Blood Platelets in Cavaliers:
Too Few (Thrombocytopenia) and
Too Large (Macrothrombocytopenia)
Are Usually Not a Serious Health Disorder

• IN SHORT
• IN DEPTH
• Details About This Benign Disorder
• Symptoms
• • not immune thrombocytopenia (ITP)
• • not immune-mediated hemolytic anemia (IMHA)
• Platelet Counting Procedures
• • automated and manual methods
• • plateletcrit method
• DNA Testing
• Treatment
• Research Studies' Findings
• • platelet size and counting issues
• • possible relationship with other disorders
• What You Can Do
• Research News
• Related Links
• Veterinary Resources

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IN SHORT

Over half of all cavalier King Charles spaniels may have both an abnormally low number of platelets and also have oversized platelets in their blood. This benign condition is called idiopathic asymptomatic thrombocytopenia and  is normal in cavaliers, requiring no treatment.

Platelets usually are the smallest cells in the blood system. They serve to bind together and clot when they come in contact with a damaged blood vessel. Despite the low platelet counts, the typical cavalier's blood platelets function normally, and the dog does not appear to experience any health problems due to either the size or fewer numbers of its platelets. There are, however, exceptions to this typical situation.

Excessively low platelet counts normally is a sign which tends to alarm general practice veterinarians, and so it is vitally important that cavalier owners alert their vets about this benign condition in the breed when blood tests are ordered. More...

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IN DEPTH

Platelets, also called thrombocytes, are blood cells which control blood clotting, to stop bleeding at open wounds. They clump together and clot when they come in contact with a damaged blood vessel, to seal it and prevent the loss of blood. Platelets are produced in the bone marrow. They are very complex cell fragments, containing a variety of components, most of which serve to stop bleeding (hemostasis). (See diagram at right.)

More than half of all cavalier King Charles spaniels may have both an abnormally low number of blood platelets and also have oversized platelets.* In most breeds, platelets are usually the smallest cells in the blood system. (See diagram above.) In the CKCS, however, the oversized platelets (called macrothrombocytes) are equal to or larger than a red blood cell.

Despite the low platelet counts, the typical cavalier's blood platelets function normally, and the dog does not appear to experience any health problems due to either the smaller size or fewer numbers of its platelets. There are, however, limited exceptions to this typical situation. See this section of this webpage.

*Other breeds reported to have similar conditions include the Japanese Akita, Cairn terrier, and Norfolk terrier.croplatelets

An excessively low platelet count normally is a sign which tends to alarm general practice veterinarians, and so it is vitally important that cavalier owners alert their vets about this benign condition in the breed when blood tests are ordered.

No treatment is recommended unless the dog shows other symptoms of a blood-related disorder. Cavaliers should not be treated for immune-mediated thrombocytopenia (IMT) as a precaution. A dog really suffering from IMT must be treated quickly, usually with intravenous doses of immunosuppressive drugs -- steroids, azathioprine, cyclosporine A, and others -- to save the dog's life. Such treatments are severe and could do major damage to the healthy cavalier with nothing more than a low platelet count.

Most commercial laboratories use an automated counting system for blood cells, which determine cell types on the basis of their size and volume. Because some of cavaliers' platelets are so large, automated blood cell counters may not recognize platelets as being platelets and undercount them (thinking they are the typically larger red blood cells), thereby inaccurately lowering the platelet count. Researchers have found that CKCS platelet counts using three different automated systems underestimated the actual counts determined manually. Antech Diagnostics, the largest veterinary diagnostic laboratory, has specifically stated on its website that:

"Platelets in this breed should be counted manually, because automated blood cell counters cannot distinguish the large platelets from erythrocytes and therefore underestimate the true platelet count."

An accurate platelet count usually can be obtained by visually counting the cells. Also, because the large platelets are so fragile, any blood samples should be extracted very carefully. Therefore, all blood samples from cavaliers should be taken in a very careful manner and preferably only from the dog's jugular vein, using a large bore needle, and then should be examined only under a microscope by an experienced clinical pathologist before making a diagnosis of low platelet count.

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Details About This Benign Disoder

Blood platelets (also called thrombocytes) are disk-shaped blood elements which aid in blood clotting. Platelets customarily are individually counted to determine whether dogs suffer from platelet disorders. Excessively low numbers are called thrombocytopenia and are the most common cause of bleeding disorders in dogs.

As many as half of all cavalier King Charles spaniels may have a congenital blood disorder called idiopathic asymptomatic thrombocytopenia, which means an abnormally low number of blood platelets but with no bleeding consequences, according to several studies. We say "may" because a 2008 Swedish study has found no thrombocytopenia in 27 CKCS when their blood was tested on a device using the plateletcrit method which measures platelet volume rather than numbers of platelets.

The platelets in the blood of many cavalier King Charles spaniels are a combination of those of normal size for dogs and others that are abnormally oversized. Cavaliers' oversized platelets are called macrothrombocytes. (See oversized CKCS platelet in blood smear at right.*) Macrothrombocytosis also is a congenital abnormality found in at least a third of CKCSs.

*Courtesy, Jessica Anne Kelley master's thesis, Univ. Minn. 

These large platelets function normally, and the typical cavalier does not appear to experience any health problems due to either the size or fewer numbers of its platelets. The theory of the 2008 Swedish study is that there appears to be an inverse relationship between platelet count and platelet size. This means that lower numbers of large platelets represent the same overall platelet mass as higher numbers of small platelets.

There are, however, exceptions to this typical situation. A June 2010 study has confirmed that "The data supports previous findings that CKCS with macrothrombocytopenia have a normal coagulation response despite low platelet counts."

Nevertheless, researchers hypothesize that cavaliers' giant platelets are the source of high levels of serotonin which may contribute to mitral valve disease in the breed. Read the details here.

In an April 2004 article, the Danish cardiologists found no relation between thrombocytopenia and femoral (hind leg) artery pulse strength in the 109 cavaliers in that study.

In a July 2015 article, the same benign disorder also has been reported, to a lesser extent, in other breeds, including Norfolk and Cairn terriers, Chihuahuas, Labrador retrievers, poodles, English toy spaniels (King Charles spaniels), shih tzus, Maltese, Jack Russell terriers, Havanese, boxers, cocker spaniels, bichons frises, and some mixed breeds.

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Symptoms

The typical CKCS with idiopathic asymptomatic thrombocytopenia does not appear to experience any health problems due to either the size or fewer numbers of its platelets. Nevertheless. many veterinarians have mis-diagnosed this benign disorder with either immune-mediated thrombocytopenia (IMT) or immune-mediated homolytic anemia (IMHA). However, in one reported case, in a November 2021 article, a cavalier correctly diagnosed with IMT and IMHA initially was thought to have only macro-platelets and not IMT.

• It is NOT immune thrombocytopenia (ITP)

However, many veterinarians who are ignorant about the cavaliers' benign disorder hurriedly conclude that the dog is suffering from  immune thrombocytopenia (ITP), or immune mediated thrombocytopenia (IMT), which is a very serious autoimmune disease in which the dog's body attacks its own blood platelets as though they are a pathogenic bacteria or virus.

IMT also has some very serious symptoms, such as an unusual susceptibility to bleeding (hemorrhaging), petechiae (pinpoint bruising -- small [<3 mm.] red or purple spots on the dog, caused by broken capillary blood vessels -- see photo at left), ecchymosis (larger bruising), bleeding from the mouth or nose or within the eye (see photo at right), pale gums, bloody urine, lethargy, weakness, an abnormally rapid heart rate, rapid beathing, and/or melana (dark, tarry stools that indicate the presence of blood in the GI tract). See this September 2015 article for more information about IMT. It may also be referred to as Evans Syndrome. Heatstroke may result in similar distressing symptoms. So, unless the CKCS also has any of those symptoms, it is extremely likely that all the cavalier has is the breed's benign platelet disorder.

See this May 2024 ACVIM Consensus Statement on ITP.

• It is NOT immune-mediated hemolytic anemia (IMHA)

Another auto-immune disease in some cases confused with idiopathic asymptomatic thrombocytopenia is immune mediated hemolytic anemia (IMHA), in which the dog's body attacks its own red blood cells, leading to low red blood cell counts and requiring blood transfusions.

• It is NOT severe fever with thrombocytopenia (SFTS) virus

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne zoonotic virus with symptoms which include low platelet counts, due to the virus attaching to the dog's platelets in the spleen. While symptoms commonly include platelet counts below the reference range, invariably there are other symptoms, such as 9as its name implies) fever, anorexia, depression, vomiting, and diarrhea. See this April 2022 article.

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Platelet Counting Procedures

• automated and manual disorders

Most commercial laboratories use an automated counting system for blood cells, which determine cell types on the basis of their size and volume. Because some of cavaliers' platelets are so large, automated blood cell counters may not recognize platelets as being platelets (treating them as if they were the larger red blood cells) and undercount them, thereby inaccurately lowering the platelet count. In a 2004 Danish study and the 2007 Italian study, the researchers found that all of their CKCS platelet counts using three different automated systems underestimated the actual counts determined manually. Antech Diagnostics, the largest veterinary diagnostic laboratory, specifically states on its website that "Platelets in this breed should be counted manually, because automated blood cell counters cannot distinguish the large platelets from erythrocytes [red blood cells] and therefore underestimate the true platelet count." In some cases, false counts of platelets by automated blood analyzers has been referred to as "Pseudothrombocytopenia" (PTCP).

An accurate platelet count usually can be obtained by visually counting the cells. However, when counting the platelets manually, technician must be aware of the likelihood of the presence of oversized  platelets, so that they are included in the count and not confused with other cells.

Not all manual counts of platelets are accurate, however.  In a June 2018 article, a team of Italian three veterinarians examined blood smears from 30 dogs to count platelet numbers and determine the mean platelet count for each dog. They report finding that variabilities of platelet count estimates are high, operator-dependent, and influenced by the area of the blood smear. They found that platelet estimates by different observers could lead to a different classifications (thrombocytopenic or not) of the same dog. They concluded that platelet estimates alone are not precise enough to allow a reliable evaluation of platelet mass, and that their findings should encourage the establishment of standard guidelines tto perform reliable platelet estimates.

Also, because the large platelets are so fragile, any blood samples should be extracted very carefully. Therefore, all blood samples from cavaliers should be taken in a very careful manner and preferably only from the dog's jugular vein, using a large bore needle, and then should be examined only under a microscope by an experienced clinical pathologist before making a diagnosis of low platelet count. The 2004 US study report recommends that the blood be anticoagulated with ethylenediamine-tetraacetic acid (EDTA) and citrate.

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• plateletcrit method

The days of mis-diagnosis of thrombocytopenia in cavaliers may be over!  IDEXX Laboratories has developed a hematology analyzer using fluorescent optics which measures the volume of platelets (called plateletcrit) in a blood sample.

This procedure has been found in a 2008 Swedish study to be superior to the customary manual and automated platelet counts for assessing the platelet status of cavaliers. The device is called the IDEXX VetAutoread Hematology Analyzer. In their report, the researchers, Harold Tvedten, Inger Lilliehöök, Anna Hillström, and Jens Häggström, reported:

"The major purpose of this study was to compare the QBC [IDEXX VetAutoread Hematology Analyzer] platelet results with platelet counts from other automated and manual methods for evaluating platelet status in CKCS dogs. ... Platelet counts were determined in fresh EDTA blood from 27 adult CKCS dogs using the QBC, Sysmex XT-2000iV (optical and impedance), CELL-DYN 3500, blood smear estimate, and manual methods. Sysmex optical platelet counts were reanalyzed following gating to determine the number and percentage of normal- and large-sized platelets in each blood sample.

"Results: None of the 27 CKCS dogs had thrombocytopenia (defined as <164 × 109 platelets/L) based on the QBC platelet count. Fourteen (52%) to 18 (66%) of the dogs had thrombocytopenia with other methods. The percentage of large platelets, as determined by regating the Sysmex optical platelet counts, ranged from 1% to 75%, in a gradual continuum. Conclusions: The QBC may be the best analyzer for assessing clinically relevant thrombocytopenia in CKCS dogs, because its platelet count is based on the plateletcrit, a measurement of platelet mass."

In view of the 2008 Swedish study's finding of no thrombocytopenia in any of the 27 cavaliers, it could be that the breed does not suffer from thrombocytopenia, but instead has been the victim of platelet counting methods which rely upon the number of platelets rather than their overall volume.  Macrothrombocytosis -- oversized platelets -- still were found in this study.  Researchers in the 2008 study found that the platelet volume is more important than the numbers for the function of the platelets.

In a 2012 study, the same team of Swedish researchers compared the results from IDEXX's VetAutoread hematology analyzer with a Bayer Diagnositics' device, the Advia 2120 plateletcrit analyzer, for 43 cavaliers and 15 other dogs. The results showed that Advia's platelcrit readings were lower than those found by the IDEXX device for cavaliers which had the lowest plateletcrits.

Similarly, in a January 2013 master's thesis, University of Minnesota student Jessica Anne Kelley studied blood tests of 139 CKCSs, to investigate the use of the plateletcrit as an assessment of total platelet biomass in cavaliers with macrothrombocytopenia. She concluded:

"In this particular model of an inherited asymptomatic macrothrombocytopenic platelet disorder, Cavalier King Charles Spaniels represent a group of individuals in which the bleeding risk is better evaluated using plateletcrit than platelet number. The platelet mass appears significantly lower in affected dogs when measured by count, but when measured by plateletcrit, more of the patients are appropriately within the reference range. Therefore, for the Cavalier King Charles Spaniels affected by this mutation, plateletcrit better represents the true total platelet biomass in peripheral circulation."

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DNA Testing

Veterinary researchers at Auburn University have devised a DNA test for CKCSs suspected of having oversized platelets. In their 2008 report, the research team identified a mutation in the gene that encodes beta1-tubulin (β1-tubulin gene), a protein involved in platelet production by megakaryocytes. Their DNA test is available to determine the presence or absence of this mutation. For more information about this DNA test, contact Dr. Peter Christopherson  at Auburn Univ., telephone 334-844-2697, email chrispw@auburn.edu, or click here for the webpage.

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Treatment

Absolutely no treatment is recommended unless the dog shows other symptoms of a blood-related disorder.

Cavaliers should not be treated for immune-mediated thrombocytopenia (IMT) as a precaution. Dog really suffering from IMT must be treated quickly, usually with intravenous doses of immunosuppressive drugs -- steroids, azathioprine, cyclosporine A and others -- to save the dog's life. Such treatments are severe and could do major damage to the healthy cavalier with nothing more than a low platelet count.

 In a March 2024 article, Taiwan veterinarians report a case study of a young male cavalier with low blood platelet counts and with observed very large platelets and no symptoms of thrombocytopenia, which the general practice clinicians nevertheless treated with high oral doses of prednisolone and other drugs, without any improvement in the platelet counts. They report that the clinicians' periodic physical examinations of the dog "revealed no abnormalities ... No abnormalities were detected by abdominal radiography or ultrasonography." Prior to medication, the "number of red blood cells and white blood cell counts were all within normal limits. No signs of immune-mediated diseases were observed."

Due to the medications, particularly the high doses of immune-suppresing prednisolone, the dog's condition worsened. He developed anemia, and his white blood cell count shot up (leukocytosis), as did his ALP and ALT levels, suggesting the onset of kidney failure. The treating veterinarians finally discontinued the steroids and referred the cavalier to specialists, Tzu-Yi Ma, Chih-Jung Kuo, Chih-Chung Chou, and Pin-Chen Liu (right, above), who also have authored this report. They diagnosed the benign condition of asymptomatic inherited macrothrombocytopenia, acknowledging that "Inherited macrothrombocytopenia of CKCS has not been documented in Taiwan till date." The specialists attributed the leukocytosis and anemia to a "systemic infection related to steroid treatment."

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Research Studies' Findings

• platelet size and counting issues

A 2002 Danish study report (Drs. Henrik D. Pedersen, Jens Häggström, Lisbeth H. Olsen, and others) concluded that cavaliers' oversized platelets could lead to erroneous diagnoses of thrombocytopenia when automated blood counters are used. An erroneous diagnosis of low platelet counts could result in unnecessary diagnostic tests for the cavaliers.

A 2005 Australian study (Drs. M. K. Singh and W. A. Lamb) of 152 cavalier King Charles spaniels, all from New South Wales, found that the platelet count of the cavaliers, as a group, was only 32% that of the mixed breed control dogs, and that 30% of the CKCS in the study had macrothrombocytes. The Australian researchers concluded that the data supported an autosomal recessive inheritance pattern.

In a 2007 Italian study (Drs. W. Bertazzolo, S. Comazzi, L. Sesso, P. Scarpa, G. Ru, and S. Paltrinieri), the researchers compared platelet counts, platelet estimations and platelet parameters in 41 cavaliers measured by different methods -- impedance cell counter, laser cell counter and microscopic estimation -- commonly used in veterinary hospitals and commercial laboratories. Quantitative buffy coat analysis was performed on 17 of the samples, selected from cavaliers which had low platelet counts detected by the cell counters. CKCSs with macrothrombocytes had significantly lower counts on impedance cell counter (34.1% dogs below normal -- < 1003×109/l), laser cell counter (26.8%) and microscopic estimation (22.0%). The quantitative buffy coat analyser result was only 5.8% below normal.

In a 2008 study at Auburn University (Drs. B. Davis, M. Toivio-Kinnucan, S. Schuller, M.K. Boudreaux) determined that "a mutation in the gene encoding β1-tubulin [TUBB1 gene] correlated with macrothrombocytopenia in CKCS." They concluded that "this information will aid in distinguishing inherited from acquired thrombocytopenia. It also provides insight into the mechanism of platelet production by megakaryocytes, and also may prove useful in understanding heart-related changes in macrothrombocytopenic CKCS with concurrent mitral valve regurgitation."

The Auburn researchers since have devised a DNA test for macrothrombocytopenia. See details at Diagnosis below.

 In a June 2018 article, a team of Italian three veterinarians examined blood smears from 30 dogs to count platelet numbers and determine the mean platelet count for each dog. They report finding that variabilities of platelet count estimates are high, operator-dependent, and influenced by the area of the blood smear. They found that platelet estimates by different observers could lead to a different classifications (thrombocytopenic or not) of the same dog. They concluded that platelet estimates alone are not precise enough to allow a reliable evaluation of platelet mass, and that their findings should encourage the establishment of standard guidelines tto perform reliable platelet estimates.

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• possible relationship with other disorders

 • mitral valve disease 

It has been shown in studies of humans that mitral valve regurgitation can cause a reduction in the quantity of platelets, as well as increase their size, and alter their aggregation. Also, an association between inherited giant platelet disease and early onset mitral valve disease (MVD) has been reported in a family of humans. See this  January 1998 article.

In a 2003 Danish study (Drs. I. Tarnow, A. T. Kristensen, H. Texel, L. H. Olsen, and H. D. Pedersen), the researchers found that CKCSs with mild, moderate, and severe mitral valve regurgitation have decreased platelet function. So, mitral valve disease may be the underlying cause of both thrombocytopenia and macrothrombocytopenia in the cavalier King Charles spaniel. However, in a 2002 US study of 42 CKCSs, the researchers reported that: "There was no association of thrombocytopenia with murmurs, and no association of abnormal platelet aggregation with murmurs or thrombocytopenia."

In the 2004 US study led by Drs. Sara M. Cowan and Rebecca Gompf of the University of Tennessee, thrombocytopenia was present in 51.43% of the 69 CKCSs in the study, and macrothrombocytes were present in one third of the cavaliers. Co-incidentally, 38% of the dogs in the US study had cardiac murmurs. The American researchers found platelet ultrastructure to be normal. They have identified the disorder as Benign Inherited Giant Platelet Disorder (IGPD). They wrote that "further studies are indicated to determine ... any association with mitral endocardiosis [MVD]."

In a January 2010 report, Dr. Mark A. Oyama of the University of Pennsylvania suggested a linkage between oversized platelets in cavaliers and their significantly higher serotonin concentrations than in other breeds of dogs.  Serotonin and transforming growth factor-β are believed to play major roles in transforming valvular interstitial cells (VIC) into a more active myofibroblast, which is an important component of MVD in cavaliers. Read here about Dr. Oyama's continued research of the link between CKCSs' giant platelets and MVD.

In an April 2014 report, members of the Danish team, Drs. S.E. Cremer, A.T. Kristensen, M.J. Reimann, N.B. Eriksen, S.F. Petersen, C.B. Marschner, I. Tarnow, and L.H. Olsen joined with USA's Dr. Mark Oyama to report finding a link between high-level serotonin-binding and highly-activated blood platelets and mitral valve disease and oversized platelets in cavaliers. They studied the levels of serotonin-binding and of platlet activation in 61 CKCSs and found that cavaliers with moderate-severe MVD and severe MVD tended to have higher levels of platelet activation, and that highly-active platelets and high-level serotonin-binding was strongly associated with oversized platelets. They concluded that further investigation into the significance of serotonin-binding.

In a July 2014 report, the international team found that platelet serotonin was elevated in cavaliers compared to other breeds, and that left ventricular myocardial and mitral valve leaflet tissue in deceased MVD dogs was elevated compared to dogs which died without cardiac disease.

However, in a June 2015 study, the Danish team and Dr. Oyama analyzed blood samples of 62 cavalier King Charles spaniels (15 healthy dogs; 18 with mild MVD; 19 with moderate-to-severe MVD; and 10 in congestive heart failure). They were looking for (a) any relationship between serotonin concentrations in blood platelets ("percentage of serotonin-positive platelets, level of surface-bound platelet serotonin expression"), and (b) platelet activation, in CKCSs with MVD. They found no differences in either surface-bound serotonin expression or platelet activation among the four categories of cavaliers in the study.

They did observe that dogs with low platelet numbers (thrombocytopenic dogs) had significantly lower serum serotonin concentrations than non-thrombocytopenic dogs. And, they found in 26 of the dogs a "flow cytometry scatterplot subpopulation (FSSP)" of platelets. Dogs with an FSSP had a higher percentage of serotonin-positive platelets, and a higher level of surface-bound serotonin expression, and higher platelet activation, than did dogs without an FSSP. An FSSP was present in 93.8% of the thrombocytopenic dogs and in 29.5% of the nonthrombocytopenic dogs. They concluded from those observations that an FSSP of highly activated platelets with pronounced serotonin binding was strongly associated with thrombocytopenia but not with MVD.

In an April 2016 abstract, a team of Sweden researchers evaluated 50 cavaliers to determine if oversized platelets affected hemostasis (the stopping of a flow of blood) in CKCSs with mitral valve disease (MVD). They determined that left ventricular fractional shortening of the heart -- a marker of progressing MVD -- combined with macrothrombocytosis, and age were shown to be associated with a more activated hemostasis "might" have an implication in MVD progression in CKCS.

In an August 2016 article, Australian researchers examined 89 cavaliers to determine if measurements of blood platelet function relate to the severity of MVD in CKCSs which are not yet in heart failure. They measured (1) "mean platelet component" (MPC) concentration; (2) "platelet component distribution width" (PCDW); and (3) "closure times" (CT). MPC and PCDW are means of measuring platelet activation. CT is a measure of the time it takes for platelets to stick together and form a "plug", which is the beginning of forming a clot. Another objective was to investigate possible associations of these variables with markers of MVD severity (murmur grade, mitral valve backflow "jet size", and left atrial and left ventricular dimensions).

They found that MVD backflow jet size had a significant affect upon CT, which is a sign of platelet dysfunction. However, they also found that platelet activation, based upon MPC concentration and PCDW, "was not a feature of subclinical chronic valvular heart disease in CKCSs."

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 • episodic falling and fly catcher's syndromes 

Some researchers have suggested that Epsiodic Falling Syndrome and Fly Catcher's Syndrome in cavaliers may be associated with the breed's form of thrombocytopenia. Drs. Jens Häggström and Clarence Kvart of Sweden have noted in a 1997 article that thromboembolic events in the cerebral circulation of blood may be involved in these syndromes.

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 • the serotonin connection 

Dr. Penny Watson (right) of the University of Cambridge, who has been studying pancreatitis in cavaliers for many years, opined at a presentation in November 2014 the hypothesis that there may be a relationship between the serotonin carried by blood platelets through the vascular system to various organs, particularly the pancreas, the kidneys, the liver, the central nervous system, and the mitral valves of the heart, all causing scarring  of and other damage to the tissues of these organs. She stated:

"We had a theory that these dogs have an increased propensity to produce scar tissue, and that in fact they are doing it in multiple organs. So, there is so link between some of these diseases. ... When we look at the central nervous system in dogs with syringomyelia histologically, we find more fibrosis around blood vessels than you would normally find in a normal dog. ... We don't know what's causing the scarring in the pancreas. There is something causing it, and it seems to be coming up the ducts because that's where a lot of this is happening. And actually my theory at the moment is that it has something to do with the duct bacteria. And that theory has developed after seeing not one or two, but actually four or five cavaliers with chronic pancreatitis who respond very well to antibiotic therapy, metronidazole therapy specifically. And that's the sort of antibiotic that we use for overgrowth of bacteria in the small intestine, not the sort of antibiotic we use for other infections. And so I either think they've got gut bacteria coming up the duct, and perhaps their normal gut bacteria and it just that cavaliers' over-responding. Or, maybe there's something about their duct flora that's driving it, but I think there is a link there, somehow or another between the cavalier's gut flora and what's happening in the pancreas.

"Now why might they [cavaliers] be forming too much scar tissue? ... A current theory revolves around their platelets. Platelets are blood clotting cells. ... In cavaliers, about 50% of cavaliers in the UK have these macro-platelets, these jumbo platelets. ... Something in these cavaliers is stimulating these stellate cells to transform and produce lots of fibrous tissue. ... We noticed in cavaliers ... that there was a pattern of increased fibrosis in multiple organs, the kidneys particularly. Mitral valve disease isn't scarring. Mitral valve disease is myxomatous change. ... But the cells that produce that are valvular interstitial cells, and they are identical to the stellate cells in the pancreas. The current theory ... is that these little dogs might have something in their platelets that they are releasing when they are going through blood vessels into different organs that's tending to cause fibrosis. And our theory ... is that this might be serotonin, which is also known as 5-hydroxytryptamine, because platelets contain a bucket load of serotonin. ...

"We already know that some cavaliers have elevated levels of serotonin, that's been shown. We also already know that serotonin is central to converting those valvular interstitial cells into myofibroblasts. ... I think what was most compelling for me was the human side of it. There is a particular horrible syndrome in people called carcinoid syndrome. People who've got serotonin secreting tumors that they've got. ... They get pancreatic, liver, and kidney fibrosis and mitral valve disease. ... So in a nutshell, the hypothesis was these big floppy platelets release serotonin easily as they pass through vessels, leading to fibrosis in perivascular areas."

However, in a June 2015 study, a Danish team and Dr. Oyama analyzed blood samples of 62 cavalier King Charles spaniels (15 healthy dogs; 18 with mild MVD; 19 with moderate-to-severe MVD; and 10 in congestive heart failure). They were looking for (a) any relationship between serotonin concentrations in blood platelets ("percentage of serotonin-positive platelets, level of surface-bound platelet serotonin expression"), and (b) platelet activation, in CKCSs with MVD. They found no differences in either surface-bound serotonin expression or platelet activation among the four categories of cavaliers in the study.

They did observe that dogs with low platelet numbers (thrombocytopenic dogs) had significantly lower serum serotonin concentrations than non-thrombocytopenic dogs. And, they found in 26 of the dogs a "flow cytometry scatterplot subpopulation (FSSP)" of platelets. Dogs with an FSSP had a higher percentage of serotonin-positive platelets, and a higher level of surface-bound serotonin expression, and higher platelet activation, than did dogs without an FSSP. An FSSP was present in 93.8% of the thrombocytopenic dogs and in 29.5% of the nonthrombocytopenic dogs. They concluded from those observations that an FSSP of highly activated platelets with pronounced serotonin binding was strongly associated with thrombocytopenia but not with MVD.

 In a June 2019 article, Danish and Swedish cardiology researchers  examined urinary excretions of serotonin (5-hydroxyindoleacetic acid [5-HIAA]) in 40 cavalier King Charles spaniels, 11 without mitral valve disease (MVD) and 29 with MVD prior to heart failure (Stage C) to determine if urine concentrations of 5-HIAA were associated with MVD severity or blood platelet count or circulating serotonin. They concluded that while female cavaliers had higher urine 5-HIAA concentrations than males, 5-HIAA concentrations in CKCSs were not associated with MVD severity or blood platelet count or circulating serotonin.

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Research News

May 2024:  ACVIM Consensus Statement on immune thrombocytopenia barely mentions cavaliers' benign version. In a May 2024 article, the American College of Veterinary Internal Medicine (ACVIM) issued a Consensus Statement by a panel of 26 specialists (Dana N. LeVine, Linda Kidd [right], Oliver A. Garden, Marjory B. Brooks, Robert Goggs, Barbara Kohn, Andrew J. Mackin, Erin R. B. Eldermire, Yu-Mei Chang, Julie Allen, Peter W. Christopherson, Barbara Glanemann, Haruhiko Maruyama, Maria C. Naskou, Lise N. Nielsen, Sarah Shropshire, Austin K. Viall, Adam J. Birkenheuer, Marnin A. Forman, Andrew S. Hanzlicek, Kathrin F. Langner, Erin Lashnits, Katharine F. Lunn, Kelly M. Makielski, Xavier Roura, Eva Spada) on the topic of the diagnosis of immune thrombocytopenia (ITP) in dogs and cats. They point out that "ITP is the most common acquired primary hemostatic disorder in dogs." In their 24-page article, they barely refer to the benign version of thrombocytopenia diagnosed frequently in cavalier King Charles spaniels. They state:

"Although not included in our systematic review, we recommend that identification of macrothrombocytes, particularly in healthy dogs lacking signs of a primary hemostatic defect and breeds, or mixed breeds, with hereditary macrothrombocytopenia, should prompt genetic testing early in the diagnostic evaluation."

They also offer a rather complicated algorithm (excerpted below), which, if followed, does offer hope that general practice veterinarians will avoid administering massive doses of potent immuno-suppressant steroid treatments to healthy members of our breed.

May 2024: Taiwan clinicians realize almost too late that a cavalier with low blood platelet counts does not need steroids. In a March 2024 article, Taiwan veterinarians report a case study of a young male cavalier King Charles spaniel with low blood platelet counts and with observed very large platelets and no symptoms of thrombocytopenia, which the general practice clinicians nevertheless treated with high oral doses of prednisolone and other drugs, without any resulting improvement in the platelet counts. They report that the clinicians' periodic physical examinations of the dog "revealed no abnormalities ... No abnormalities were detected by abdominal radiography or ultrasonography." Prior to medication, the "number of red blood cells and white blood cell counts were all within normal limits. No signs of immune-mediated diseases were observed."

Due to the medications, particularly the high doses of immune-suppressing prednisolone, the dog's condition worsened. He developed anemia, and his white blood cell count shot up (leukocytosis), as did his ALP and ALT levels, suggesting the onset of kidney failure. The treating veterinarians finally discontinued the steroids and referred the cavalier to specialists, Tzu-Yi Ma, Chih-Jung Kuo, Chih-Chung Chou, and Pin-Chen Liu (right, above), who also have authored this report. They diagnosed the benign condition of asymptomatic inherited macrothrombocytopenia, acknowledging that "Inherited macrothrombocytopenia of CKCS has not been documented in Taiwan till date." The specialists attributed the leukocytosis and anemia to a "systemic infection related to steroid treatment."

EDITOR'S NOTE: This report is a poster child for how to nearly kill a perfectly healthy cavalier because of inexcusable ignorance on the part of the "treating" veterinarians. Had they administered the steroids by injection rather than orally, he surely would have been dead before the specialty vets had a go at him. If ever a case for Dr. Google existed, this is it. Google would have told them everything they needed to know about cavaliers with low platelet counts, in less than 0.34 seconds. (See image below.) Take the advice given by veterinary neurologist Dr. Clare Rusbridge:

"It is always worth doing a Google search for different breeds that you are not so familiar with just to see if there is any inherited diseases coming up."

This cavalier had no signs of any bleeding disorder.  "No abnormalities were detected. ...  [the] number of red blood cells and white blood cell counts were all within normal limits. No signs of immune-mediated diseases were observed." They ignored all of that data and pumped him with high doses of steroids, plus doxycycline and famotidine, for at least 3 weeks!

June 2019: Danish and Swedish researchers find no connection between urinary serotonin concentration and blood platelet counts in cavaliers. In a June 2019 article, Danish and Swedish cardiology researchers (L.B.Christiansen, S.E.Cremer, A. Helander, Tine Madsen, M.J. Reimann, J.E. Møller, K. Höglund, I. Ljungvall, J. Häggström, L. Høier Olsen [right]) examined urinary excretions of serotonin (5-hydroxyindoleacetic acid [5-HIAA]) in 40 cavalier King Charles spaniels, 11 without mitral valve disease (MVD) and 29 with MVD prior to heart failure (Stage C) to determine if urine concentrations of 5-HIAA were associated with MVD severity or blood platelet count or circulating serotonin. They concluded that while female cavaliers had higher urine 5-HIAA concentrations than males, 5-HIAA concentrations in CKCSs were not associated with MVD severity or blood platelet count or circulating serotonin.

September 2018: UK cardiologists find no association between macroplatelets and pulmonary hypertension. In an April 2018 abstract, UK cardiologists Siddharth Sudunagunta and Jo Dukes-McEwan (left) report their study of 94 MVD-affected cavalier King Charles spaniels and 93 MVD-affected non-CKCSs to determine if cavaliers are more likely to develop pulmonary hypertension (PH) due to mitral valve disease, and also determine whether there is any association between CKCSs' oversized blood platelets (macroplatelets) and PH. All dogs had enlarged hearts due to their MVD. 57 of the 94 cavaliers were in congestive heart failure (CHF) compared to 45 of the non-CKCSs. 71 of the cavaliers had PH, compared to 52 of the non-CKCSs. They found:

• PH was associated with a greater likelihood of CHF and death (cardiac-related and all-cause mortality).
• CKCSs were more likely to experience cardiac death than non-CKCSs.
• Macroplatelets were not associated with PH development.
• CKCS were more likely than non-CKCS to develop PH due to MVD.

June 2018: Italian researchers find that platelet estimates from blood smears are too imprecise to be reliable. In a June 2018 article, a team of Italian three veterinarians, led by a board certified pathologist (Saverio Paltrinieri [right], Veronica Paciletti, Jari Zambarbieri), examined blood smears from 30 dogs to count platelet numbers and determine the mean platelet count for each dog. They report finding that variabilities of platelet count estimates are high, operator-dependent, and influenced by the area of the blood smear. They found that platelet estimates by different observers could lead to a different classifications (thrombocytopenic or not) of the same dog. They concluded that platelet estimates alone are not precise enough to allow a reliable evaluation of platelet mass, and that their findings should encourage the establishment of standard guidelines tto perform reliable platelet estimates.

May 2018:  Australian researcher reports on the affect of MVD severity upon platelet function and activation in CKCSs. In a 2017 master's thesis, Australian veterinary internal medicine specialist Linda Tong (right) reports on her study of blood platelets in 89 cavalier King Charles spaniels and a 39-dog control group, to investigate associations between markers of Stage B1 and B2 mitral valve disease (MVD) and platelet function or activation. As a part of her study, she examined the 89 CKCSs to determine the frequency of MVD in the dogs. She found at least minimal mitral regurgitation via echocardiography in 86 of the 89 dogs (97%), and an MVD murmur using auscultation in 47% of the cavaliers at age 6 years or less. She concluded:

"In the present study, a significant effect of mitral valve regurgitant jet size on closure time was consistent with platelet dysfunction. However, platelet activation, as determined by MPC [mean platelet component] concentration and PCDW [platelet component distribution width], was not a feature of subclinical CVHD [MVD] in CKCS."

(See aslo this July 2016 item below.)

November 2016: Belgian researchers recommend all cavaliers be tested for oversized platelets and mated accordingly. In an October 2016 report, a team of Belgian researchers (E. Beckers, M. Van Poucke, L. Ronsyn, Luc Peelman) found 46.6% of 57 Belgian cavalier King Charles spaniels had the macrothrombocytopenia (MTC) mutation. They acknowledged that:

"This disorder is not a disease per se, since affected animals do not usually have bleeding tendencies. The main problem is situated in unnecessary treatments with antibiotics or corticosteroids, which are often given because of the abnormal blood parameters."

Nevertheless, they raise the spectre that, "Animals with this mutation have a shortage of platelets and may potentially develop problems in the primary hemostasis [the stopping of a flow of blood]." They conclude:

"Macrothrombocytopenia should be tested in all Cavalier King Charles spaniels. Heterozygotes for these mutations and even homozygotes for the less severe disorders should not be routinely excluded from breeding programs, since this may lead to an even more important decrease in genetic diversity of breeds with an already (relatively) small genetic basis. Instead, the results of the genotyping should be used to make a well-reasoned partner choice."

EDITOR'S NOTE: The researchers make two recommendations here which appear to be unfounded. They certainly do not offer any evidence to support the recommendations. First, they suggest "Animals with this mutation have a shortage of platelets and may potentially develop problems in the primary hemostasis [the stopping of a flow of blood]." It is not nice to unnecessarily scare cavalier owners, don't you know?

Second, they recommend that "Macrothrombocytopenia should be tested in all Cavalier King Charles spaniels." They apparently do so because they think that CKCS breeders should use the resulting information in their mating selections. That is rather absurd when you consider that probably more than half of all cavaliers have oversized platelets and that condition has not caused any health problems in the breed, at all. What we have here is a textbook example of "over-diagnosis" (a syndrome affecting more and more veterinarians everyday).

July 2016: Australian researchers measure blood platelet function in cavaliers with pre-heart failure MVD. In an August 2016 report, a team of Australian researchers (Linda J. Tong, Giselle L. Hosgood, Peter J. Irwin, Robert E. Shie) and a Scottish researcher (Anne T. French) examined 89 cavalier King Charles spaniels to determine if measurements of blood platelet function relate to the severity of MVD in CKCSs not yet in heart failure. They measured (1) "mean platelet component" (MPC) concentration; (2) "platelet component distribution width" (PCDW); and (3) "closure times" (CT). MPC and PCDW are means of measuring platelet activation. CT is a measure of the time it takes for platelets to stick together and form a "plug", which is the beginning of forming a clot. Another objective was to investigate possible associations of these variables with markers of MVD severity (murmur grade, mitral valve backflow "jet size", and left atrial and left ventricular dimensions).

They found that MVD backflow jet size had a significant affect upon CT, which is a sign of platelet dysfunction. However, they also found that platelet activation, based upon MPC concentration and PCDW, "was not a feature of subclinical chronic valvular heart disease in CKCSs." (See also this May 2018 item above.)

July 2015: Univ. of Minnesota pathologists report more breeds with the CKCS giant platelet disorder. In a July 2015 article, University of Minnesota veterinary pathologists Drs. Leslie Sharkey (right) and Daniel Heinrich report that the benign giant platelet disorder so common in cavalier King Charles spaniels also has been discovered in several other breeds. They state:

"Keep in mind that an expanding number of breeds have congenital macrothrombocytopenia initially characterized in Cavalier King Charles spaniels; these breeds include Norfolk and Cairn terriers, Chihuahuas, Labrador retrievers, poodles, English toy spaniels, shih tzus, Maltese, Jack Russell terriers, Havanese, boxers, cocker spaniels, bichons frises, and some mixed breeds."

They make the important note that a lack of history of unusual bleeding usually is a sign of this syndrome.

May 2015: Researchers do not find a relationship between serotonin in blood platelets and development of MVD in cavaliers. In a June 2015 study, an international team of veterinary researchers (Signe E. Cremer, Annemarie T. Kristensen, Maria J. Reimann, Nynne B. Eriksen, Stine F. Petersen, Clara B. Marschner, Inge Tarnow, Mark A. Oyama, Lisbeth H. Olsen) analyzed blood samples of 62 cavalier King Charles spaniels (15 healthy dogs; 18 with mild MVD; 19 with moderate-to-severe MVD; and 10 in congestive heart failure). They were looking for (a) any relationship between serotonin concentrations in blood platelets ("percentage of serotonin-positive platelets, level of surface-bound platelet serotonin expression"), and (b) platelet activation, in CKCSs with MVD. They found no differences in either surface-bound serotonin expression or platelet activation among the four categories of cavaliers in the study.

They did observe that dogs with low platelet numbers (thrombocytopenic dogs) had significantly lower serum serotonin concentrations than non-thrombocytopenic dogs. And, they found in 26 of the dogs a "flow cytometry scatterplot subpopulation (FSSP)" of platelets. Dogs with an FSSP had a higher percentage of serotonin-positive platelets, and a higher level of surface-bound serotonin expression, and higher platelet activation, than did dogs without an FSSP. An FSSP was present in 93.8% of the thrombocytopenic dogs and in 29.5% of the nonthrombocytopenic dogs. They concluded from those observations that an FSSP of highly activated platelets with pronounced serotonin binding was strongly associated with thrombocytopenia but not with MVD.

February 2015: Swedish study finds serotonin levels increase in spayed bitches. In a February 2015 report by veterinary doctoral student Elin Larsson, she studied 7 female dogs and 3 males, including on cavalier King Charles spaniel male, she found that "Among the bitches, the serotonin levels tended to increase after castration [sic]. The male dogs were few in number and no obvious changes in hormone levels were shown."

January 2015: Dr. Penny Watson discusses CKCS platelets and serotonin's possible connection with MVD, SM, and pancreatitis. In  "Pancreatitis in Cavaliers: What is it and what can I do about it?" A DVD (right) of a seminar presented by Dr. Penny Watson of the University of Cambridge, UK in November 2014, is available for purchase from Cavalier Matters.

In her presentation, Dr. Watson discussed a current hypothesis which links mitral valve disease and pancreatitis and kidney disease in cavaliers through the secretion of serotonin by the cavaliers' blood platelets. She stated:

"We noticed in cavaliers ... that there was a pattern of increased fibrosis in multiple organs, the kidneys particularly. Mitral valve disease isn't scarring. Mitral valve disease is myxomatous change. ... But the cells that produce that are valvular interstitial cells, and they are identical to the stellate cells in the pancreas. The current theory ... is that these little dogs might have something in their platelets that they are releasing when they are going through blood vessels into different organs that's tending to cause fibrosis. And our theory ... is that this might be serotonin, which is also known as 5-hydroxytryptamine, because platelets contain a bucket load of serotonin. ... We already know that some cavaliers have elevated levels of serotonin, that's been shown. We also already know that serotonin is central to converting those valvular interstitial cells into myofibroblasts. ... I think what was most compelling for me was the human side of it. There is a particular horrible syndrome in people called carcinoid syndrome. People who've got serotonin secreting tumors that they've got. ... They get pancreatic, liver, and kidney fibrosis and mitral valve disease. ... So in a nutshell, the hypothesis was these big floppy platelets release serotonin easily as they pass through vessels, leading to fibrosis in perivascular areas."

July 2014: International team of cardiologists find cavaliers have higher serotonin concentrations in platelets. In a July 2014 study, cardiologist researchers from Denmark, the USA, and France (S.E. Cremer, G.E. Singletary, L.H. Olsen, K. Wallace, J. Häggström, I. Ljungvall, K. Höglund, C.A. Reynolds, N. Pizzinat, M.A. Oyama) compared serotonin concentrations in blood plasma of 26 cavaliers (12 healthy and 14 with mitral valve disease) and 19 non-CKCSs (8 healthy and 11 with MVD). They found that platelet serotonin was elevated in cavaliers compared to the other breeds. They also found that left ventricular myocardial and mitral valve leaflet tissue in deceased MVD dogs was elevated compared to dogs which died without cardiac disease.

May 2014: International team finds link between high-level serotonin-binding and highly-activated blood platelets and mitral valve disease and oversized platelets in cavaliers. In an April 2014 report, a team of researchers from Denmark and the USA studied the levels of serotonin-binding and of platlet activation in 61 CKCSs. They found that cavaliers with moderate-severe MVD and severe MVD tended to have higher levels of platelet activation, and that highly-active platelets and high-level serotonin-binding was strongly associated with oversized platelets. They concluded that further investigation into the significance of serotonin-binding is warranted.

January 2013: University of Minnesota student's master's thesis confirms superiority of Advia's plateletcrit method. In a January 2013 master's thesis, University of Minnesota student Jessica Anne Kelley studied blood tests of 139 cavalier King Charles spaniels, to investigate the use of the plateletcrit as an assessment of total platelet biomass in cavaliers with asymptomatic congenital macrothrombocytopenia. She concluded:

"In this particular model of an inherited asymptomatic macrothrombocytopenic platelet disorder, Cavalier King Charles Spaniels represent a group of individuals in which the bleeding risk is better evaluated using plateletcrit than platelet number. The platelet mass appears significantly lower in affected dogs when measured by count, but when measured by plateletcrit, more of the patients are appropriately within the reference range. Therefore, for the Cavalier King Charles Spaniels affected by this mutation, plateletcrit better represents the true total platelet biomass in peripheral circulation."

See also, the January 2014 published version of this article, below.

September 2012: IDEXX's VetAutoread hematology analyzer tops Bayer Diagnostic's Advia 2120 in measurement of CKCS plateletcrits. Swedish researchers find that Bayer Diagnositics' Advia 2120 plateletcrit analysis of cavaliers was lower than expected, when compared to results from IDEXX's VetAutoread hematology analyzer. Read more here.

September 2011: Auburn Univ. offers DNA test for inherited macrothrombocytopenia in cavaliers. Veterinary researchers at Auburn University have devised a DNA test for CKCSs suspected of having oversized platelets. In their 2008 report, the research team identified a mutation in the gene that encodes beta1-tubulin, a protein involved in platelet production by megakaryocytes. Their DNA test is available to determine the presence or absence of this mutation. For more information about this DNA test, contact Dr. Mary K. Boudreaux at Auburn Univ., telephone 334-844-2692, email boudrmk@auburn.edu, or click here for the webpage.

The researchers advise that inherited macrothrombocytopenia should be suspected in any dog that has a persistently low platelet counts and that is non-responsive to treatment with antibiotics or steroids and has no history or evidence of abnormal bleeding. Since the identification of this mutation in CKCS, the identical mutation has also been documented in other breeds of dogs with inherited macrothrombocytopenia including Chihuahua, Labrador retriever, Poodle, English toy spaniel, Labradoodle, Shih Tzu, Maltese, and Jack Russell.

Editor's Note: Oversized platelets in the cavalier King Charles spaniel should not come as a surprise, and in view of the widespread extent of severely symptomatic disorders in the CKCS, such as mitral valve disease and syringomyelia, it is unreasonable to exclude cavaliers with idiopathic asymptomatic thrombocytopenia from being bred. So, we see little value in testing cavalier breeding stock to detect macrothrombocytopenia.

July 2011: Geneticist Lowell Ackerman opposes breeding cavaliers with genetic platelet disorders. In his just-released second edition of his book, Genetic Connection: A Guide to Health Problems in Purebred Dogs, geneticist Dr. Lowell Ackerman states:

"An asymptomatic thrombocytipenia typically, but not always, associated with large to giant platelets has been reported in the Cavalier King Charles spaniel. The condition, macrothrombocytopenia, has been reported as an autosomal recessive trait in the breed, and the molecular basis for the condition is a mutation in the gene encoding β-1 tubulin. The diagnosis should be suspected when thrombocytopenia and large platelets are reported in this breed without evidence of bleeding diathesis. No treatment is necessary. Despite the fact that this disorder appears to be asymptomatic, it would seem prudent not to use affected animals for breeding. Genetic testing is now available for identifying affected, carrier, and clear individuals."

Editor's Note: In view of the widespread extent of severely symptomatic disorders in the CKCS, such as mitral valve disease and syringomyelia, it is unreasonable to exclude cavaliers with idiopathic asymptomatic thrombocytopenia from being bred.

December 2010: Dr. Oyama studies links between cavaliers' giant platelets and MVD. Dr. Mark A. Oyama of the University of Pennsylvania is continuing his research into links between cavaliers' giant platelets and the breed's high incidence of mitral valve disease. His previous research has shown that CKCSs have elevated levels of serotonin (5-HT). The hypothesis is that 5-HT signaling is an important component of MVD in dogs. He suspects that the source of elevated serum 5HT is the blood platelets, since platelets are believed to contain 99% of all circulating 5-HT. It has been recently shown that platelet contents can activate disease changes within the heart muscle of experimental animals. The platelet, heart muscle, and valve-specific content of 5-HT in dogs with heart disease has not been previously reported. Dr. Oyama wants to determine if platelet 5-HT is the source of elevated serum 5-HT in cavaliers with MVD, as well as to quantify the amount of 5-HT in both the left ventricular muscle and mitral valve leaflets of affected dogs.

May 2008: Auburn University team finds gene mutation related to macrothrombocytopenia in CKCSs. In a 2008 study at Auburn University (Drs. Jennifer Brooke Davis, M. Toivio-Kinnucan, S. Schuller, Mary K. Boudreaux) determined that "a mutation in the gene encoding β1-tubulin correlated with macrothrombocytopenia in CKCS." They concluded that "this information will aid in distinguishing inherited from acquired thrombocytopenia. It also provides insight into the mechanism of platelet production by megakaryocytes, and also may prove useful in understanding heart-related changes in macrothrombocytopenic CKCS with concurrent mitral valve regurgitation."

2007: Auburn Univ. student Jennifer Brooke Davis finds genetic mutation in cavaliers' blood platelets. Morris Animal Foundation reports the results of a funded study by an Auburn University student, Jennifer Brooke Davis, who examined the molecular basis for inherited macrothrombocytopenia in CKCSs.

2007: Dr. Inge Tarnow, at the University of Copenhagen's Department of Animal and Veterinary Basic Sciences, heads a group of specialists studying pathophysiological aspects of early mitral valve diseases in cavaliers, including changes in platelet function, hemostatic changes, and prognostic factors. They currently are performing a large longitudinal study of 100 Cavaliers with examinations (echocardiographic and blood tests) at ages 2, 4, and 8 years.

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