Acanthocytes are red blood cells that have lost their normal smooth, disc-like shape and instead sprout irregular, thorn-like projections from their surface. The name comes from the Greek word acanthos, meaning spine, and these cells were first described in 1950 in two siblings with vision problems and neurological abnormalities.1Blood. Of Acanthocytes, Spurs, Burrs and Membranes Their presence on a blood smear is never normal, and they point to a surprisingly wide range of underlying conditions, from severe liver disease to rare inherited neurological disorders to simple starvation.
What Acanthocytes Look Like and Why They Matter
Under a microscope, acanthocytes stand out because of their few, unevenly spaced spikes that vary in length and width. A normal red blood cell is a smooth biconcave disc, built to flex as it squeezes through tiny capillaries. Acanthocytes have lost that uniform shape due to a structural defect in the cell membrane itself. The projections are not just cosmetic: they make the cell stiffer, less deformable, and more likely to be trapped and destroyed by the spleen. That destruction is the root of the anemia that accompanies many conditions where acanthocytes appear.
The clinical threshold for calling a blood sample “acanthocytic” is typically set above 3% of total red cells. Below that, the odd spiky cell can be an artifact of sample preparation. In patients with confirmed acanthocyte-producing conditions, the percentage is highly variable and can range anywhere from about 5% to 50%, with no clear relationship between the percentage and how severe the underlying disease is.2ASH Image Bank. Peripheral Blood Smear is more contributory than we think – Diagnosing a case of Chorea
Acanthocytes Versus Echinocytes
One of the most common sources of confusion in lab work is telling acanthocytes apart from echinocytes, another type of spiky red cell. The distinction matters because the two have completely different causes and clinical significance. Echinocytes (sometimes called burr cells) have many evenly spaced, uniform projections around their surface, like a sea urchin. Acanthocytes have fewer spikes that are irregularly placed and vary in size, giving them a more chaotic, jagged look.
The critical difference is deeper than appearance. Echinocytes can be created and reversed by changes in pH, salt concentration, and other lab conditions, meaning they often show up as preparation artifacts and do not necessarily signal disease. Acanthocytes, on the other hand, reflect a permanent structural defect in the red cell membrane. You cannot reverse an acanthocyte by changing the conditions in the test tube.3Swiss Medical Weekly. The acanthocyte-echinocyte differential When a blood smear shows large numbers of echinocytes alongside some acanthocytes, the challenge is picking out the true acanthocytes. Experienced hematologists look for the “grotesque” membrane abnormalities and the irregular spike distribution that set acanthocytes apart from the more orderly echinocyte shape.
What Goes Wrong in the Membrane
A healthy red blood cell membrane is a carefully balanced sandwich of lipids and proteins. When that balance tips, the membrane buckles and deforms. In acanthocytes, the problem involves the lipids that make up the outer layer of the membrane. Specifically, many acanthocyte-producing conditions lead to an abnormal ratio between two major membrane lipids: sphingomyelin increases while lecithin (phosphatidylcholine) decreases. This shift makes the membrane less fluid and less flexible, and the cell’s surface distorts into the characteristic spiky shape.4PubMed Central. Decreased fluidity of red cell membrane lipids in abetalipoproteinemia
In other acanthocyte-producing conditions, excess cholesterol loading into the membrane produces a similar stiffening effect. This is what happens in spur cell anemia, where severe liver disease floods red cells with cholesterol they cannot handle. And in the neuroacanthocytosis syndromes, the problem operates through a different route entirely: abnormal signaling inside the cell alters how the membrane skeleton connects to the outer membrane. Research on chorea-acanthocytosis has shown that an enzyme called Lyn kinase becomes overactive, causing excessive chemical modification of key structural proteins like band 3, β-spectrin, and adducin. This disrupts the anchoring system that normally holds the membrane in its smooth disc shape.5PubMed Central. Erythrocyte membrane changes of chorea-acanthocytosis are the result of altered Lyn kinase activity Computational analysis of the signaling networks involved in neuroacanthocytosis has identified a cluster of kinases that regulate both cytoskeleton organization and neuronal development, which may help explain why these diseases affect both red blood cells and the brain simultaneously.6PLoS ONE. Computational Identification of Phospho-Tyrosine Sub-Networks Related to Acanthocyte Generation in Neuroacanthocytosis
Liver Disease and Spur Cell Anemia
The most common clinical setting where acanthocytes turn up is advanced liver disease, particularly alcoholic cirrhosis. When the liver fails badly enough, it can no longer regulate lipid metabolism properly. Cholesterol and abnormal lipoproteins accumulate in the blood and get incorporated into red cell membranes, producing the rigid, spiky cells known as spur cells. Spur cell anemia is the formal name for the resulting hemolytic anemia, and it carries a grim prognosis: it is an independent predictor of death in cirrhosis patients.7SpringerLink. Spur cell anemia related to alcoholic liver cirrhosis managed without liver transplantation: a case report and literature review
In spur cell anemia, the stiffened red cells get trapped in the spleen, which recognizes them as defective and destroys them faster than the bone marrow can replace them. Investigation of the lipoprotein profile in affected patients has found significant reductions in apolipoprotein AI and the HDL3 subclass, pointing to disordered lipoprotein handling as a driving factor.8PubMed Central. An unusual cause of anemia in cirrhosis: spur cell anemia, a case report with review of literature The most effective treatment is liver transplantation, which corrects the underlying metabolic chaos. Managing spur cell anemia without transplantation remains extremely difficult.9SpringerLink. Spur cell anemia related to alcoholic liver cirrhosis managed without liver transplantation: a case report and literature review
The Neuroacanthocytosis Syndromes
A handful of rare inherited diseases combine acanthocytes on the blood smear with progressive neurological deterioration. These are grouped under the umbrella term “neuroacanthocytosis,” and they represent some of the most diagnostically challenging conditions in neurology.
Chorea-Acanthocytosis (VPS13A Disease)
Now more precisely called VPS13A disease, chorea-acanthocytosis is caused by mutations in both copies of the VPS13A gene, which normally produces a protein involved in lipid transport between cellular compartments. When the protein is reduced or absent, patients develop involuntary movements (chorea), difficulty eating and speaking due to tongue and lip biting, seizures, cognitive decline, and psychiatric symptoms. Brain imaging and autopsy studies show neuronal loss concentrated in the caudate nucleus of the striatum, accompanied by marked scarring from support cells.10PubMed Central. An autopsy series of seven cases of VPS13A disease (chorea-acanthocytosis) Symptoms typically begin in the twenties or thirties and worsen over one to two decades. There is no disease-modifying treatment; care focuses on managing symptoms.
McLeod Syndrome
McLeod syndrome is an X-linked condition, meaning it primarily affects males. It involves mutations in the XK gene, which encodes a protein found on the surface of red blood cells. The XK protein is closely linked to the Kell blood group system, so affected individuals have weakened Kell antigens. This has real consequences for blood transfusion: McLeod patients can develop severe transfusion reactions if they receive Kell-positive blood, and their own blood can cause problems if transfused to others. Neurologically, McLeod syndrome resembles chorea-acanthocytosis but tends to start later, often in the forties or fifties, and may include heart muscle disease.
PKAN
Pantothenate kinase-associated neurodegeneration, or PKAN, is a different kind of neurodegenerative disease caused by mutations in the PANK2 gene. It belongs to the broader category of brain iron accumulation disorders, with iron deposits building up in the basal ganglia. Acanthocytes appear in about 10% of PKAN patients, making it an occasional rather than consistent feature.11PubMed Central. Acanthocytosis and the c.680 A>G Mutation in the PANK2 Gene: A Study Enrolling a Cohort of PKAN Patients from the Dominican Republic Among those who do have acanthocytosis, the degree varies widely: roughly half show elevated counts above 20%, while the rest have only mild or negligible levels. PKAN is also associated with iron deposition visible on brain MRI, which can be a useful diagnostic clue.12PubMed Central. PKAN neurodegeneration and residual PANK2 activities in patient erythrocytes
Lipid Disorders and Abetalipoproteinemia
The very first patients described with acanthocytes, back in 1950, turned out to have abetalipoproteinemia, a rare inherited inability to produce certain fat-carrying proteins in the blood.13Blood. Of Acanthocytes, Spurs, Burrs and Membranes Without these lipoproteins, fat-soluble vitamins (A, D, E, and K) are poorly absorbed, and the lipid composition of red cell membranes becomes abnormal. Affected individuals develop vision loss from retinal degeneration, neurological problems from vitamin E deficiency, and fat malabsorption causing fatty stools. The acanthocytosis in abetalipoproteinemia has been specifically linked to the increased sphingomyelin-to-lecithin ratio in red cell membranes, which reduces membrane fluidity and distorts cell shape.14PubMed Central. Decreased fluidity of red cell membrane lipids in abetalipoproteinemia Early treatment with high-dose vitamin E and dietary fat restriction can slow the neurological and retinal damage if started in childhood.
Starvation and Malnutrition
You do not need a rare genetic mutation or end-stage liver disease to develop acanthocytes. Severe malnutrition alone can do it. A study of patients with extreme nutritional depletion, including cases of anorexia nervosa and involuntary starvation, found acanthocytes in the blood of every single patient examined. Severe malnutrition was the one factor all patients shared, and the finding was accompanied by bone marrow cell death.15PubMed. Marrow cell necrosis in anorexia nervosa and involuntary starvation The mechanism likely involves the same membrane lipid disruption seen in other acanthocyte conditions: when the body’s lipid pools are severely depleted or imbalanced, red cell membranes lose their normal composition. This is worth knowing because acanthocytes on a blood smear in a severely underweight patient are not just a laboratory curiosity; they signal that malnutrition has progressed far enough to cause structural changes in blood cells.
Drug-Induced Acanthocytosis
Certain medications can produce acanthocytes as a side effect, typically by disrupting red cell membrane lipids or ion transport. In animal studies, an experimental compound called SCH 900875 caused severe hemolytic anemia with acanthocytosis in rats at higher doses, accompanied by drops in platelet counts and changes in membrane lipid composition.16PubMed. Drug-induced hemolytic anemia and thrombocytopenia associated with alterations of cell membrane lipids and acanthocyte formation
In humans, a case of acute hemolytic anemia with acanthocytosis was reported following high-dose misoprostol (a prostaglandin analogue). The patient’s blood smear showed acanthocytes that gradually disappeared after the drug was stopped. Investigation revealed abnormalities in red cell sodium and potassium content along with disrupted membrane ion transport channels, suggesting the drug was directly damaging red cell membranes. The anemia was self-limited once the drug was withdrawn.17PubMed. Acute hemolytic anemia with acanthocytosis associated with high-dose misoprostol for medical abortion Drug-induced cases are important to recognize because they are reversible, unlike the genetic or cirrhotic causes.
Why Finding Acanthocytes Is Harder Than It Sounds
Identifying acanthocytes reliably on a blood smear is trickier than most clinicians realize. Standard blood collection tubes contain the anticoagulant EDTA, and the way smears are typically prepared can cause normal red cells to develop echinocyte-like crenations that mimic or obscure true acanthocytes. A prospective, blinded study of patients with movement disorders tested several preparation methods head to head and found that the standard dry blood smear approach was the least sensitive. Diluting the blood sample with isotonic saline and examining it as a wet (unfixed) preparation dramatically improved detection. That combination achieved high specificity (0.98) and was the only method that correctly identified every genetically confirmed chorea-acanthocytosis patient in the study. The researchers recommended a cutoff of 6.3% of total red cells to define significant acanthocytosis using this method.18PubMed. Testing for acanthocytosis A prospective reader-blinded study in movement disorder patients
This has practical implications. If a neurologist suspects neuroacanthocytosis and orders a routine blood smear, the lab may report no acanthocytes simply because the preparation method was not sensitive enough. A negative result from a standard dry smear does not rule out the diagnosis. When the clinical suspicion is strong, the sample should be specifically requested with dilution and wet preparation.
Acanthocytes in Urine
Acanthocytes are not only found in blood. When they appear in urine, a condition called acanthocyturia, they serve as a surprisingly useful diagnostic marker in nephrology. When someone has blood in their urine, the key clinical question is whether the bleeding comes from the kidneys’ filtering units (the glomeruli) or from somewhere else in the urinary tract, like the bladder or ureters. Acanthocytes in urine strongly suggest glomerular origin.
An early study of this phenomenon found that in patients with biopsy-proven glomerulonephritis, acanthocytes made up an average of about 12% of excreted red cells. In patients with non-glomerular bleeding or healthy subjects, acanthocytes were below 2% or absent entirely. Using a threshold of 5% or more, urinary acanthocytes had a sensitivity of 52% and a specificity of 98% for glomerular disease.19PubMed. Acanthocyturia–a characteristic marker for glomerular bleeding More recent work has explored combining acanthocyte detection with other markers like red blood cell casts and found that the combination can push sensitivity up to about 75% while keeping specificity at 86%.20PubMed Central. Glomerular Hematuria for the Diagnosis of Nephritis: Acanthocytes and RBC Casts in GN Because the test can be informative even when very few red cells are present in the urine, it is particularly useful in early or mild cases of glomerulonephritis where other signs may be subtle.
Acanthocytes in Veterinary Medicine
Acanthocytes are not unique to humans. In dogs, they show up in association with several diseases, most notably certain cancers. A retrospective study of dogs with hemangiosarcoma, an aggressive cancer of blood vessel walls, found acanthocytes in half of the dogs examined, though there was no clear link between acanthocyte presence and the tumor’s location or the breed of dog involved.21PubMed Central. A retrospective study of canine hemangiosarcoma and its association with acanthocytosis A broader survey of 123 dogs with acanthocytosis found that over half had some form of cancer, with hemangiosarcoma, osteosarcoma, and lymphoma being the most common types.22PubMed. Disease distribution in canine patients with acanthocytosis: 123 cases
For veterinarians, spotting acanthocytes on a dog’s blood smear can serve as an early alert to look for hidden tumors, particularly hemangiosarcoma of the spleen or liver. The mechanism is thought to be similar to humans: tumor-related disruption of lipid metabolism or direct damage to red cells as they pass through abnormal tumor vasculature. While acanthocytes in dogs are not specific enough to diagnose any one cancer, their presence in an otherwise unexplained anemia should prompt further imaging and workup.