Page 328 - WSAVA2018
P. 328

 25-28 September, 2018 | Singapore
do not provide a clear-cut indication whether heparin use is beneficial. Heparin effects may be variable, depending on the underlying cause and the stage of DIC.8 Various studies have shown either positive effects, no effect or negative effects of heparin treatment and therefore its use in DIC is still under debate.
Heparin enhances thrombin and factor Xa inactivation through activation of AT III inhibitory actions and therefore is ineffective when AT III plasma activity is insufficient. Because AT III activity in DIC is usually low (as a result of consumption and possibly due to inactivation), it is advisable to provide the patient with sufficient quantities of this anticoagulant, most efficiently through blood component replacement. In a single study in dogs with different coagulopathies, FFP therapy did not result in increase plasma AT III activity.15
Heparin has another anti-clotting activity, through induction of the release of low affinity, microvasculature glycosaminoglycan-bound tissue factor pathway inhibitor (TFPI) pools into the circulation. Enhancement of TFPI activity represents an upstream, even more specific anticoagulatory action compared to AT III, in cases where coagulation is triggered by bacterial lipopolysacharides in sepsis.16
To the best of our knowledge, there are no controlled studies determining the appropriate heparin dose for DIC in veterinary patients, or even substantiating its
use in this syndrome. Extrapolation from the human literature is difficult because human patients at risk
for DIC are generally also at high risk for deep vein thrombosis (DVT). They are consequently usually treated with aggressive heparin for DVT risk. This is generally not an issue for our patients. Controlled studies are difficult to perform since DIC is not a primary disease, and populations with DIC vary widely in terms of manifestation and prognosis due to variability in the underlying disease. Several authors have, however, proposed that in DIC sodium heparin is given at dose
of 50-100 IU/kg SQ q8h. This dose should be adjusted through monitoring of the aPTT and AT III activity, with the aim to prolong the aPTT by up to 30% above the upper reference interval in a hypercoagulable state or, when such value is achieved through replacement and supportive therapy.2
Low molecular weight heparin (LMWH) is composed of heparin fractions with molecular weights of 4000 to 8000 daltons. LMWH was found to be more advantageous than unfractionated heparin (UFH)
in dampening the activated coagulation. In human patients with endotoxemia, it has been shown to significantly reduce mortality. In a double-blind, controlled study in human DIC Patients, LMWH was more beneficial compared to UFH in decreasing bleeding complications.17
UFH binds to AT III, resulting in a conformation change of AT III that leads to greatly enhanced inhibition of many coagulation factors, such as thrombin, Xa, XIa, XIIa and IXa. Unlike UFH, LMWH, due to its small molecular size, cannot simultaneously bind to both AT III and thrombin, and therefore inhibits thrombin to a lesser extent. However, when compared to UFH, LMWH has greater affinity to and enhanced inhibitory efficiency of factor Xa. LMWH also has a lesser tendency to bind to macrophages, plasma proteins and platelets, accounting for its limited hepatic clearance, prolonged half life and better bioavailability. In humans, LMWH has been found to have a 2-4-fold longer half-life than UFH, with greater bioavailability and more predictable anticoagulant effects.18 In addition, with LMWH, the likelihood of developing heparin induced thrombocytopenia is reduced compared to UFH.18,19
Antifibrinolytic agents
A large body of evidence in human medicine supports the use of antifibrinolytic drugs for control of hemorrhage in a variety of clinical settings. Antifibrinolytic therapy
is commonly used in human patients undergoing cardiovascular, pediatric and orthopedic surgery,
dental procedures, or in cases of severe menstrual or postpartum bleeding, and mainly in major trauma. To date, antifibrinolytic drugs are clinically used in people for hemorrhage control, including ε-aminocaproic acid (EACA), tranaxemic acid (TxA), and aprotinin. The lysine analogues, EACA and TA, inhibit plasminogen, and to a lesser extent, increase antiplasmin activity, resulting in decreased fibrinolysis, with TxA having a 10-fold activity compared to EACA. The results of the large CRASH-2 trial showed that the administration of TxA within the
first three hours after hospital admission reduced mortality in trauma patients. Mortality rates were lowest among patients who received TxA within the first hour after hospital admission, and authors concluded that TxA should be given as early as possible to bleeding trauma patients.20
1. Levi M, de Jonge E, van der Poll T, et al. Disseminated intravascular coagula- tion. Thrombosis and Haemostasis 1999;82:695-705.
2. Feldman BF, Kirby R, Caldin M. Recognition and treatment of disseminated intravascular coagulation. In: Bonagura JD, ed. Kirk’s Current Veterinary Therapy XIII: Small Animal Practice, 13th ed. Philadelphia: W.B Saunders Company; 2000:190-194.
3. Bruchim Y, Aroch I, Saragusty J, et al. Disseminated intravascular coagulation. Compendium 2008;30:E3.
4. Wada H, Hasegawa K, Watanabe M. DIC: an update on diagnosis and treat- ment. [Rinsho ketsueki] The Japanese journal of clinical hematology 2017;58:523- 529.
5. Bruchim Y, Ginsburg I, Segev G, et al. Serum histones as biomarkers of the severity of heatstroke in dogs. Cell stress & chaperones 2017;22:903-910.
6. Couto CG. Disseminated intravascular coagulation in dogs and cats. Veteri- nary Medicine 1999;June, 1999:547-553.
7. Bateman SW, Mathews KA, Abrams-Ogg ACG. Disseminated intravascular coagulation in dogs: review of the literature. Journal of Veterinary Emergency
  326
43RD WORLD SMALL ANIMAL VETERINARY ASSOCIATION CONGRESS AND 9TH FASAVA CONGRESS










































































   326   327   328   329   330