of lethargy and fatigue. She was found to be anemic with hemoglobin of 7.8 g/dL. Antibody screening was positive for anti-K antibody. Hemolysis persisted despite receiving K-negative red blood cells, twice during the next 30 days. Both times, her hemoglobin decreased to a level lower than the pre-transfusion value. No other source of bleeding could be identified and a normal hemoglobin electrophoresis was noted. She responded well to 4 weeks of oral prednisone, with no further hemolysis after discontinuation of prednisone therapy. Hyperhemolysis syndrome can occur in patients without hemoglobinopathy, and oral prednisone is an effective treatment. J Hematol. 2016;5(1):38-40 doi: http://dx.doi.org/10.14740/jh266e
TL;DR: Comparing and contrasted calculations for dosing recombinant activated factor VII (rFVIIa) in a morbidly obese patient using estimation of blood volume rather than actual weight or ideal body weight (IBW) compared and contrasted with a specific case report in a critically ill patient with new diagnosis of acquired hemophilia A.
Abstract: This case report compared and contrasted calculations for dosing recombinant activated factor VII (rFVIIa) in a morbidly obese patient using estimation of blood volume rather than actual weight or ideal body weight (IBW). A specific case report in a morbidly obese, critically ill patient with new diagnosis of acquired hemophilia A (AHA) was presented. A 64-year-old morbidly obese patient with AHA required emergent surgery for perforated diverticulitis and peritonitis. The patient required bypass treatment with rFVIIa and was initially dosed based on actual weight of 167 kg (body mass index 61). The patient had a history of deep vein thrombosis and new onset of atrial fibrillation. Based on numerous risk factors for both bleeding and the potential for thromboembolism, the rFVIIa dose was adjusted based on calculations using adjusted body weight and blood volume principles, which decreased dosage by 40%, from 15 to 9 mg. With no active bleeding, rFVIIa dosage was adjusted and rotating thromboelastography testing was added to coagulation parameter monitoring. With this change in dosage, hemostasis was maintained and 132 mg of rFVIIa was saved over an 8-day treatment period. There is very limited literature to direct clinicians on rFVIIa dosing in morbidly obese patients. Since obesity is prevalent in all patient populations, clinicians should consider an estimation of blood volume as a means to dose rFVIIa. Adjusting the dose of rFVIIa to account for changes in blood volume is a physiologic target that should help balance the risk of underdosing using IBW and the risk of overdosing using actual body weight. J Hematol. 2016;5(2):60-66 doi: http://dx.doi.org/10.14740/jh256w
TL;DR: A 77-year-old woman with a history of bronchial asthma presenting with cough and shortness of breath who was initially treated for exacerbation of asthma is described, demonstrating the importance of considering lymphoma as a differential diagnosis of an isolated endobronchial lesion.
Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma (NHL). DLBCL normally presents with nodal involvement in the neck or the abdomen. Extranodal extramedullary disease is seen in up to 40% of cases. However, endobronchial involvement is very rare. Here we describe a 77-year-old woman with a history of bronchial asthma presenting with cough and shortness of breath who was initially treated for exacerbation of asthma. Persistent symptoms lead to further evaluation including CT scan and bronchoscopy, resulting in the diagnosis of DLBCL in this woman presenting as an endobronchial lesion. This case demonstrates the importance of considering lymphoma as a differential diagnosis of an isolated endobronchial lesion. J Hematol. 2016;5(3):106-109 doi: http://dx.doi.org/10.14740/jh283w
TL;DR: The distribution of haplotypes β S and β C and α-thalassemia deletion 3.7 kb is presented in a population sample with SCD from the Occidental Brazilian Amazon, and hematological and biochemical profiles are analyzed.
Abstract: Background: Sickle cell disease (SCD) includes a group of inherited red blood cell disorders. SCD patients vary widely from person to person. We describe β S and β C haplotypes and α-thalassemia 3.7 kb genotypes from SCD patients Fundacao Hospitalar de Hematologia e Hemoterapia do Amazonas, Manaus, AM. Methods: Our survey included 139 HbSS and 11 HbSC patients. Molecular genotypes have been identified by PCR-RFLP and α-thalassemia 3.7 kb deletion by ASO-PCR. Male/female distribution was 42.3%/57.7%. Results: The average age at enrolment was 19.1 years for HbSS and 25.85 years for HbSC. Average fetal hemoglobin was 11.27% for HbSS and 7.86% for HbSC. Anemia in HbSS patients was more severe and hemolysis twice as stronger as HbSC individuals. The frequency distribution of the most common β-globin haplotypes among HbSS patients was 52.5% CAR/CAR, 23.7% CAR/Ben and 18% Ben/Ben. For the HbSC group, the haplotype distribution was 36.3% CAR/CI, 27.3% Benin/CI, 18.2% CAR/CII, 9.1% CAR/CIII and 9.1% Benin/CII. Of the HbSS patients, 13.7% and 2.8% were heterozygous and homozygous for the α-thalassemia 3.7 kb deletion, respectively. No HbSC patients presented the deletion. Conclusions: Here we present the distribution of haplotypes β S and β C and α-thalassemia deletion 3.7 kb in a population sample with SCD from the Occidental Brazilian Amazon. Results have been analyzed in the context of hematological and biochemical profiles. J Hematol. 2016;5(4):123-128 doi: https://doi.org/10.14740/jh310w
TL;DR: Clinicians must maintain vigilance with regard to patients’ neutrophil counts when prescribing treatment with ceftaroline for prolonged periods of time.
Abstract: Ceftaroline is a fifth generation cephalosporin with bactericidal activity against both gram-negative and gram-positive organisms, and is the only cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA). A 23-year-old female with a history of frequent intravenous drug use was admitted to the medical intensive care unit with an MRSA infection resulting in bacterial meningitis, bacteremia and multifocal pneumonia. MRSA therapy was escalated during the admission to a combination of daptomycin and ceftaroline with subsequent clearance of her blood cultures. However, following the introduction of these medications, the patient developed agranulocytosis without parallel involvement of her other cell lines. This agranulocytosis resolved with discontinuation of ceftaroline. Clinicians must maintain vigilance with regard to patients’ neutrophil counts when prescribing treatment with ceftaroline for prolonged periods of time. J Hematol. 2016;5(3):103-105 doi: http://dx.doi.org/10.14740/jh281w
TL;DR: An 80-year-old man suffering from ulcerative colitis and a prostate adenocarcinoma and due to melena, colon biopsies were taken and Laboratory studies showed a normal platelet count and a prolongation of the activated partial thromboplastin time (aPTT).
Abstract: We report an 80-year-old man suffering from ulcerative colitis and a prostate adenocarcinoma. Due to melena, colon biopsies were taken. Diffuse bleeding and a cardiac infarction complicated this procedure. Laboratory studies showed a normal platelet count and a prolongation of the activated partial thromboplastin time (aPTT). Von Willebrand factor (VWF) antigen level and ristocetin cofactor activity were low. Several disorders are known to be associated with acquired von Willebrand disease (AVWD), the commonest being hematoproliferative and cardiovascular disorders. Non-hematologic neoplasms causing AVWD are rarely documented. The underlying mechanisms differ among these disorders or may overlap. These include development of autoantibodies and mechanical destruction of VWF under high shear stress. Absorption of VWF on or inside malignant cells is believed to be the main mechanism in non-hematologic malignancies. In this report, we give a concise overview of the underlying disorders and the mechanisms that we encountered in this complex case. J Hematol. 2016;5(3):110-112 doi: http://dx.doi.org/10.14740/jh284w
TL;DR: This patient is a 29-year-old Caucasian female with HCP who presented with new-onset seizures, diffuse abdominal pain and significant anion gap metabolic acidosis.
Abstract: Hereditary coproporphyria (HCP) by itself can pose significant diagnostic and management difficulties. Together with seizures and renal failure, management can be even more challenging. This poses a dilemma with treatment and requires a unique approach. Our patient is a 29-year-old Caucasian female with HCP who presented with new-onset seizures, diffuse abdominal pain and significant anion gap metabolic acidosis. She had a 7-year history of admissions for severe abdominal pain and was diagnosed with HCP 3 years ago. HCP is a rare disorder that can be complicated by seizures. Many anti-seizure medications can exacerbate acute porphyria attacks. To further complicate management, the anti-seizure drugs of choice in porphyrias are renally excreted and must be adjusted for renal function. Liver transplantation may be a last resort in patients with HCP and seizures. J Hematol. 2016;5(2):67-69 doi: http://dx.doi.org/10.14740/jh258w
TL;DR: The first case of plasmablastic MM leading to acute kidney injury through renal and ureteral infiltration is reported, and it is reported that this is a rare but aggressive form of multiple myeloma.
Abstract: Plasmablatic cell myeloma is a rare but aggressive form of multiple myeloma (MM) with a poor survival. Extramedullary localization of plasmablastic myeloma may be observed in more than two-thirds of patients mainly in the upper digestive tract. Herein, we report the first case of plasmablastic MM leading to acute kidney injury through renal and ureteral infiltration. J Hematol. 2016;5(2):76-78 doi: http://dx.doi.org/10.14740/jh274w
TL;DR: A 69-year-old patient with rheumatoid arthritis for 6 years with ecchymoses, hematomas and macroscopic hematuria, diagnosed with acquired hemophilia A secondary to rheumatic arthritis is treated with methylprednisolone, desmopressin, activated prothrombin complex concentrate and cyclophosphamide, with remission.
Abstract: Acquired hemophilia is a bleeding disorder caused by the development of autoantibodies against plasma coagulation factors, most frequently against the factor VIII, or type A. We report a case of a 69-year-old patient with rheumatoid arthritis for 6 years with ecchymoses, hematomas and macroscopic hematuria, diagnosed with acquired hemophilia A secondary to rheumatoid arthritis, treated with methylprednisolone, desmopressin, activated prothrombin complex concentrate and cyclophosphamide, with remission. J Hematol. 2016;5(1):34-37 doi: http://dx.doi.org/10.14740/jh255w
TL;DR: A 3-year-old boy from Ghana who was found to have hemoglobin S+ Osu-Christiansborg on screening hemoglobin electrophoresis is reported.
Abstract: Hemoglobin Osu-Christiansborg is a rare beta globin chain variant reported mostly in the families of Ghana, though a few cases have been reported in other parts of the world as well. This variant is mostly reported in combination with hemoglobin S but has not been identified to cause an overt sickle cell disease. Here, we report a case of a 3-year-old boy from Ghana who was found to have hemoglobin S+ Osu-Christiansborg on screening hemoglobin electrophoresis. J Hematol. 2016;5(2):74-75 doi: http://dx.doi.org/10.14740/jh273w
TL;DR: An unusual case of IgG 4-RD in a 55-year-old African-American female, who presented with an isolated chronic indurated painful mass in the thigh with a normal IgG4, is presented.
Abstract: IgG4-related disorder (IgG4-RD) is a recently defined systemic disorder characterized by a unique fibro-inflammatory response that involves multiple organs including lymph nodes, salivary, lacrimal glands, and the pancreas as well as other endocrine organs. These organs display lymphoplasmacytic infiltrate with positive staining for IgG4 and high levels of circulating IgG4. We present an unusual case of IgG4-RD in a 55-year-old African-American female, who presented with an isolated chronic indurated painful mass in the thigh with a normal IgG4. Increased awareness with variable manifestations of IgG4-RD will facilitate the diagnosis of this condition. J Hematol. 2016;5(3):113-115 doi: http://dx.doi.org/10.14740/jh287w
TL;DR: MM with AKI was found to be a more aggressive disease, being associated with worse hematological features and increased risk of short-term death, andMM-related renal failure is a medical emergency with the need for rapid diagnosis and prompt supportive care, RRT and MM-directed therapy.
Abstract: Background: This study aimed to describe the baseline renal, histopathological and hematological characteristics and any clinical or biochemical associations of patients with a first coded diagnosis of multiple myeloma (MM). The incidence of renal replacement therapy (RRT) and association with mortality were also investigated. Methods: A retrospective case review was performed to identify 287 MM patients from two European centers. Statistical analyses were performed using SPSS version 2.0 and SAS version 9.2. Results: MM patients referred to renal centers were more likely to be elderly and male. The most common form of renal impairment was acute kidney injury (AKI). The most common paraprotein-associated lesions were myeloma cast nephropathy (MCN, 51%), light chain deposition disease (17%) and AL-amyloidosis (9.4%). MM with AKI was found to be a more aggressive disease, being associated with worse hematological features and increased risk of short-term death. Of the AKI patients requiring RRT, 80% required it at presentation. There was no increased risk of death in the RRT requiring vs. non-RRT requiring cohort. Monoclonal gammopathy of undetermined significance (MGUS) may predispose to renal damage and may increase likelihood of AKI in context of MM. Conclusion: MM-related renal failure is a medical emergency with the need for rapid diagnosis and prompt supportive care, RRT and MM-directed therapy. J Hematol. 2016;5(1):8-16 doi: http://dx.doi.org/10.14740/jh229w
TL;DR: It is proposed that these syndromes result in delayed gastric emptying leading to anorexia, which may be a prodromal sign of an acute attack.
Abstract: Atypical hemolytic uremic syndrome (aHUS) and systemic capillary leak syndrome (SCLS) are rare conditions with high mortality rates. Eculizumab and intravenous immune globulin (IVIG) are improving outcomes and enabling focused supportive care. We present a case of a 57-year-old male who was admitted to the hospital after a 9.07-kg weight loss over 4 weeks. He was subsequently diagnosed with aHUS, monoclonal gammopathy of undetermined significance (MGUS), and SCLS. He suffered from recurrent episodes of flash edema preceded by nausea and regurgitation that required intubation and dialysis. His condition improved after treatment with eculizumab and IVIG. The mechanism that causes anorexia in aHUS and SCLS has not previously been described. We propose that these syndromes result in delayed gastric emptying leading to anorexia, which may be a prodromal sign of an acute attack. J Hematol. 2016;5(2):79-81 doi: http://dx.doi.org/10.14740/jh279w
TL;DR: It is important to consider a possibility of the complication of PTE in the management of AIHA patients, as severe AIHA and PTE share common symptoms.
Abstract: A 56-year-old woman presented with mixed-type autoimmune hemolytic anemia (AIHA) and was complicated with deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE). While DVT/PTE has been recently recognized as a complication of AIHA, there has been no reported case of mixed-type AIHA complicated with DVT/PTE. Mixed-type AIHA is a rare subtype of AIHA and both warm- and cold-type autoantibodies were assumed to have contributed to the development of VTE/PTE in the present case. As severe AIHA and PTE share common symptoms, it is important to consider a possibility of the complication of PTE in the management of AIHA patients. J Hematol. 2016;5(2):70-73 doi: http://dx.doi.org/10.14740/jh263w
TL;DR: A 66-year-old man with a long-standing history of squamous cell carcinoma of the head and neck region who developed nodular-sclerosing subtype of classical Hodgkin lymphoma and primary cutaneous CD8-positive, cytotoxic variant of mycosis fungoides over a 1-year period of time is described.
Abstract: We describe a 66-year-old man with a long-standing history of squamous cell carcinoma of the head and neck region who developed nodular-sclerosing subtype of classical Hodgkin lymphoma and primary cutaneous CD8-positive, cytotoxic variant of mycosis fungoides over a 1-year period of time. Within a few months of his diagnosis of primary cutaneous T-cell lymphoma, he developed systemic involvement of T-cell lymphoma in an axillary lymph node, bone marrow and lung. Interestingly, his lung infiltrates had an Ebstein-Barr virus (EBV)-negative, mature clonal plasma cell proliferations intermingled with neoplastic T cells. It showed cytoplasmic κ light chain restriction by in situ hybridization and also revealed clonal immunoglobulin light chain rearrangements in both κ and λ. No morphological or immunohistochemical evidence of his prior Hodgkin lymphoma was identified in the bone marrow or lung. In the short available follow-up (2 months to date), the patient is doing well and being evaluated for possible allogeneic stem cell transplant. The association of EBV-positive B-cell expansions in T-cell lymphomas, especially angioimmunoblastic T-cell lymphoma, is well recognized. However, EBV-negative, clonal B-cell or plasma cell proliferations in T-cell lymphoma may represent a specific phenomenon and its significance still needs further clarification. J Hematol. 2016;5(4):129-137 doi: https://doi.org/10.14740/jh300w
TL;DR: A superficial skin biopsy may be sufficient in diagnosing SPTL; however, presence of vasculitis on a superficial punch biopsy specimen should be followed by deep incisional biopsy (sometimes multiple) in all cases with atypical presentation or those who do not respond appropriately to treatment.
Abstract: Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a rare subtype of cutaneous T-cell lymphoma. These cases can remain undiagnosed and are often treated with prolonged and ineffective immunosuppressive agents before a diagnosis of T-cell lymphoma is made. A 76-year-old white male presented with a 3-month history of fatigue, weight loss, night sweats, low grade fevers, gradual cognitive decline, and new onset skin lesions. Skin examination revealed mildly tender, indurated, dull red subcutaneous nodules on face, chest, back, upper, and lower extremities, most numerous on the chest and back. A punch biopsy from one of the skin nodules revealed small and medium vessel vasculitis with associated neutrophilic lobular panniculitis. A full thickness skin biopsy showed inflammatory infiltrate composed predominantly of atypical small to medium sized lymphocytes with hyperchromatic nuclei. A diagnosis of T-cell lymphoma was made on clinical presentation, histopathology, immunohistochemical and molecular studies. SPTL can mimic autoimmune diseases including primary vasculitis disorder in presentation. A superficial skin biopsy may be sufficient in diagnosing SPTL; however, presence of vasculitis on a superficial punch biopsy specimen should be followed by deep incisional biopsy (sometimes multiple) in all cases with atypical presentation or those who do not respond appropriately to treatment. J Hematol. 2016;5(1):25-29 doi: http://dx.doi.org/10.14740/jh232w
TL;DR: Thalassemia syndromes are the most common hereditary genetic diseases of mankind and constitute the entity of nontransfusion-dependent thalassemias (NTDT).
Abstract: Thalassemia syndromes are the most common hereditary genetic diseases of mankind. They result from an imbalance between the number of alpha-and beta-globin chains. When the amount of beta-globin chains are absent or reduced, the disease is called beta thalassemia. However, the pathology is entirely related to the relative excess of alpha-globin chains. These highly unstable chains precipitate within erythroid precursors in the bone marrow causing direct membrane damage and premature cell death by apoptosis. This central hemolysis is termed as ‘ineffective erythropoiesis’ and is the main determinant of anemia in beta thalassemia [1]. Peripheral hemolysis of mature red blood cells is caused by this mechanism but has a trivial contribution to anemia in these patients. Instead, it has been linked to pulmonary hypertension with secondary heart failure and thromboembolic phenomena [2]. Beta thalassemia has two main clinicopathologic forms: heterozygous and homozygous. In its homozygotic form, beta thalassemia overwhelms patients with a vicious cycle of ineffective erythropoiesis and iron overload. However, this form is clearly divided into two phenotypes on the basis of transfusion dependence; thalassemia major (β-TM) which represents the major domain and thalassemia intermedia (β-TI). The latter is one of three thalassemia syndromes that constitute the entity of nontransfusion-dependent thalassemias (NTDT). β-TI has a characteristic molecular structure owing to certain genetic modifiers that skew the imbalance between the number of alpha-and beta-globin chains, thus alleviating the degree of anemia. These genetic modifiers include co-inheritance of abnormal alphaor gamma-chain genes or inheritance of a mild or silent beta-chain mutation [3]. β-TI is clinically important in certain geographic areas and is legion in the Sultanate of Oman for two main reasons: exceptional occurrence of Hb Dhofar and prevalence of alpha thalassemia trait in the native population [4]. Hb Dhofar is a variant hemoglobin unique to the Sultanate of Oman that clinically behaves as β-TI phenotype [5]. As β-TI is NTDT, the compensatory mechanisms in response to the chronic anemic state results in erythropoietin production become unchecked [6]. Erythropoietin drives the proliferation of erythroid precursors in the bone marrow and extramedullary sites. Erythroid marrow hypertrophy can reach up to 25 30 times the normal marrow cavity volume and leads to the characteristic skeletal deformities, osteoporosis and pathological fractures of long bones [7]. More interestingly is the extramedullary expansion. This results from the arrest at differentiation of erythroid precursors in response to sustained erythropoietin surge leading to sustained proliferation of the erythropoietic tissue that sweep past the bone marrow to invade and colonize all body sites but predominantly homing the spleen and liver. This is termed ‘extramedullay hematopoiesis’ (EMH) which can result in devastating complications as these masses can grow up in tumor-like forms. The most debilitating complication is the spinal cord compression secondary to paraspinal masses [8]. Intrathoracic masses have been also reported in patients with EMH [9]. Splenomegaly can exacerbate anemia and increases transfusion requirements in β-TI patients [10]. On the other hand, by virtue of their indigenous transfusion dependence, the ineffective erythropoiesis erythropoietin drive axis is suppressed leading to the rare occurrence of excessive medullary or EMH in patients with β-TM [11]. This means that ineffective erythropoiesis is unique to β-TI. This was clearly demonstrated in OPTIMAL CARE study where EMH ranked the second most frequent complication encountered in β-TI patients. The study included 584 β-TI patients, the largest cohort of patients published so far. Notably, osteoporosis ranked the most frequent complication. Interestingly, both osteoporosis and EMH are induced by ineffective erythropoiesis. However, the study value was limited to highlighting the complications of the disease rather than evaluating the potential benefits of current therapeutic options. The study concluded desperately that no clear guidelines exist for managing β-TI patients [12]. Traditionally, treatment options for EMH are splenectomy [3], radiotherapy [13], transfusion therapy [14], hydroxyurea [15] or even surgery [16]. In the era of modern molecular biology, emerging alternative therapies for β thalassemia are being sought. Two important upcoming agents are transferrin injections and JAK-2 inhibitors. Research into transferrin injections is still a murine model where long-term administration of transferrin injections to Hbbth1/th1 mice increased Hb production, decreased serum erythropoietin levels and reversed splenomegaly [17]. However, the most convincing theory is the role of Janus kinase-2 (JAK2) inhibitors in preventing the complications of EMH associated with β thalassemia. The principle is that persistent phosphorylation of JAK2 as a consequence Manuscript accepted for publication November 30, 2016
TL;DR: In this paper, the clinical course and prognosis in patients with essential thrombocythemia, treated with hydroxyurea and low-dose aspirin, and complications of treatment in a 12-year follow-up with a precise and regular control were determined.
Abstract: Background: The main objective of this study was to determine the clinical course and prognosis in patients with essential thrombocythemia, treated with hydroxyurea and low-dose aspirin, and complications of treatment in a 12-year follow-up with a precise and regular control. Methods: In this study, 76 patients with high-risk essential thrombocytosis were retrospectively studied. Data obtained from initial examinations, sonography, complications, and treatment were analyzed. Results: The mean follow-up was 66.8 months (minimum, 3 months; maximum, 137 months). The mean age of patients was 46.9 years. The mean platelet count of patients at diagnosis and the last follow-up were 818,000/mm 3 and 422,000/mm 3 , respectively. In 60 patients, a gene mutation test for JAK2 V617F was performed and was reported as 36.7% positive. Nine patients had bleeding, two of whom were reported after treatment, and eight cases had thrombosis. Macrocytosis and myelofibrosis were seen in 32 and one cases, respectively. Moreover, no cases of leukemia or malignancy due to cytoreduction therapy were seen. One case of skin lesion was seen. Conclusion: A rapid diagnosis, accurate and regular control, and timely treatment can improve the quality of life and reduce morbidity and threatening complications. This study showed that complications using aspirin and hydroxyurea treatment are at the minimum level. J Hematol. 2016;5(4):117-122 doi: https://doi.org/10.14740/jh305w