While various specific treatment strategies have been used, none have proved more effective than supportive therapy alone,
and some treatments have resulted in worse outcomes. The main therapeutic modalities specifically targeting the thrombus involve
heparin, thrombolytic therapy, surgery, or combinations of the three modalities.
Heparin is a polysulfated glycosaminoglycan anticoagulant that complexes with antithrombin to inhibit mainly factor IIa (thrombin)
and factor Xa (factors IXa, XIa, and XIIa are also inhibited to a lesser degree).34 Heparin exists in two forms—unfractionated and fractionated or low-molecular-weight heparin (LMWH). Unfractionated heparin
molecules are larger and have less predictable activity than LMWH molecules.34 LMWH molecules are small enough that they cannot bind thrombin and antithrombin at the same time, so only factor Xa is inhibited.34 This makes therapy with LMWH less likely to result in bleeding complications as factor II (thrombin) activity is not inhibited.
The current unfractionated heparin recommendation of 300 U/kg given subcutaneously every eight hours is based on a study in
healthy cats that found that this dosing regimen achieved a heparin concentration similar to that which is considered therapeutic
in people.35 No studies have been performed in cats to determine an effective plasma concentration.9
Unfractionated heparin therapy requires close monitoring because of a wide variation in bioavailability. Ideally, aPTT should
be monitored with unfractionated heparin therapy, so a baseline coagulation profile should be a part of the minimum database.
The goal is a prolongation of aPTT by 1.5 to 2.5 times baseline, which has been extrapolated from human medicine.2 Frequent monitoring of the aPTT has been advised, but standardized protocols have not been validated in cats.
Three thrombolytic drugs have been used in cats with thromboembolism—streptokinase, tissue plasminogen activator (TPA), and
Streptokinase is produced from Streptococcus species bacteria.9 The drug results in fibrinolysis by binding to plasminogen, forming a complex that is capable of converting other plasminogen
molecules to plasmin. Streptokinase causes nonspecific degradation of fibrinogen, prothrombin, and factors V, VII, and XII,
which has the potential to cause excessive bleeding.36 Streptokinase has shown no therapeutic benefit and has resulted in severe side effects in cats. In a retrospective study
of 46 cats with ATE, only 33% of treated cats were discharged from the hospital.37 Life-threatening hyperkalemia developed in 35% of cats, and 24% had bleeding complications. Since streptokinase can cause
life-threatening complications and there is no evidence of improved survival time, streptokinase treatment is not recommended.
TPA and urokinase are endogenous thrombolytic agents that form a complex with fibrin to cleave plasminogen to plasmin. TPA
is more selective in targeting thrombi and has less potential for bleeding than streptokinase because of its fibrin binding
site.36 In a recent small prospective study of TPA in cats with ATE, only 27% of the cats survived to discharge.38 All cats in the study suffered adverse events such as azotemia (45%), neurologic signs (45%), arrhythmias (45%), hyperkalemia
(36%), and acidosis (18%); sudden death occurred in one cat. The study was stopped early because of the number of severe side
effects. Thus, treatment with TPA is not recommended.
A recent case report outlined successful thrombolysis using an infusion of urokinase directly at the thrombus site.39 Clinical trials are needed to determine whether this will become a worthwhile treatment.
Historically, surgical removal of the clot has been attempted with poor outcomes. Another method of surgical treatment is
catheter-directed thrombectomy. This procedure has been used successfully in people with thromboembolic disease. One study
evaluated its use in six cats with ATE; half of the cats survived to discharge.40 Of the three that survived, two died within four months of the procedure. One cat died and one was euthanized, both while
anesthetized. Other adverse events included hypotension, neurologic signs, and acidosis. Because of the severity of adverse
events, this treatment is not recommended. Further research is needed to determine whether surgical procedures will be beneficial
in cats with ATE.