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Causes of Non-Regenerative Anemia in Dogs

Non-Regenerative Anemia in Dogs

Non-regenerative anemia in dogs is a type of anemia where there is a decrease in the production of red blood cells. As the name implies, the anemia is non-regenerative, meaning that some abnormality is occurring in the dog's bone marrow affecting its regular production of red blood cells. The causes of non-regenerative anemia in dogs can be several and therefore require some in depth investigation through several diagnostic tests.

Erythropoiesis in dogs

Good production of red blood cells happens courtesy of a well functioning bone marrow.

Non-Regenerative Anemia in Dogs

There are two different types of anemia in dogs: regenerative anemia and non-regenerative anemia.

Regenerative anemia is seen when there is excessive bleeding or the destruction of red blood cells, a process that is medically known as "hemolysis." As the name implies, regenerative anemia indicates that the dog's body is trying to fix the condition (regenerate) by producing new red blood cells to replace the lost ones.

Red blood cells are produced in the bone marrow, the spongy tissue inside the bones. The process of the bone marrow manufacturing red blood cells is known as erythropoiesis.  This term derives from the word erythrocytes, which is the more technical medical term for red blood cells

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In regenerative anemia, therefore, once the underlying cause for the bleeding is addressed, there is hope that the bone marrow will provide support by makings its own blood, explains veterinarian Dr. Will. A well-functioning bone marrow is primarily judged by its release of reticulocytes - immature red blood cells.

Non-regenerative anemia in dogs instead is seen when there is a decreased production of red blood cells and this is often caused by some abnormality affecting the dog's bone marrow, causing it to no longer fix the blood loss (regenerate). In such a case, there is a malfunction in the release of reticulocytes - immature red blood cells.

Affected dogs typically may not show particular symptoms especially if they lead rather sedentary lives. Later on though, dogs may appear weak, lethargic, have pale gums, sleep more, groom themselves less and get tired easily. They may also breath faster and have a higher heart rate to compensate for the decrease in red blood cells.

Diagnosing Non-Regenerative Anemia in Dogs

rash on a dog's belly

The first step in diagnosing a non-regenerative anemia in dogs is through bloodwork. A common complete blood test (CBC) provides some valuable preliminary information suggestive of anemia (lowered red blood cells).

In particular, non-regenerative anemia is suspected when there is absence of reticulocytosis, the increased production in reticulocytes following blood loss.

Reticulocytes are immature red blood cells without nuclei that are produced by the bone marrow when dogs undergo excessive blood loss or when red blood cells are destroyed by the immune system. Increasing reticulocyte production is reflective of the bone marrow's ability in regenerating red blood cells.

In non-regenerative anemia though, as mentioned, such regeneration and increased production of red blood cells doesn't occur. A specific blood test known as a reticulocyte count therefore tells whether or not the anemia is regenerative or nonregenerative.

Non-regenerative anemias are often categorized as extramarrow (occurring outside the bone marrow) or intramarrow (involving the bone marrow directly). A bone marrow aspirate may help determine whether or not the bone marrow is still producing functional stem cells.

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Causes of Non-Regenerative Anemia in Dogs 

As mentioned, in non-regenerative anemia, the production of blood is disrupted and there are chances that the dog's body will not regenerate or produce blood. It's important to find the underlying cause so to find out what the next step may be. Following are several causes of non-regenerative anemia in dogs.

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Anemia of Chronic Disease 

Non-regenerative anemia often occurs secondary to other disease processes. Probably the most common cause of anemia in dogs is anemia of chronic disease which develops in response to several infectious diseases (bacterial, viral, fungal, or tick-borne diseases such as ehrlichiosis, babesiosis), non infectious diseases and several cancerous disorders.

Anemia of chronic disease may be seen with chronic health issues such as gingivitis, abscesses, skin diseases, chronic bleeding into the gastrointestinal tract (as seen as dark tarry stool and sometimes vomiting and diarrhea) and various cancers. In anemia of chronic disease, correction of the underlying disorder may result in resolution of the anemia.

Anemia of Chronic Kidney/Liver Failure 

Another possible condition associated with non-regenerative anemia in dogs is chronic, long-term kidney disease. This is because the dog's kidneys are known for producing a special hormone (erythropoietin) that stimulates the development of red blood cells from the bone marrow.

In dogs with long-term kidney disease, this hormone is no longer produced as it should. In affected dogs, the chemistry profile shows abnormally high level of nitrogen waste products in the blood such as creatinine and urea. The anemia in this case can be corrected by administering the synthetic form of erythropoietin.

Chronic liver disease may too cause non-regenerative anemia, Affected dogs may appear weak and lethargic due to the anemia. Their liver enzymes, bile acids, bilirubin levels tend to be elevated.

In the case of anemia due to kidney or liver disease, diseases of these organs should have been evident on blood and urine tests.

Anemia of Endocrine Disorders

Endocrine disorders known to potentially cause mild to moderate non-regenerative anemia in dogs include hypothyroidism and hypoadrenocorticism. In anemia due to underlying endocrine disorders the anemia is expected to resolve once the dog is prescribed the most appropriate hormone replacement therapy. In most cases, it may take weeks to months to see improvement in the anemia.

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Anemia Due to Bone Marrow Diseases 

In this form of non-regenerative anemia, there is a reduction of all types of blood cells. In widespread bone marrow involvement the production of white blood cells is affected at first, then platelets and then red blood cells.

There are several possible causes for anemia involving the bone marrow directly including various toxicities such as exposure to estrogen, phenylbutazone, chloramphenicol, antiseizure drugs, griseofulvin, meclofenamic acid, trimethoprim-sulfadiazine, methimazole and several chemotherapy agents. Lead poisoning may also trigger this form of anemia.

Other causes include several hypoplastic anemias such as myeloaplasia, also known as aplastic anemia, which is an anemia occurring when the bone marrow fails to produce normal quantities of all blood cells (lowered numbers of red blood cells; anemia, lowered numbers of white blood cells; leukopenia and lowered numbers of platelets; thrombocytopenia), and pure cell aplasia (PRCA), a non-regenerative anemia resulting from a reduction in the elements that produce the red blood cells in the bone marrow.

Cancers of the bone marrow are possible too. These are slow-growing blood cancers known as chronic myeloproliferative disorders. Myelofibrosis is an uncommon type of bone marrow cancer which disrupts the normal production of blood cells.

Primary leukemias are also a type of cancer where there is lack of normal white blood cells and platelets. Although primary leukemias are not common, it has been occasionally reported in dogs.

Treatment of Non-Regenerative Anemia in Dogs 

As seen, there are various causes of non-regenerative anemia in dogs. Treatment varies based on the underlying cause. For example, if the anemia is caused by low thyroid levels, then thyroid medicine can help correct the issue, in the case of toxin exposure, stopping the exposure may lead to resolution of the problem.

Supportive care with fluid therapy can help the dog feel better. Transfusions may be needed for severe cases

The prognosis tends to vary widely based on underlying cause. Generally, when there is accompanying pancytopenia present (other low numbers of blood cells—like white cells or platelets), then there may be an extremely guarded prognosis. Other causes may have a better prognosis, albeit if the underlying cause cannot be sufficiently addressed, the anemia will keep progressing.

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