What Causes Crenated Red Blood Cells?

Crenated red blood cells are normally smooth, disc-shaped cells that have sprouted small spikes around their edge. Most often the spikes form after the blood is drawn, when the sample sits too long in its tube or the tube is underfilled, so a finding on a smear report is frequently an artifact rather than disease.1International Journal of Current Pharmaceutical Review and Research. Anti-Coagulant EDTA Induced Storage Artifacts on Peripheral Blood Smear When the spikes are genuinely present in the body, they usually point to conditions that alter the blood around the cells, such as kidney failure, liver disease, severe burns, heart-lung bypass, an inherited enzyme problem called pyruvate kinase deficiency, or snake venom, rather than a flaw in the cells themselves.2Swiss Medical Weekly. The acanthocyte-echinocyte differential Crenation is also one of the few red-cell shape changes that can usually be undone once the trigger is removed.3Swiss Medical Weekly. The acanthocyte-echinocyte differential

Most Often It Happens in the Tube, Not in Your Body

Your report may say “crenated RBCs,” “echinocytes,” or “burr cells.” All three describe red cells with many small, evenly spaced spikes.4Swiss Medical Weekly. The acanthocyte-echinocyte differential5International Journal of Current Pharmaceutical Review and Research. Anti-Coagulant EDTA Induced Storage Artifacts on Peripheral Blood Smear Most blood counts and smears use a tube with a purple top, called an EDTA tube, which contains a chemical that stops blood from clotting. Blood left standing in that tube slowly changes, and crenated cells are one of the main changes it produces.6International Journal of Current Pharmaceutical Review and Research. Anti-Coagulant EDTA Induced Storage Artifacts on Peripheral Blood Smear

Freshly drawn EDTA blood showed no crenated cells.7International Journal of Current Pharmaceutical Review and Research. Anti-Coagulant EDTA Induced Storage Artifacts on Peripheral Blood Smear After 2 hours of storage, crenated cells appeared in 48% of samples.8International Journal of Current Pharmaceutical Review and Research. Anti-Coagulant EDTA Induced Storage Artifacts on Peripheral Blood Smear By 6 hours, 92% of samples had them.9International Journal of Current Pharmaceutical Review and Research. Anti-Coagulant EDTA Induced Storage Artifacts on Peripheral Blood Smear A sample that waited several hours, such as one couriered from a clinic to a distant lab, is especially prone to this. Because storage-crenated cells can be mistaken for true burr cells, smear readers are taught to keep the timing in mind before calling it disease.10International Journal of Current Pharmaceutical Review and Research. Anti-Coagulant EDTA Induced Storage Artifacts on Peripheral Blood Smear

Putting too little blood in the purple-top tube can create crenated cells, as can a delay before the slide is made.11VIN. Abnormalities in the Canine and Feline Blood Film The way the slide is dried, and the glass itself, can also make cells spiky.

Artifact crenation often looks uniform across the slide, with most cells at the thin feathered edge spiky in the same way. That is one clue among several, not a definitive test. Many real conditions come with other abnormal findings.

The lab reports it anyway because smear readers describe what they see on the slide, not its cause. The report rarely says whether crenation is an artifact, so interpretation falls to your doctor. A comment like “few” or “occasional” crenated cells usually carries less weight than “many.”

If your report mentions crenated cells, you can ask how long the sample waited before the slide was made and whether it was processed on site. Ask whether your kidney and liver results were normal, since those are the main real causes, and whether a fresh sample would settle the question.

Why Red Cells Turn Spiky

A red cell’s outer skin is made of two thin layers of fat-like molecules pressed back to back. Normally the layers are balanced, so the cell stays a smooth disc with a dimple. If the outer layer gains area while the inner one doesn’t, the outer surface has nowhere to go but out, and it forms spikes.12PubMed Central. Washing stored red blood cells in an albumin solution improves their morphological and hemorheological properties Substances that slip mainly into the outer layer make cells crenate, while ones that settle in the inner layer make them cup-shaped instead.13PubMed Central. Biological Membranes as Bilayer Couples. A Molecular Mechanism of Drug-Erythrocyte Interactions Drugs and detergents that slip into the membrane can trigger either shape this way.14PubMed. A basis of echinocytosis and stomatocytosis in the disc-sphere transformations of the erythrocyte

The change needed is tiny. Expanding the outer layer by under 2% is enough to turn a disc into a cell with about 35 spikes.15PubMed. Membrane bilayer balance and erythrocyte shape: a quantitative assessment A fat-like substance called lysolecithin, which builds up in stored blood and is made by some venoms, is a well-known trigger.16PubMed Central. Washing stored red blood cells in an albumin solution improves their morphological and hemorheological properties17PubMed. Mechanisms of echinocytosis induced by Crotalus atrox venom

Water loss can do it as well. Red cells crenate when the fluid around them is saltier than their insides, so water flows out and they shrink.18PubMed Central. Spatially variant red blood cell crenation in alternating current non-uniform fields Changes in the fluid’s acidity or salt balance can cause crenation and, when corrected, reverse it.19Swiss Medical Weekly. The acanthocyte-echinocyte differential Cells low on energy lose their flexibility and can crenate, because energy powers the pumps that keep their salt and water balance.20PubMed. Erythrocyte populations in pyruvate kinase deficiency anaemia following splenectomy. II. Cell deformability

The blood’s salt level is tightly controlled in the body, so shrinkage mostly explains changes in tubes and labs. Crenation in the body usually comes from substances in the blood, covered below.

Because spikes come from what’s touching the membrane, removing that substance lets the cell flatten again. Washing crenated cells in a protein solution that soaks up fats turned them back into discs.21PubMed. Erythrocyte crenation induced by free fatty acids in patients undergoing extracorporeal circulation The cell’s internal structure is usually not damaged, unlike in some other shape changes.

Kidney Failure

Kidney failure is the condition most classically linked with true burr cells. When kidneys fail, waste products the body would normally filter out stay in the blood. In people with end-stage kidney disease on dialysis, red cells show more chemical stress than in healthy people.22PubMed. Oxidative stress-associated shape transformation and membrane proteome remodeling in erythrocytes of end stage renal disease patients on hemodialysis Their membranes become unstable, lose surface area, and take on spiky as well as cup-like shapes.23PubMed. Oxidative stress-associated shape transformation and membrane proteome remodeling in erythrocytes of end stage renal disease patients on hemodialysis

These cells generally show up when kidney function is badly reduced, not in mild kidney problems. Dialysis removes some waste but not all of it, which is why spiky cells can persist in people being treated.

Alongside crenated cells you would expect abnormal kidney blood tests such as high creatinine. People with kidney failure are also often anemic, so the count of red cells may be low. Burr cells alone, with normal kidney results, are not a sign of hidden kidney failure.

Liver Disease

In some people with jaundice from liver disease, the HDL particles that carry cholesterol are abnormal.24PubMed Central. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins When healthy red cells were exposed to these particles, they became spiky within seconds.25PubMed Central. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins The more strongly a person’s HDL triggered the change, the more crenated cells they had in their own blood.26PubMed Central. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins The particles appear to work by latching onto spots on the cell surface rather than adding or removing cholesterol.27PubMed Central. Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins Liver-related crenation tends to appear with jaundice, a yellowing of the skin and eyes, and liver blood tests such as bilirubin are usually abnormal at the same time.

Advanced cirrhosis can look different. In alcoholic cirrhosis, red cell membranes carry extra cholesterol and fewer of their usual fats.28PubMed. Liver alcoholic cirrhosis and spur-cell (acanthocytic) anaemia. A study of erythrocyte ghost composition and fluidity Severe cirrhosis can produce a different spiky cell, the spur cell, which is a fixed defect rather than reversible crenation.29PubMed. Liver alcoholic cirrhosis and spur-cell (acanthocytic) anaemia. A study of erythrocyte ghost composition and fluidity30Swiss Medical Weekly. The acanthocyte-echinocyte differential The smear reader may mention spur cells as well, which suggests advanced cirrhosis. Spur cells are tied to a lasting membrane change and to faster red cell breakdown, unlike reversible crenation.

Burns, Heart Surgery, Inherited Enzyme Problems and Venom

After severe burns, the blood fills with crenated cells and red cells survive for a shorter time, contributing to anemia.31PubMed. The pathogenesis of abnormal erythrocyte morphology in burns Burned patients’ blood carries far more free fatty acids relative to albumin, the protein that normally holds them.32PubMed. The pathogenesis of abnormal erythrocyte morphology in burns Albumin acts like a sponge, keeping fatty acids away from cell membranes. After a severe burn the balance tips, and loose fatty acids can settle into red cell membranes. The cause lies in the blood, not heat damage: burned patients’ cells returned to normal in healthy people’s blood.33PubMed. The pathogenesis of abnormal erythrocyte morphology in burns Healthy cells placed in a burned patient’s blood crenated. Cell shapes also change in stages after a burn, with severe changes first and a milder phase later.34PubMed Central. Thermal damage to red cells

People on a heart-lung machine during surgery can develop crenated cells driven by free fatty acids.35PubMed. Erythrocyte crenation induced by free fatty acids in patients undergoing extracorporeal circulation Washing those cells with fat-free albumin restored their normal disc shape.36PubMed. Erythrocyte crenation induced by free fatty acids in patients undergoing extracorporeal circulation

Pyruvate kinase deficiency is an inherited condition in which red cells can’t make enough energy, leading to anemia. Its energy-starved cells become crenated and stiff.37PubMed. Erythrocyte populations in pyruvate kinase deficiency anaemia following splenectomy. II. Cell deformability The energy shortfall shifts the balance between the two membrane layers.38Pediatric Research. SHAPE CHANGE (ECHINOCYTOSIS) IN PYRUVATE KINASE DEFICIENT RED CELLS IS MEDIATED BY THE COUPLED BILAYER HYPOTHESIS After spleen removal, a common treatment, these cells may last longer before the energy shortage crenates them.39PubMed. Erythrocyte populations in pyruvate kinase deficiency anaemia following splenectomy. II. Cell deformability PK deficiency is usually known from childhood and diagnosed with a specific enzyme test.

Rattlesnake venom contains an enzyme that produces lysolecithin, which turns red cells spiky.40PubMed. Mechanisms of echinocytosis induced by Crotalus atrox venom Crenated cells on a smear can therefore support a diagnosis of rattlesnake bite.41PubMed. In-vitro exposure of feline red blood cells to rattlesnake venom causes echinocytosis They appear quickly after a bite and come with obvious bite symptoms.

Crenated Cells Versus Acanthocytes

Acanthocytes have a few spikes of uneven length scattered irregularly over the cell.42Swiss Medical Weekly. The acanthocyte-echinocyte differential Crenated cells have many spikes spaced regularly around the surface.43Swiss Medical Weekly. The acanthocyte-echinocyte differential Acanthocytes come from a built-in structural flaw in the membrane, while crenation responds to acidity, salt balance and chemistry around the cell.44Swiss Medical Weekly. The acanthocyte-echinocyte differential Acanthocytes reflect a lasting change in the membrane’s fat and cholesterol makeup, so putting them in fresh surroundings does not flatten them. An acanthocyte finding therefore cannot be explained away as a tube artifact.

On a report, “burr cells” and “echinocytes” mean crenated cells, while “spur cells” usually means acanthocytes. Some reports list both, which can happen in liver disease. If the wording is unclear, asking which spiky cell was seen is a reasonable question.

The difference changes what comes next. Crenated cells often prompt a repeat on fresh blood first. Acanthocytes prompt a search for liver disease, nutritional problems or rare inherited conditions, and a repeat test won’t make true acanthocytes disappear.

Are Crenated Cells Harmful

Spiky cells snag on each other, making blood thicker.45PubMed Central. Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network They also can’t stack together normally the way smooth cells do.46PubMed Central. Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network Blood full of crenated cells flows less well through small arteries and veins, mostly in vessels 13 to 70 thousandths of a millimetre wide.47PubMed Central. Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network The problem isn’t that single cells can’t squeeze through the tiniest capillaries.48PubMed Central. Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network

This effect shows up in laboratory studies of blood full of crenated cells, not as a symptom people feel. Mild or occasional crenation, especially from a tube artifact, has no effect on a living person’s circulation. The concern becomes relevant only when a large share of cells is truly crenated in the body.

Stored donor blood develops crenated cells as lysolecithin builds up.49PubMed Central. Washing stored red blood cells in an albumin solution improves their morphological and hemorheological properties Washing stored red cells in an albumin solution reversed the shape and improved how they flowed.50PubMed Central. Washing stored red blood cells in an albumin solution improves their morphological and hemorheological properties

If everything else is normal and you feel well, a repeat smear on fresh blood is the usual next step. There is no treatment aimed at the cells themselves; treating the cause lets them return to normal. Seek care promptly if crenation comes with jaundice, reduced urine, or marked fatigue.

Crenated Cells in Dogs and Cats

In dogs and cats, crenated cells often come from underfilled EDTA tubes or slow slide preparation.51VIN. Abnormalities in the Canine and Feline Blood Film Low numbers of crenated cells are commonly seen in healthy cats.52VIN. Abnormalities in the Canine and Feline Blood Film Cats and dogs have red cells that differ from human cells in size and appearance, and vets read smears with those norms in mind, so the number matters more than the mere presence of the word on the report.

Rattlesnake venom turns cat red cells spiky.53PubMed. In-vitro exposure of feline red blood cells to rattlesnake venom causes echinocytosis Vets may check a smear for crenated cells to support a suspected rattlesnake bite and speed treatment.54PubMed. In-vitro exposure of feline red blood cells to rattlesnake venom causes echinocytosis Purified venom enzyme crenated dog red cells too, with more venom causing more change.55PubMed. Mechanisms of echinocytosis induced by Crotalus atrox venom

Useful questions for your vet: was the number seen more than expected for the species, and was the sample run in-clinic or sent out, since delay raises artifact risk? After a possible snakebite outdoors, mention it right away, as the smear helps confirm it.