Cyclic Hematopoiesis in Dogs

Collies affected by cyclic hematopoiesis also develop neutropenia, defined as abnormally low levels of neutrophils in the blood. Neutrophils help to coordinate the inflammatory response against pathogens, and make up about half of the white blood cells circulating in the body. A deficiency of neutrophils predispose the body to infection. With cyclic hematopoiesis, lowered levels of neutrophils occur in 10 to 14 day intervals. This is when symptoms of this condition are seen for about 2 to 4 days, after which time the neutrophils rebound and cause an abundance of the blood cell in the body.

Cyclic hematopoiesis is a genetic disorder of the immune system of Collie dogs, and is also referred to as cyclic neutropenia and gray collie syndrome. Affected puppies will grow a silver-gray coat and exhibit a lack of growth and an increased weakness compared to littermates. Within a few months, other signs such as fever and joint pain will appear. Death by 2 to 3 years of age due to recurring bacterial infections is common.

Affected puppies are usually noticed right away due to their distinctive gray coats and lack of growth. By 8 to 12 weeks of age, other signs can appear every 10 to 14 days. Symptoms of this condition include:

• Gray hair coat, sometimes mixed with light beige
• Light colored nose
• Lack of growth
• Weakness
• Fever
• Diarrhea 
• Joint pain
• Loss of appetite
• Recurring bacterial infections, including of the respiratory system, gastrointestinal tract, kidneys, skin, or eyes
• Jaundice 
• Lethargy
• Bleeding episodes
• Anemia 
• Pale or white gums
• Pneumonia
• Liver failure
• Kidney failure
• Premature death

Hematopoiesis is the natural process that forms new blood cells. Cyclic hematopoiesis is a disruption of this process, which slows it down to around 2 week intervals. This disruption is caused by an abnormality in the stem cells within the bone marrow, and can cause a reduction in the number of blood cells created. This results in fluctuations of the numbers of various blood cells that are circulating in the blood, including platelets, lymphocytes and neutrophils. A lack of platelets in the blood can result in bleeding episodes. When neutrophils reach low levels, the body’s susceptibility to bacterial infections increase. This is typically when symptoms are seen in affected dogs.

The disruption in the normal blood cell growth process is caused by an inherited autosomal recessive gene that affects Collies. Both parents must carry the gene for a puppy to be affected. Asymptomatic carriers can still pass on the abnormal gene even if they do not show symptoms. Studies have shown that the mutation is located in the ELA2 gene.

A diagnosis is based on characteristic symptoms, such as a gray coat color and a lack of growth in the first weeks of life, and the results of testing. Blood counts are taken to measure the cyclic fluctuations of blood cell counts, including neutrophils. Signs of anemia, excessive blood nitrogen levels, and other blood abnormalities are noted. These blood counts may be taken several times throughout the 10 to 14 day intervals. The presence of low neutrophil levels during regular intervals can give a definitive diagnosis.

Treatment is generally supportive, and includes administering antibiotics during episodes of low neutrophil levels. Affected puppies usually die within 6 months of age without such treatment, as they are highly susceptible to infections. Anemic dogs may receive whole blood transfusions. 

Gene therapy can be prescribed, which involves injections of recombinant granulocyte colony-stimulating factor (rG-CSF). This can increase neutrophil production. An injection of a lentivirus can also be used to the same effect, and often follows the gene therapy. Cyclic hematopoiesis can be cured with a bone marrow transplant taken from a healthy dog, often a littermate.

While there is a cure for this condition, it can be expensive and may not be possible. Supportive care can treat symptoms during drops in neutrophil levels. You may need to administer antibiotics and monitor your dog for signs of infections. Even with constant care, many affected dogs will die before they reach 2 or 3 years old from chronic infections or organ failures.

Prevent this inherited condition by ensuring that affected dogs do not breed. DNA based testing is available to identify affected dogs and carriers, and a pedigree analysis should be kept updated. If your puppy suffers from cyclic hematopoiesis, then both parents carry the abnormal gene, and should be taken out of the breeding stock.