Prolonged Activated Partial Thromboplastin Time
The PTT is a measure of the intrinsic (contact activation) and common coagulation pathways (see Fig. 27.1). The activated PTT is now the only test used, and it measures time from the addition of calcium to plasma with partial thromboplastin reagent and a surface activator until clot formation.
The PTT is prolonged with deficiencies or defects in factors XII, XI, IX, and VIII coagulant (VIITC) as well as prekallikrein (PK). Most PTT assays detect PK deficiency, and the assay can be corrected to prove that a PK abnormality is the cause of prolonged PTT. The activated coagulation time (ACT) is a simplified variation of the PTT that can be tested by mixing whole blood with activator and calcium. It is less sensitive to factor defects, as prolonged ACT may not occur until a single factor is at 5% to 10% of normal function, and can be prolonged■ BOX 27.5
■ BOX 27.7
Causes of Prolonged Activated Partial Thromboplastin Time in Horses
Common Causes
Disseminated intravascular coagulation (DIC) Anticoagulant or rodenticide toxicosis
Acute hepatic necrosis
Less Common Causes
Moldy sweet clover toxicosis
Hemophilia A (deficient factor VIII coagulant [VIII:C]) Congenital deficiencies of factor IX, factor XI, prekallikrein, or high molecular weight kininogen
Hepatotoxins (pyrrolizidine alkaloids, rubratoxins, aflatoxins, bitterweed)
■ BOX 27.6
Causes of Prolonged Activated Partial Thromboplastin Time in Ruminants
Common Causes
Moldy sweet clover toxicosis Disseminated intravascular coagulation (DIC)
Less Common Causes
Congenital deficiency of factor XI Anticoagulant or rodenticide toxicosis Hepatotoxins (pyrrolizidine alkaloids, rubratoxins, aflatoxins, bitterweed)
Hereditary fibrinogen deficiency
also with severe thrombocytopenia.1 As with all tests, reference values vary by species; for example, alpacas have substantially shorter PTTs normally than horses or cattle.31 Age may also play a role, as healthy newborn foals have PTTs and PTs that are longer than adult reference values.
The most common cause of a prolonged PTT is increased consumption of clotting factors induced by DIC (Boxes 27.5 and 27.6). Liver failure and vitamin K antagonism prolong both PTT and PT. Single factor defects will prolong the PTT and not affect the PT. Inherited deficiencies of factors VIIIa (the precursor form of VIII:C) and XI and PK have been described in horses.32-36 Congenital factor VIIIa deficiency (hemophilia A) is sex-linked, and males are clinically affected; carriers cannot be detected via PTT, as factor levels are insufficiently decreased. The level of factor VIIIa must drop below 5% of normal before spontaneous bleeding occurs. Clinical signs of coagulation factor deficiencies are those of hemorrhagic diathesis, as described in the previous section. Inherited factor XI deficiency is transmitted in Holstein cattle by an autosomal recessive trait.37 Cattle deficient in factor XI rarely demonstrate bleeding tendencies.
Although both PT and PTT can be prolonged during DIC, it is not uncommon for only one test to be abnormal initially. Serial analyses should reveal a trend toward prolongation of both tests along with decreasing platelet count. When a persistently prolonged PTT is the only laboratory abnormality, hereditary factor deficiency should be suspected. As with PT, the PTT is a relatively insensitive screening test. The assays generally have prolonged times when at least one factor is decreased to 30% or less of normal function or when combined factor activity is at least mildly decreased. Both PT and PTT can be shortened (times will be below reference interval) with increased fibrinogen, factor V, and/or factor VIII (PTT only). Shortened coagulation times are not traditionally used as Causes of Elevated Fibrin and Fibrinogen Degradation Products in Large Animals
Common Causes
Disseminated intravascular coagulation (DIC) Thrombophlebitis
Postoperative state
Severe inflammation
Immune-mediated thrombocytopenia (IMT)
Uncommon Causes
Massive internal hemorrhage Primary hyperfibrinolysis
indicators of clinical hypercoagulability, as other causes of shortened coagulation times include traumatic venipuncture and insufficient anticoagulation. However, there is evidence in other species that shortened PT and/or PTT can correlate with evidence of hypercoagulability via thromboelastography and/or clinical thromboembolic disease.38-40 Hypercoagulability should therefore be considered a differential for shortened PT and/or PTT in a large animal patient.