I’d appreciate any information about this problem because I’m going to write and publish an article in our little club newsletter.

• Do you have some experiences with this problem?
• Do you know exactly which colour the concerned rats are? I only know “Blue” (English, Irish...?).
• Is there any scientific opinion about the connection between the colour and the hemophilia syndrome or any other illness?

Many thanks beforehand.

Under normal circumstances, the endothelial cells that line the intact blood prevent platelets and the coagulation factors in the blood plasma from ever meeting the extracellular matrix below the endothelial cells. When a blood vessel is injured, the extracellular matrix is exposed to the platelets in the blood and a procoagulant situation is initiated.

Platelets are made in the bone marrow by megakaryocytes and circulate in the blood with the primary function to bind at the site of a wound to begin the clotting process. Any condition that results in decreased platelet production or survival can result in abnormal bleeding. Circulating platelets are normally smooth disks with an outer cell membrane with surface receptors (glycoproteins). They contain granules comprised of substances essential for the clotting process including: fibrinogen, factor V, von Willebrand Factor (vWF), ADP, and TXA2, etc. Note, endothelial cells also can produce vWF and aid in the clotting process. Thus, when platelets encounter the underlying collagen in the extracellular matrix of an injured blood vessel, they undergo three general reactions: 1. They stick to the collagen(adhesion) and change their shape from round to flat, 2. They release their granules, and 3. They stick to each other (platelet aggregation).

There is an absolute requirement for vWF to stabilize the initial platelets to the underlying collagen in the presence of the high sheer forces of the flowing blood. vWF is essential to bridge the collagen to the 1b glyocprotein receptors on the surface of the platelets. Thus, a genetic deficiency in vWF (von Willebrand disease) or the glyocprotein 1b surface receptor (Bernard-Soulier syndrome) results in defective platelets adhesion and bleeding disorders.

The next phase of platelet involvement (release of granules or secretion) is essential for the initiation of the coagulation cascade. The release of ADP is a potent mediator for the next phase where platelets adhere to other platelets. The initial platelet plug (primary hemostatic plug) is reversible; however, with activation of the coagulation cascade, thrombin is generated, which binds to a platelet surface receptor with ADP and TXA2 and results in further platelet aggregation followed by platelets contraction. This creates an irreversibly fused mass of platelets and is considered a secondary hemostatic plug. At the same time, thrombin converts fibrinogen (an important cofactor in platelet aggregation) to fibrin which stabilizes and anchors the aggregated platelets in place.

ADP-activated platelets bind to fibrinogen via another glycoprotein receptor (GbIIb-IIIa) to generate large platelet aggregates. Thus, a genetic mutation that causes a deficiency in the amount or function in this glycoprotein results in a severe bleeding disorder due to defective platelet aggregation known as Glanzmann thrombasthenia.

The third component to the hemostatic process involves the coagulation cascade (See Figure 2) that is essentially a series of conversion of inactive proenzymes to activated enzymes with culmination in the formation of thrombin. As mentioned above, thrombin is essential for the conversion of soluble fibrin in the blood plasma into the insoluble protein fibrin and the stabilized blood clot. Although divided into the intrinsic and extrinsic pathways with convergence at factor X (ten), the pathways are interconnected. In the interest of space, the intricacies of the coagulation cascade will not be discussed.

There is a hereditary deficiency of every one of the known clotting factors. Some are transmitted as sex-linked recessive disorders and most of the other follow an autosomal pattern. In most hereditary disorders there is only deficiency of one clotting factor.

Hemophilia A and von Willebrand disease (frequency of 1% in the human population) are two of the most common inherited disorders of bleeding in humans. In addition to its function in platelet aggregation, vWF serves as a carrier for factor VIII (eight) and is important for the stability of factor VIII. In normal humans, the stability of factor VIII in the circulation is 12 hours, and only about 2.4 hours in patients with von Willebrand disease. There are more than 20 variants of von Willebrand disease. In most cases it is transmitted as an autosomal dominant disorder, but several rare autosomal recessive variants have been identified. There are two major categories.

• In type 1 and 3 von Willebrand disease there is a reduction in the amount of circulating vWF. This accounts for 70% of the human cases. Type 1 diseases are autosomal dominant and type 3 are autosomal recessive.
• In type 2 von Willebrand disease there are qualitative defects in vWF (vWF is present but the functionality is poor or nonexistent). Type 2 variants account for 25% of all human cases. The most common is type 2A which is inherited in an autosomal dominant pattern.

Hemophilia B is caused by a deficiency of factor IX (nine) and in severe factor IX deficiency it is clinically indistinguishable from hemophilia A. HemophiliaBis also inherited as an X-linked recessive trait and may occur without symptoms or be associated with hemorrhage. In 14% of these human patients, factor IX is present but nonfunctional.

There is a balance to excessive blood clot formation and thrombosis known as anticoagulation. The key players in anticoagulation are antithrombin III, protein C, and protein S. Mutation in factor C (five) (Leiden mutation) or mutation resulting in the reduction or activity of antithrombin III, protein C, or protein S in humans presents with recurrent venous thrombosis.

We have only heard of this problem in the Blue rats (English Blue is the same as AFRMA’s Blue), never in the Russian Blue. Irish is a marking, not a specific color.

Blood clotting tests would be beneficial to breeders that have concerns that their Blue rats may have a problem so they would know whether or not to breed them and continue a flawed line.

As far as skin problems, yes, Blue rats seem to have more issues with breaking out in scabs when fed a diet that is too rich. Usually the owner is feeding a mixture of seeds along with other high-protein, high-fat foods. When they change the diet to only lab blocks and cut out all seeds and fattening treats, give them a bath, and clip their nails, they will see the scabs clear up and disappear. If they then give a treat later down the road of seeds/nuts/etc., and the rat immediately breaks out again in scabs, that shows it is the diet causing the problem. Elimination from further bad treats should keep your pet free from any scab issues.
See the update to testing on http://www.afrma.org/med_ratbitefever.htm.

AFRMA
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