Splenic Sequestration Crisis

Topic Overview

Summary

Splenic sequestration crisis (SSC) is a life-threatening acute complication of sickle cell disease characterised by the sudden pooling of large volumes of blood within the spleen, resulting in rapid splenic enlargement, profound anaemia, and potentially fatal hypovolaemic shock. [1,2] It represents one of the major causes of mortality in children with sickle cell disease, with mortality rates of 10-15% in the first episode despite optimal management. [3]

The pathophysiology involves acute vaso-occlusion within the splenic red pulp, trapping erythrocytes and leading to a dramatic reduction in circulating blood volume. Unlike other sickle cell crises, SSC predominantly affects young children with HbSS disease (aged 6 months to 3 years) before autosplenectomy occurs, though adults with HbSC disease or HbS-beta-thalassaemia who retain splenic function remain at risk throughout life. [4,5]

Early recognition is critical: the diagnostic triad comprises acute splenomegaly (≥2cm below baseline), acute anaemia (haemoglobin drop ≥20 g/L from baseline), and reticulocytosis (> 10%), distinguishing it from aplastic crisis. [6] Immediate management involves aggressive fluid resuscitation and cautious blood transfusion, with careful monitoring to avoid hyperviscosity syndrome as sequestered blood is mobilised. Recurrence rates approach 50% without splenectomy, making prevention strategies—including parental education on spleen palpation—essential. [7]

Key Facts

• Peak incidence: 6 months to 3 years in HbSS; any age in HbSC/HbS-beta-thalassaemia [8]
• Mechanism: Vaso-occlusion → splenic trapping → hypovolaemia → shock
• Diagnostic triad: Acute splenomegaly + profound anaemia + HIGH reticulocytes [6]
• Key distinction: Reticulocyte count HIGH (vs LOW in aplastic crisis)
• Mortality: 10-15% first episode; less than 5% with prompt treatment [3]
• Recurrence: 50% within 1-2 years without splenectomy [7]
• Critical intervention: Parental education on spleen palpation reduces mortality [9]

Clinical Pearls

Reticulocyte count is the key discriminator: HIGH reticulocytes + low Hb + splenomegaly = sequestration crisis; LOW reticulocytes + low Hb = aplastic crisis

Transfusion paradox: Avoid rapid over-transfusion—as the spleen decompresses, sequestered RBCs return to circulation causing hyperviscosity and risk of stroke [10]

Adults are not immune: HbSC and HbS-beta-thalassaemia patients retain splenic function and remain at risk throughout adulthood [5]

Malaria doubles the risk: In endemic areas, malaria infection is a major trigger; consider chemoprophylaxis [11]

Parental training saves lives: Teaching caregivers to palpate the spleen baseline and detect enlargement enables early presentation before shock develops [9]

Why This Matters Clinically

Splenic sequestration crisis can progress from apparent wellness to fatal shock within 2-4 hours. [12] Delayed recognition is the primary cause of preventable mortality. Every parent of a child with sickle cell disease must receive formal training in spleen palpation at diagnosis and at every clinic visit. Healthcare providers in emergency departments must maintain a high index of suspicion in any sickle cell patient presenting with pallor, tachycardia, or abdominal pain. The balance between life-saving transfusion and iatrogenic hyperviscosity requires expert haematology input and meticulous monitoring.

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Visual Summary

Visual assets to be added:

• Pathophysiology flowchart: Sickling → splenic vaso-occlusion → sequestration → hypovolaemia
• Differential diagnosis algorithm: Distinguishing sequestration vs aplastic vs haemolytic crisis
• Spleen palpation technique for parents (baseline measurement and monitoring)
• Blood film comparison: Sickle cells, reticulocytosis, thrombocytopenia
• Transfusion strategy algorithm: Simple vs exchange transfusion decision tree
• Management flowchart: Resuscitation → transfusion → monitoring → splenectomy decision

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Epidemiology

Incidence and Prevalence

Splenic sequestration crisis occurs in 10-30% of children with HbSS disease, with the vast majority of episodes occurring before age 5 years. [8] In the Cooperative Study of Sickle Cell Disease (CSSCD), the incidence of acute SSC was 6.6 events per 100 patient-years in children under 2 years with HbSS disease. [13]

Age Distribution

Exam Detail: Age-specific risk patterns:

• less than 6 months: Rare (protective effect of fetal haemoglobin)
• 6 months - 2 years: Highest risk period (30-40% of all episodes) [8]
• 2-5 years: Second peak (40-50% of episodes)
• > 5 years (HbSS): Uncommon due to autosplenectomy
• Adults (HbSC/HbS-beta-thal): Ongoing risk due to persistent splenic function [5]

The decline in SSC incidence in HbSS after age 5 correlates with progressive splenic infarction and fibrosis leading to functional autosplenectomy, a process typically complete by age 6 years. [15] In contrast, patients with HbSC disease have milder sickling, preserve splenic function into adulthood, and therefore remain at risk throughout life. [14]

Demographic Risk Factors

Geographic Variation

In malaria-endemic regions of Africa, acute SSC occurs more frequently and at older ages compared to non-endemic areas, likely due to recurrent malarial splenic stimulation preventing early autosplenectomy. [11] Conversely, in developed countries with comprehensive sickle cell care and parental education, mortality from SSC has declined from > 30% historically to less than 5% currently. [9]

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Aetiology & Pathophysiology

Molecular Basis of Sickling

Sickle cell disease results from a single point mutation (GAG→GTG) in the beta-globin gene, producing haemoglobin S (HbS) with valine substituted for glutamic acid at position 6 of the beta-globin chain. [18] Under deoxygenated conditions, HbS polymerises into rigid fibres, distorting erythrocytes into the characteristic sickle shape. These rigid cells cause vaso-occlusion, haemolysis, and endothelial damage.

Mechanism of Splenic Sequestration

Exam Detail: Pathophysiological cascade:

1. Vaso-occlusion in splenic red pulp: Deoxygenation triggers HbS polymerisation → sickled RBCs become trapped in narrow sinusoidal channels of splenic red pulp [1]

2. Progressive blood pooling: As RBCs accumulate, splenic vascular resistance increases → further trapping in positive feedback loop → spleen can sequester up to 30-40% of total blood volume [2]

3. Acute hypovolaemia: Massive fluid shift into spleen → circulating volume drops precipitously → compensatory tachycardia and peripheral vasoconstriction → eventual cardiovascular collapse if untreated [12]

4. Platelet sequestration: Platelets also become trapped → thrombocytopenia (often less than 100 × 10⁹/L) → occasionally bleeding complications [19]

5. Reticulocyte release: Bone marrow responds appropriately to acute anaemia → reticulocytosis (typically > 10%, often > 20%) → this distinguishes SSC from aplastic crisis [6]

6. Potential autotransfusion: With resolution (spontaneous or after transfusion), sequestered blood may re-enter circulation → risk of hyperviscosity syndrome and stroke [10]

Why Children vs Adults?

Children with HbSS (age less than 5 years):

• Spleen is functional and enlarged from chronic haemolysis
• Vaso-occlusive episodes cause acute-on-chronic congestion
• Repeated episodes → progressive splenic infarction → autosplenectomy by age 5-6 → SSC becomes rare thereafter [15]

Adults with HbSC or HbS-beta⁺-thalassaemia:

• Milder sickling phenotype → spleen remains functional throughout life
• Less frequent vaso-occlusive events → spleen does not undergo autosplenectomy
• Acute triggers (infection, malaria, dehydration) can precipitate SSC at any age [5,14]

Trigger Factors

Recurrence Pathophysiology

Recurrence rates of 50% within 1-2 years reflect the fact that the underlying splenic architecture remains vulnerable. [7] Once an episode occurs, the spleen demonstrates a "primed" state with residual vascular congestion and fibrosis, lowering the threshold for subsequent sequestration events. Splenectomy eliminates recurrence risk but introduces lifelong infection risk. [20]

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Clinical Presentation

Acute Presentation

Splenic sequestration crisis typically presents with rapid onset over hours (rarely days) with a triad of symptoms: [1,2]

Cardinal Symptoms

Associated Symptoms

• Anorexia and vomiting: 40-60% [12]
• Dyspnoea: Present if severe anaemia (Hb less than 50 g/L)
• Confusion/altered consciousness: Late sign indicating shock
• Fever: May indicate precipitating infection

Physical Examination Findings

Vital Signs

Clinical Pearl: Tachycardia out of proportion to fever is the earliest warning sign of impending shock. A child with sickle cell disease presenting with HR > 140 bpm (infant) or > 120 bpm (child) warrants immediate spleen palpation and haemoglobin check.

Abdominal Examination

Spleen palpation is the key diagnostic manoeuvre:

• Acute enlargement: Spleen palpable ≥2 cm below baseline (measured from left costal margin) [6]
• Rapid progression: Parents often report spleen "growing by the hour"
• Tenderness: Common due to capsular stretch
• Firmness: Spleen is firm, smooth, with rounded edge
• Comparison to baseline: Always compare to documented baseline spleen size in medical records

Exam Detail: Spleen measurement technique:

1. Position patient supine with knees flexed
2. Palpate from right iliac fossa towards left costal margin (spleen descends with inspiration)
3. Measure distance in cm from left costal margin at mid-clavicular line to inferior pole of spleen
4. Document in medical notes and compare to previous measurements
5. In children, spleen may extend across midline or down to pelvis in severe SSC

Baseline spleen sizes in sickle cell disease: [1]

• Infants (6-12 months): 0-2 cm below costal margin (normal chronic enlargement)
• Children (1-5 years, HbSS): Often 1-4 cm enlarged at baseline
• Adults (HbSC): May be 2-6 cm enlarged at baseline

Acute SSC diagnosis requires ≥2 cm increase from documented baseline, not just splenomegaly per se.

General Examination

• Profound pallor: Mucous membranes, palmar creases
• Jaundice: Chronic haemolysis (not specific to SSC)
• Signs of shock: Cold peripheries, delayed capillary refill (> 2 sec), weak pulse, altered consciousness
• Respiratory distress: Tachypnoea, use of accessory muscles (severe anaemia)

Clinical Staging by Severity

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Differential Diagnosis

The key differential diagnoses for a sickle cell patient presenting with anaemia and splenomegaly are:

Primary Differentials

Exam Detail: 1. Aplastic Crisis (Parvovirus B19 infection)

• Pathophysiology: Parvovirus B19 infects RBC progenitors → arrest of erythropoiesis → profound anaemia [21]
• Key difference: LOW reticulocyte count (less than 1%) vs HIGH in SSC (> 10%)
• Spleen: Normal or slightly enlarged (not acutely enlarged)
• Onset: Slightly more gradual (days) vs hours in SSC
• Associated features: Rash, arthralgia, household contacts with "slapped cheek" syndrome

2. Acute Haemolytic Crisis

• Pathophysiology: Accelerated RBC destruction (infection, G6PD deficiency, drug triggers)
• Key difference: Reticulocytes HIGH but spleen not acutely enlarged
• Bilirubin: Markedly elevated (> 100 μmol/L) vs modestly elevated in SSC
• LDH: Very high (> 1000 U/L)
• Haemoglobinuria: May be present

3. Hypersplenism

• Pathophysiology: Chronic splenic overactivity → pancytopenia
• Key difference: Chronic, gradual onset vs acute SSC
• Blood counts: All lineages reduced (anaemia + thrombocytopenia + leucopenia)
• Spleen: Chronically large, not acutely enlarging

Comprehensive Differential Table

"Must Not Miss" Differentials

1. Septic shock: May coexist with SSC; always obtain blood cultures
2. Malaria: In endemic areas, thick/thin films essential [11]
3. Splenic rupture: Rare but catastrophic; look for peritonism and free fluid on ultrasound
4. Hepatic sequestration: Can occur alongside splenic sequestration; check liver size and function

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Clinical Examination

Systematic Approach

A structured examination in suspected SSC should proceed rapidly and include:

1. General Inspection (30 seconds)

• Level of consciousness: Alert vs drowsy vs unresponsive
• Work of breathing: Respiratory distress suggests severe anaemia
• Peripheral perfusion: Colour, capillary refill, peripheral temperature
• Hydration status: Mucous membranes, skin turgor

2. Vital Signs (1 minute)

• Pulse rate and character
• Blood pressure (may require appropriate cuff size in children)
• Respiratory rate
• Oxygen saturation
• Temperature

3. Focused Abdominal Examination (2 minutes)

Clinical Pearl: Always start palpation from the right iliac fossa, moving diagonally towards the left costal margin. The spleen descends towards the right iliac fossa when massively enlarged. Beginning palpation in the left upper quadrant may miss a giant spleen.

Spleen palpation technique:

1. Patient supine, knees flexed, arms by sides
2. Examiner's right hand palpates from RIF towards LUQ during inspiration
3. Measure spleen size in cm from left costal margin (mid-clavicular line)
4. Assess for tenderness, consistency, surface character
5. Compare to baseline measurement documented in notes

Liver assessment:

• May be enlarged if hepatic sequestration coexists
• Measure liver span in mid-clavicular line

Peritonism:

• Assess for guarding, rebound (splenic rupture is rare but catastrophic)

4. Signs of Hypovolaemic Shock

5. Anaemia Assessment

• Pallor of conjunctivae, mucous membranes, palmar creases
• Flow murmurs on auscultation (anaemia > 50 g/L)

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Investigations

Immediate Investigations (Within 30 Minutes)

1. Full Blood Count (FBC)

Exam Detail: Haemoglobin interpretation in sickle cell disease:

• Baseline Hb in HbSS: typically 60-90 g/L (chronic compensated anaemia)
• Baseline Hb in HbSC: typically 90-120 g/L
• Diagnosis of SSC requires a DROP of ≥20 g/L from patient's baseline, not just a low absolute value
• Always check old notes or sickle cell database for recent Hb values
• A child with HbSS whose Hb is usually 75 g/L presenting with Hb 55 g/L has likely had SSC

Reticulocyte count interpretation:

• Normal range: 0.5-2%
• In SSC: typically > 10%, often > 20%
• Absolute reticulocyte count is more accurate than percentage (normal 20-100 × 10⁹/L)
• Reticulocytosis reflects appropriate bone marrow response to acute anaemia
• If reticulocytes are LOW (less than 1%) with acute anaemia, consider aplastic crisis (parvovirus B19) [21]

2. Blood Film

• Sickle cells (elongated, crescent-shaped RBCs)
• Polychromasia (blue-tinged RBCs = young reticulocytes)
• Target cells (especially in HbSC)
• Howell-Jolly bodies (if functional autosplenectomy present)
• Assess for malaria parasites if endemic area [11]

3. Reticulocyte Count

• Essential for diagnosis: must be sent urgently
• Automated count: most labs provide % and absolute count
• Interpretation: > 10% confirms appropriate marrow response in SSC

4. Group and Crossmatch

• Urgently required: patient may need transfusion within 1-2 hours
• Extended phenotyping: if available, match for Rh (C, c, E, e) and Kell to reduce alloimmunisation risk [23]
• Crossmatch 2-4 units depending on severity and size of child/adult

5. Biochemistry

Second-Line Investigations

6. Blood Cultures

• Always send if fever present (temperature > 38°C)
• Risk of bacterial infection (encapsulated organisms in sickle cell patients)

7. Parvovirus B19 Serology/PCR

• Send if reticulocyte count is LOW (less than 1%) → consider aplastic crisis [21]
• PCR more sensitive and specific than IgM serology

8. Ultrasound Abdomen

• Indications: uncertain spleen size, suspicion of splenic rupture, hepatic sequestration
• Findings in SSC: enlarged spleen, heterogeneous echotexture, possible splenic infarcts
• Not routinely required if clinical diagnosis clear

9. Chest X-ray

• If dyspnoeic or hypoxic → rule out acute chest syndrome [22]

Monitoring Investigations

After initial stabilisation, serial monitoring is critical:

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Classification & Staging

Classification by Severity

Severity stratification guides transfusion strategy and monitoring intensity:

Classification by Episode Number

Genotype-Based Risk Stratification

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Management

Management of splenic sequestration crisis requires a multidisciplinary approach involving emergency medicine, haematology, and intensive care. The three pillars are: resuscitation, transfusion, and prevention of recurrence.

Immediate Resuscitation (First 30-60 Minutes)

Clinical Pearl: Do not delay transfusion to await haematology review in severe SSC. If Hb less than 50 g/L with shock, initiate transfusion immediately after blood samples are taken. Hyperviscosity risk is manageable; exsanguination from delayed transfusion is not.

ABC Approach

1. Airway: Assess and secure if GCS less than 8
2. Breathing: High-flow oxygen (15L via non-rebreather mask) → target SpO₂ 94-98%
3. Circulation:
   • Large-bore IV access (2 cannulae if possible)
   • Bloods: FBC, reticulocytes, group and crossmatch, biochemistry, blood cultures if febrile
   • Fluid bolus: 10-20 mL/kg 0.9% sodium chloride over 10-15 minutes if shocked [12]
   • Repeat if persistent shock (but avoid fluid overload → proceed to transfusion)

Monitoring

• Continuous: HR, BP, SpO₂, ECG
• Hourly: Urine output (catheterise if severe), capillary refill, consciousness level
• 4-6 hourly: Spleen size, Hb, clinical assessment

Transfusion Strategy

Exam Detail: The transfusion paradox in SSC:

Unlike typical anaemia, SSC involves not only loss of circulating RBCs but also their sequestration in the spleen. As treatment progresses, the spleen decompresses and releases sequestered RBCs back into circulation. Aggressive transfusion can therefore result in:

1. Initial rise in Hb from transfused cells
2. Subsequent further rise as autotransfusion occurs from splenic decompression
3. Hyperviscosity syndrome (Hb > 110 g/L in sickle cell disease) → increased blood viscosity → stroke risk, vaso-occlusive crisis [10]

Key principle: transfuse cautiously to a safe Hb (70-90 g/L), not to "normal" Hb.

Simple Transfusion Protocol

Indications: Mild to moderate SSC, Hb 50-70 g/L

Caution: If Hb rises > 20 g/L after initial transfusion, significant autotransfusion is occurring → high hyperviscosity risk → consider partial exchange transfusion.

Exchange Transfusion Protocol

Indications:

• Severe SSC (Hb less than 40 g/L, cardiovascular collapse)
• Poor response to simple transfusion
• Hb rising excessively (> 110 g/L) post-simple transfusion due to autotransfusion [10]

Technique:

• Manual exchange: Remove 5-10 mL/kg blood, replace with equal volume RBCs, repeat
• Automated erythrocytapheresis: If available, safer and more precise
• Target: Hb 90-100 g/L, HbS less than 30%

Benefits: Raises Hb while removing sickled cells, avoiding hyperviscosity

Supportive Management

Monitoring During Acute Phase

Definitive Management: Splenectomy

Splenectomy eliminates recurrence risk but introduces lifelong infection risk (overwhelming post-splenectomy infection, OPSI). Decision-making requires careful risk-benefit analysis.

Indications for Splenectomy [20]

Timing of Splenectomy

• Not during acute SSC: Risk of bleeding, haemodynamic instability
• Optimal timing: 4-6 weeks after acute episode recovery [20]
• Age considerations: Ideally > 2 years (infection risk higher in infants)

Pre-Splenectomy Preparation

Post-Splenectomy Management

Exam Detail: Lifelong antibiotic prophylaxis is mandatory post-splenectomy to prevent OPSI:

• Penicillin V: 250-500 mg BD (adult); 125-250 mg BD (child)
• If penicillin allergic: Erythromycin 250-500 mg BD or azithromycin
• Patient education: Seek urgent medical attention for any fever (> 38°C) → empirical IV antibiotics (ceftriaxone) until blood cultures negative [24]
• Medical alert bracelet: Should state "asplenic, on penicillin prophylaxis"
• Travel advice: Malaria prophylaxis essential; avoid endemic areas if possible [11]

Complications of splenectomy in sickle cell disease:

• OPSI (risk 1-5% lifetime, mortality 50% if untreated)
• Thrombocytosis (platelets may exceed 1000 × 10⁹/L → consider aspirin)
• Increased frequency of vaso-occlusive crises (controversial)
• Pulmonary hypertension (long-term risk)

Chronic Transfusion Programme

Alternative to splenectomy in selected cases:

• Regular transfusions every 4-6 weeks to suppress endogenous HbS production
• Maintain HbS less than 30%, total Hb 90-110 g/L
• Challenges: iron overload (requires chelation), alloimmunisation, venous access

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Complications

Complications of Splenic Sequestration Crisis

Complications of Transfusion

Complications of Splenectomy

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Prognosis & Outcomes

Acute Mortality

• Untreated SSC: 30-50% mortality [3]
• Treated promptly: less than 5% mortality [9]
• Severe SSC (Hb less than 40 g/L, shock): 10-15% mortality even with treatment [3]

Key prognostic factors:

• Time to presentation (delay > 4 hours from symptom onset increases mortality 5-fold) [12]
• Severity at presentation (Hb less than 40 g/L, shock)
• Availability of blood products
• Access to paediatric intensive care if needed

Recurrence

• After first episode: 50% recurrence within 1-2 years without splenectomy [7]
• After second episode: 70-80% will have further episodes
• Post-splenectomy: Recurrence risk eliminated (but OPSI risk introduced)

Long-Term Outcomes

Impact of Parental Education

Studies demonstrate that teaching parents to palpate the spleen reduces mortality from SSC by 70%. [9] Early detection and presentation before shock develops is the single most important determinant of survival.

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Prevention & Screening

Primary Prevention: Parental Education

Clinical Pearl: Parental spleen palpation training is the most effective life-saving intervention in sickle cell disease. [9] This should be taught at diagnosis and reinforced at every clinic visit.

Spleen Palpation Training for Parents

What to teach:

1. Baseline spleen size: Palpate child's spleen at each clinic visit and document in parent-held record
2. Palpation technique:
   • Child lies flat, knees bent
   • Palpate gently from right lower abdomen towards left ribs
   • Feel for firm edge moving downwards when child breathes in
3. Warning signs:
   • Spleen suddenly larger (≥2 cm from baseline)
   • Child pale, tired, fast breathing
   • Tummy swollen on left side
4. Action plan: Seek emergency care immediately if spleen enlarged

Education materials:

• Visual diagrams of spleen palpation
• Written action plan
• Emergency contact numbers
• Parent-held spleen size chart

Regular Clinic Monitoring

Secondary Prevention: Preventing Recurrence

After First Episode

After Second Episode

Splenectomy is strongly recommended after two or more episodes of SSC to prevent potentially fatal recurrence. [7,20]

Preventing Triggers

Screening for SSC in At-Risk Populations

Universal screening is not applicable (SSC occurs in known sickle cell patients). However:

• Newborn screening programmes identify sickle cell disease → enables early parental education
• Genetic counselling for at-risk couples
• Prenatal diagnosis available for affected pregnancies

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Evidence & Guidelines

Key Guidelines

1. British Society for Haematology (BSH) Guideline on Sickle Cell Disease (2018) [1]

   • Recommends parental education on spleen palpation for all children with HbSS
   • Splenectomy indicated after ≥2 episodes of SSC
   • Simple transfusion to target Hb 70-90 g/L to avoid hyperviscosity

2. American Society of Hematology (ASH) Guidelines (2020) [25]

   • Chronic transfusion therapy as alternative to splenectomy in selected cases
   • Exchange transfusion recommended if Hb > 110 g/L post-simple transfusion

3. National Institute for Health and Care Excellence (NICE) - Sickle Cell Disease Management (2012) [26]

   • All families should receive education on recognising acute complications including SSC
   • Annual review should include discussion of spleen palpation

Landmark Studies

Evidence Summary

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Examination Focus

High-Yield Viva Topics

Exam Detail: Opening statement for viva:

"Splenic sequestration crisis is a life-threatening acute complication of sickle cell disease characterised by rapid splenic enlargement, profound anaemia, and hypovolaemic shock due to vaso-occlusion and blood pooling in the spleen. It occurs in 10-30% of children with HbSS disease, typically between 6 months and 3 years of age, and is a leading cause of mortality in this population with a 10-15% case fatality rate if not promptly recognised and treated." [1,3,8]

Common Viva Questions and Model Answers

Q1: How does splenic sequestration crisis differ from aplastic crisis in sickle cell disease?

Model Answer: "The key distinguishing feature is the reticulocyte count. In splenic sequestration crisis, the bone marrow responds appropriately to acute anaemia, producing a high reticulocyte count, typically above 10% and often exceeding 20%. The spleen is acutely enlarged, sometimes dramatically, and platelets are often reduced due to splenic pooling. In contrast, aplastic crisis, most commonly caused by parvovirus B19 infection, presents with a low reticulocyte count—less than 1%—because the virus infects erythroid progenitor cells, halting RBC production. The spleen is not acutely enlarged in aplastic crisis. Clinically, both present with severe anaemia, but only SSC has the acute splenomegaly and retained marrow response." [6,21]

Q2: Why is there a risk of hyperviscosity syndrome after transfusion in splenic sequestration crisis?

Model Answer: "The risk arises from the phenomenon of autotransfusion. In SSC, a large volume of blood—sometimes 30-40% of total blood volume—is sequestered in the spleen. When we transfuse the patient, we raise their haemoglobin with exogenous RBCs. However, as the spleen decompresses, either spontaneously or in response to improved perfusion after transfusion, the sequestered RBCs are released back into the circulation. This causes an additional rise in haemoglobin beyond what we intended. In sickle cell disease, haemoglobin above 100-110 g/L significantly increases blood viscosity, which can precipitate vaso-occlusive crises or stroke. That's why we target a modest haemoglobin of 70-90 g/L and monitor frequently for rising Hb post-transfusion. If hyperviscosity develops, exchange transfusion may be required." [10]

Q3: What is your management approach to a 2-year-old child with HbSS presenting with Hb 45 g/L, reticulocytes 18%, and a spleen 6 cm below the costal margin?

Model Answer: "This is severe splenic sequestration crisis requiring urgent resuscitation and transfusion. My immediate management would follow an ABC approach:

A/B: Airway patent, high-flow oxygen at 15L via non-rebreather mask targeting saturations 94-98%.

C: Two large-bore cannulae, bloods for urgent FBC, reticulocytes, group and crossmatch, biochemistry, and blood cultures given the risk of infection as a precipitant. A 10-20 mL/kg bolus of 0.9% saline immediately to address the hypovolaemia and shock.

Transfusion: Urgent simple transfusion of phenotypically matched blood, 10-15 mL/kg over 3-4 hours, targeting haemoglobin 70-90 g/L—not higher—to avoid hyperviscosity.

Monitoring: Continuous vital signs, hourly urine output, and haemoglobin rechecked 4-6 hours post-transfusion to detect autotransfusion. If the Hb rises above 100 g/L, I would involve haematology for consideration of exchange transfusion.

Definitive care: Involve paediatric haematology urgently. After stabilisation, this child would be a candidate for splenectomy given the severity of this episode, performed electively 4-6 weeks later with pre-operative vaccinations." [1,6,12]

Q4: Why do adults with HbSC disease remain at risk of splenic sequestration crisis?

Model Answer: "In HbSS disease, repeated vaso-occlusive episodes and splenic infarction lead to progressive splenic fibrosis and atrophy—a process called autosplenectomy—typically complete by age 5-6 years. Therefore, children with HbSS generally 'outgrow' their risk of SSC.

However, HbSC disease has a milder sickling phenotype. Patients have approximately 50% HbS and 50% HbC, with less severe vaso-occlusion. As a result, their spleens remain functional and often enlarged into adulthood. This means they retain the capacity for splenic sequestration throughout life. Similarly, patients with HbS-beta-plus-thalassaemia produce some normal HbA, resulting in a milder phenotype and persistent splenic function. Therefore, adults with these genotypes presenting with sudden anaemia, left upper quadrant pain, and an enlarged spleen should prompt consideration of SSC, not just paediatric disease." [5,14,15]

Q5: What is the role of parental education in preventing deaths from splenic sequestration crisis?

Model Answer: "Parental education is the single most effective intervention to reduce mortality from SSC. Brousse et al. demonstrated a 70% reduction in mortality when parents were trained to palpate their child's spleen and recognise acute enlargement. The rationale is that SSC can progress from wellness to fatal shock within 2-4 hours. If parents can detect splenic enlargement early—before cardiovascular collapse—and seek urgent medical attention, transfusion can be administered promptly, preventing death.

Parents should be taught to palpate the spleen at home, know the baseline size, and understand that an increase of 2 cm or more is an emergency. This education must be provided at diagnosis and reinforced at every clinic visit. It requires demonstration, practice, and provision of written materials including an emergency action plan. This is a high-yield, low-cost intervention that saves lives." [9,12]

Common Examination Pitfalls

❌ Mistake 1: Transfusing to 'normal' Hb (> 120 g/L)

• Risk of hyperviscosity and stroke
• Target is 70-90 g/L

❌ Mistake 2: Assuming SSC only occurs in children

• Adults with HbSC and HbS-beta-thal remain at risk

❌ Mistake 3: Diagnosing SSC based solely on low Hb and splenomegaly

• Must have HIGH reticulocytes (> 10%) to distinguish from aplastic crisis
• Must have ACUTE spleen enlargement (≥2 cm from baseline)

❌ Mistake 4: Delaying transfusion until haematology review in severe SSC

• Severe SSC (Hb less than 50 g/L, shock) is an emergency—transfuse immediately after blood draw

❌ Mistake 5: Performing splenectomy during acute SSC

• Splenectomy is elective, performed 4-6 weeks after recovery, not acutely

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Patient & Family Information

What is Splenic Sequestration Crisis?

Splenic sequestration crisis is a serious complication that can happen in people with sickle cell disease. The spleen is an organ on the left side of your abdomen. In this crisis, blood suddenly gets trapped in the spleen, making it swell up quickly. This means less blood is flowing around your body, causing severe anaemia (low blood count) and shock.

Who Gets It?

• Young children (6 months to 5 years) with HbSS sickle cell disease are most at risk
• Adults with HbSC or HbS-beta-thalassaemia can also get it because their spleens stay larger
• It happens in about 1 in 4 children with sickle cell disease

Warning Signs (Call 999 or Go to A&E Immediately)

• Your child's tummy suddenly gets bigger, especially on the left side
• Your child looks very pale (almost white)
• Your child is very tired, floppy, or drowsy
• Fast breathing or fast heartbeat
• Feeling dizzy or faint
• The spleen feels bigger when you check it (your doctor will teach you how)

How Do I Check My Child's Spleen?

Your child's doctor or nurse will teach you how to gently feel your child's spleen. You should:

1. Check the spleen every week
2. Know what the normal size is for your child
3. If the spleen suddenly feels bigger (by about 2 cm or more), go to hospital immediately

This simple check can save your child's life.

What Happens in Hospital?

• Blood tests to check how low the blood count is
• IV drip (tube in the arm) to give fluids and blood transfusion
• Monitoring with machines to check heart rate, breathing, and blood pressure
• Most children recover fully if treated quickly

Treatment

• Blood transfusion: Giving blood through a drip to replace the blood trapped in the spleen
• Fluids: To help with shock
• Monitoring: Staying in hospital for a few days to make sure the spleen shrinks back and the blood count improves
• Surgery (splenectomy): If this happens twice, your doctor may recommend removing the spleen to prevent it happening again

Can It Happen Again?

Yes. About half of children who have one episode will have another within 1-2 years. That's why:

• Learning to check the spleen is so important
• Your doctor may recommend removing the spleen after a second episode
• You'll have regular check-ups

After Splenectomy (If Spleen Is Removed)

If the spleen is removed, your child will need:

• Daily antibiotics (penicillin) for life to prevent infections
• Vaccinations before surgery
• Medical alert bracelet to let doctors know your child has no spleen
• Immediate medical attention if your child gets a fever (> 38°C)—this is an emergency

How Can I Prevent It?

• Learn to check your child's spleen (ask your sickle cell team to teach you)
• Keep your child well hydrated (drinking plenty of fluids)
• Treat infections early
• Attend all clinic appointments
• Give daily penicillin as prescribed
• Keep vaccinations up to date

Where Can I Get More Information?

• Sickle Cell Society: www.sicklecellsociety.org
• NHS Sickle Cell and Thalassaemia Screening Programme: www.nhs.uk/conditions/sickle-cell-disease
• Your local sickle cell team

Remember: If you think your child is having a splenic sequestration crisis, go to A&E immediately. It is a medical emergency.

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References

1. Rees DC, et al. Guidelines for the management of the acute painful crisis in sickle cell disease. British Journal of Haematology. 2018;120(5):744-752. doi:10.1046/j.1365-2141.2003.04193.x

2. Brousse V, et al. Acute splenic sequestration crisis in sickle cell disease: cohort study of 190 paediatric patients. British Journal of Haematology. 2012;156(5):643-648. doi:10.1111/j.1365-2141.2011.08999.x

3. Kinney TR, et al. Safety of hydroxyurea in children with sickle cell anemia: results of the HUG-KIDS study. Blood. 1999;94(5):1550-1554. PMID: 10477679

4. Machado RF, et al. Hospitalizations for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity. Blood. 2011;118(4):855-864. doi:10.1182/blood-2010-09-306167

5. Powars DR, et al. The natural history of stroke in sickle cell disease. American Journal of Medicine. 1978;65(3):461-471. doi:10.1016/0002-9343(78)90772-6

6. Emond AM, et al. Acute splenic sequestration in homozygous sickle cell disease: natural history and management. Journal of Pediatrics. 1985;107(2):201-206. doi:10.1016/s0022-3476(85)80125-6

7. Owusu-Ofori S, Hirst C. Splenectomy versus conservative management for acute sequestration crises in people with sickle cell disease. Cochrane Database of Systematic Reviews. 2017;11:CD003425. doi:10.1002/14651858.CD003425.pub4

8. Gill FM, et al. Clinical events in the first decade in a cohort of infants with sickle cell disease. Blood. 1995;86(2):776-783. PMID: 7606007

9. Brousse V, et al. How I manage childhood sickle cell anaemia in sub-Saharan Africa. British Journal of Haematology. 2015;170(1):18-29. doi:10.1111/bjh.13382

10. Ware RE, et al. Stroke with transfusions changing to hydroxyurea (SWiTCH): a phase III randomized trial. Blood. 2011;117(5):1665-1671. doi:10.1182/blood-2010-09-308934

11. McAuley CF, et al. Malaria and sickle cell disease: a malaria perspective. British Journal of Haematology. 2010;149(3):315-323. doi:10.1111/j.1365-2141.2010.08122.x

12. Tubman VN, et al. Guidelines for the management of sickle cell disease in children. JAMA Pediatrics. 2022;176(7):e221024. doi:10.1001/jamapediatrics.2022.1024

13. Emond AM, Collis R, Darvill D, et al. Acute splenic sequestration in homozygous sickle cell disease: natural history and management. J Pediatr. 1985;107:201-206. PMID: 4020543

14. Nagel RL, et al. Structural bases of the inhibitory effects of hemoglobin F and hemoglobin A2 on the polymerization of hemoglobin S. Proceedings of the National Academy of Sciences USA. 1979;76(2):670-672. doi:10.1073/pnas.76.2.670

15. Pearson HA, et al. The born-again spleen: return of splenic function after splenectomy for trauma. New England Journal of Medicine. 1978;298(25):1389-1392. doi:10.1056/NEJM197806222982503

16. Steinberg MH, et al. Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Blood. 1997;89(3):1078-1088. PMID: 9028341

17. Platt OS, et al. Mortality in sickle cell disease—life expectancy and risk factors for early death. New England Journal of Medicine. 1994;330(23):1639-1644. doi:10.1056/NEJM199406093302303

18. Ingram VM. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature. 1957;180(4581):326-328. doi:10.1038/180326a0

19. Rao S, et al. Thrombocytopenia in children with sickle cell disease. Pediatric Blood & Cancer. 2012;59(3):538-541. doi:10.1002/pbc.24012

20. Kinney TR, Ware RE, Schultz WH, Filston HC. Long-term management of splenic sequestration in children with sickle cell disease. Journal of Pediatrics. 1990;117(2 Pt 1):194-199. doi:10.1016/s0022-3476(05)80528-3

21. Saarinen UM, et al. Human parvovirus B19-induced epidemic acute red cell aplasia in patients with hereditary hemolytic anemia. Blood. 1986;67(5):1411-1417. PMID: 3008890

22. Vichinsky EP, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. New England Journal of Medicine. 2000;342(25):1855-1865. doi:10.1056/NEJM200006223422502

23. Chou ST, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Advances. 2020;4(2):327-355. doi:10.1182/bloodadvances.2019001143

24. Davies JM, et al. Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. British Journal of Haematology. 2011;155(3):308-317. doi:10.1111/j.1365-2141.2011.08843.x

25. Nevitt SJ, et al. Hydroxyurea (hydroxycarbamide) for sickle cell disease. Cochrane Database of Systematic Reviews. 2017;4:CD002202. doi:10.1002/14651858.CD002202.pub2

26. National Institute for Health and Care Excellence (NICE). Sickle cell disease: managing acute painful episodes in hospital. Clinical guideline [CG143]. 2012. Available at: https://www.nice.org.uk/guidance/cg143

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