scholarly journals Thrombomodulin and Multi‐Organ Failure in Sickle Cell Anemia

2021 ◽  
Author(s):  
Maria Armila Ruiz ◽  
Binal N. Shah ◽  
Guohui Ren ◽  
David Shuey ◽  
Richard D. Minshall ◽  
...  
Keyword(s):  
Organ Failure ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Multi Organ Failure

Evaluating Thrombocytopenia and Other Biomarkers in Multi-Organ Failure during Sickle Cell Crisis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4858-4858
Author(s):  
Krithika Shanmugasundaram ◽  
Ixavier Higgins ◽  
Fuad A El Rassi ◽  
Morgan L. McLemore
Keyword(s):  
Platelet Count ◽  
Organ Failure ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Laboratory Data ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Time To Death ◽  
Multi Organ Failure ◽  
Sickle Cell Crisis

Background: In sickle cell anemia, very few markers of disease have been shown to correlate with activity and severity of crisis. We aimed to identify any patterns amongst biomarkers and co-morbidities that correlate with death from multi-organ failure when admitted for sickle cell crisis. Methods: We identified 20 patients with sickle cell anemia who died of multi-organ failure at Grady Memorial Hospital from 2010-2016. We described baseline characteristics, such as hemoglobin phenotype, age, gender as well as features at presentation such as vital signs, laboratory data, clinical signs and symptoms (I.e. worsening pain), and co-morbidities. We examined bivariate associations between clinical characteristics and the length of survival after multi-organ failure. In a secondary analysis, we investigated clinical and demographic features that most accurately predict infection with gram-negative bacteria. To achieve this, we fit a multivariate logistic regression model and perform leave-one-out cross validation to assess the predictive performance of the fitted model on unseen data. Results: At baseline, the average age of a patient is 43.8 years (sd=14.7 years). A majority of our cohort are women (60%), do not smoke (70%), and were not on hydroxyurea (80%). Time to death from multi-organ failure was 3.05 days (95% C.I.: 0.20, 5.90), and only 43% identified having "worsening pain." Among complications, 23% had a stroke and 25% had an infection with gram-negative bacteria. With regards to laboratory data, average WBC was 13.4 (95% C.I.: 11.04, 15.70), Platelets 155 (95% C.I.: 102.22, 208.38), d-dimer 12,892 (95% C.I.: -2498.47, 33437.87) and ferritin 3108 (95% C.I.: 795.07, 5421.63). When using a univariate analysis, we identified that stroke (p=0.008), age (p=0.022) and platelet count at the time of presentation (p=0.039) correlated with time to death. We also identified a statistically significant decrease in the platelet count from baseline to time of multi-organ failure (-105.6, p<0.001). Body mass index (BMI) and worsening pain jointly predict infection with gram-negative bacteria with small error (0.133). Conclusion: We have described a cohort of patients with sickle cell anemia who died of multi-organ failure and found that some factors may have correlated with time to death. The most poignant factors include age, platelet count, and drop in platelet count from baseline. It is also interesting that a proportion of these patients developed a gram-negative bacterial infection, which is a common cause of mortality in sepsis. Although our cohort is small, these data may help guide future studies with larger cohorts of patients to identify what puts these patients at risk of death from multi-organ failure. Disclosures No relevant conflicts of interest to declare.

Sickle Cell Anemia and Major Organ Failure

Hemoglobin ◽  
1990 ◽  
Vol 14 (6) ◽  
pp. 573-598 ◽  
Author(s):  
Darleen R. Powars
Keyword(s):  
Organ Failure ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Major Organ

scholarly journals Successful Use of Plasma Exchange Preceding RBC Exchange in Sickle Cell Disease Hyperhemolytic Crisis with Hepatic Sequestration: A Case Report

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4279-4279
Author(s):  
Samir Atiya ◽  
Rosalyn I Marar ◽  
Aleh Bobr
Keyword(s):  
Case Report ◽  
Liver Failure ◽  
Organ Failure ◽  
Plasma Exchange ◽  
Sickle Cell ◽  
Case Reports ◽  
Multiorgan Failure ◽  
Multi Organ Failure ◽  
Free Heme ◽  
Pain Crisis

Abstract Introduction Hyperhemolytic crisis is an uncommon complication of SCD that may cause multiorgan failure and lead to significant mortality. There are no current national or international guidelines for management of hyperhemolytic crisis and associated complications. There have been limited number of case reports and series that demonstrated utility of plasma exchange in the patients with multiorgan failure resulting from hemolysis complications (Zaidi GZ et al.,2020). We are presenting the case where hyperhemolytic crisis was complicated by hepatic sequestration and acute liver failure, that was dramatically reversed by 2 plasma exchange treatments followed by RBC exchange. Case report We present a case of a 35-year-old African American male with SCD and beta thalassemia trait with frequent hospitalizations for sickle cell pain crisis. He presented with pain typical for his acute pain crises and was admitted for intravenous hydration and pain control. The next morning, lab work showed bicytopenia with a drop in hemoglobin from 10.5 to 5.8 g/dL and platelets (PLT) from 100 to 22 X10E3/uL. Lactate dehydrogenase (LDH) increased from 434 to 2848 U/L, haptoglobin was 36 mg/dL, but disseminated intravascular coagulation (DIC) and Heparin-induced Thrombocytopenia (HIT) antibody panel were negative. The blood urea nitrogen (BUN) creatinine (Cr) ratio was also elevated (30.6) suggesting renal damage as well. He was transferred to the intensive care unit and started on Intravenous Immunoglobulin (IVIG) 0.4 grams/kilogram daily for 5 days and methylprednisolone 500 mg daily for 2 days followed by a prednisone taper. Liver enzymes continued to trend upward with AST of 19,866 U/L and ALT of 3,675 U/L on day 3 of hospitalization. Ultrasound of abdomen demonstrated mild splenomegaly with a spleen measuring 13.3 cm. The clinical presentation and hepatocellular pattern of injury was consistent with hepatic sequestration crisis. Despite receiving 1 unit of platelet 3 units of pRBC, there was little improvement and apheresis service was consulted. Plasma exchange was initiated for 2 procedures on consecutive days followed by RBC exchange with rapid improvement in clinical status and laboratory findings with a reduction of LDH (1304), AST (129), ALT (204), Hgb (8.0), PLT (41), BUN/Cr (20.0). He was discharged on day 7 at baseline status. Discussion Although the mechanism of development of hyperhemolysis in SCD is not fully understood, the hemolysis leads to release of free hemoglobin (Hb) and free heme that activate neutrophils, and vascular endothelial cells via TLR-4. This ultimately leads to inflammatory, coagulative, and cytotoxic damages and decreased nitric oxide (NO) bioavailability which further contributes to SCD complications such as pulmonary and systemic vasculopathy, pain crisis and acute chest syndrome and multi organ failure (Louie JE et al., 2018). This provides a rationale for plasma exchange - removal of free heme from the patient plasma and replenishing exhausted haptoglobin and hemopexin reserves from donor plasma. Hemolytic crisis causing visceral organ damage is relatively rare. There are no current guidelines for management of such patients. In 1996 Betrosian et al. discussed the first case of liver failure in a SCD with vasa-occlusive crisis treated with RBC and plasma transfusions (Betrosian A et al., 1996). Since then, there have been case reports/series of plasma exchange/plasma transfusions in SCD with multi organ failure (Geigel EJ et al., 1997, Louie JE et al., 2018) but reports about use of plasma exchange in SCD patients with hepatic sequestration have not been identified by our literature review. Our case demonstrates that plasma exchange in hyperhemolysis and hepatic sequestration is: Safe Leads to quick and significant improvement in hemolysis laboratory values. Results in quick and durable reversal of hepatic sequestration and associated liver failure. Adds plasma exchange as therapeutic apheresis modality in addition to previously accepted RBC exchange. Provides data about priority of plasma exchange over RBC exchange in this clinical situation. Disclosures No relevant conflicts of interest to declare.

Improved Survival of Children and Adolescents with Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1425-1425
Author(s):  
Charles T. Quinn ◽  
Kimberly Thomas ◽  
Zora R. Rogers ◽  
George R. Buchanan
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Sickle Cell Disease ◽  
Organ Failure ◽  
Sickle Cell ◽  
Adolescents And Young Adults ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Multi Organ Failure

Abstract The survival of children with sickle cell disease (SCD) has improved over the past several decades, especially for very young children. However, we know less about mortality during adolescence, and we do not accurately know the current proportion of children born with SCD who survive to adulthood. The first report from the Dallas Newborn Cohort (DNC), which included follow-up through June 2002, estimated overall survival at 18 years of age to be 85.6% (95% C.I.: 73.4 – 97.8) for individuals with sickle cell anemia (SS) or sickle-β0-thalassemia (Sβ0) (Blood2004;103:4023–7). The confidence interval of this estimate was wide because only 8 cohort subjects were 18 years old at the time. Here we update the survival analysis with 5 more years of accrual and follow-up to provide an accurate, contemporary estimate of mortality for patients with SCD through 18 years of age. The DNC includes all individuals with SS, Sβ0, sickle-hemoglobin C disease (SC), or sickle-β+-thalassemia (Sβ+) who were diagnosed by the newborn screening program of Texas (initiated November 1, 1983) and seen at least once in our center. Subjects were analyzed in two separate groups because of clinical similarity: SS/Sβ0 and SC/Sβ+. Overall survival was analyzed by the Kaplan-Meier method. Subjects were censored at the time of their last clinical encounter. Between July 2002 and July 2007 we identified 229 new members of the DNC and added 3,201 additional patient-years of follow-up. The cohort now includes 940 subjects (572 SS, 284 SC, 63 Sβ+, 21 Sβ0; 52.8% male), and it provides a total of 8,857 patient-years of follow-up (5,819 SS/Sβ0 patient-years, 3,039 SC/Sβ+ patient-years). Mean follow-up is 9.4 years (range 0.1– 20.6 years), and 97 subjects are now at least 18 years of age at last follow-up. To date, 92 subjects (9.8%) have been lost to follow-up (not seen for &gt;5 years), and 33 subjects have died (30 SS/Sβ0, 3 SC/Sβ+). There were 7 new deaths in DNC patients since 2002, all of which occurred in patients who were 18 years of age or older. Of all deaths, 23 were SCD-related (5 acute chest syndrome, 5 sepsis, 4 multi-organ failure syndrome, 9 other), and 10 were apparently unrelated to SCD (4 trauma or accidental death, 6 unrelated medical conditions). All SC/Sβ+ deaths were apparently unrelated to SCD. Overall survival at 18 years was 93.9% (95% C.I. 90.3 – 96.2; 81 patients &gt; 18 years of age) for SS/Sβ0 subjects and 98.4% (95% C.I. 94.4 – 99.5; 16 patients &gt; 18 years) for SC/Sβ+ subjects. The overall incidence of death in the SS/Sβ0 and SC/Sβ+ subgroups was 0.52 and 0.10 per 100 patient-years, decreased from 0.59 and 0.24 in the original DNC analysis. Survival also appears to be improving across cohort eras (Figure). In conclusion, approximately 6% of children with SS or Sβ0 die during childhood, but almost all children with SC or Sβ+ live to become adults. Although early childhood mortality has greatly decreased, we show that many adolescents and young adults still die from SCD. Notably, acute chest syndrome and multi-organ failure have now surpassed sepsis as the leading causes of death. These data provide the accurate, contemporary foundation for the counseling of parents of newborns with SCD and for genetic counseling for prospective parents. Finally, given the marked decrease in early mortality we show here, new efforts to improve survival in SCD should focus on adolescents and young adults. Figure Figure

Erythrocytapheresis in Sickle Cell Disease and Multi-Organ Failure in the Intensive Care Unit.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4627-4627
Author(s):  
Shatha Y. Farhan ◽  
Ileana Lopez_Plaza
Keyword(s):  
Organ Failure ◽  
Sickle Cell ◽  
Carrying Capacity ◽  
Exchange Transfusion ◽  
Red Cell ◽  
Cell Disease ◽  
The Third ◽  
Multi Organ Failure ◽  
Liver And Kidney ◽  
Oxygen Carrying Capacity

Abstract Abstract 4627 Introduction Patients with sickle cell disease (SCD), including those with homozygosity for hemoglobin (Hb) S (SCD-SS) or compound heterzygosity for sickle and Hb C (SCD-SC), suffer from chronic variable intravascular hemolysis, microvascular ischemia and organ damage. Vaso-occlusion results from a dynamic combination of abnormalities in hemoglobin S structure and function, red blood cell membrane integrity, erythrocyte density, endothelial activation, microvascular tone, inflammatory mediators, and coagulation. HbC enhances, by dehydrating the SC red cell, the pathogenic properties of HbS, resulting in a clinically significant disorder, but somewhat milder sickle cell anemia. The management of SCD continues to be supportive and includes hydration, pain relief, blood transfusion and psychosocial support. However, transfused red cells will significantly increase blood viscosity, potentially reducing blood flow, if the Hb level rises above 10 g/dL. Therefore, if the goal is an acute reduction in the proportion of sickled red cells in addition to an increase in oxygen-carrying capacity, exchange transfusion is the therapy of choice. We report 3 cases of (SCD-SS) and (SCD-SC) disease with multi-organ failure syndrome who were admitted to our intensive care unit (ICU) between January and July 09 where Erythrocyatperesis was effective but somewhat delayed. Report The first patient is a 46-year old male with SCD-SC disease who presented with severe leg, back, and chest pain. He was treated with intravenous fluid and nasal oxygen supplementation. Chest pain was sustained with severe hypoxemia, elevated troponins and somnolence developed third day of hospitalization. Fourth day he became more lethargic, breathing at 35/ min. His labs showed acute liver and kidney injury. The patient was transferred to ICU. In spite of respiratory and medical support, his medical status worsened, so hematology team was consulted and red cell exchange transfusion was made with subsequent improvement in mental status. The second patient was a 45 year old patient with SCD-SC disease who was found at home confused, complaining of back, chest and extremities pain, with unsteady gait and labored breathing. In Emergency Department (ED) he was hypotensive with abdominal tenderness and hypoactive bowel movements. His labs showed acute hepatic and renal injury with severe metabolic acidosis. Patient was resuscitated with IV fluids and intubated. CT scan of the abdomen showed diffuse bowel inflammation. On the third day of admission, hematology team was consulted and Erythrocytapheresis was started. His mental status improved slowly but he continued to have a seizure disorder and had to be on hemodialysis. The third patient is a 46 year old with SCD-SS disease and chronic lower extremity ulcers who had recurrent admissions for hyperpigmented gallstones and endoscopic retrograde cholangiopancreatography with stent placements. He presented to ED with nausea, vomiting, diarrhea and fever for 3 days. He was found hypotensive, tachycardic, with respiratory distress and acute liver and kidney abnormalities on labs. He was intubated and started on fluids and antibiotics. Thirty hours post admission he underwent erythrocytapheresis. Conclusion Red cell exchange transfusions remain an effective but possibly underutilized and delayed therapy in acute sickle cell complications, especially acute chest and the multi-organ failure syndromes. It can provide needed oxygen carrying capacity while reducing the overall viscosity of the blood. Although the need for a central line and the requirement for sickle- negative, as-fresh-as-possible blood, matched for minor antigens are major reasons for delay, it seems that it is mostly delayed for clinical reasons, trying to rule out other disorders or contributing factors and when the apheresis starts the patients are in the hospital/ICU for days already. We conclude that in patients with sickle cell disorder (SS or SC) being hypoxic and with chest or multi-organ failure syndrome, red cell exchange transfusion is effective treatment modality and should be initiated as soon as possible. Disclosures: No relevant conflicts of interest to declare.

The orientation of sickle hemoglobin fibers within fascicles

1988 ◽  
Vol 46 ◽  
pp. 400-401
Author(s):  
Christopher A. Miller ◽  
Bridget Carragher ◽  
William A. McDade ◽  
Robert Josephs
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Relative Orientation ◽  
Unit Cell ◽  
Red Cell ◽  
High Ph ◽  
Sickle Hemoglobin ◽  
Polar Crystal ◽  
Helical Configuration

Highly ordered bundles of deoxyhemoglobin S (HbS) fibers, termed fascicles, are intermediates in the high pH crystallization pathway of HbS. These fibers consist of 7 Wishner-Love double strands in a helical configuration. Since each double strand has a polarity, the odd number of double strands in the fiber imparts a net polarity to the structure. HbS crystals have a unit cell containing two double strands, one of each polarity, resulting in a net polarity of zero. Therefore a rearrangement of the double strands must occur to form a non-polar crystal from the polar fibers. To determine the role of fascicles as an intermediate in the crystallization pathway it is important to understand the relative orientation of fibers within fascicles. Furthermore, an understanding of fascicle structure may have implications for the design of potential sickling inhibitors, since it is bundles of fibers which cause the red cell distortion responsible for the vaso-occlusive complications characteristic of sickle cell anemia.

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