sickle cell disease and multiorganic failure

Sickle cell disease (SCD) is a hereditary hematological disease with high morbidity and mortality rates worldwide. Despite being monogenic, SCD patients display a plethora of disease-associated complications including anemia, oxidative stress, sterile inflammation, vaso-occlusive crisis-related pain, and vasculopathy, all of which contribute to multiorgan dysfunction and failure. Over the past decade, numerous small molecule drugs, biologics, and gene-based interventions have been evaluated; however, only four disease-modifying drug therapies are presently FDA approved...

Fat embolization syndrome (FES) is often seen as a complication of fractures and has been known to cause respiratory failure, rashes of the skin, thrombocytopenia, and neurological damage. Nontraumatic FES is uncommon and occurs due to bone marrow necrosis. Vaso-occlusive crisis in sickle cell patients secondary to steroid therapy is a rare entity and not widely acknowledged. We report a case of FES secondary to steroid therapy administered for a patient with intractable migraine. FES is an uncommon yet serious complication that occurs due to bone marrow necrosis and is usually associated with increased mortality or damaging neurologic sequelae for the surviving patient...

Sickle Cell Disease (SCD) is one of the most inherited hematologic diseases affecting humans. Clinically, there is a progressive multiorgan failure and increased mortality in severe cases. The highest prevalence is in West Africa, India, the Mediterranean region, and Middle East countries. Hydroxyurea was the primary drug available for SCD and remains first-line therapy for patients with SCD. Three additional drug therapies, L-glutamine, Voxelotor, and Crizanlizumab, have been approved as adjunctive agents...

Although a higher prevalence of antiphospholipid autoantibodies (aPL) has been observed in some cohorts of sickle cell disease (SCD) patients, the clinical risk factors for the development of aPL and its associated complications remain unclear. In a retrospective study of 63 SCD patients, a lower hemoglobin concentration and higher white blood cell count were independently associated with an elevated aPL. SCD patients with elevated aPL had increased pregnancy complications (≥3 miscarriages, preterm delivery, pre-eclampsia) and venous thrombotic events...

Sickle cell disease (SCD) is an autosomal recessive genetic condition characterized by the presence of a mutated form of haemoglobin (HbS). HbS polymerises into long needle-like fibres under low oxygen conditions, leading to the erythrocytes forming sickle shaped red blood cells. With repeated sickling, the red blood cells become irreversibly sickled and trapped within the circulation, and this leads to vaso-occlusive crisis. The patient, a 25-year-old female, previously undiagnosed with SCD, presented with high grade fever, splenomegaly and succumbed due to heat exertion precipitating sickling crisis, multiorgan failure and shock...

Haptoglobin (HP) is an acute phase protein and the main scavenger of cell-free hemoglobin. When haptoglobin is depleted, as observed in hemolytic conditions such as sickle cell disease (SCD), cell-free hemoglobin can lead to acute organ damage. The impact of the HP 1-1, 2-1, and 2-2 isoforms on HP and cell-free hemoglobin concentrations and SCD-related complications is unclear. In a longitudinal cohort of SCD patients, the HP 1 allele was associated with higher HP and lower cell-free hemoglobin concentrations at a routine clinic visit as well as during hospitalization for a vaso-occlusive episode (VOE) or acute chest syndrome...

Aluminum phosphide (AIP) is a fumigant commonly used in agricultural areas. AIP is frequently misused for suicidal purposes because it is easily accessible. AIP poisoning causes severe metabolic acidosis, resistant hypotension, acute respiratory distress syndrome, and multiorgan failure with cardiogenic shock. Despite supportive management and intensive care, most patients die following AIP ingestion because there is no specific antidote. In this case report we present a 15-year-old female who presented with vomiting, coma and epigastric pain...

Acute multiorgan failure syndrome (MOFS) remains a significant cause of mortality in sickle cell disease (SCD) patients despite red cell exchange (RCE). In small case series and reports, therapeutic plasma exchange (TPE) has shown benefit in MOFS. As further support for consideration of this modality, we present two patients with SCD and MOFS refractory to RCE who were subsequently treated with TPE. Fresh frozen plasma was used as the replacement fluid. Despite estimated hospital mortality of 40% at the time of intensive care unit admission, both patients showed marked clinical improvement with TPE treatment...

Sickle hepatopathy comprises a spectrum of disorders that vary in severity. Intravascular sickling and sinusoidal occlusion are the principal drivers of sickle hepatopathy, but infection or autoimmunity can act as triggers. We describe two cases of acute sickle hepatopathy initiated by primary Epstein-Barr virus (EBV) infection, a previously unreported association. The first case entailed a 14-year-old girl with hemoglobin SC (HbSC) disease who developed hepatic sequestration crisis that responded to a simple transfusion of erythrocytes...

Background: Sickle cell disease (SCD) is characterized by vaso-occlusive crisis (VOC), acute chest syndrome (ACS) and multiorgan failure (MOF) complicated by thrombosis. Von Willebrand factor (VWF) is a strong marker of SCD-related endothelial injury. Objectives: To decipher the role of VWF and its specific-cleaving metalloprotease, ADAMTS13, in the vaso-occlusive and thrombotic process of SCD. Patients/Methods: We investigated the VWF antigen (Ag), ADAMTS13 activity, ADAMTS13 Ag and ADAMTS13 IgGs in a cohort of 65 patients with SCD prospectively enrolled in a 20-month period from three centers...

Prevalence of haemoglobin sickle-β+ thalassaemia (Hb S/β+thal) is variable with geography ranging from 0.2% to 10% among sickle cell patients. Clinical presentation of Hb S/β+thal patients depends on HbA level, with milder disease often going undiagnosed. However, rarely these patients can present with a fulminant vaso-occlusive crisis (VOC). Given VOC can present with non-specific symptoms, the diagnosis and treatment is often delayed. Here, we present a patient who initially developed altered mental status, pancytopenia and multiorgan failure due a critical VOC resulting in bone marrow necrosis and fat embolism...

OBJECTIVE: To describe the outcomes of sickle-cell disease in pregnancy according to the different treatments adopted before and during pregnancy and to propose a systematic approach to treat sickle-cell disease (SCD) during pregnancy. METHODS: A retrospective descriptive study compared pregnancy outcomes among women with SCD who stopped hydroxyurea (HU) once pregnant (Group 1), were never treated before and during pregnancy (Group 2) or were treated by HU before conception who received prophylactic transfusion during pregnancy (Group 3)...

In the US, mortality in sickle cell disease (SCD) increases after age 18-20 years. Biomarkers of mortality risk can identify patients who need intensive follow-up and early or novel interventions. We prospectively enrolled 510 SCD patients aged 3-20 years into an observational study in 2006-2010 and followed 497 patients for a median of 88 months (range 1-105). We hypothesized that elevated pulmonary artery systolic pressure as reflected in tricuspid regurgitation velocity (TRV) would be associated with mortality...

Sickle cell disease (SCD) is an inherited disorder; despite significant improvements in supportive care, SCD continues to cause substantial morbidity, mortality, and reduced life expectancy. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only widely available curative therapy for SCD, which is offered as a standard of care for patients with a matched sibling donor (MSD). Donor availability is limited to a minority of patients. Thus, αβ/CD3-depleted haploidentical HSCT, as an efficient means for depletion of graft-versus-host disease (GvHD)-mediating T cells, can be offered as an alternative curative therapy, particularly for nonmalignant diseases such as SCD...

BACKGROUND: Hyperhemolysis syndrome (HHS) is a posttransfusion complication most frequently seen in sickle cell disease (SCD), characterized by rapid destruction of transfused and autologous red blood cells (RBCs), resulting in reticulocytopenia and a decrease in hemoglobin to below pretransfusion levels. Additional RBC transfusion can be life threatening. Most patients improve with intravenous immune globulin and steroids, but in refractory cases, hyperhemolysis may result in multiorgan failure and death in the absence of salvage therapy...

BACKGROUND: To describe the characteristics of dengue in sickle cell children and try to identify risk factors of severity. METHODS: In this retrospective study, we describe the evolution according to genotype (SS or SC and controls) and severity. RESULTS AND CONCLUSIONS: From 2005 to 2013, 106 hospitalizations for dengue fever were recorded, 35 SS genotype, 35 SC and 36 without SCD or any other chronic disease. The clinical evolution was quite different...

OBJECTIVE: Red blood cell exchange (RBCE) is the standard of care for patients with sickle cell disease (SCD) who present with severe vaso-occlusive crisis (VOC). However, subsets of these critically ill patients have progressive multiorgan failure (MOF) despite RBCE therapy. The purpose of this case series is to describe the use of plasma exchange (PLEX) for the treatment of SCD-related MOF that is refractory to RBCE. METHODS: A retrospective case review of patients with severe MOF from sickle cell crisis unresponsive to RBCE who underwent PLEX in a 14-bed adult medical intensive care unit (ICU) at a tertiary care university hospital over a 4-year time period...

Hemolytic diseases are frequently linked to multiorgan failure subsequent to vascular damage. Deciphering the mechanisms leading to organ injury upon hemolytic event could bring out therapeutic approaches. Complement system activation occurs in hemolytic disorders, such as sickle cell disease, but the pathological relevance and the acquisition of a complement-activating phenotype during hemolysis remain unclear. Here we found that intravascular hemolysis, induced by injection of phenylhydrazine, resulted in increased alanine aminotransferase plasma levels and NGAL expression...

While packed red blood cell (PRBC) transfusion therapy is a mainstay in the treatment of certain patients with sickle cell disease (SCD) and the standard of care for preoperative management, there are associated risks. Delayed hemolytic transfusion reaction (DHTR) is a risk of PRBC transfusion occurring 2 to 20 days from transfusion and typically presents with severe pain characteristic of vaso-occlusive crisis, fever, and hemolytic anemia. DHTRs are uncommon, occurring in only 4% to 11% of transfused patients with SCD, but may be catastrophic in nature with progression to multiorgan failure within hours...

Sickle cell disease is now a chronic adult illness characterized by progressive multiorgan failure, particularly involving the brain and kidney. The etiology is multifactorial; it includes hemolysis and nitric oxide deficiency. As patients age, most experience neurologic insult. Twenty-five percent of older adults have had a clinical stroke and at least half of the population have had a silent infarct, cortical atrophy, and neurocognitive impairment. Periodic screening with neuroimaging and neurocognitive testing is recommended...