Overview
Aplastic Crisis in Sickle Cell Disease
Topic Overview
Summary
Aplastic crisis is a sudden, severe drop in haemoglobin caused by temporary cessation of red cell production, most commonly triggered by parvovirus B19 infection. It occurs in patients with underlying haemolytic anaemias, particularly sickle cell disease, who depend on high rates of erythropoiesis to compensate for shortened RBC lifespan. Presentation is profound anaemia (Hb often under 50 g/L) with absent reticulocytes. Treatment is supportive with blood transfusion; the crisis is usually self-limiting.
Key Facts
- Cause: Parvovirus B19 infects erythroid progenitors → temporary erythropoietic arrest
- At-risk: Patients with chronic haemolytic anaemias (sickle cell, thalassaemia, hereditary spherocytosis)
- Hallmark: Profound anaemia + reticulocytopenia (under 1%)
- Treatment: Blood transfusion; recovery usually within 7-14 days
- Contagious: Parvovirus B19 can spread to other vulnerable patients (immunocompromised, pregnant)
Clinical Pearls
In sickle cell patients, low Hb + LOW reticulocytes = aplastic crisis; low Hb + HIGH reticulocytes = haemolytic crisis or acute splenic sequestration
Parvovirus B19 is a risk to pregnant women (fetal hydrops) — isolate patient
Aplastic crisis is usually self-limiting once antibodies develop; supportive care is key
Why This Matters Clinically
Aplastic crisis is a sickle cell emergency. Profound anaemia can cause cardiac failure if untreated. Prompt recognition, transfusion, and isolation (to protect vulnerable contacts) are essential.
Visual Summary
Visual assets to be added:
- Blood film showing absence of reticulocytes
- Parvovirus B19 life cycle diagram
- Sickle cell crisis differential diagnosis flowchart
- Reticulocyte count interpretation chart
Epidemiology
Incidence
- Aplastic crisis occurs in all chronic haemolytic anaemias
- Lifetime risk in sickle cell disease: ~65%
- Usually a single episode (immunity develops)
Demographics
- Children and young adults (first exposure to parvovirus B19)
- Rare in older adults (most already immune)
Cause
- Parvovirus B19: Most common trigger (over 80%)
- Other triggers: Other viral infections (rarely)
Who is at Risk?
| Condition | Why Vulnerable |
|---|---|
| Sickle cell disease | Shortened RBC lifespan (~10-20 days) |
| Thalassaemia | High erythropoietic rate |
| Hereditary spherocytosis | Chronic haemolysis |
| Hereditary elliptocytosis | Chronic haemolysis |
| Autoimmune haemolytic anaemia | Chronic haemolysis |
Pathophysiology
Parvovirus B19 Mechanism
- Parvovirus B19 binds to P antigen (globoside) on erythroid progenitors
- Virus replicates in and lyses erythroid precursors
- Red cell production stops for 7-14 days
- In healthy individuals: Mild, transient drop in Hb (unnoticed)
- In chronic haemolysis: Profound anaemia (Hb can drop to under 50 g/L)
Why Reticulocytes Disappear
- Reticulocytes are young RBCs (normally 0.5-2%)
- In haemolytic disease, reticulocytes are elevated (compensation)
- During aplastic crisis, reticulocytes fall to under 1% (often under 0.1%)
Recovery
- Host develops IgM then IgG against parvovirus B19
- Viral clearance → erythropoiesis resumes
- Reticulocyte count rises dramatically (reticulocyte "storm")
- Hb recovers over 1-2 weeks
Clinical Presentation
Symptoms
Signs
Prodrome (Parvovirus B19)
Red Flags
| Finding | Significance |
|---|---|
| Hb under 50 g/L | Severe — needs urgent transfusion |
| Reticulocytes under 1% | Confirms aplastic crisis |
| Hypotension | Cardiovascular decompensation |
| Dyspnoea at rest | Heart failure risk |
Fatigue — often rapid onset
Common presentation.
Dyspnoea on exertion — or at rest if severe
Common presentation.
Dizziness, presyncope
Common presentation.
Palpitations
Common presentation.
Preceding viral illness (fever, rash, arthralgias)
Common presentation.
Clinical Examination
Vital Signs
- Tachycardia
- Hypotension (severe cases)
- Tachypnoea
General Examination
- Profound pallor (conjunctivae, palms)
- Jaundice (may be present from prior haemolysis, less prominent in aplastic crisis)
Cardiovascular
- Flow murmur
- Signs of heart failure (elevated JVP, oedema, crackles)
Respiratory
- Tachypnoea
- Crackles if pulmonary oedema
Investigations
Blood Tests
| Test | Findings |
|---|---|
| FBC | Profound anaemia (Hb often under 50 g/L) |
| Reticulocyte count | Very low (under 1%, often under 0.1%) |
| Blood film | Reduced reticulocytes; sickle cells (if SCD) |
| LDH, bilirubin | May be less elevated than usual (less haemolysis) |
| Parvovirus B19 serology | IgM positive (acute infection) |
| Parvovirus B19 PCR | Positive in serum |
Group & Screen
- Crossmatch blood urgently
- May be difficult in sickle cell patients (alloimmunisation)
Other
- Reticulocyte count is KEY — distinguishes aplastic crisis from other causes
Classification & Staging
Sickle Cell Acute Crises — Differential
| Crisis Type | Key Feature |
|---|---|
| Aplastic crisis | Low Hb + LOW reticulocytes |
| Haemolytic crisis | Low Hb + HIGH reticulocytes + high LDH/bilirubin |
| Acute splenic sequestration | Low Hb + HIGH reticulocytes + rapidly enlarging spleen |
| Acute chest syndrome | Lung infiltrate + respiratory symptoms |
| Vaso-occlusive crisis | Pain + no significant Hb drop |
Management
Acute Management
1. Blood Transfusion:
- Transfuse to stabilise (not necessarily to normal Hb)
- Aim Hb 70-90 g/L (higher if symptomatic)
- Use phenotypically matched blood (reduce alloimmunisation)
- Avoid over-transfusion (hyperviscosity in sickle cell)
2. Supportive Care:
- IV fluids
- Oxygen if hypoxic
- Monitor for heart failure
3. Infection Control:
- Isolate patient (parvovirus B19 is contagious)
- Protect pregnant staff and visitors (risk of fetal hydrops)
- Protect immunocompromised contacts
Chronic/Immunocompromised Patients
- Parvovirus can cause chronic infection in immunocompromised
- Treatment: IVIG (provides neutralising antibodies)
Follow-Up
- Monitor reticulocyte count (rises as recovery occurs)
- Check Hb recovery
- Counselling on future immunity (usually lifelong)
Complications
Of Aplastic Crisis
- Cardiac failure (high-output or hypovolaemic)
- Death (if untreated)
- Rarely, persistent infection in immunocompromised
Of Transfusion
- Alloimmunisation (common in sickle cell)
- Transfusion reactions
- Iron overload (if repeated transfusions)
Prognosis & Outcomes
Recovery
- Usually complete recovery within 7-14 days
- Lifelong immunity to parvovirus B19 after infection
Mortality
- Low with prompt transfusion
- Higher risk if diagnosis delayed or heart failure develops
Evidence & Guidelines
Key Guidelines
- BCSH Guideline on Sickle Cell Disease (2019)
- NHS England Clinical Commissioning Policy for Sickle Cell Disease
Key Evidence
- Blood transfusion is life-saving in aplastic crisis
- IVIG effective for chronic parvovirus infection in immunocompromised
Patient & Family Information
What is an Aplastic Crisis?
An aplastic crisis is when your body temporarily stops making new red blood cells. This happens when a virus called parvovirus B19 affects your bone marrow. It can make you very anaemic.
Who is at Risk?
People with sickle cell disease or other conditions causing chronic anaemia.
Symptoms
- Feeling very tired and weak
- Shortness of breath
- Fast heartbeat
- Pale skin
Treatment
- Blood transfusion to bring your blood count up
- Most people recover fully within 1-2 weeks
Prevention
- After you've had an aplastic crisis, you are usually immune and won't get it again
- Tell your healthcare team if you're feeling unwell
Resources
References
Primary Guidelines
- BCSH. Guidelines for the Management of Patients with Sickle Cell Disease. 2019. b-s-h.org.uk
Key Studies
- Serjeant GR, et al. Human parvovirus infection in homozygous sickle cell disease. Lancet. 1993;341(8855):1237-1240. PMID: 8098391
- Young NS, Brown KE. Parvovirus B19. N Engl J Med. 2004;350(6):586-597. PMID: 14762186