Clinical and laboratorial description of the differential diagnoses of hemostatic disorders in the horse

Document Type : Review article

Authors

1 Department of Animal Medicine and Surgery, Faculty of Veterinary, CEU-Cardenal Herrera University, Valencia, Spain

2 Department of Experimental Sciences and Mathematics, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain

3 Department of Animal Medicine and Surgery, Faculty of Veterinary Medicine, University of Córdoba, Córdoba, Spain

Abstract

The process of fibrin clot formation is a series of complex and well-regulated reactions involving blood vessels, platelets, procoagulant plasma proteins, natural inhibitors, and fibrinolytic enzymes. Vasculitis can be caused by a variety of different agents as bacteria, viruses, protozoal, rickettsial organisms, toxic, drugs, medications, and neoplasms. The most common cause of vasculitis is the purpura hemorrhagica, which is associated with exposure to Streptococcus equi ssp. equi or less commonly, equine influenza. Deficiencies or defects of the hemostatic components may result in bleeding and/or thrombosis. Inherited alterations of primary hemostasis (von Willebrand disease: vWD and Glanzmann’s thrombasthenia: GT) and of secondary hemostasis (hemophilia A and prekallikrein: PK deficiency) are scarcely reported in equine clinic. On the contrary, acquired alterations of primary and secondary hemostasis are commonly found. They include thrombocytopenia, platelet dysfunction due to the administration of some drugs and targeted antiplatelet agents, decreased factor synthesis (liver disease or deficiency of vitamin K), release of inactive factors, inhibition of factor activity, or excessive consumption and depletion of factors (platelets, coagulation factors, and anticoagulants factors as antithrombin (AT) and protein C). Disseminated intravascular coagulation (DIC) is the most common and complex hemostatic disorder in horses and appears to be associated with sepsis, inflammatory and ischemic gastrointestinal tract disorders and other systemic severe diseases. These alterations are commonly found in patients in intensive care units.

Keywords

Main Subjects


Armengou, L; Monreal, L; Tarancón, I; Navarro, M; Ríos, J and Segura, D (2008). Plasma D-dimer concentration in sick newborn foals. J. Vet. Intern. Med., 22: 411-417.
Ayala, I; Rodríguez, MJ; Martos, N; Ziberschtein, J; Ruíz, I and Motas, M (2007). Fatal brodifacoum poisoning in a pony. Can. Vet. J., 48: 627-629.
Balasuriya, JB (2014). Equine viral arteritis. Vet. Clin. North Am.: Equine Pract., 30: 543-560.
Barrell, EA; Asakawa, MG; Felippe, MJB; Divers, TJ and Stokol, T (2017). Acute leukemia in six horses (1990-2012). J. Vet. Diagn. Investig., 29: 529-535.
Blond, AG; Epstein, KL and Brainard, BM (2013). In vitro effects of three formulations of hydroxyethyl starch solutions as coagulation and platelet function in horses. Am. J. Vet. Res., 74: 712-720.
Boudreaux, MK and Humphries, DM (2013). Identification of potential platelet alloantigens in the Equidae family by comparison of gene sequences encoding major platelet membrane glycoproteins. Vet. Clin. Pathol., 42: 437-442.
Brooks, MB (2008). Equine coagulopathies. Clin. Vet. North Am.: Equine Pract., 24: 335-355.
Brooks, M; Leith, GS; Allen, AK; Woods, PR; Benson, RE and Dodds, WJ (1991). Bleeding disorder (von Willebrand disease) in a quarter horse. J. Am. Vet. Med. Assoc., 198: 114-116.
Brooks, AC; Menzies-Gow, NJ; Wheeler-Jones, C; Bailey, SR; Cunningham, FM and Elliott, J (2007). Endotoxin-induced activation of equine platelets: evidence for direct activation of p38 MAPK pathways and vasoactive mediator production. Inflamm. Res., 56: 154-161.
Buechner-Maxwell, V; Scott, MA; Godber, L and Kristensen, A (1997). Neonatal alloimmune thrombocyto-penia in a quarter horse foal. J. Vet. Intern. Med., 11: 304-308.
Burke, CW (2013). Vitamin K deficiency bleeding: overview and considerations. J. Pediatr. Health Care. 27: 215-281.
Burkett, BN; Thomason, JM; Hurdle, HM; Wills, RW and Fontenott, RL (2016). Effects of firocoxib, flunixin meglumine and phenylbutazone on platelet function and thromboxane synthesis in healthy horses. Vet. Surg., 45: 1087-1094.
Cattaneo, M (2003). Inherited platelet-based bleeding disorders. J. Thromb. Haemost., 1: 1628-1636.
Cesarini, C; Cotovio, M; Ríos, J; Armengou, L and Jose-Cunilleras, E (2016). Association between necropsy evidence of disseminated intravascular coagulation and hemostatic variables before death in horses with colic. J. Vet. Intern. Med., 30: 269-275.
Christopherson, PW; Insalaco, TA; Van Santen, VL; Livesey, L; Bournce, C and Boudreaux, MK (2006). Characterization of the cDNA encoding alphaIIb and beta3 in normal horses and two horses with Glanzmann thrombasthenia. Vet. Pathol., 43: 78-82.
Cian, F; Tyner, G; Martini, V; Comazzi, S and Archer, J (2013). Leukemic small cell lymphoma or chronic lymphocytic leukemia in a horse. Vet. Clin. Pathol., 43: 301-306.
Clabough, DL; Gebhard, D; Flaherty, MT; Whetter, LE; Perry, ST; Coggins, L and Fuller, FJ (1991). Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus. J. Virol., 65: 6242-6251.
Clarke, P and Shearer, MJ (2007). Vitamin K deficiency bleeding: the readiness is all. Arch. Dis. Child. 92: 741-743.
Cooper, CJ; Keller, SM; Arroyo, LS; Hewson, J; Kenney, D and Bienzle, D (2018). Acute leukemia in horses. Vet. Pathol., 55: 159-178.
Cotovio, M; Monreal, L; Armengou, L; Prada, J; Almeida, JM and Segura, D (2008). Fibrin deposits and organ failure in newborn foals with severe septicemia. J. Vet. Intern. Med., 22: 1403-1410.
Cotovio, M; Monreal, L; Navarro, M; Segura, D; Prada, J and Alves, A (2007). Detection of fibrin deposits in tissues from horses with severe gastrointestinal disorders. J. Vet. Intern. Med., 21: 308-313.
Dickinson, CE; Gould, DH; Davidson, AH; Avery, RR; Legare, ME; Hyatt, DR and DebRoy, C (2008). Hemolytic-uremic syndrome in a postpartum mare concurrent with encephalopathy in the neonatal foal. J. Vet. Diagn. Invest., 20: 239-242.
Dolente, BA; Wilkins, PA and Boston, RC (2002). Clinicopathologic evidence of disseminated intravascular coagulation in horses with acute colitis. J. Am. Vet. Med. Assoc., 220: 1034-1038.
Dong, R; Wang, N; Yang, Y; Ma, L; Du, Q; Zhang, W; Tran, AH; Jung, H; Soh, A; Zheng, Y and Zheng, S (2018). Review on vitamin K deficiency and its biomarkers: focused on the novel application of PIVKA-III in clinical practice. Clin. Lab., 64: 413-424.
Eberhardt, C; Malbon, A; Riond, B and Schoster, A (2018). κ-light chain monoclonal gammopathy and cast nephropathy in a horse with multiple myeloma. J. Am. Vet. Med. Assoc., 253: 1177-1183.
Epstein, KL (2014). Coagulopathies in horses. Clin. Vet. North Am.: Equine Pract., 30: 437-452.
Fry, MM; Walker, NJ; Blevins, GM; Magdesian, KG and Tablin, F (2005). Platelet function defect in a thoroughbred filly. J. Vet. Intern. Med., 19: 359-362.
Geor, RJ; Jackson, ML; Lewis, KD and Fretz, PB (1990). Prekallikrein deficiency in a family of Belgian horses. J. Am. Vet. Med. Assoc., 197: 741-745.
Giguère, S and Polker, AC (2005). Immunologic disorders in foals. Vet. Clin. North Am.: Equine Pract., 21: 241-272.
Gilbertie, JD; Davis, JL; Davidson, GI; McDonald, AM; Schirmer, JM and Schnabel, VL (2018). Oral reserpine administration in horses results in low plasma concentrations that alter platelet biology. Equine Vet. J., 51: 537-543.
Girolami, A; Scarparo, P; Candeo, N and Lombardi, AM (2010). Congenital prekallikrein deficiency. Expert. Rev. Hematol., 3: 685-695.
Henninger, RW (1988). Hemophilia A in two related quarter horse colts. J. Am. Vet. Med. Assoc., 193: 91-94.
Hinton, M; Jones, DR; Lewis, IM and Thomson, PE (1977). A clotting defect in an Arab colt foal. Equine Vet. J., 9: 1-3.
Humber, KA; Beech, J; Cuud, TA; Palmer, JE; Gardner, SY and Sommer, MM (1991). Azathioprine for treatment of immune-mediated thrombocytopenia in two horses. J. Am. Vet. Med. Assoc., 199: 591-594.
Johns, I; Stephens, JO; Del Piero, F; Richardson, DW and Wilkins, PA (2005). Hemangiosarcoma in 11 young horses. J. Vet. Intern. Med., 19: 564-570.
Johns, IC and Sweeney, RW (2008). Coagulation abnormalities and complications after percutaneous liver biopsy in horses. J. Vet. Intern. Med., 22: 185-189.
Kaese, HJ; Valberg, SJ; Hayden, DW; Wilson, JH; Charlton, P; Ames, TR and Al-Ghamdi, GM (2005). Infartive purpura hemorrhagica in five horses. J. Am. Vet. Med. Assoc., 226: 1893-1898.
Laan, TT; Goehring, LS and Sloet van Oldruitenborgh-Oosterbaan, MM (2005). Von Willebrand’s disease in an eight-day-old quarter horse foal. Vet. Rec., 157: 322-324.
Lillicrap, D (2007). Von Willebrand disease - phenotype versus genotype: deficiency versus disease. Thromb. Res., 120: S11-S16.
Lisman, T and Leeveek, FW (2007). Hemostatic alterations in liver disease: a review on pathophysiology, clinical consequences, and treatment. Dig. Surg., 24: 250-258.
Littlewood, JD; Bevan, SA and Corke, MJ (1991). Haemophilia A (classic haemophilia, factor VIII deficiency) in a Thoroughbred colt foal. Equine Vet. J., 23: 70-72.
Livesey, L; Christopherson, P; Hammond, A; Perkins, J; Toivio-Kinnucan, M; Insalaco, T and Boudreaux, MK (2005). Platelet dysfunction (Glanzmann’s thrombasthenia) in horses. J. Vet. Intern. Med., 19: 917-919.
Macieira, S; Lussier, J and Bedard, C (2011). Characterization of the cDNA and genomic DNA sequence encoding for the platelet integrin alpha IIB and beta III in a horse with Glanzmann thrombasthenia. Can. J. Vet. Res., 75: 222-227.
Macieira, S; Rivard, GE; Champagne, J; Lavoie, JP and Bédard, C (2007). Glanzmann thrombasthenia in an Oldenbourg filly. Vet. Clin. Pathol., 36: 204-208.
Mateos-Trigos, G; Evans, RJ and Heath, MF (2002). Effects of a P2Y(12) receptor antagonist on the response of equine platelets to ADP. Comparison with human platelets. Res. Vet. Sci., 73: 171-175.
Mazurier, C and Meyer, D (1996). Molecular basis of von Willebrand disease. Baillieres Clin. Haematol., 9: 229-241.
McGorum, BC; Henderson, IS; Stirling, D; Wallace, R; Haggart, C and Thomas, AE (2009). Vitamin K deficiency bleeding in a Standardbred colt. J. Vet. Intern. Med., 23: 1307-1310.
McGorum, BC; Murphy, D; Love, S and Miline, EY (1999). Clinicopathological features of equine primary hepatic disease: a review of 50 cases. Vet. Rec., 145: 134-139.
McGovern, KH; Lascola, KM; Davis, G; Fredrickson, RL and Tan, R (2011). T-cell lymphoma with immune-mediated anemia and thrombocytopenia in a horse. J. Vet. Intern. Med., 25: 1181-1185.
McGurrin, MK; Arroyo, LG and Bienzle, D (2004). Flow cytometric detection of platelet-bound antibody in three horses with immune-mediated thrombocytopenia. J. Am. Vet. Med. Assoc., 224: 83-87.
Mills, JN and Bolton, JR (1983). Haemophilia A in a 3-year-old thoroughbred horse. Aust. Vet. J., 60: 63-64.
Monreal, L; Anglés, A; Espada, Y; Monasterio, J and Monreal, M (2000). Hypercoagulation and hypo-fibrinolysis in horses with colic and DIC. Equine Vet. J., 32: 19-25.
Muñoz, A; Riber, C; Satué, K; Trigo, P; Gómez-Díez, M and Castejón, FM (2013). Multiple myeloma in horses, dogs and cats: a comparative review focused on clinical signs and pathogenesis. In: Hajek, R (Eds.), Multiple myeloma: a quick reflection on the fast progress. 1st Edn., InTech Open Access Publisher. PP: 289-326.
Muñoz, A; Trigo, P; Riber, C and Castejón, F (2011). Spontaneous bilateral epistaxis associated with the administration of phenylbutazone in a horse. Revue Med. Vet., 162: 421-424.
Norris, JW; Pombo, M; Shirley, E; Blevins, G and Tablin, F (2015). Association of Factor V secretion with protein kinase B signaling in platelets from horses with atypical equine thrombasthenia. J. Vet. Intern. Med., 29: 1387-1394.
Norris, JW; Pratt, SM; Auh, JH; Wilson, SJ; Clutter, D; Madgesian, KG; Ferraro, GL and Tablin, F (2006). Investigation of a novel, heritable bleeding diathesis of Thoroughbred horses and development of a screening assay. J. Vet. Intern. Med., 20: 1450-1456.
Norton, EM; Wooldridge, AA; Stewart, AJ; Cusimano, L; Schwartz, DD; Johnson, CM; Boudreaux, MK and Christopherson, PW (2016). Abnormal coagulation factor VIII transcript in a Tennessee Walking Horse colt with hemophilia A. Vet. Clin. Pathol., 45: 96-102.
Nurden, AT; Freson, K and Seligsohn, U (2003). Inherited platelet disorders. Haemophilia. 18: 154-160.
Ouellette, AL; Evans, RJ and Heath, MF (2004). Platelets enhance endotoxin-induced monocyte tissue factor (TF) activity in the horse. Res. Vet. Sci., 76: 31-35.
Parker, RI (2013). Coagulopathies in the PICU: dic and liver disease. Crit. Care Clin., 29: 319-333.
Pusterla, N; Luff, JA; Meyers, CJ; Vernau, W and Affolter, VK (2007). Disseminated intravascular coagulation in a horse with Streptococcus equi subspecies zooepidemicus
meningoencephalitis and interstitial pneumonia. J. Vet. Intern. Med., 21: 344-347.
Pusterla, N; Watson, JL; Affolter, VK; Magdesian, KG; Wilson, WD and Carlson, GP (2003). Purpura haemorrhagica in 53 horses. Vet. Rec., 153: 118-121.
Rathgeber, RA; Brooks, MB; Bain, FT and Byars, TD (2001). Von Willebrand disease in a thoroughbred mare and foal. J. Vet. Intern. Med., 15: 63-66.
Rodríguez, R; Cerón, JJ; Riber, C; Castejón, F; Gómez-Díez, M; Serrano-Rodríguez, JM and Muñoz, A (2014). Acute phase proteins in Andalusian horses infected with Theileria equi. Vet. J., 202: 182-183.
Ruby, RE; Wong, DW; Sponseller, BA and Yaeger, N (2018). Suspected case of hypersplenism as a cause of anaemia, thrombocytopenia and leucopenia in a Miniature horse gelding. Equine Vet. Educ., 31: 530-534.
Sabatino, DE; Nichols, TC; Merricks, E; Bellinger, DA; Herzog, RW and Monahan, PE (2012). Animal models of hemophilia. Prog. Mol. Biol. Transl. Sci., 105: 151-209.
Sanz, MG; Wills, TB; Christopherson, P and Hines, MT (2011). Glanzmann thrombasthenia in a 17-year-old Peruvian Paso mare. Vet. Clin. Pathol., 40: 48-51.
Satué, K; Gardón, JC and Muñoz, A (2013). Use of laboratory testing to diagnose liver and biliary dysfunction in the horse. J. Gastroenterol. Hepat. Res., 2: 807-813.
Satué, K; Gardón, JC and Muñoz, A (2017). Interpretation of platelets in the horse. J. Hematol. Res., 4: 19-25.
Satué, K; Hernández, A and Muñoz, A (2012). Physiological factors influencing equine hematology. In: Lawrie, C (Ed.), Hematology; science and practice. 1st Edn., InTech Open Access Publisher. PP: 573-596.
Satué, K; Muñoz, A and Gardon, JC (2014). Interpretation of alterations in the horse erythrogram. J. Hematol. Res., 1: 1-10.
Sellon, DC (1998). Thrombocytopenia in horses. J. Vet. Intern. Med., 10: 133-143.
Shen, YM and Frenkel, EP (2007). Acquired platelet dysfunction. Hematol. Oncol. Clin. North Am., 21: 647-661.
Sockett, DC; Traub-Dargatz, J and Weiser, MG (1987). Immune-mediated hemolytic anemia and thrombocytopenia in a foal. J. Am. Vet. Med. Assoc., 190: 308-310.
Weiss, DJ and Evanson, OA (2004). Comparison of three arginine-glycine-aspartate-containing peptides as inhibitors of equine platelet aggregation. J. Vet. Pharmacol. Ther., 27: 377-379.
Wilson, ME; Holz, CL; Kopec, AK; Dau, JJ; Luyendyk, JP and Soboll Sussey, G (2019). Coagulation parameters following equine herpesvirus type 1 infection in horses. Equine Vet. J., 51: 102-107.
Winfield, LS and Brooks, MB (2014). Hemorrhage and blood loss-induced anemia associated with an acquired coagulation factor VIII inhibitor in a thoroughbred mare. J. Am. Vet. Med. Assoc., 244: 719-723.
Yarovaga, GA; Blokhina, TB and Neshkova, EA (2002). Contact system. New concepts on activation mechanisms and bioregulatory functions. Biochemistry (Mosc). 67: 13-24.
Zangani, M; Elice, F; Fink, L and Tricott, G (2007). Hemostatic dysfunction in paraproteinemias and amyloidosis. Seminars Thromb. Hemost., 33: 339-349.