Hemophilia in cats
Hemophilia is a group or rare hereditary bleeding disorders in which the cat’s blood doesn’t clot appropriately in case of an injury. Although uncommon, hemophilia is a severe condition that can be inborn or acquired. Today we aim to explain to you what happens when bleeding in cats occurs, how bleeding disorders develop and what hemophilia actually is.
Whenever bleeding occurs in an organ or a body part, a process called hemostasis is activated to stop the bleeding. Hemostasis is the first stage of healing of all wounds and serves to keep the blood within a damaged blood vessel. Let’s take it step by step to see how this process develops exactly (Figure 1):
1. The first response after an injury is vascular spasm or vasoconstriction. If bleeding occurred, that means that the wall of the blood vessel broke. A healthy blood vessel is responsive and will narrow down immediately to slow down the blood flow and allow the clotting process to begin. The constriction of the vessels allows less blood to be lost.
2. Thrombocyte plug formation. Thrombocytes rush to the broken wall to form a clot and plug the break in the vessel wall. Thrombocytes stick together and form a temporary seal to cover the break.
3. The last step is the coagulation (blood clotting). Once the thrombocyte creates the plug, the clotting factors (13 proteins in the blood) are activated in a sequence known as coagulation cascade. Coagulation cascade leads to the formation of fibrin. Fibrin is produced by the thrombocytes and acts like a glue helping to hold thrombocytes them in place. During this process, some erythrocytes and leukocytes are being trapped into this structure, and the resultant plug is called CLOT. Therefore, clot contains thrombocytes, fibrin and red and white blood cells.
Figure 1: Steps of Hemostasis (credits)
Therefore, for hemostasis to work correctly, it requires an adequate number of circulating platelets in the blood (thrombocytes), blood vessels that constrict properly and the appropriate activation of the coagulation cascade (clotting factors). Abnormalities in any of these factors can lead to abnormal hemostasis. Hemostatic abnormalities are classified into four categories: 1) thrombocytopenia (low levels of thrombocytes), 2) dysfunction of thrombocytes, 3) vasculopathies(abnormalities with blood vessels) and 4) low levels or activity of coagulation factors.
And how is hemostasis troubled in hemophilia exactly?
Hemophilia belongs to the fourth mentioned hemostatic abnormality, and it is caused by the decreased levels of coagulation factors. There are 13 coagulation factors in total (numbered from I to XIII). Deficiency in any of these factors will result in hemophilia. Hemophiliac cats can’t coagulate blood properly, and the bleeding isn’t controlled adequately.
Types of hemophilia
Hemophilia in cats is most common congenital (inherited, inborn), although it can also be acquired (for example due to vitamin K absence or rodenticide poisoning). Best known variants of congenital hemophilia in cats are hemophilia A and B and Hageman deficiency.
Some cat breeds have the higher genetic predisposition to these conditions. It is suspected that Maine coon may have such predisposition, and it is confirmed in British shorthairs and Devon Rex’.
Hemophilia A, or classical hemophilia, is a rare disease among cats and has also been reported in humans, dogs, and horses. Hemophilia A includes the deficiency of a coagulation factor VIII, and it is an X-linked recessive disorder. This means that the gene for coagulation factor VIII is located on the X chromosome and that the mutated variant of the gene won’t express itself in the presence of the normal variant (more about this in the section "3. GENETICS").
The severity and frequency of bleeding in hemophilia A is determined by the degree of factor VIII deficiency.
Hemophilia B, also known as the Christmas disease, is an X chromosome-linked recessive deficiency of coagulation factor IX. Hemophilia B is reported to be inherited in British shorthair cats.
This type of hemophilia is an autosomal recessive disorder and is defined by the deficiency in coagulation factor XII. This deficiency does not result in spontaneous bleeding like in hemophilia A and B.
Hemophilia A is caused by a mutation in the gene for coagulation factor VIII, and hemophilia B by a mutation in the gene for coagulation factor IX. Both of these genes are located on the X chromosomes and the healthy variants are dominant over the mutated variants.
Female cats carry two X chromosomes, while males carry one X and one Y chromosome. Therefore, female cats will always carry two genes for these coagulation factors, but males only one. The mutated variants of the genes express itself only when there are no healthy, dominant variants in the genotype. The following inheritance rules apply when it comes to hemophilia A and B:
1. All males who inherit a mutated gene for a coagulation factor will always be affected by the condition and will pass the mutated gene to the offspring.
2. Males who inherit the healthy gene are never affected and cannot transmit the disease to the offspring.
3. Females who carry one mutated gene on one of their X chromosomes, and a healthy gene on the other X chromosome will be silent carriers. This means that they won’t be affected by the condition themselves, but they can pass it on to their offspring.
4. Females who carry two mutated genes on both of their X chromosomes are always affected and can only pass on the mutated gene to their offspring.
While hemophilia A and B are X-linked disorders, Hageman deficiency is an autosomal disorder. That means that the gene for the factor XII is located on an autosomal chromosome and not a sex chromosome. In humans, the gene coding for this factor is identified as F12 gene.
Symptoms and diagnosis
The clinical symptoms of hemophilia are similar to all types. Hemophiliacs often show weakness, fever and lack of appetite. Lameness and swelling of the joints may occur due to spontaneous bleeding into the joints. Bleeding under the skin can cause hematomas (soft swellings). Internal bleedings in organs and body cavities can result in bloody or dark stool and vomit, rectal or vaginal bleeding and nose bleeding. If a feline affected by the condition undergoes trauma or surgery, then excessive hemorrhage can occur at the affected place. Because of regular episodes of internal or external bleeding, due to loss of blood, hemophiliac cats can suffer from regenerative anemia and experience weakness, lethargy, shortness of breath and irregular heartbeats.
When veterinarians suspect the cat may be suffering from hemophilia, they usually run tests to determine the source of the disorder. Some diagnostic tests that can be used to diagnose hemophilia are: in vivo bleeding time, coagulation assays, prothrombin time, thrombin clotting time and fibrinogen determination.
Unfortunately, there are currently no genetic tests known to us used to detect the mutations causing these conditions. However, since the genes responsible for them are identified, it is possible to develop a genetic test in the future.
Treatment and prognosis
Unfortunately, congenital hemophilia cannot be cured, and the treatment depends on the severity of the condition. For example, in cases of severe bleeding, blood transfusions may be required.
Furthermore, cats with inherited hemophilia should be spayed/neutered and kept indoors. Intensive playing should be minimized to reduce the risk of bleeding into the joints. Certain medications and surgeries should also be avoided. If a surgery really is necessary, then a blood transfusion before it is highly recommended.
Despite the fact that the condition is somewhat rare, breeding from affected cats should be avoided, because it would result in the creation of both affected cats and silent carriers. Silent carriers are problematic (always females!), as they do not show the signs of the disease but can produce affected offspring.
In case of acquired hemophilia, the treatments depend on the cause. If vitamin K deficiency is the cause, then vitamin K will be prescribed. For cats who acquired hemophilia due to poisoning (for example rodenticide poisoning), then medication for induced vomiting will be prescribed alongside activated charcoal and vitamin K injection.
The prognosis for cats with mild to moderate hemophilia is generally good, while severe cases must be guarded. These conditions are relatively rare among cats, but they are critical and problematic. It is necessary to have enough information on disposal to be able to adequately recognize and address the symptoms of both congenital and acquired hemophilia as soon as possible.