Acanthocytes: Definition, Associated Disorders, and Clinical Management
What Are Acanthocytes?
Acanthocytes are abnormally shaped red blood cells with irregular, thorn-like projections ("spurs") on their surface, derived from the Greek word for "thorn." 1, 2 These dysmorphic erythrocytes have a shortened lifespan and can be detected on peripheral blood smear examination. 3, 2
Diagnostic Detection Methods
For optimal detection of clinically significant acanthocytosis, use isotonically diluted blood samples combined with unfixed wet blood preparation, with abnormal levels defined as ≥6.3% of total erythrocytes (99th percentile). 4 This method provides:
- Specificity of 0.98 4
- Higher sensitivity than standard dry blood smears (all genetically confirmed chorea-acanthocytosis patients were detected) 4
- Significantly more acanthocytes detected in wet preparations compared to standard EDTA dry smears 4
Standard peripheral blood smear evaluation by a qualified hematologist or pathologist remains essential for initial screening, as emphasized for general cytopenia workup. 3
Primary Disease Associations
Neuroacanthocytosis Syndromes
The core neuroacanthocytosis syndromes include chorea-acanthocytosis (autosomal recessive) and McLeod syndrome (X-linked), both presenting with Huntington's disease-like phenotypes. 1, 5
Chorea-acanthocytosis presents with: 1, 5
- Choreatic movements and orofaciolingual dyskinesia
- Dysphagia and dysarthria
- Areflexia and seizures
- Progressive dementia
- Elevated serum creatine kinase
- Myopathy and axonal neuropathy
- Absence of chorein protein on Western blot of red blood cells 5
McLeod syndrome shares features with chorea-acanthocytosis but additionally includes: 1, 5
- Cardiomyopathy (requires regular cardiac monitoring) 5
- Abnormal or absent Kell and Kx blood group antigens 5
- Permanent hemolytic state 1
- Risk of transfusion complications (must avoid) 5
Other neuroacanthocytosis associations: 1, 5
- Huntington's disease-like 2 (autosomal dominant) - acanthocytes found in a proportion of patients 5
- Pantothenate kinase-associated neurodegeneration (autosomal recessive) 5
- Hallervorden-Spatz disease (occasional association) 1
Lipoprotein Metabolism Disorders
Abetalipoproteinemia (Bassen-Kornzweig syndrome) and hypobetalipoproteinemia cause acanthocytosis through: 1, 5
- Absence or reduction of apolipoprotein B-containing lipoproteins 1
- Fat-soluble vitamin deficiency (especially vitamin E malabsorption) 5
- Progressive spinocerebellar ataxia with peripheral neuropathy 1
- Retinitis pigmentosa 1
- Notably, these do NOT cause movement disorders or cognitive impairment (distinguishing feature from neuroacanthocytosis syndromes) 5
Advanced Liver Disease
Spur cell anemia is an acquired non-autoimmune hemolytic anemia occurring in advanced liver disease, characterized by acanthocytes with shortened lifespan causing transfusion-unresponsive anemia. 2
- Classical severe form was considered rare with ominous prognosis 2
- Recent prospective studies demonstrate a milder, more common variant with smaller numbers of acanthocytes but still associated with hemolysis and poor outcomes 2
- The only known cure is liver transplantation 2
Evaluation Algorithm
Initial Screening
When acanthocytes are suspected or detected: 3
- Complete blood count with differential and peripheral smear review by qualified hematologist/pathologist 3
- Reticulocyte count to distinguish production vs. destruction 3
- Red cell distribution width (RDW) and mean corpuscular volume (MCV) 3
- Serum creatine kinase (elevated in chorea-acanthocytosis and McLeod syndrome) 1, 5
Hemolysis Workup
If hemolysis suspected: 3
Neuroacanthocytosis-Specific Testing
For patients with movement disorders and acanthocytosis: 5, 4
- Kell and Kx blood group antigen testing (reduced/absent in McLeod syndrome) 5
- Western blot for chorein protein in red blood cells (absent in chorea-acanthocytosis) 5
- Cerebral MRI to detect striatal atrophy 5
- Genetic testing (available for all neuroacanthocytosis syndromes) 5
- Cardiac evaluation mandatory in McLeod syndrome 5
Liver Disease Assessment
For suspected spur cell anemia: 2
- Liver function tests and synthetic function assessment
- Evaluation for advanced cirrhosis
- Liver transplant candidacy assessment (only curative treatment) 2
Lipoprotein Disorder Testing
If abetalipoproteinemia/hypobetalipoproteinemia suspected: 1, 5
- Fasting lipid panel
- Apolipoprotein B levels
- Fat-soluble vitamin levels (A, D, E, K)
- Ophthalmologic examination for retinitis pigmentosa 1
Management Approach
Neuroacanthocytosis Syndromes
There are no curative therapies for neuroacanthocytosis syndromes; management is symptom-oriented with disease-specific monitoring. 5
For McLeod syndrome specifically: 5
- Regular cardiologic studies are mandatory (monitor for cardiomyopathy) 5
- Strict avoidance of transfusion complications (due to abnormal Kell antigens) 5
For hyperkinetic movement disorders: 5
- Treat similarly to Huntington disease protocols 5
- Manage psychiatric manifestations symptomatically 5
Expected course: Relentlessly progressive over two to three decades 5
Spur Cell Anemia
Liver transplantation is the only known cure for spur cell anemia. 2
- Anemia is typically unresponsive to transfusion 2
- Supportive care until transplant candidacy can be established 2
Lipoprotein Disorders
Management focuses on fat-soluble vitamin supplementation (especially vitamin E) and dietary fat restriction. 1, 5
Critical Pitfalls to Avoid
- Do not rely on standard EDTA dry blood smears alone - use isotonically diluted wet preparations for optimal sensitivity 4
- Do not transfuse McLeod syndrome patients without specialized blood banking consultation due to abnormal Kell antigens 5
- Do not assume all acanthocytosis indicates neurological disease - consider liver disease and lipoprotein disorders 2, 5
- Do not overlook cardiac screening in McLeod syndrome - cardiomyopathy is a major cause of morbidity 5
- Do not confuse acanthocytes with other dysmorphic RBCs such as schistocytes (seen in TTP-HUS) 3