scholarly journals Predictors of Mortality and Outcomes of Liver Transplant in Spur Cell Hemolytic Anemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1995-1995
Author(s):  
Zain M Virk ◽  
Arpan A Patel ◽  
Rebecca Karp Leaf ◽  
Hanny Al-Samkari
Keyword(s):  
Liver Transplant ◽  
Hemolytic Anemia ◽  
Research Funding ◽  
Logistic Models ◽  
Decompensated Cirrhosis ◽  
Prognostic Impact ◽  
Red Cell ◽  
Predictors Of Mortality ◽  
Red Cell Transfusion ◽  
Standardized Mortality Ratios

Abstract BACKGROUND : Spur cell hemolytic anemia (SCHA) is a rare, acquired, non-immune hemolytic anemia of decompensated cirrhosis resulting from abnormal lipid composition of the red cell membrane. Treatment is limited to red cell transfusion. Data describing prognostic impact, outcomes of liver transplant, and clinical hematologic characteristics of SCHA are absent or limited; published data on SCHA are limited to single-patient case reports and small single-center case series. The independent prognostic impact of SCHA on patients with cirrhosis remains unclear, and it is not known if hemolytic anemia severity has a significant impact on survival of these patients. As a result, SCHA is not formally considered during liver transplant evaluation, and patients do not receive MELD exception points for this diagnosis. METHODS : We performed a multicenter, 24-year observational cohort study of patients with SCHA, retrospectively analyzing hepatic and hematologic parameters, independent predictors of mortality, and long-term outcomes of liver transplant. Strict diagnostic criteria for SCHA were applied, requiring all of the following: (1) decompensated cirrhosis; (2) anemia; (3) objective laboratory evidence of hemolysis; (4) no alternate contributing cause of hemolysis or acanthocytosis; and (5) chart documentation of a confirmed diagnosis of SCHA incorporating peripheral blood film examination. The primary outcome was mortality at 3 months after date of SCHA diagnosis. The impact of hemolytic parameters on 3-month mortality was evaluated utilizing multivariable logistic models. Observed mortality vs. expected mortality (per MELD-Na score and Child-Turcotte-Pugh class) was compared using standardized mortality ratios. Given the limited survival of this population, red cell transfusion dependence was defined as 4 or more units of red cells transfused during the 60-day peri-diagnostic period. RESULTS : Patients: 69 patients with SCHA were included (FIGURE 1). The median (interquartile range) age was 53 (42-59) years; 46.4% were female, and 11 (15.9%) received liver transplant. Alcohol contributed to the etiology of cirrhosis in 53 patients (76.8%). The median (IQR) survival from SCHA diagnosis of patients not receiving liver transplant was 58 (23-113) days. 39 patients (56.5%) were red cell transfusion-dependent. Hematologic parameters are described in TABLE 1. Outcomes of Liver Transplant: All 11 patients undergoing transplant had rapid and complete resolution of SCHA, with an improvement in median hematocrit from 22.1% to 34.6% post-transplant (P=0.001) (TABLE 2) and excellent post-transplant outcomes, with 9 patients still alive after 6.1 years median follow-up. Independent Predictors of Mortality in SCHA: In multivariable logistic models adjusting for age, sex, etiology of cirrhosis, active/recent variceal bleeding, and Child-Turcotte-Pugh score, transfusion dependence had an OR for 90-day mortality of 9.14 (95% CI, 2.46-34.00) and reduced pre-transfusion hematocrit had an OR of 4.73 (95% CI, 1.42-15.82) per 6% decrease; increased red cell transfusion requirement, reduced hemoglobin, increased lactate dehydrogenase, and increased indirect bilirubin were also independently predictive of higher 90-day mortality (FIGURE 2). Performance of MELD-Na and Child-Turcotte-Pugh Scores in Estimating 90-Day Mortality: MELD-Na and Child-Turcotte-Pugh scores consistently significantly underestimated 90-day mortality, with standardized mortality ratios (SMRs) >1 across all scores/classes [MELD-Na 20-29, SMR 2.42 (1.18-4.44); Child-Turcotte-Pugh class B, SMR 4.46 (1.64-9.90)], FIGURE 3. CONCLUSIONS : In this largest study of SCHA to date, SCHA was associated with substantial excess mortality than was predicted by MELD-Na or Child-Turcotte-Pugh scores. Several clinical and laboratory parameters of hemolytic anemia severity, including transfusion burden, hemoglobin, and markers of hemolysis were each independent predictors of 90-day mortality in SCHA. Despite its unique morbidity as a complication of decompensated cirrhosis, outcomes of liver transplant were excellent in all 11 patients undergoing this intervention, with total resolution of SCHA and no evidence of recurrence. These findings should promote greater awareness of SCHA as a clinical entity and broader consideration of MELD exception points for afflicted patients when transplant-eligible. Figure 1 Figure 1. Disclosures Al-Samkari: Novartis: Consultancy; Amgen: Research Funding; Argenx: Consultancy; Rigel: Consultancy; Dova/Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Moderna: Consultancy.

Survival, Prognostic Factors, and Rates of Leukemic Transformation in a Multicenter Study of 303 Untreated Patients with MDS and Del(5q).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 945-945 ◽  
Author(s):  
Ulrich Germing ◽  
Michael Lauseker ◽  
Barbara Hildebrandt ◽  
Argiris Symeonidis ◽  
Jaroslav Cermak ◽  
...  
Keyword(s):  
High Risk ◽  
Median Survival ◽  
Research Funding ◽  
Risk Group ◽  
Competing Risk ◽  
Refractory Anemia ◽  
Red Cell ◽  
Kaplan Meier ◽  
Red Cell Transfusion

Abstract Abstract 945 In 2001, the WHO defined the category MDS with del(5q) due to unique cytogenetic, morphologic, hematologic, clinical, prognostic and therapeutic features. The survival of these patients, as well as patients with refractory cytopenia with unilineage dysplasia (RCUD) and refractory anemia with ring sideroblasts is favorable in comparison to other MDS types. Data on disease progression to a more advanced MDS category or to acute leukemia (AML) are sparse and have not been examined in detail. In order to address this issue we collated data of all patients with MDS and del(5q) characterized by low or intermediate-1 IPSS risk score that had been included into various collaborating MDS registries. Patients were followed from diagnosis and data on cell counts, transfusion dependency, and MDS progression were documented. No patients received treatment other than best supportive care. The status of 62 patients was censored at the time of the initiation of Lenalidomide therapy. AML progression was defined as >20% marrow blasts. Estimates of survival probability were calculated with the Kaplan-Meier method. The cumulative incidence of progression to AML was calculated both with the Kaplan-Meier method and with the competing risk method where “death without progression to AML” is considered as competing event, not as censoring. For both events the cumulative incidences are estimated simultaneously. This method has the advantage that it takes into account that there is a difference between end of follow-up and death. Depending on the number of competing events, the curves are lower than those calculated with the Kaplan-Meier estimator. We identified 303 patients, median age at diagnosis 65 years (28-91), 71% were females. Median follow up time was 3 years. Median survival was 71.5 months. Patients with del(5q) as a sole chromosomal aberration had a median survival of 73 months as compared to 19.3 months in patients with more than 1 additional aberrations. Patients who had red cell transfusion need at diagnosis had a median survival of 39 months vs. 97 months in transfusion independent patients (p=0.00005). Transfusion need at diagnosis was the most important parameter for survival. Patients in the WPSS very low risk group had a median survival of 107 months, as compared to 73 and 56 months in the low and intermediate risk group and 37 months in the high risk group. 44 of the 303 patients (15%) progressed to AML (>20% marrow blasts). The cumulative AML progression rate calculated with the Kaplan-Meier method was 7% at 2 years and 18.2% at 5 years. The cumulative risk of AML progression calculated with the competing risk method was 6.6% at 2 years and 15.1% at 5 years. Factors associated with the risk of AML transformation were intermediate-I IPSS risk and high risk WPSS score, marrow blast count >5%, and red-cell transfusion need at diagnosis. Survival and progression rates did not differ among the participating centers. In conclusion, survival of patients with MDS and del(5q) is high and is comparable to patients with RCUD and RARS, but is associated with a risk of AML-transformation similar to RCMD without del(5q). Further cytogenetic and molecular studies are warranted in order to identify patients at greater risk of progression. Disclosures: Germing: Novartis, Celgene: Honoraria, Research Funding. Lauseker:Celgene: Research Funding. Hildebrandt:Celgene: Research Funding. Symeonidis:Celgene: Research Funding. Cermak:Celgene: Research Funding. Pfeilstöcker:Celgene: Research Funding. Nösslinger:Celgene: Research Funding. Sekeres:Celgene: Research Funding. Maciejewski:Celgene: Research Funding. Haase:Celgene: Research Funding. Schanz:Celgene: Research Funding. Seymour:Celgene: Research Funding. Weide:Celgene: Research Funding. Lübbert:Celgene: Research Funding. Platzbecker:Celgene: Research Funding. Valent:Celgene: Research Funding. Götze:Celgene: Research Funding. Stauder:Celgene: Research Funding. Blum:Celgene: Research Funding. Kreuzer:Celgene: Research Funding. Schlenk:Celgene: Research Funding. Aul:Celgene: Research Funding. Kündgen:Celgene: Research Funding. Hasford:Celgene: Research Funding. Giagounidis:Celgene: Research Funding.

Acute Effects of Blood Transfusion on Spermatogenesis and Pituitary Gonadal axis in Eugonadal Males with Beta Thalassemia Major (pilot study)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1027-1027
Author(s):  
Mohamed A. Yassin ◽  
Ashraf T Soliman ◽  
Ahmed S Elawa ◽  
Hanadi Rafii El-Ayoubi ◽  
Vincenzo Desanctis
Keyword(s):  
Blood Transfusion ◽  
Research Funding ◽  
Sperm Count ◽  
Thalassemia Major ◽  
Semen Parameters ◽  
Red Cell ◽  
Acute Effects ◽  
Seminal Parameters ◽  
Igf I ◽  
Red Cell Transfusion

Abstract Abstract 1027 Objective: To evaluate semen parameters and measure serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and insulin-like growth factor-I (IGF-I) concentrations before and 7 days after packed red cell transfusion (PCTx) in young adults with thalassemia major (TM). Design: Prospective study. Setting, Patients, Interventions: We studied the effect of blood transfusion on semen parameters, the endocrine functions in 10 young adults with TM, aged from 17 to 32 years, with full pubertal development (Tanner's stage 5) (euogonadal),and capacity to ejaculate. They were regularly transfused since early childhood and underwent chelation therapy using desferrioxamine which was replaced by deferasirox for the last 4 –5 years. At the time of the study their serum ferritin levels ranged from 500 to 5922 ng/ml (mean2686 ng/ml). Basal serum concentrations of FSH, LH, T and IGF-I were evaluated before and 7 days after packed red cell transfusion (PCTx). Main Outcome Measures and Results: After PCTx significant increase of Hb from 8.7 +/− 0.86 g/dl to 11.1 +/− 0.82 g/dl was associated with increased testosterone (from 16.5 +/− 8 nmol/L to 20 +/− 8.8 nmol/L, IGF-I (from 173 +/− 46ng/ml to 214 +/− 61ng/ml) and gonadotropins' concentrations. Total sperm count increased significantly from 57.8 +/− 38.3 million/ml to 166 +/− 132 million/ml and rapid progressive sperm motility progressive motility increased from 20.6+/− 16.6 % to 79.7 +/− 67.4 %. After PCTx, LH concentrations were correlated significantly with T concentrations (r = 0.434, p < 0.001) and sperm volume and count (r = 0.439 and r = 0.376 respectively, p: 0.01). The increase of IGF-I concentration was correlated significantly with Hb level after PCTx (r = 0.535, p < 0.001) and negatively with ferritin concentration (r = −0.458, p < 0.001). Significant correlation were found between serum T concentrations and semen parameters before and after PCTx including sperm count (r = 0.658 and r = 0.73 respectively, p < 0.001)rapid progressive motility (r = 0.675 and r = 0.758 respectively p < 0.001), and the number of sperms with normal morphology (r = 0.752 and r = 0.834 respectively, p < 0.001) IGF-I levels and seminal parameters. No correlations were found between serum FSH and IGF-I concentrations and seminal parameters. Conclusion: Our study suggests that in thalassemic males blood transfusion is associated with significant acute enhancement of sperm parameters and with an increased concentrations of serum testosterone, LH, FSH and IGF-I. These “acute” effects on spermiogenesis are reached with an unknown mechanism/s and suggest a number of pathways that need further human and/or experimental studies. Disclosures: Yassin: Hamad medical corporation MRC: Employment, Research Funding. Soliman:Hamad medical corporation MRC: Employment, Research Funding. Elawa:Hamad medical corporation MRC: Employment, Research Funding.

scholarly journals Decreased Activity and Stability of Pyruvate Kinase in Hereditary Hemolytic Anemia: A Potential Target for Therapy By AG-348 (Mitapivat), an Allosteric Activator of Red Blood Cell Pyruvate Kinase

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3506-3506
Author(s):  
Minke A.E. Rab ◽  
Brigitte A. van Oirschot ◽  
Stephanie van Straaten ◽  
Bart J. Biemond ◽  
Jennifer Bos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Cell ◽  
Pyruvate Kinase ◽  
Hemolytic Anemia ◽  
Red Blood Cell ◽  
Research Funding ◽  
Reticulocyte Count ◽  
Compound Heterozygous ◽  
Healthy Controls ◽  
Red Cell

Background: Reactive oxygen species (ROS) play an important role in the complex and multifactorial pathophysiology of hereditary hemolytic anemia like sickle cell disease (SCD), β-thalassemia and hereditary xerocytosis (HX). Increased intracellular levels of oxidative stress disrupt normal cell functioning and may contribute to premature red blood cell (RBC) clearance from the circulation. Pyruvate kinase (PK) is a key regulatory enzyme of glycolysis, the cell's main source of energy. Because PK is very sensitive to redox balance we hypothesized that increased levels of oxidative stress in SCD, β-thalassemia and HX impairs proper enzyme function, thereby compromizing RBC energy metabolism. This may contribute to disease pathophysiology. Aims: To investigate if secondary deficiency of PK is common in SCD, thalassemia, and HX, and to investigate if PK in these disorders is able to respond to treatment with the allosteric PK activator AG-348 (mitapivat). Methods: Enzymatic activities of red cell PK and hexokinase (HK) were measured together with PK-thermostability in order to assess relative PK activity and enzyme stability. Purified RBCs were incubated with AG-348 (3.33μM) for 24 hours after which PK activity and ATP response was measured. RBCs of SCD patients were also analyzed with the oxygenscan, a newly developed method that characterizes individual sickling behavior by oxygen gradient ektacytometry (Rab et al, Am J Hematol, 2019). Individual tendency to sickle is reflected by Point-of-Sickling (PoS) that indicates the specific pO2 at which RBCs start to sickle during deoxygenation under shear stress. Results: Thirty-eight patients and 21 healthy controls (HC) were included. The patient cohort consisted of patients homozygous for HbS (HbSS, n=26), patients compound heterozygous for HbS and HbC (HbSC, n=4), β-thalassemia major (regularly transfused, n=3), and hereditary xerocytosis (n=5). Patients showed reticulocytosis and, in line with this, a concomitant increase in HK activity. In contrast however, relative PK activity was decreased significantly compared to HK in HbSS, β-thalassemia and HX patients, but not in HbSC patients (Figure 1A). PK thermostability was significantly decreased compared to healthy controls in HbSS patients and patients with HX (Figure 1B). In HbSC and β-thalassemia patients, PK-thermostability was comparable to HC. PK thermostability strongly correlated with absolute reticulocyte count (ARC), indicating that patients displaying the highest degree of PK instability had the highest reticulocyte count (Figure 1C). This suggests that in general, a higher degree of PK instability is associated with more severe anemia due to a high hemolytic rate. In SCD patients, PK-thermostability inversely correlated with PoS, indicating that decreased PK stability is associated with sickling at higher pO2 (r=-0.646, p&lt;0.001, Figure 1F). When purified RBCs were incubated with 3.33μM of the allosteric PK-activator AG-348, an increase in PK activity was seen in all patients and HCs, with a mean increase of 122% in HbSS (range 111-139%, n=6), 137% in β-thalassemia (n=1), 163% in HX (range 152-174%, n=2) and 143% in HC (range 113-173%, n=9, Figure 1E). Accordingly, ATP-levels increased in all patients and HCs, with a mean increase of 133% in HbSS (range 125-141%, n=5), 144% patient with β-thalassemia (n=1), 121% in HX (range 112-129, n=3), and 132% in HCs (range 101-149%, n=9, Figure 1E). Conclusion: PK enzyme activity and stability is compromised in patients with various forms of hereditary hemolytic anemia. This implies that PK stability and, hence, compromised red cell metabolism could contribute to the complex pathophysiology of these diseases. In SCD patients, reduced PK-thermostability is associated with higher PoS, which we previously have shown to be associated with more severe disease (Rab et al, Am J Hematol, 2019, ASH 2019 abstract ID128870). This is confirmed by the correlation of decreased PK-thermostability with increased reticulocyte count as presented in this study. Current studies are in progress to further substantiate the underlying mechanism(s) involved, and to investigate whether AG-348 may ameliorate clinical features such as hemolysis, sickling tendency and iron overload. Disclosures Rab: RR Mechatronics: Research Funding. Bos:RR Mechatronics: Research Funding. Kosinski:Agios Pharmaceuticals, Inc: Employment, Other: Stakeholder. Kung:Agios Pharmaceuticals, Inc: Employment, Other: Stakeholder. van Beers:Agios Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Research Funding; RR Mechatronics: Research Funding. van Wijk:Agios Pharmaceuticals: Consultancy, Research Funding; RR Mechatronics: Research Funding.

Comparison of the Impact of Two Different Definitions of Red-Cell Transfusion Dependence on the Natural History of Myeloproliferative Neoplasm (MPN)-Associated Myelofibrosis (MF)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3180-3180
Author(s):  
Justyna Bartoszko ◽  
Tony Panzerella ◽  
Anthea Lau ◽  
Naheed Alam ◽  
Aaron D Schimmer ◽  
...  
Keyword(s):  
Natural History ◽  
Prognostic Impact ◽  
Red Cell ◽  
Leukemic Transformation ◽  
Co Morbidity ◽  
Significant Difference ◽  
History Of ◽  
Red Cell Transfusion ◽  
Definition Of ◽  
The Impact

Abstract The current definitions of red-cell transfusion dependence (TD) for MPN-associated MF are based on expert opinion. The optimal definition of TD, and its impact on the natural history of MF is not well studied. We evaluated the impact of two definitions of red-cell TD on the natural history of 306 patients (pts.) with WHO/IWG-MRT-defined primary MF (PMF, n=202, 66%), post-polycythemia vera MF (PPV-MF, n=45, 15%) or post-essential thrombocythemia MF (PET-MF, n=59, 19%). Red-cell TD was defined according to IWG-MRT 2006 criteria (Tefferi et al, Blood, 2006), and on the results of the expert consensus RAND-Delphi panel (Gale et al, Leukemia Research, 2011). The IWG-MRT criteria require patients to have received ≥2 Units (U) packed red blood cells (PRBC) in the preceding 28 days for hemoglobin (Hb) <85 g/l. On the other hand, the more stringent Gale definition requires patients to receive ≥2 U of PRBC per month over 3 months without any specification for the Hb level. Patients were evaluated for disease risk stratification according to dynamic international prognostic scoring system (DIPSS), co-morbidities according to ACE-27, and red-cell TD at their first presentation to Princess Margaret Cancer Center or diagnosis. The study cohort was divided in 4 groups (gp.): Non-transfusion dependent (NTD) pts. with Hb ≥100 g/dl (gp1, n=156, 51%); patients with Hb <100 g/dl, but no transfusion in preceding 12 weeks (gp2, n=65, 21%); pts. qualifying IWG-MRT 2006 criteria of TD, but not qualifying Gale definition (gp3, n=41, 13%); and pts. qualifying the Gale definition of TD (gp4, n=44, 14%). There was no significant difference among the 4 groups with relation to age, disease distribution (primary vs. secondary), cytogenetics, blasts%, and ACE-27 co-morbidity scores. There was significant difference in the gp1, gp2, gp 3, and gp4 in relation to constitutional symptoms (35% vs. 45% vs. 46% vs.64%, p=0.006), median WBC count (x109/L) (11.5 vs. 8.3 vs. 6.8 vs. 6.5, p<0.0001), platelets (x109/l) (317 vs. 154 vs. 124 vs. 127, p<0.0001), and Int-2/high DIPSS (24% vs. 82% vs. 90% vs. 82%, p<0.0001). In a univariate analysis, probability of survival among the 4 groups at 3-years was 80%, 55%, 68%, 30%, respectively (Fig 1, p=0.0016). No difference in leukemic transformation was observed among the 4 groups (p=0.68). In a multivariate analysis, after adjusting for DIPSS and co-morbidity scores, hazard ratios among the gp2, gp3, and gp 4 were 1.58 (95% CI 0.78-3.19, p=0.21), 2.17 (95% CI 0.88-5.34, p=0.09), 2.82 (95% CI 1.29-6.16, p=0.009) in comparison to gp 1 (ref. group). There was no significant difference between NTD patients with Hb <100 vs. TD patients according to IWG-MRT 2006 criteria, but not meeting Gale Criteria (p=0.47). DIPSS was the only other independent prognostic factor for survival. Our study shows the independent prognostic impact of TD on survival defined according to Gale criteria, but not according to previous IWG-MRT 2006 definition, which does not meet Gale criteria. No impact of anemia or TD was observed on leukemic transformation. Fig 1: Survival in 4 groups according to Hb levels and transfusion needs Fig 1:. Survival in 4 groups according to Hb levels and transfusion needs Disclosures Schuh: Celgene: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Novel COL4A1 mutations identified in infants with congenital hemolytic anemia in association with brain malformations

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Hiromi Ogura ◽  
Shouichi Ohga ◽  
Takako Aoki ◽  
Taiju Utsugisawa ◽  
Hidehiro Takahashi ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Hemolytic Anemia ◽  
Congenital Malformations ◽  
Red Cell ◽  
Whole Exome ◽  
Brain Malformations ◽  
Chronic Hemolysis ◽  
Red Cell Transfusion ◽  
The Brain ◽  
Congenital Hemolytic Anemia

AbstractGenetic causes of undiagnosed hemolytic anemia in nineteen patients were analyzed by whole-exome sequencing, and novel COL4A1 variants were identified in four patients (21%). All patients were complicated with congenital malformations of the brain, such as porencephaly or schizencephaly. In these patients, hemolysis became less severe within 2 months after birth, and red cell transfusion was no longer required after 50 days, whereas chronic hemolysis continued.

Acute Effects of Blood Transfusion On Pituitary Gonadal Axis and Sperm Parameters in Young Males with Sickle Cell Disease (SCD) Pilot Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3209-3209
Author(s):  
Mohamed A. Yassin ◽  
Ashraf T Soliman ◽  
Ahmed S Elawwa ◽  
Hanadi Rafii El-Ayoubi ◽  
Vincenzo Desanctis
Keyword(s):  
Research Funding ◽  
Exchange Transfusion ◽  
Sperm Count ◽  
Sperm Parameters ◽  
Semen Parameters ◽  
Red Cell ◽  
Acute Effects ◽  
Cell Disease ◽  
Before And After ◽  
Red Cell Transfusion

Abstract Abstract 3209 Objective: To evaluate semen parameters and measure serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations before and 7 days after packed red cell transfusion (PCTx) in young adults with sickle cell disease (SCD). Design: Prospective study. Setting, Patients: This study investigated 18 young adults with transfusion – dependent SCD, aged 20.7 +/− 2.88 years, with full pubertal development (Tanner's stage 5) (euogonadal), and capacity to ejaculate. They were regularly transfused since early childhood and underwent chelation therapy using desferrioxamine which was replaced by deferasirox for the last 4–5 years. Ten were on top-up transfusion (TTx) and 8 were on exchange transfusion (ETx) regimen. At the time of the study their serum ferritin levels were 1488 +/− 557ng/ml. Basal serum concentrations of FSH, LH, T and IGF-I were evaluated before and 7 days after packed red cell transfusion (PCTx). Interventions: We studied the effect of PCTx on semen parameters and the endocrine functions in these 18 patients with SCD. Main Outcome Measures and Results: After Packed RBCs Transfusion(PCTx) significant increase of Hb from 8.5 +/− 1.17 g/dl to 10.5 +/− 0.4 g/dl was associated with increased testosterone (12.3 +/− 1.24 nmol/L to 14.23 +/− 1.22nmol/L and gonadotropins' concentrations. Total sperm count increased significantly from 87.4 +/− 24.6 million/ml to 146.2 +/− 51.25 million/ml and total progressive sperm motility (TPM) from 40.8 +/− 11.1 million/ml to 93.4 +/− 38.3 million/ml, and rapid progressive sperm motility progressive motility (RPM) increased from 29.26 +/− 8.75 million/ml to 67.4 +/− 29 million/ml. After PCTx the total sperm count, TPM and RPM were significantly higher in the ETx group versus the TTx group. Before and after PCTx, Testosterone (T) concentrations were correlated significantly with sperm total count, volume, TPM and RPM (r = 0.53, 0.55, 0.42 and 0.38 respectively, p: 0.01). Before and after PCTx, hemoglobin (Hb) concentrations were correlated significantly with Sperm count, TPM, RPM and % of sperms with normal morphology (r= 0.60, 0.69, 0.66 and 0.86 respectively, p < 0.001). Conclusion: Our study suggests that in males with SCD blood transfusion is associated with significant acute enhancement of sperm parameters and with an increased concentration of serum testosterone, LH and FSH. Improvements of sperm parameters were significantly higher in the Exchange Transfusion group vs. the Top up Transfusion group. These “acute” effects on spermatogenesis are reached with an unknown mechanism/s and suggest a number of pathways that need further human and/or experimental studies. Disclosures: Yassin: Hamad medical corporation MRC: Employment, Research Funding. Soliman:Hamad medical corporation MRC: Employment, Research Funding. Elawwa:Hamad medical corporation MRC: Consultancy, Research Funding.

Pure Red Cell Aplasia In Major ABO Mismatched Allogeneic Hematopoietic Cell Transplantation Is Associated With Severe Pancytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5449-5449
Author(s):  
Fleur M. Aung ◽  
Benjamin Lichtiger ◽  
Amin Alousi ◽  
Sairah Ahmed ◽  
Paolo Anderlini ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Pure Red Cell Aplasia ◽  
Red Cell ◽  
Advisory Committees ◽  
Post Transplant ◽  
Red Cell Aplasia ◽  
Severe Pancytopenia ◽  
Red Cell Transfusion

Abstract Introduction The persistence of anti-donor isohemagglutinins in Major ABO mismatched allogeneic stem cell transplantation (HCT) leads to pure red cell aplasia (PRCA). In our previous report of 12 patients with PRCA, severe pancytopenia was observed in one patient who eventually had a second transplant (Aung et al. B J Haematol 2013 Mar; 160(6):798-805). Furthermore, ABO antigens are expressed on or adsorbed from plasma on granulocyte and platelets and these may be affected by isohemagglutinins. To further investigate this observation we analyzed a larger cohort of patients with PRCA to determine the frequency of pancytopenia and natural history of pancytopenia in patients with PRCA after Major ABO incompatible HCT. Patients and Methods We reviewed 758 patients who received a Major ABO-mismatched HCT between January 2003 and December 2012 at our institution. Pure red call aplasia was determined to be present when the bone marrow biopsy on post-transplant day 30 demonstrated absent or nearly absent erythroid precursors with absence of donor red cells on forward red cell typing of the recipient and the recipient being red cell transfusion dependent. Pancytopenia was defined as ANC < 1.5 x 109/L or requiring G-CSF, Platelets < 50 x 109/L or transfusion dependent, and PRCA with red cell transfusion dependence as above at 90 days after allogeneic SCT. Results 83 patients had PRCA. Of these 16 (19%) had pancytopenia at day 90 after transplant. None of these patients had any other reason for persistent pancytopenia like CMV or other viral infection or use of drugs like ganciclovir or disease recurrence. On post-transplant day 90, median absolute neutrophil counts (ANC) was 1.01 K/UL with 15 (94%) patients having intermittent G-CSF and median platelet count was 14 KL/UL (range 6-49) with 13(81%) patients platelet transfusion dependent. All patients were red cell transfusion dependent. Of the 16 PRCA patients with pancytopenia, 2 (12%) received a second transplant due to persistent pancytopenia/graft failure and 2 (12%) relapsed. 2 (12%) patients have still not recovered their platelet counts despite red cell and ANC recovery. In the remaining 10 (63%) patients, neutropenia and thrombocytopenia resolved after resolution of PRCA. Red cell recovery occurred at a median of 226 (95-549) days post transplant, ANC recovered at median of 325 (105-1080) days post-transplant, and Platelets recovered at median of 296 (94-2738) days post-transplant. Conclusion Severe pancytopenia is frequently (19%) associated with PRCA in Major ABO incompatible HCT. Neutropenia and thrombocytopenia resolve after resolution of red cell aplasia in the majority of patients. Disclosures: Andersson: Otsuka Pharmaceuticals: Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees. Shah:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding.

scholarly journals Phosphatidylserine-Exposing Extracellular Vesicles after Splenectomy Are Associated with Increased D-Dimers and Fibrin Generation in Hereditary Hemolytic Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 630-630
Author(s):  
Stephanie Van Straaten ◽  
Chi Hau ◽  
Najat Hajji ◽  
Jill Verhoeven ◽  
Roger Schutgens ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Hemolytic Anemia ◽  
Extracellular Vesicles ◽  
Research Funding ◽  
Hypercoagulable State ◽  
Red Cell ◽  
Advisory Committees ◽  
Increased Risk ◽  
D Dimer

Abstract Background Thrombosis is a common complication of hereditary hemolytic anemia (HHA). Etiology of a hypercoagulable state in patients with HHA involves inflammation and splenectomy, although the etiology of the latter is insufficiently established. Because the concentration of circulating extracellular vesicles (EVs) has been reported to increase after splenectomy, and because in patients with sickle cell disease (SCD) circulating EVs are associated with coagulation, we analyzed the concentration of circulating EVs and their procoagulant activity in plasma from splenectomized and non-splenectomized patients with HHA. Methods This is a cross sectional, observational study in adult patients with HHA (SCD, other hemoglobin disorders, red cell enzyme disorders, red cell membrane disorders). Blood samples were collected with a 21-gauge butterfly needle and collected in 9 mL citrate phosphate dextrose adenine (CPDA) vacutainers, without use of a tourniquet. The tubes were mixed gently and the time between blood collection and centrifugation was maximum one hour. EVs in platelet-depleted plasma were labeled for Heat Shock Protein 70, CD14 (monocyte-derived EVs), CD61 (platelet EVs), CD62e (endothelial EVs), CD62p (P-selectin-exposing platelet EVs), CD71 (reticulocyte EVs), CD144 (endothelial EVs), CD235a (erythrocyte EVs) and lactadherin (phosphatidylserine (PS)-exposing EVs), and measured with a dedicated flow cytometer for EVs (A60-micro, Apogee Flow systems; lower limit of detection 170-180 nm single EVs). The coagulant activity of EVs was studied by a fibrin generation test, which measures the EV-dependent clotting time of plasma. The time to fibrin formation (1/2max) was measured using optical densitometry (λ = 405 nm) and an arbitrary cut off of V1/2max <1,500s was used to consider FGT as positive. Samples with >25% difference between duplicates or from patients that used anticoagulant medication were excluded from analysis Results Ninety seven patients were included in the study. Baseline characteristics are shown in Table 1. FGT of 63 patients were included. Thirteen patients (21%) had a positive FGT. Patients with positive FGT had increased concentrations of circulating EVs (CD61, CD71, lactadherin: p=<0.001; HSP70, CD62p, CD61/CD62p, CD62e, CD235a: p=<0.05) compared to patients with a negative FGT. Of the patients with a positive FGT, 11 patients (85%) were splenectomized, versus 2 patients (28%) in the FGT-negative group (p=0.002, patients with SCD regarded as splenectomized). Splenectomized patients had increased concentrations of lactadherin-binding EVs (p<0.001), as well as increased concentrations of CD61- and CD61/CD62p-exposing EVs (p<0.001) and of CD235a- and CD71-positive EVs (p<0.01, Table 2). FGT V1/2max and D-dimer correlated with lactadherin-binding EVs (ρ=-0.631, p=<0.001, and ρ=0.331, p=0.001). Conclusion In this study we show that in HHA patients the plasma concentration of lactadherin-binding and thus PS-exposing EVs correlates with fibrin generation in vitro and plasma D-dimer concentration, indicating that EVs may be associated with the hypercoagulable state that is observed in patients with HHA. Splenectomized patients had higher concentrations of lactadherin-binding EVs, and their plasma samples were prone to clot, as shown by fibrin generation in vitro. As the spleen is the main organ removing PS-exposing cells, higher levels of PS-exposing EVs in such patients may be due to reduced clearance, which in turn may contribute to the increased risk of thrombosis in patients after splenectomy. Disclosures Schutgens: Novo Nordisk: Research Funding; Uniqure BV: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Bayer: Research Funding; Baxalta/Shire: Research Funding. van Wijk:Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; RR Mechatronics: Research Funding. van Beers:RR Mechatronics: Research Funding; Bayer: Research Funding; Pfizer: Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Alloantibodies and Drug-Induced Immune Hemolytic Anemia in Liver Transplantation

2011 ◽  
Vol 2011 ◽  
pp. 1-3
Author(s):  
Surekha Devi Allanki
Keyword(s):  
Liver Transplantation ◽  
Blood Cell ◽  
Hemolytic Anemia ◽  
Red Blood Cell ◽  
Preoperative Evaluation ◽  
Red Cell ◽  
Drug Induced ◽  
Immune Hemolytic Anemia ◽  
Red Cell Transfusion ◽  
Compatible Blood

Red blood cell alloantibodies can cause severe delayed hemolysis, despite immunosuppression which they receive posttransplantation. A female patient with Hepatitis C-related chronic liver disease reported to our center for liver transplantation. During preoperative evaluation, she was found to have significant red blood cell alloantibodies which gave rise to problems during pre transfusion compatibility test. Stringent measures were taken by the transplant team to minimize blood loss during surgery. It was decided to have lower transfusion trigger for red cell transfusion, and blood conservation was done by intraoperative red cell salvage and use of antifibrinolytic agent. During immediate postoperative period, she developed drug-related immune hemolytic anemia. Presence of both warm autoantibodies and alloantibodies posed a big challenge for us to get cross-match compatible blood. She received 22 units of crossmatch compatible red cell transfusions during her hospital stay, which was uneventful. Hence, we reported this case.

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