Macrothrombocytopenia in the Cavalier King Charles Spaniel
Meg Carriere, DVM; Kenneth S. Latimer, DVM, PhD; Bruce E. LeRoy, DVM, PhD; Heather L. Tarpley, DVM
Class of 2006 (Carriere) and Department of Pathology (Latimer, LeRoy, Tarpley), College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7388
Introduction
Cavalier King Charles spaniels (CKCS) have been reported to have idiopathic, asymptomatic thrombocytopenia (<100,000 platelets /µL) accompanied frequently by macrothrombocytes.1,3,5,7 Approximately 50% of CKCS have thrombocytopenia and an overlapping 30% have macrothrombocytes.2,6 There has been no correlation with macrothrombocytopenia and age, gender, neuter status, coat color, weight, or heart murmur status.2,3,6 This disorder is detected by a routine complete blood count. Clotting malfunctions are not associated with the decrease in platelet count. Affected CKCS may have a decreased number of platelets but the total platelet volume or mass remains comparable to unaffected dogs.
Problems arise when using automated blood counters to enumerate platelets because the macroplatelets may be counted as red blood cells instead of platelets.5 Thus, the degree of thrombocytopenia appears worse that it actually is. Manual counts may be necessary to determine the true platelet count.5,6 This idiopathic disorder can complicate issues when trying to determine if a CKCS does in fact have a platelet disorder that is or could cause bleeding. Knowing that the platelet number will be decreased in about 50% of all CKCS, manual platelet counts and possible preemptive treatment may be the only way to determine if a platelet malfunction is occurring.
Platelet Production
Megakaryocytes in the bone marrow are platelet precursors. Upon maturation, the megakaryocytes release the platelets directly into the blood. In dogs, platelets have a circulating lifespan of approximately 5 to 9 days. Platelet production is regulated mainly by thrombopoietin, a small glycoprotein. Thrombopoietin maintains a certain mass of platelets, not a specific platelet count or number.4 Thus, the CKCS with macrothrombocytopenia tends to have a normal platelet mass although the actual platelet numbers are decreased when compared to reference intervals for other breeds of dogs. Additionally, the macroplatelets may have normal to possibly increased function.3,5,7
Mechanisms of Thrombocytopenia
There are four primary mechanisms that may produce thrombocytopenia. One is a decrease in platelet production. This is caused by selective megakaryocytic hypoplasia, bone marrow panhypoplasia, myelophthisis, and certain infectious agents. A second mechanism is increased platelet consumption or destruction. This form of thrombocytopenia is caused by immune-mediated disease, adverse drug reactions, intravascular parasites, disseminated intravascular coagulation (DIC), and certain infections such as rickettsial infections, septicemia, or some viral infections. Sequestration of platelets is a third mechanism of thrombocytopenia that occurs with splenic congestion, neoplasia, and DIC. The final proposed mechanism of thrombocytopenia is excessive loss of platelets through hemorrhage, rodenticide toxicosis, DIC, and neoplasia.4 These four mechanisms, however, do not account for the thrombocytopenia of the CKCS. The thrombocytopenia of the CKCS is hereditary and has been attributed to an autosomal recessive trait since it is seen only within this breed and an underlying etiology has not been found.6
Mechanism of CKCS Thrombocytopenia and Macrothrombocytes
Not much is understood about CKCS macrothrombocytopenia except that it has been shown to be an autosomal recessive trait. The same study also documented that thrombocytopenia was found in 56% of the dogs that were evaluated. Penderson suggests that the high occurrence of this disorder in the CKCS indicates that there is a low prevalence of normal individuals (noncarriers) in the population.6 Thus, breeding two apparently healthy dogs that do not have laboratory evidence of thrombocytopenia often produces affected offspring. There are no examples of disorders in human medicine that fit this type of genetic thrombocytopenia. The human disorders present with abnormal platelet activity, mitral valve insufficiency, or hearing loss in concurrence with thrombocytopenia.6,7
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| Figure 1. Macroplatelets may approach or exceed the diameter of leukocytes in the Romanowsky-stained blood smear. |
The mechanism of production of macrothrombocytes in the CKCS remains unknown. Four theories have been proposed to explain the production of macrothrombocytes. First, there may be an abnormality in the thrombopoietic signaling to megakaryocytes. Another theory suggests that an abnormal megakaryocyte glycoprotein may result in abnormally large platelet fragmentation. A third theory speculates that platelet lifespan is decreased by continual minor damage to the platelets by an abnormal endothelium. A fourth theory for the production of macrothrombocytes proposes that a decreased platelet lifespan is caused by valvular lesions that continually damage platelets. Since all studies performed to date have not found a correlation between murmur status and macrothrombocytopenia, this last theory seems unlikely. Additionally, diffuse endothelial abnormalities in the CKCS have not been documented, suggesting that the third theory unlikely.2 Cytologic and histologic evaluation of the bone marrow in CKCS with macrothrombocytopenia indicates normal megakaryocyte production, normal megakaryocyte morphology, and adequate platelet granulation.2 Thus, the mechanism of the production of macrothrombocytes is currently unknown but additional research may eventually identify the mechanism.
Determining Platelet Counts
Automated counters frequently overestimate the degree of thrombocytopenia in the CKCS because macroplatelets are counted as red blood cells. Manual platelet counts are therefore recommended in dogs with macrothrombocytopenia. The manual count will also exclude the presence of platelet aggregates (Fig. 2) and altered platelet morphology that could interfere with automated platelet counting. In other healthy dogs, significant differences in platelet number were not found when using automated and manual counting techniques.5 Thus, it can be inferred that manual platelet counts on blood specimens from a CKCS with macrothrombocytopenia will produce reliable and accurate platelet enumeration.
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| Figure 2. Platelet aggregates are present as the result of poor venipuncture technique or inadequate anticoagulation of the blood sample. |
Conclusion
Approximately 50% of all Cavalier King Charles Spaniels are affected with macrothrombocytopenia.2,6 This benign condition is hereditary in the CKCS and warrants no medical treatment. It is now known that the thrombocytopenia is an autosomal recessive trait but the mechanism for macrothrombocytosis remains elusive.6 Macrothrombocytosis may occur in some CKCS. Therefore, the clinician should not be misled into inappropriately treating this hereditary platelet disorder. All automated counts that report thrombocytopenia should be corroborated by blood smear examination and followed up with a manual platelet count, if necessary. This process will determine whether the low platelet count is due to macrothrombocytopenia of the CKCS or to a pathologic process. If clinical signs of a platelet disorder, such as petechiae exist, a disease etiology should be considered instead of attributing the low platelet count to an hereditary process.
References
1. Brown SJ, Simpson KW, Baker S, et al. Macrothrombocytosis in Cavalier King Charles Spaniels. Vet Rec 1994; 135:281-283.
2. Cowan SM, Bartges JW, Gompf RE, et al. Giant platelet disorder in the Cavalier King Charles Spaniel. Exp Hem 2004; 32:344-350.
3. Eskell P, Haggstrom J, Kvart C, Karlsson A. Thrombocytopenia in the Cavalier King Charles Spaniel. J Small Anim Pract 1994; 35:153-155.
4. Latimer KS, Mahaffey EA, Prasse KW (eds): Duncan & Prasse’s Veterinary Laboratory Medicine: Clinical Pathology. 4th ed. Ames, Iowa: Iowa State Press, 2003, pp. 101-102, 114-116.
5. Olsen LH, Kristensen AT, Qvortrup K, Pedersen HD. Comparison of manual and automated methods for determining platelet counts in dogs with macrothrombocytopenia. J Vet Diagn Invest 2004; 16:167-170.
6. Pedersen HD, Haggstrom J, Olsen LH, et al. Idiopathic asymptomatic thrombocytopenia in Cavalier King Charles Spaniels is an autosomal recessive trait. J Vet Intern Med 2002; 16:169-173.
7. Smedile LE, Houston DM, Taylor SM, et al. Idiopathic, asympotmatic thrombocytopenia in Cavalier King Charles Spaniels: 11 cases (1983-1993). J Am Animal Hosp Assoc 1997; 33:411-415.
Acknowledgement
The painting by Joyce Decker of the Cavalier King Charles Spaniel is from the cover of the 2000 Annual of the American Cavalier King Charles Spaniel Club, Inc. and is used with permission.
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