scholarly journals Drug-Induced Hemolytic Anemia: A Fatal Complication Further Under-Recognized in Sickle Cell Disease

2017 ◽  
Vol 07 (03) ◽  
pp. 79-85
Author(s):  
Monica Khurana ◽  
Shekhar S. Raj
Keyword(s):  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Cell Disease ◽  
Fatal Complication ◽  
Drug Induced

scholarly journals Sickle Cell Disease Model Mice Lacking 2,3-Dpg Show Reduced RBC Sickling and Improvements in Markers of Hemolytic Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Kelly M. Knee ◽  
Amey Barakat ◽  
Lindsay Tomlinson ◽  
Lila Ramaiah ◽  
Zane Wenzel ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Organ Damage ◽  
Complete Elimination ◽  
Cell Disease ◽  
The Impact ◽  
2,3 Dpg

Sickle cell disease (SCD) is a severe genetic disorder caused by a mutation in hemoglobin (b6Glu-Val), which allows the mutant hemoglobin to assemble into long polymers when deoxygenated. Over time, these polymers build up and deform red blood cells, leading to hemolytic anemia, vaso-occlusion, and end organ damage. A number of recent therapies for SCD have focused on modulating the mutant hemoglobin directly, however, reduction or elimination of 2,3-DPG to reduce Hb S polymerization and RBC sickling has recently been proposed as a therapeutic strategy for SCD. Current clinical studies focus on activation of pyruvate kinase to reduce 2,3-DPG, however, direct targeting of the enzyme which produces 2,3-DPG; Bisphosphoglycerate Mutase (BPGM) may also be possible. In this study we evaluate the impact of elimination of 2,3-DPG on SCD pathology by complete knockout of BPGM in Townes model mice. Animals with complete knockout of BPGM (BPGM -/-) have no detectable 2,3-DPG, while animals that are heterozygous for BPGM (BPGM -/+) have 2,3-DPG levels comparable to Townes mice. Western Blot analysis confirms that BPGM -/- animals completely lack BPGM, while BPGM -/+ animals have BPGM levels that are nearly equivalent to Townes mice. As expected from the lack of 2,3-DPG, BPGM -/- animals have increased oxygen affinity, observed as a 39% decrease in p50 relative to Townes mice. Complete elimination of 2,3-DPG has significant effects on markers of hemolytic anemia in BPGM -/- mice. Mice lacking 2,3-DPG have a 60% increase in hemoglobin (3.7 g/dL), a 53% increase in red blood cell count, and a 29% increase in hematocrit relative to Townes mice. The BPGM -/- mice also have a 57% decrease in reticulocytes, and a 61% decrease in spleen weight relative to Townes animals, consistent with decreased extramedullary hematopoiesis. Consistent with the reduction in hemolysis, BPGM -/- animals had a 59% reduction in red blood cell sickling under robust hypoxic conditions. BPGM -/+ animals had hemoglobin, RBC, and hematocrit levels that were similar to Townes animals, and a similar degree of RBC sickling to Townes mice. Liver phenotype was similar across all variants, with areas of random necrosis observed in BPGM -/-, BPGM -/+ and Townes mice. Higher percentages of microcytic and/or hyperchromic RBCs were observed in BPGM -/- animals relative to BPGM -/+ or Townes animals. These results suggest that modulation of 2,3-DPG has a positive effect on RBC sickling and hemolytic anemia, which may have therapeutic benefits for SCD patients. However, the lack of improvement in organ damage suggests that modulation of 2,3-DPG alone may not be sufficient for complete elimination of SCD phenotypes, and further investigation of this therapeutic avenue may be necessary. Disclosures No relevant conflicts of interest to declare.

Severity of Sickle Cell Disease: Modeling Interrelationships among Hemolysis, Pulmonary Hypertension and Risk of Death.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 786-786
Author(s):  
Paola Sebastiani ◽  
Vikki G. Nolan ◽  
Clinton T. Baldwin ◽  
Maria M. Abad-Grau ◽  
Ling Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Disease Severity ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Risk Of Death

Abstract A single point mutation in the β hemoglobin gene causes sickle cell disease (SCD), but patients have extremely variable phenotypes. Hemolysis-related complications include pulmonary hypertension (PHT), priapism, stroke and leg ulceration; blood viscosity and sickle vasoocclusion are associated with painful episodes, acute chest syndrome and osteonecrosis. Predicting who is at highest risk of death would be useful therapeutically and prognostically. Applying Bayesian network modeling that describes complex interactions among many variables by factorizing their joint probability distribution into modules, to data from 3380 SCD patients, we constructed a disease severity score (DSS: 0, least severe; 1, most severe), defining severity as risk of death within 5 years. A network of 24 variables described complex associations among clinical and laboratory complications of SCD. The analysis was validated in 140 patients whose SCD severity was assessed by expert clinicians and 210 adults where severity was also assessed by the echocardiographic diagnosis of PHT and death. Information about PHT allowed a comparison of the DSS with the tricuspid regurgitant jet velocity (TRJV), an objective marker of PHT and an independent risk factor for death. DSS and three indices of clinical severity (severity ranking of individuals by expert clinicians; objective measurement of the presence and severity of PHT; risk of prospective death) were correlated. Among living subjects, the median score was 0.57 in 135 patients without PHT, 0.64 in 40 patients with mild PHT and 0.86 in 15 patients with severe PHT. The difference in average score between living patients with and without PHT is significant. The same increasing trend was noticeable in the subjects who died during follow-up: 0.60 in subjects without PHT; 0.68 in subjects with mild PHT; 0.79 in subjects with severe PHT. The utility of the DSS is also supported by the ability to assign a score to subjects for whom the TRJV cannot be measured. Surprisingly, besides known risk factors like renal insufficiency and leukocytosis, we identified the intensity of hemolytic anemia and clinical events associated with hemolytic anemia as contributing to risk for death. Priapism, an excellent reflection of the hemolytic anemia-related complications of SCD, is associated with PHT and its association with death was unexpected. Laboratory variables predictive of disease severity included LDH and reticulocytes that reflect the intensity of hemolytic anemia. Elevated systolic blood pressure increased the odds of death by 3.4, consistent with hypertension as a marker of early death in SCD. Subjects with sickle cell anemia are at greatest risk compared with subjects with sickle cell anemia-α thalassemia and with subjects with HbSC disease. Our model suggests that the intensity of hemolytic anemia, estimated by LDH, reticulocyte count and AST, and shown previously to be associated with PHT, priapism, leg ulceration and possibly stroke, is an important contributor to death. This model can be used to compute a personalized measure of disease severity that might be useful for guiding therapeutic decisions and designing clinical trials.

Acute chest syndrome: A potentially fatal complication of sickle cell disease — Report of 2 cases

2013 ◽  
Vol 24 ◽  
pp. e173
Author(s):  
M. Cortes ◽  
S. Fernandes ◽  
P. Aranha ◽  
F. Rego ◽  
J.L. Ducla-Soares
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Fatal Complication

scholarly journals Study of chronic hemolytic anaemia patients in Rio de Janeiro: prevalence of anti-human parvovirus B19 IgG antibodies and the developement aplastic crises

2002 ◽  
Vol 44 (4) ◽  
pp. 187-190 ◽  
Author(s):  
Anadayr L.M. SANT'ANNA ◽  
Rita de Cássia N. Cubel GARCIA ◽  
Mônica MARZOCHE ◽  
Heloisa Helena A. Gallo da ROCHA ◽  
Maria Tereza M. PAULA ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Parvovirus B19 ◽  
Human Parvovirus B19 ◽  
Igg Antibodies ◽  
Cell Disease ◽  
Antibody Prevalence ◽  
Igg Antibody ◽  
Chronic Hemolytic Anemia

The prevalence of anti-human parvovirus B19 IgG antibodies was determined in sera from 165 chronic hemolytic anemia patients, receiving medical care at Instituto Estadual de Hematologia (IEHE), Rio de Janeiro, during the year of 1994. This sample represents around 10% of the chronic hemolytic anemia patients attending at IEHE. Most of these patients (140) have sickle cell disease. Anti-B19 IgG antibodies were detected in 32.1% of patients. No statistically significant difference (p > 0.05) was seen between IgG antibody prevalence in male (27.8%) and female (35.5%) patients. Anti-B19 IgG antibodies were more frequent in older (37.6%) than younger (28.2%) than 20 years old patients, although this difference had no statistical significance (p > 0.05). Anti-B19 IgG antibody prevalence showed that 67.9% of patients enrolled in the study were susceptible to B19 acute infection. With the aim to detect acute B19 infection, patients follow up continued until February 1996. During this period four patients presented transient aplastic crisis due to human parvovirus B19 as confirmed by the detection of specific IgM antibodies. All four patients were younger than 20 years old, and 3 were younger than 10 years old. Three of them were sickle cell disease patients. Three of the four acute B19 infection occurred during 1994 springtime.

Association of Pulmonary Hypertension with Sickle Cell Disease Subtypes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4824-4824
Author(s):  
Alice J. Cohen ◽  
Chaim Tuckman-Vernon
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Doppler Echocardiography ◽  
Beta Thalassemia ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Hemoglobin C ◽  
Baseline Hemoglobin

Abstract Pulmonary hypertension (PH) is a common complication of sickle cell disease (SD) and a significant cause of morbidity and mortality. PH, measured by Doppler echocardiography and defined as a tricuspid regurgitant jet velocity (TRV) > 2.5 m per second (m/s), is hypothesized to be related to the chronic hemolytic anemia of SD, but causality is unproven. If so, the presence of hemoglobin C, which reduces hemolysis, would be expected to have a reduced likelihood of PH. This study reviewed the prevalence of PH in 3 categories of patients with SD: homozygous S (SS), sickle-beta thalassemia (SB), and SC. Methods: Sickle cell disease patients registered at a state funded community comprehensive care adult sickle cell center were routinely screened for PH by Doppler echocardiography. The presence of PH, the incidence of a related complication, acute chest syndrome (ACS), and baseline hemoglobin (hgb) were reviewed. Results: 16 patients with SC type, 30 with SS and 39 with SB disease underwent screening. The prevalence of PH, ACS and hgb are listed in the table below. Conclusion: SC patients have PH and ACS similar to patients with SS and SB patients. These patients have higher baseline hemoglobin and may have hyperviscosity as a cause of PH and ACS as opposed to hemolytic anemia. Further study of PH and ACS in SC patients is warranted. SC SS SB p value PH 6/16 (38%) 12/40 (40%) 11/39 (28%) p= NS ACS 7/16 (44%) 10/30 (33%) 19/39 (49%) p=NS PH + ACS 4/16 (25%) 5/30 (17%) 4/39 (10%) p=NS ACS in PH patients 4/6 (67%) 5/12 (42%) 4/11 (36%) p-=NS Hgb 10.8 7.89 8.57 p=0.000

scholarly journals Senicapoc trial results support the existence of different sub-phenotypes of sickle cell disease with possible drug-induced phenotypic shifts

2011 ◽  
Vol 155 (5) ◽  
pp. 636-638 ◽  
Author(s):  
Oswaldo L. Castro ◽  
Victor R. Gordeuk ◽  
Mark T. Gladwin ◽  
Martin H. Steinberg
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Drug Induced

Thrombotic Thrombocytopenic Purpura in a Patient with Sickle Cell Crisis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3963-3963
Author(s):  
Jumana S. Chatiwala ◽  
Gunwant Guron ◽  
Ibrahim Sidhom
Keyword(s):  
Platelet Count ◽  
Sickle Cell Disease ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Microangiopathic Hemolytic Anemia ◽  
Cell Disease ◽  
Thrombocytopenic Purpura ◽  
Sickle Cell Crisis

Abstract Thrombotic thrombocytopenic purpura (TTP) in association with sickle cell crisis is rare. We present a case of sickle cell crisis and TTP. This is 48 years old Nigerian male with history of mild sickle cell anemia since childhood presented with sickle cell crisis and mental state changes. On admission labs are hematocrit of 20 and platelet count of 212,000. He was treated for sickle cell crisis but developed acute dysuria and progressively worsening anemia (Hct-13.7) and thrombocytopenia (Plt-9000) with sickle cell and fragmented RBCs on peripheral smear with LDH of 8772. This picture was consistent with TTP. Patient was immediately started on plasma exchange. Patient received a course of plasma exchange as well as hemodialysis and his condition improved, with return of platelet count to normal (232), LDH to baseline (276). Patient was discharged with mild renal insufficiency (serum creatinine-2.3) off dialysis and plasma exchange. Conclusion: TTP is a micro vascular occlusive disorder characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes. It is associated with pentard of signs and symptoms: thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on peripheral blood smear), neurological abnormalities, renal failure and fever. In practice thrombocytopenia, microangiopathic hemolytic anemia and elevated lactate dehydrogenase levels are often sufficient for the diagnosis. Our patient with sickle cell crisis was a diagnostic challenge and it is our belief that TTP evolved during inpatient therapy for painful crisis. We believe his hemolysis was due to sickle cell disease and TTP. The syndrome was reversed with prompt and aggressive treatment with plasmapharesis. (1, H. E. Lee, V. J. Marder, L. J. Logan, S. Friedman, B. J. Miller, Life-threatening thrombotic thrombocytopenic purpura (TTP) in a patient with sickle cell-hemoglobin C disease. Ann Hematol. 2003 Nov 82(11): 702–4. 2, Epub 2003 Aug 16. Chehal A, Taher A, Shamseddine A, Sicklemia with multi-organ failure syndrome and thrombotic thrombocytopenic purpura. Hemoglobin. 2002 Nov; 26(4): 345–51. 3, J. Bolanos-Meade, Y. K. Keung, C. Lopez-Arvizu, R. Florendo, E. Cobos, Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis. Ann Hematol. 1999 Dec 78(12): 558–9. 4, Geigel EJ, Francis CW, Reversal of multiorgan system dysfunction in sickle cell disease with plasma exchange. Acta Anaesthesiol Scand. 1997 May; 41(5): 647–50.)

scholarly journals Cardiovascular complications in patients with sickle cell disease

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 423-430 ◽  
Author(s):  
Mark T. Gladwin
Keyword(s):  
Sickle Cell Disease ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Single Point ◽  
Systolic Pressure ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Pulmonary Artery Systolic Pressure ◽  
Single Point Mutation ◽  
Cell Disease

Abstract Sickle cell disease (SCD) is an autosomal recessive disease in which homozygosity for a single point mutation in the gene encoding the β-globin chain produces hemoglobin S molecules that polymerize within the erythrocyte during deoxygenation; the result is sustained hemolytic anemia and vaso-occlusive events. As patients live to adulthood, the chronic impact of sustained hemolytic anemia and episodic vaso-occlusive episodes leads to progressive end-organ complications. This scenario culminates in the development of 1 or more major cardiovascular complications of SCD for which there are no approved or consensus therapies. These complications include elevated pulmonary artery systolic pressure, pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, sudden death, and chronic kidney disease with associated proteinuria, microalbuminuria, and hemoglobinuria. In patients with advancing age, cardiopulmonary organ dysfunction and chronic kidney injury have significant effects on morbidity and premature mortality. Over the last 15 years, a number of tests have been validated in multiple replicate cohort studies that identify patients with SCD at the highest risk of experiencing pulmonary and systemic vasculopathy and death, providing for screening strategies tied to targeted, more aggressive diagnostic and therapeutic interventions.

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