CHAPTER 49 Coagulopathies

Coagulopathies are inherited or acquired pathologic conditions that influence blood coagulability. The latter most often develop secondary to an underlying disease or treatment and can be further divided into those affecting coagulation factors, platelets, vessel walls, or any combination of these elements. Clinical signs attributed to coagulopathy may include either bleeding tendency with findings of petechiation, exsanguinating hemorrhage, or both or diffuse thrombus formation, leading to ischemia and organ failure. Diagnosis of coagulopathy is made primarily on the basis of prolonged coagulation times and low platelet numbers. Vasculitis is diagnosed on the basis of a biopsy specimen evaluation and detection of typical lesions involving the vessel wall. Treatment options directed against coagulopathies are generally sparse, and prognosis most often depends on successful treatment of the underlying disorder.


Inherited coagulopathies have been described in individual case reports but are rare in horses. Congenital factor VIII deficiency (hemophilia A) has most often been diagnosed in Thoroughbreds, Standardbreds, Quarter Horses, and Arabians. Hemophilia is a sex-linked recessive trait that arises only in males. Von Willebrand disease has been reported in a Quarter Horse and a Thoroughbred, and prekallikrein deficiency has been described in Belgian horses and in American Miniature horses.

Unless they are severe, deficiencies of single coagulation factors often do not lead to a bleeding tendency because activation of the coagulation cascade can be achieved by alternative pathways. In contrast, multiple coagulation factor deficiencies are associated with a much higher risk of hemorrhage and prolonged bleeding time from larger vessels. Clinical signs include epistaxis, melena, hyphema, or hematuria. Formation of subcutaneous hematomas or prolonged bleeding from wounds or after venipuncture may also occur. Petechiae or ecchymoses can be seen but are uncommon in horses with single coagulation factor deficiencies.

Coagulation proteins are involved in activation of the intrinsic coagulation pathway. Thus, deficiencies usually lead to a prolonged activated partial thromboplastin time (aPTT) but do not affect the prothrombin time (PT). A tentative diagnosis can be made on the basis of these findings, but diagnosis should be confirmed by specific clotting factor assays.

Palliative treatment consisting of replacement of coagulation factors by administration of fresh or fresh frozen plasma (FFP; see the following section on disseminated intravascular coagulation [DIC]) can be considered in horses determined to have a bleeding tendency. However, inherited coagulopathies cannot be cured, and the long-term prognosis of affected horses is poor.


Disseminated Intravascular Coagulation

DIC is a complex systemic thrombohemorrhagic disorder. Activation of coagulation, inhibition of fibrinolysis, and consumption of coagulation inhibitors and platelets lead to a hypercoagulant state and small- and large-vessel thrombosis with resultant organ ischemia and organ failure.

DIC develops as a sequela of primary pathologic processes. The most common causes are acute gastrointestinal diseases, endotoxemia, sepsis or severe infection, and protein-losing enteropathy. Additionally, DIC has been reported after severe inflammation, incompatible blood transfusion, immune-mediated thrombocytopenia, hemolytic anemia, hepatic failure, trauma causing major tissue injury, tumors, renal diseases, and obstetric problems.

Subclinical hyperactivation of coagulation without clinical signs of DIC is not uncommon in horses with colic. In these instances, DIC is thought to result from severe hemostatic disturbances accompanied by hypercoagulation and hyperfibrinolysis. In horses that have undergone surgical treatment for colic, a hypercoagulable state is expected in the postsurgical phase as a result of not only the primary disorder leading to colic but also from tissue trauma associated with surgery.


The pathophysiologic features of DIC involve systemic activation of the coagulation cascade through either damage of the vascular endothelium or tissue injury and subsequent release of procoagulant mediators (more specifically, cytokines), complement, and tissue factors. Interleukin-1, -6, -8 and tumor necrosis factor may be the most influential cytokines involved in the activation of coagulation. Further, in the setting of sepsis, neutrophils and their secretory products may promote platelet-mediated fibrin formation.

In the pathogenesis of DIC, two proteolytic enzymes, thrombin and plasmin, are activated and circulate systemically. Their balance determines whether a given horse develops a bleeding or thrombotic tendency. Thrombin-activated proteolysis of fibrinogen leads to increased fibrin formation. The activated coagulation state leads to inadequate fibrin removal and fibrin deposition in the microvasculature. As a consequence, microvascular thrombosis contributes to ischemic tissue lesions and multiple organ dysfunction.

At the same time, anticoagulation mechanisms are suppressed. Inhibitory proteins of the coagulation cascade, such as tissue factor pathway inhibitor, antithrombin, and activated protein C, are largely defective. As a consequence, impairment of fibrinolysis becomes obvious, although plasmin is highly activated. Because of the consumption of coagulation factors and platelets, concurrent excessive bleeding can occur, especially in advanced stages of DIC.


Because the sequelae of DIC can be devastating, early recognition of clinical and laboratory findings is essential. Diagnosis is made on the basis of clinical signs but can be difficult to arrive at, particularly in the subclinical stage, because there are no definitive and reliable diagnostic tests. However, subclinical DIC may be diagnosed if three coagulation variables of the following are altered: aPTT, PT, fibrinogen concentration, antithrombin concentration, D-dimer concentration, and platelet count. Of the coagulation tests, aPTT is the more sensitive parameter. The activity of antithrombin is usually severely decreased. Antithrombin exerts its primary effect via inactivation of thrombin and coagulation factors IXa, Xa, XIa, and XIIa and is considered the main procoagulant inhibitor. D-dimer concentration is typically markedly high in horses with DIC. High D-dimer concentrations develop as a consequence of intravascular or extravascular fibrin formation but also increase after traumatic incidents or surgical interventions. Therefore, determination of D-dimer is suitable for early diagnosis of an emerging thrombotic state or DIC.

In contrast, thrombocytopenia is rarely observed and is seen only in association with severe DIC. Fibrinogen concentration is usually within normal limits. Because fibrinogen is a component of the acute-phase reaction, initial hypofibrinogenemia secondary to consumption in DIC may be masked by induction of fibrinogen synthesis during the acute-phase reaction.

Hypoproteinemia is a common sign in horses with DIC and can be caused by loss of coagulation and anticoagulation proteins. Loss of coagulation factors may also be a sequela of protein-losing enteropathy with gastrointestinal disease. Protein loss can also explain, at least in part, the decreases in the activities of factors V and VIII and consequent increases in coagulation times observed in horses with DIC.

May 28, 2016 | Posted by in EQUINE MEDICINE | Comments Off on Coagulopathies

Full access? Get Clinical Tree

Get Clinical Tree app for offline access