Sickle cell disease: Overview of management during hospital admission

INTRODUCTION — 

This topic discusses management when an individual with sickle cell disease (SCD) is admitted to the hospital.

Separate topics discuss:

●Prevention of complications – Primary prevention of the acute complications of SCD includes routine health management with a hematologist or a health care provider with expertise in SCD. Initial prevention of complications includes the use of penicillin prophylaxis started in the newborn period, appropriate immunizations, and blood transfusions for those at risk for stroke. (See "Overview of preventive/outpatient care in sickle cell disease" and "Sickle cell disease in infancy and childhood: Routine health care maintenance and anticipatory guidance".)

Therapies to prevent pain episodes in SCD including hydroxyurea, L-glutamine, and others are discussed separately. (See "Hydroxyurea use in sickle cell disease" and "Disease-modifying therapies to prevent pain and other complications of sickle cell disease" and "Investigational pharmacologic therapies for sickle cell disease".)

●Curative therapies – A life-long cure for SCD is available only through hematopoietic stem cell transplantation or gene therapy/gene editing approaches. (See "Curative therapies in sickle cell disease including hematopoietic stem cell transplantation and gene therapy".)

●Pregnancy and pre-pregnancy care – (See "Sickle cell disease: Obstetric considerations" and "Hemoglobinopathy: Screening and counseling in the reproductive setting and fetal diagnosis".)

●Transition from pediatric to adult care – (See "Sickle cell disease (SCD) in adolescents and young adults (AYA): Transition from pediatric to adult care".)

●Treatment of complications – Separate topics discuss management of:

•Bone and joint complications – (See "Acute and chronic bone complications of sickle cell disease".)

•Acute chest syndrome – (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)".)

•Cerebrovascular disease – (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease".)

•Fever – (See "Evaluation and management of fever in children and adults with sickle cell disease".)

•Liver disease and gallstones – (See "Hepatic manifestations of sickle cell disease".)

•Pain management – (See "Acute vaso-occlusive pain management in sickle cell disease".)

•Priapism – (See "Priapism and erectile dysfunction in sickle cell disease".)

•Pulmonary complications – (See "Overview of the pulmonary complications of sickle cell disease".)

•Pulmonary hypertension – (See "Pulmonary hypertension associated with sickle cell disease".)

•Kidney manifestations – (See "Sickle cell disease effects on the kidney".)

•Transfusion-associated iron overload – (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications".)

OVERVIEW — 

Individuals with SCD who are hospitalized require vigilance for many of the same conditions as those without SCD, as well as some that are specific to their disease. It is important to review the patient's entire problem list and history of complications. These findings will influence management regardless of the initial reason for admission.

Most deaths occur in patients with SCD during a hospitalization, and acute events often occur in patients who at admission were thought to be relatively stable. Unexpected events may develop after admission including acute chest syndrome, pulmonary embolism, fat embolism syndrome, stroke, acute kidney injury, cardiac events, and thrombosis. Knowledge of these risk factors and comorbid chronic disease may improve early detection and treatment. Knowledge of existing risk factors for each patient may require modification of routine orders to minimize complications during hospitalization.

Inpatient management issues that should be considered regardless of the admission diagnosis include:

●Building rapport. (See 'Communication' below.)

●Hydration status. (See 'Hydration' below.)

●Incentive spirometry and prevention of acute chest syndrome. (See 'Incentive spirometry' below.)

●Venous thromboembolism (VTE) prophylaxis. (See 'Thromboembolism prophylaxis' below.)

●Adequate pain control, regardless of the reason for admission. (See 'Pain control' below.)

●Appropriate use of transfusions. (See 'Role of transfusions' below.)

●Review of medications to continue during hospitalization and on discharge, and medications to avoid. (See 'Medication management' below.)

●Monitoring of hematologic parameters, liver and kidney function (hyperkalemia and metabolic acidosis is common due to renal tubular dysfunction and may lead to worsening disease). (See 'Monitoring pulmonary, hematologic status and liver and kidney function' below.)

Communication — Racial bias and health-related stigmas can lead to maladaptive or distrustful patient behavior that can impact hospital outcomes.

Studies indicate patients with SCD report poorer provider communication compared with controls (African-American patients without SCD) in several communication domains [1]. This includes reports that providers do not listen (22 percent, versus 12 percent in controls; p<0.0001); they do not show respect (26 percent, versus 10 percent in controls; p<0.0001); and they do not spend enough time addressing patient needs (38 percent, versus 16 percent in controls; p<0.0001). Providers should be aware of the risk of poor-quality interactions and minimize this by optimal communication from the onset of the admission.

Children with SCD with mental health disorders have an independent increase in the rate of hospitalization, and adults with mental health disorders have early mortality [2,3]. (See "Overview of preventive/outpatient care in sickle cell disease", section on 'Mental health'.)

The dehumanizing term "sickler" should never be used to refer to an individual with SCD. Individuals with SCD and their families/caregivers consider the term derogatory. Providers in the emergency department who used the term "sickler" were demonstrated to have a negative attitude toward individuals with SCD [4]. Other terms to avoid and additional discussion of provider attitudes that interfere with appropriate care are discussed separately. (See "Acute vaso-occlusive pain management in sickle cell disease", section on 'Overview of the role of provider attitudes on effective treatment'.)

Hydration — Adequate hydration is important to reduce complications of SCD during hospitalization. Inadequate hydration leads to increased plasma osmolality and Hb S polymerization. The choice of replacement fluid depends on the patient's volume status and whether transfusion is required.

●Transfusions – For those who require transfusion (such as for splenic sequestration crisis or transient aplasia from infection), transfusion should not be delayed while giving other fluids, but modification of crystalloid infusion rate may be needed to prevent fluid overload. Extended crossmatching is appropriate. (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Symptomatic or severe anemia'.)

●Hypovolemia – If the patient is hypovolemic, lactated ringers solution may be a better choice than normal saline (0.9 percent saline). This is due to emerging preclinical and clinical evidence indicating a possible benefit of lactated ringers solution over normal saline [5-7].

As an example, a 2024 observational study comparing the effectiveness of lactated ringers solution and normal saline in patients hospitalized with pain demonstrated a small but significant increase in hospital-free days and lower readmission rate in the patients treated with lactated ringers solution [7]. (See "Treatment of severe hypovolemia or hypovolemic shock in adults" and "Shock in children in resource-abundant settings: Initial management".)

●Maintenance fluids – If the patient is euvolemic (or has become euvolemic after fluid replacement), maintain euvolemia using oral fluids, intravenous fluids, or a combination of oral and intravenous fluids.

•Avoid fluid overload – Attention should be paid to avoiding fluid overload. In one study involving electronic medical record review of 230 consecutive hospital admissions for vaso-occlusive pain in 100 patient with SCD, fluid overload developed during 25 hospitalizations (11 percent) [8]. This emphasizes the importance of close monitoring of weight and fluid balance. (See 'Monitoring pulmonary, hematologic status and liver and kidney function' below.)

•Encourage oral fluids – If the patient is euvolemic and able to take oral fluids adequately, this should be encouraged.

•Choice of intravenous fluids – For those receiving maintenance intravenous fluids, we use one-quarter or one-half normal saline with or without glucose. This approach differs from maintenance fluid replacement in patients without SCD [7].

We do not use normal saline as a maintenance fluid in individuals with SCD. Patients with SCD may have a decreased ability to excrete urinary sodium and may become hypernatremic from receiving normal saline. Hypernatremia in turn may lead to RBC dehydration, which increases sickling. Normal saline should only be used when a patient is hypovolemic. (See "Maintenance intravenous fluid therapy in children" and "Maintenance and replacement fluid therapy in adults".)

Incentive spirometry — Incentive spirometry is used to reduce the risk of acute chest syndrome. Nurses and patients must be instructed to ensure the patient does 10 incentive spirometry breaths every two hours when awake. (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Incentive spirometry during hospitalization' and "Atelectasis in children", section on 'Prevention' and "Strategies to reduce postoperative pulmonary complications in adults".)

A randomized controlled trial demonstrated the clear benefit of using incentive spirometry to reduce the risk of acute chest syndrome [9].

For young children and adults in low-middle income settings, where incentive spirometry is not available, balloons should be offered as an alternative. (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Respiratory support' and "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Incentive spirometry during hospitalization'.)

Thromboembolism prophylaxis — Patients with SCD appear to have a hypercoagulable state at baseline, and they often have other factors that further increase the risk of venous thromboembolism (VTE) (eg, indwelling catheter, immobility, infection) [10].

●Adults – For all individuals >18 years with SCD who are admitted to the hospital for an acute medical condition, we recommend thromboprophylaxis. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults" and "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".)

●Children and adolescents – We do not use routine thromboprophylaxis for VTE in hospitalized children and adolescents under 18 years of age. General recommendations regarding thromboprophylaxis in children are discussed separately. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Approach to VTE prophylaxis'.)

Pain control — Vaso-occlusion can cause severe pain. However, it is important not to assume that all pain is not vaso-occlusive pain. Individuals with SCD can develop other complications including serious infections (appendicitis, pelvic inflammatory disease, pneumonia), gallstones, splenic infarction or sequestration, pulmonary embolism/infarction, and others. Also, these individuals can have serious causes of pain unrelated to SCD. (See "Evaluation of acute pain in sickle cell disease", section on 'Potentially serious conditions associated with pain'.)

Pain in the abdomen or chest requires a thorough evaluation for these other conditions, especially if there is also fever and/or elevated white blood cell (WBC) count (algorithm 1). The table summarizes other potential complications that may present with acute pain (table 1).

While it is critical to consider and appropriately evaluate for these other causes of pain, analgesia should be provided promptly and not withheld while performing the evaluations. There are no validated objective measures on examination or laboratory findings that correlate with pain severity. The patient's report is the gold standard to assess severity and quality of pain, as well as response to therapies. When available, the individual's personalized pain plan should be followed, with frequent monitoring of efficacy and attention to monitoring for sedation and hypoxia. The tables summarize acute pain management principles (table 2) and long-term pain management considerations (table 3); these are discussed in more detail separately. (See "Acute vaso-occlusive pain management in sickle cell disease", section on 'Management in the ED and hospital'.)

Monitoring pulmonary, hematologic status and liver and kidney function — An acute pain admission is often associated with or precedes other complications and can be minimized by close monitoring of vital signs, examination findings, and laboratory results.

●Vital signs – Daily temperature, heart rate, respiratory rate, pulse oximetry, weight, and fluid balance are essential to detect common inpatient complications.

•BP – Some individuals with SCD have lower baseline systolic and diastolic blood pressure compared to individuals without SCD. Mild elevations, or relative hypertension, may become clinically significant and may lead to disease manifestations such as stroke. (See "Sickle cell disease effects on the kidney", section on 'Blood pressure abnormalities'.)

•Fever – Individuals with SCD are functionally asplenic due to splenic infarction and are at increased risks for sepsis, acute chest syndrome, and other infections. All fevers require evaluation and usually empiric antibiotics. (See 'Infections' below and "Evaluation and management of fever in children and adults with sickle cell disease".)

●Respiratory status – Acute pulmonary disease often complicates hospital admission. Imaging is needed in patients with fever, hypoxia, or respiratory symptoms. Rib infarction-induced splinting, opioid-related hypoventilation, and overhydration-induced pulmonary edema can initiate acute chest syndrome. Acute pulmonary embolism is common in adults with SCD and must be considered. (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)".)

●Laboratory – Serial monitoring of complete blood count (CBC), reticulocyte count, and metabolic panel are helpful in detecting emerging complications. Many patients have red blood cell alloantibodies and require extended crossmatching to identify compatible units of blood. Early phenotyping for units may be needed to obtain appropriate units.

•CBC – A clinically significant fall in hemoglobin may occur and is often associated with developing problems that may require transfusion. The reticulocyte count and hemolysis markers may suggest a hemolytic event such as a delayed transfusion reaction or hypoplastic complication.

•Metabolic panel – Metabolic and electrolyte changes caused by acute kidney injury (AKI), including renal tubular acidosis, can result in anion gap and potassium and electrolyte abnormalities.

AKI is common in hospitalized patients and is often diagnosed late. It usually resolves, but it is a risk factor for increased proteinuria, hypertension, and chronic kidney disease. An increase in serum creatinine by ≥0.3 mg/dL within a 48 hour period or by ≥1.5 times the individual's baseline is a cause for concern and warrants nephrology evaluation.

Role of transfusions — Transfusions are used in the acute and chronic management of many complications related to SCD, as discussed separately. The goals of red blood cell transfusion are to treat clinically symptomatic anemia by increasing hemoglobin for oxygen delivery and/or to lower the percentage of sickle hemoglobin (Hb S) to decrease sickling. (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Indications for transfusion'.)

Some of the main considerations include:

●There is no role for transfusions in routine treatment of acute vaso-occlusive pain episodes, unless there is severe, acute anemia.

●For acute anemia, transfusions should be based on symptoms rather than a specific hemoglobin threshold.

●Simple transfusion is used preoperatively to reduce the risk of complications. (See 'Surgical considerations' below and "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Prophylactic preoperative transfusion'.)

●Exchange transfusion is used for:

•Acute stroke – (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease", section on 'Transfusion'.)

•Acute chest syndrome – (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Transfusion'.)

•Acute splenic or hepatic sequestration – (See 'Splenic and hepatic sequestration' below.)

•Multi-organ failure – (See 'Multi-organ failure' below.)

●For individuals who require transfusion and have a high baseline hemoglobin, exchange transfusion is needed. Exchange transfusion may be manual or automated. (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Simple versus exchange transfusion'.)

Transfusions carry risks of acute and delayed hemolytic transfusion reactions as well as iron overload. (See "Transfusion in sickle cell disease: Management of complications including iron overload".)

Discharge instructions — Prior to discharge, it should be ensured that the patient has adequate hemoglobin and pain control. For younger adults who may have less experience managing pain at home, we often recommend 24 hours of an oral regimen to ensure that pain control is adequate. For older adults with more experience managing pain at home, we often monitor for at least 12 hours off of intravenous opioids.

Additional considerations include:

●Make sure the individual has sufficient and appropriate home pain medication available, coordinated with their primary care physician.

●Follow up within two weeks decreases the high readmission rate.

●Communication with the primary clinician, including discussions clarifying what to do or who to call if symptoms return.

●When indicated, review withdrawal symptoms and management.

MEDICATION MANAGEMENT

Continue hydroxyrea and other oral medications — Most oral medications are continued during hospitalization if they are well-tolerated.

●Hydroxyurea should be continued during hospitalization, if there is no excess hematologic toxicity. (See "Hydroxyurea use in sickle cell disease".)

●L-glutamine is continued. (See "Disease-modifying therapies to prevent pain and other complications of sickle cell disease", section on 'L-glutamine (pharmaceutical grade)'.)

●Children taking penicillin should continue it unless started on broad spectrum antibiotics. (See "Overview of preventive/outpatient care in sickle cell disease", section on 'Prophylactic penicillin'.)

●Folic acid is continued. (See "Overview of preventive/outpatient care in sickle cell disease", section on 'Nutrition'.)

Caution with NSAIDs — Nonsteroidal antiinflammatory drugs can be an important component of management, but extra caution is required in people with SCD due to risks of kidney, gastrointestinal, and potentially cardiac toxicities [11]. (See "Nonselective NSAIDs: Overview of adverse effects" and "NSAIDs: Adverse cardiovascular effects".)

For treating fever and mild pain, acetaminophen is preferred. In patients with normal kidney function and no history of gastrointestinal ulcers, we will use an NSAID for up to five consecutive days if needed, such as for treatment of mild pain. (See "Acute vaso-occlusive pain management in sickle cell disease", section on 'Role of NSAIDs'.)

Young patients with SCD have glomerular hyperfiltration, which lowers creatinine. A rising trend in creatinine in a patient with SCD of any age indicates possible NSAID kidney toxicity even if the creatinine is in the normal range.  

Avoid G-CSF — Case reports have indicated that the use of granulocyte colony-stimulating factor (G-CSF) in individuals with SCD, including some compound heterozygous SCD syndromes (Hb SC disease and Hb S-beta⁺ thalassemia), has been associated with sickle cell vaso-occlusion and multiorgan failure; at least one individual (a hematopoietic stem cell donor for a sibling) died as a result of this complication [12-14]. G-CSF may also play a role in the acute chest syndrome and the complications associated with it [15].

We and others therefore do not use G-CSF in individuals with Hb SS or compound heterozygous SCD syndromes [16,17]. However, there may be a rare case in which the potential benefits of G-CSF therapy outweigh the risks (eg, treatment of chemotherapy-induced fever with sepsis), and the judicious use of G-CSF may be justified [16,18]. Instead of G-CSF, the ongoing gene therapy trials in SCD are using the CXCR4 antagonist plerixafor for stem cell mobilization. (See "Curative therapies in sickle cell disease including hematopoietic stem cell transplantation and gene therapy", section on 'Gene therapies'.)

In contrast to those with sickle cell disease, individuals with sickle cell trait may receive G-CSF [16,19]. (See "Sickle cell trait", section on 'Blood and stem cell donation'.)

ACUTE SCD COMPLICATIONS

Infections — Infection is a frequent complication of SCD, as individuals with SCD are functionally asplenic. Historically, infections have been the major cause of death in children.

Infection can be the reason for presenting to the hospital or it can develop in patients with SCD who are hospitalized for other reasons. Fever may be the first indication of a serious bacterial infection, and as such should be considered a medical emergency. Patients should seek prompt medical attention and be rapidly evaluated for a temperature >38.5°C (101.5°F).

An overview of infection management in individuals with SCD is presented separately. (See "Evaluation and management of fever in children and adults with sickle cell disease".)

●The evaluation should include a brief history for localizing symptoms and an abbreviated physical examination focused on hemodynamic stability, signs of localized or generalized infection, splenic size, and evidence of stroke. (See "Evaluation and management of fever in children and adults with sickle cell disease", section on 'Initial evaluation'.)

●Individuals with chest pain, respiratory symptoms, or hypoxia should be evaluated for acute chest syndrome and treated if indicated. (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Diagnostic evaluation'.)

●During the COVID-19 pandemic, testing for SARS-CoV-2 infection is appropriate for any individual with SCD who presents with fever. (See "Clinical features, evaluation, and management of fever in patients with impaired splenic function", section on 'COVID-19 considerations'.)

●Blood cultures and complete blood count (CBC) with differential and reticulocyte count should be obtained. Empiric parenteral antibiotics should be started as soon as possible, ideally within 60 minutes of triage. Evaluation for pneumonia is important [20]; however, antibiotics should not be delayed while awaiting chest radiography. (See "Evaluation and management of fever in children and adults with sickle cell disease", section on 'Empiric antibiotic therapy'.)

Splenic and hepatic sequestration

Clinical presentation of splenic sequestration — Splenic sequestration is a potentially life-threatening complication of SCD that requires admission to the hospital for maintenance of hemodynamic stability [21,22]. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Splenic or hepatic sequestration crisis'.)

Splenic sequestration in SCD is characterized by the following four features:

●Splenic enlargement, often tender

●A drop in hemoglobin concentration of at least 2 g/dL

●Thrombocytopenia

●Reticulocytosis

It is possible to have splenomegaly without splenic sequestration; the difference is that splenic sequestration is characterized by the constellation of findings listed above. Involvement of a SCD expert should be sought whenever possible.

Splenic sequestration is commonly observed in infants and children, including those as young as two months of age [23,24]. Less commonly, acute splenic sequestration episodes may occur in adolescents and adults, particularly those with hemoglobin SC (Hb SC) disease [25,26]. (See "Overview of compound sickle cell syndromes", section on 'Hb SC disease'.)

The primary concern in the event of a splenic sequestration episode is hypovolemic shock resulting from a disproportionate amount of the intravascular blood volume being sequestered in the spleen because of ensnared red and white blood cells. Hence, management should be directed at maintaining the individual in a euvolemic state.

Hepatic sequestration can also occur; this complication and its management are discussed separately. (See "Hepatic manifestations of sickle cell disease", section on 'Acute hepatic sequestration'.)

Splenic sequestration initial management — The optimal management of an acute splenic sequestration episode is based on the following principles:

●A high index of suspicion when an individual presents with a sudden drop in hemoglobin, thrombocytopenia, reticulocytosis, and an enlarged spleen.

●Assessment of volume status and immediate intravenous fluid resuscitation if needed, with the goal of maintaining the individual in a euvolemic state [27,28]. This may require administration of isotonic solution. (See 'Hydration' above.)

When the individual is hypovolemic and is symptomatic from anemia (tachycardia, increased respiratory rate or respiratory effort, orthostatic hypotension, decreasing oxygen saturation [and/or increasing oxygen requirement to maintain saturation]), a simple blood transfusion should be considered. Individuals who do not have symptomatic anemia do not require transfusion. Oxygen should be administered to maintain the oxygen saturation ≥95 percent but should not be used prophylactically as it may mask desaturation. (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Respiratory support'.)

However, caution should be used when transfusing the individual, as the blood trapped in the spleen is still available to re-enter the circulation. Accordingly, following such transfusion the individual's hemoglobin may rise acutely to levels that result in hyperviscosity syndrome. (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Symptomatic or severe anemia'.)

To decrease the likelihood of hyperviscosity syndrome occurring after a simple blood transfusion, we typically transfuse the individual with approximately 50 percent of what we would commonly transfuse. Thus, instead of transfusing an adult with two units of blood, we transfuse a single unit of blood or calculate (and deliver) the amount of blood needed to get the individual back to their baseline level and re-evaluate the clinical status after transfusion. For a child, we would use 5 mL/kg instead of 10 mL/kg. (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Risk of hyperviscosity syndrome from simple transfusion'.)

Prevention of splenic sequestration is discussed separately. (See "Overview of preventive/outpatient care in sickle cell disease", section on 'Prevention of splenic sequestration'.)

Hepatic sequestration — Management of hepatic sequestration is discussed separately. (See "Hepatic manifestations of sickle cell disease", section on 'Acute hepatic sequestration'.)

Multi-organ failure — Multiorgan failure is an acute emergency in SCD that carries a high mortality rate [29]. It is defined as dysfunction in two of three major organ-systems (lungs, liver, kidneys). The mechanism is incompletely understood; it is thought to involve vaso-occlusion resulting in bone marrow necrosis and fat emboli, causing widespread sickling throughout the body affecting multiple organ systems simultaneously with ischemia or infarction. It can progress rapidly, especially in patients with preexisting organ dysfunction. The clinical course may include hypoxemic respiratory distress and acute liver injury, with hyperbilirubinemia, neurologic disorientation, and thrombocytopenia. (See "Overview of the clinical manifestations of sickle cell disease", section on 'Multi-organ failure'.)

Rapidly progressive acute chest syndrome may occur as the precipitating event, or acute chest syndrome may occur later in the course of multiorgan failure. (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)", section on 'Clinical features'.)

Key principles of management in patients with SCD include:

●Exchange transfusion – Prompt red blood cell (RBC) exchange transfusion to reduce the percentage of Hb S to <30 percent is the most important intervention. Hypotension is not a contraindication to performing exchange transfusion.

The decision to initiate exchange transfusion is individualized and time-sensitive; this is because rapid clinical deterioration can occur, and the complexity of the procedure requires coordination of multiple services. This includes mobilization of the apheresis service, need for a central line, and need to obtain sufficient units of compatible RBCs. These details are discussed separately. (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Exchange blood transfusion'.)

In the absence of a randomized trial, we recommend RBC exchange for a patient with multi-organ failure due to the high mortality rate. If there is any delay in initiating an exchange transfusion, a simple transfusion may be provided in the interim, with a target hemoglobin of 10 g/dL; this can help protect the patient while an apheresis team is mobilized.

Case reports and case series suggest improved outcomes with exchange transfusion in patients with multi-organ failure [29,30]. A randomized trial comparing simple transfusion to exchange transfusion is not likely to be performed in multi-organ failure, since this is a relatively rare complication. RBC exchange remains a Category III indication according to the American Society for Apheresis (ASFA), since the data are limited and the role for apheresis is not well established [31]. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology", section on 'ASFA therapeutic categories'.)

●Plasma exchange – Because some presentations have features of thrombotic microangiopathies (disseminated intravascular coagulation [DIC], thrombotic thrombocytopenic purpura [TTP], or complement-mediated thrombotic microangiopathy [CM-TMA]), a trial of plasma exchange to remove free heme, hemoglobin, and inflammatory mediators and give back haptoglobin, hemopexin, and ADAMTS13 could be considered, especially if RBC exchange transfusion is ineffective [32]. (See "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)".)

If the patient’s clinical condition is not improved in 24 hours, we would consider a trial of plasma exchange procedure. For patients with multi-organ failure unresponsive to RBC exchange, two case series have reported therapeutic benefit from plasma exchange therapy [33,34]. (See "Therapeutic apheresis (plasma exchange or cytapheresis): Indications and technology".)

●Supportive care – Aggressive supportive care in the intensive care unit (ICU) may include (but is not limited to) intubation and hemodialysis. Extracorporeal membrane oxygenation (ECMO) support may be used, since the process is potentially reversible [35,36]. Anti-complement therapies have also been tried. (See "Extracorporeal life support in adults in the intensive care unit: Overview" and "Complement-mediated hemolytic uremic syndrome in children" and "Thrombotic microangiopathies (TMAs) with acute kidney injury (AKI) in adults: CM-TMA and ST-HUS".)

Other complications — Separate topic reviews discuss management of other complications:

•Bone and joint complications – (See "Acute and chronic bone complications of sickle cell disease".)

•Acute chest syndrome – (See "Acute chest syndrome (ACS) in sickle cell disease (adults and children)".)

•Cerebrovascular disease – (See "Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease".)

•Fever – (See "Evaluation and management of fever in children and adults with sickle cell disease".)

•Hepatic disease – (See "Hepatic manifestations of sickle cell disease".)

•Pain management – (See "Acute vaso-occlusive pain management in sickle cell disease".)

•Priapism – (See "Priapism and erectile dysfunction in sickle cell disease".)

•Pulmonary complications – (See "Overview of the pulmonary complications of sickle cell disease".)

•Pulmonary hypertension – (See "Pulmonary hypertension associated with sickle cell disease".)

•Kidney manifestations – (See "Sickle cell disease effects on the kidney".)

•Transfusion-associated iron overload – (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications".)

•Transition from pediatric to adult care – (See "Sickle cell disease (SCD) in adolescents and young adults (AYA): Transition from pediatric to adult care".)

SURGICAL CONSIDERATIONS — 

A thorough preoperative evaluation, intraoperative monitoring, and interventions to reduce postoperative complications are required [37]. The table summarizes considerations related to each phase of the surgical hospitalization (table 4).  

Use of simple transfusion to reduce surgical complications and other major surgical considerations are discussed separately.

●Simple transfusions – (See "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Prophylactic preoperative transfusion'.)

●Anesthesia considerations – (See "Management of adults with sickle cell disease or thalassemia during cardiac surgery", section on 'Sickle cell disease'.)

SURVIVAL AND PROGNOSIS — 

The survival for individuals with SCD who have access to comprehensive care has improved dramatically, with the major causes of death shifting from infections to progressive end-organ damage.

Overall survival — Survival of individuals with SCD is reduced compared with those without SCD, but the prognosis for SCD has been steadily improving following the institution of comprehensive care that includes newborn screening, immunizations, antibiotics, hydroxyurea, and more rapid prevention and treatment of disease complications (eg, stroke). In regions where comprehensive care is available, the disease has shifted from a fatal pediatric illness to a chronic disease often associated with progressive deterioration in quality-of-life and organ function [38-42].

Adults — Survival well into adulthood is typical for those with access to comprehensive care.

This has been illustrated in various studies, such as a 2014 study involving a cohort of adults with SCD followed at a tertiary care medical center in the United States, in which median survival for Hb SS and Hb S-beta⁰ thalassemia was 58 years, and median survival for Hb SC and Hb S-beta⁺ thalassemia was 66 years [43]. In a 2016 study involving 712 patients followed at a tertiary center in the United Kingdom, the median survival for Hb SS and Hb S-beta⁰ thalassemia was 67 years [44]. This improved survival was attributed to care at a specialist hematology clinic, inpatient management by a dedicated team, involvement of specialists in other organ systems, availability of on-site red blood cell (RBC) exchange, and a focused "transition program" to facilitate safe transition from pediatric to adult care. Studies of the general United States population have shown median ages of death from 43 to 53 years with an overall trend toward improved survival over time [42,45].

Data regarding the impact of hydroxyurea on survival include the following:

●In a cohort study that evaluated risk factors for death in 383 adults with Hb SS, hydroxyurea use was associated with improved survival (hazard ratio [HR] 0.58, 95% CI 0.34-0.97) [46]. The greatest benefit of hydroxyurea therapy was seen in the subgroup taking the recommended dose of 15 to 35 mg/kg/day (HR 0.36, 95% CI 0.17-0.73). Participants with higher fetal hemoglobin (an indication of better response to therapy or greater medication adherence) had the greatest benefit.

●In a cohort study that compared outcomes in 131 patients with SCD of various genotypes who were treated with hydroxyurea versus 199 patients who did not receive hydroxyurea, 10-year survival was 86 versus 65 percent [47].

●In the Belgian cohort discussed above, the use of hydroxyurea therapy was not associated with prolonged survival; however, the analysis only included hydroxyurea prescription, and did not take into account the hydroxyurea dose.

These data are especially impressive because in many cases the individuals treated with hydroxyurea are likely to have had more severe disease and thus would have been expected to have a higher overall mortality rate than those with less severe disease. Collectively, these data support the premise that at a minimum all adults with SCD who have genotypes of Hb SS and Hb S-beta⁰ thalassemia should be treated with hydroxyurea. (See "Hydroxyurea use in sickle cell disease".)

Individuals who survive into later adulthood may have long-term disease complications not seen in younger patients. This was illustrated in a cohort of individuals who survived beyond age 60 with SCD [48]. Chronic kidney disease was seen in 34 of 40 (85 percent).

Children — The mortality rate of infants and young children with SCD who have access to comprehensive care has decreased more dramatically than that of adults, in large part because of the decrease in sepsis from early use of prophylactic antibiotics and immunizations. Less dramatic decreases in the mortality rate of older children may reflect increased survival beyond infancy, lapses in care during the transition from pediatric to adult care providers, and lack of adequate preventive measures for non-infectious complications of SCD (eg, acute chest syndrome, organ failure). (See "Sickle cell disease (SCD) in adolescents and young adults (AYA): Transition from pediatric to adult care", section on 'Health care transition as a vulnerable time'.)

The improvements in survival for infants and young children are illustrated by the following studies:

●The Center for Disease Control and Prevention's National Center for Health Statistics analyzed trends in pediatric SCD-related mortality from 1983 through 2002 [49]. Mortality declined over the course of the study in all age cohorts, with decreases of 68, 39, and 24 percent for children aged zero to three years, four to nine years, and 10 to 14 years, respectively. By 1999 to 2002, all-cause death rates per 100,000 were as follows:

•Zero to three years – 0.78

•Four to nine years – 0.43

•Ten to 14 years – 0.44

These declines were temporally correlated with the introduction of the 7-valent pneumococcal conjugate vaccine.

●Retrospective data from 94,616 individuals with SCD in the United States that used period life tables to estimate survival found that the overall survival probability for children with SCD was 0.98 [45].

Data on survival benefits related to hydroxyurea use in children include:

●In a cohort of children in Belgium with SCD who were treated with either hydroxyurea, hematopoietic stem cell transplantation, or observation, the estimated 15-year survival rates were 99, 94, and 95 percent, respectively [50].

●In a cohort of 1760 children in the Paediatric Hydroxycarbamide Program, survival was greater in the 267 who received hydroxyurea even after a median of only two years of treatment (99.5 versus 94.5 percent) [51]. The survival benefit was primarily due to fewer deaths from acute chest syndrome and infection.

Details of the use of hydroxyurea in children are discussed separately. (See "Hydroxyurea use in sickle cell disease".)

Causes of death — In regions where comprehensive care is available, the causes of death in patients with SCD have shifted following the introduction of infection prevention measures. As examples:

●In a 2024 report that evaluated 128 deaths among over 2000 adults with SCD, the most common causes of death were cardiac (18 percent), acute chest syndrome or respiratory failure (11 percent), and sudden unexplained death (8 percent) [52].

●In the Dallas Newborn cohort of 940 patients, acute chest syndrome and multi-organ failure have replaced bacterial sepsis as the leading causes of death [53].

●In a study that analyzed clinical and/or autopsy findings among 141 adults with SCD from 1976 to 2001, leading causes of death included pulmonary hypertension (26 percent), sudden death (23 percent), kidney failure (23 percent) and infection (18 percent) [54].

●Another study that analyzed the cause of death in 209 adults with SCD found that 18 percent of deaths occurred in individuals with overt organ failure, predominantly kidney failure [38].

In contrast, in regions of Africa where newborn screening for SCD and prophylactic antibacterials are not routinely used, infections are a leading cause of death, including bacterial sepsis and malaria [55]. Despite the protective effect of the sickle mutation against malaria, a study of 1393 children in Kenya with severe malaria reported higher mortality in children with SCD than those without SCD (death rate 80 versus 10 percent, respectively) [55].

Predictors of morbidity and mortality — The risk of death in children and adolescents up to 18 years living in high-income countries is low (<3 percent); as a result, studies in the modern era have not provided reproducible predictions of mortality rates in these children and adolescents.

Overall, markers of more severe disease tend to predict greater morbidity and mortality in individuals with SCD, although some modifiable risk factors (eg, stroke) may be declining in importance [56-58]. Examples of available studies include:

●Two large comprehensive studies have demonstrated the high survival rate of children with SCD in resource-rich countries in the modern era. In a 2015 study from Belgium, 469 children with SCD were prospectively followed, many since diagnosis, for a total of over 5110 patient-years [50]. Children with more severe SCD treated with hydroxyurea had a Kaplan Meir survival estimate of 99 percent at 15 years. Similar results were seen in a 2016 study from France, in which 1033 children with SCD born between 1995 and 2009 were followed for 6776 patient-years [59]. The five-year survival was over 98 percent for the entire cohort, and over 99 percent for those born after 2006. These studies illustrate that SCD is no longer a life-threatening disease of childhood, but rather is a chronic childhood disease with life-threatening episodes.

●An attempt to identify risk factors for mortality in adults was made using computer modeling in a cohort of 964 individuals with SCD, 209 of whom died [38]. Predictors of an increased risk of early death in this model included acute chest syndrome, kidney failure, a baseline white blood count >15,000/microL, and a fetal hemoglobin (Hb F) ≤8.6 percent. Other studies have corroborated an increased mortality rate in individuals with SCD who develop kidney failure, even if they are treated with dialysis [60].

●Risk factors for death in two cohorts of adults from tertiary medical centers included [43,44]:

•Greater frequency of hospitalization

•Iron overload

•Elevated tricuspid regurgitant jet velocity (TRJV) on Doppler echocardiography (>2.5 m/sec)

•History of any cerebrovascular event

•Lower estimated GFR

•At least one pain episode in the last year

Laboratory findings associated with increased risk of death in these cohorts included low hemoglobin, high WBC count, low baseline Hb F, high lactate dehydrogenase (LDH), high C-reactive protein, and elevated NT-proBNP.

●Analysis of data from children enrolled in the Silent Cerebral Infarct Multi-Center Clinical (SIT) trial suggests that higher baseline hemoglobin levels and higher education level of the head of the household correlated with improved growth, whereas household income did not [61].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sickle cell disease and thalassemias".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Sickle cell disease (The Basics)" and "Patient education: When your child has sickle cell disease (The Basics)")

PATIENT PERSPECTIVE TOPIC — 

Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Sickle cell disease".)

SUMMARY AND RECOMMENDATIONS

●General principles – These principles of inpatient management apply to all individuals with SCD:

•Good communication free of racial bias and health-related stigmas. (See 'Communication' above.)

•Adequate hydration. (See 'Hydration' above.)

•Incentive spirometry to reduce the risk of acute chest syndrome. (See 'Incentive spirometry' above.)

•Thromboembolism prophylaxis for all inpatients >18 years old admitted for an acute medical condition. (See 'Thromboembolism prophylaxis' above.)

•Adequate pain evaluation (table 1). (See "Evaluation of acute pain in sickle cell disease", section on 'Potentially serious conditions associated with pain'.)

•Adequate pain control (table 2), regardless of the cause (algorithm 1). (See 'Pain control' above and "Acute vaso-occlusive pain management in sickle cell disease".)

•Appropriate use of transfusions for symptomatic anemia and acute stroke, acute chest syndrome, splenic or hepatic sequestration, and multi-organ failure. (See 'Role of transfusions' above.)

•Close monitoring of vital signs and laboratory values. (See 'Monitoring pulmonary, hematologic status and liver and kidney function' above.)

•Clear discharge planning and follow-up within two weeks. (See 'Discharge instructions' above.)

●Medications – Most oral outpatient medications are continued during hospitalization, including hydroxyurea, folic acid, and prophylactic penicillin (unless receiving broad spectrum antibiotics). Care must be taken with nonsteroidal antiinflammatory drugs to avoid kidney toxicity. Granulocyte colony-stimulating factor is avoided due to risks of precipitating sickle cell vaso-occlusion and multiorgan failure, which may be fatal. (See 'Medication management' above.)

●Infections – Infection is a frequent complication. Fever may be the first indication of a serious bacterial infection and is a medical emergency. Blood cultures, CBC with differential, and reticulocyte count should be obtained, and evaluation for pneumonia is especially important. Empiric parenteral antibiotics should be started as soon as possible, ideally within 60 minutes of triage. (See 'Infections' above.)

●Splenic and hepatic sequestration – Splenic sequestration is a life-threatening complication with painful splenic enlargement due to blood pooling in the spleen, with a drop in hemoglobin of at least 2 g/dL. It occurs in infants and children and individuals with preserved splenic function such as those with Hb SC disease. Immediate intravenous fluid resuscitation is used, along with simple transfusion if hypovolemia is associated with symptomatic anemia, with caution not to over-transfuse so that blood reentering the circulation does not cause hyperviscosity. Oxygen is provided to maintain oxygen saturation ≥95 percent but is not used prophylactically as it may mask new hypoxemia. (See 'Splenic and hepatic sequestration' above.)

●Multi-organ failure – This potentially life-threatening complication is defined as dysfunction in two of three major organ-systems (lungs, liver, kidneys). The mechanism is thought to involve vaso-occlusion resulting in bone marrow necrosis, fat embolization, and organ infarction. (See 'Multi-organ failure' above.)

•For individuals with multi-organ failure, we recommend urgent exchange transfusion (Grade 1C).

•Plasma exchange may be appropriate if features of thrombotic microangiopathy are present.

•Aggressive supportive care (intubation, blood pressure support) may be needed.

●Surgery – Surgical planning often includes simple transfusion to reduce surgical complications. Other anesthesia considerations are summarized in the table (table 4) and may apply depending on the surgical procedure. (See 'Surgical considerations' above and "Red blood cell transfusion in sickle cell disease: Indications, RBC matching, and modifications", section on 'Prophylactic preoperative transfusion' and "Management of adults with sickle cell disease or thalassemia during cardiac surgery", section on 'Sickle cell disease'.)

●Survival and prognosis – Survival for individuals with SCD who have access to comprehensive care has improved dramatically, with the major causes of death shifting from infections to progressive end-organ damage. Median survival for individuals with access to comprehensive care is in the sixth or seventh decade. Hydroxyurea and infection prophylaxis are major contributors to improved survival. Markers of more severe disease tend to predict greater morbidity and mortality. (See 'Survival and prognosis' above.)