Control excessive intravascular coagulation
Based on the pathophysiology of DIC and the likelihood the syndrome is being driven by both thrombin and plasmin, attenuating
intravascular coagulation would prevent microvascular thrombosis and the consumption of platelets and coagulation inhibitors.
This can be achieved by administering exogenous coagulation inhibitors. Antithrombin is the most important endogenous inhibitor
of coagulation, so systemic therapy with heparin sodium, a cofactor of antithrombin, is recommended in veterinary medicine.
No controlled studies of heparin therapy in DIC exist in the veterinary or human medical literature. So the benefit of such
therapy is controversial. In addition, without appropriate antithrombin activity (which can be low secondary to consumption),
heparin therapy will be of little benefit. Natural anticoagulants (i.e. antithrombin activity) may be decreased in patients with severe inflammatory diseases that predispose patients to DIC.15 Plasma antithrombin activity has to be below 70% for heparin therapy to be ineffective.16
As a sole treatment, heparin is contraindicated in patients with acute DIC and secondary hemostatic abnormalities. These patients
should receive antithrombin and coagulation factors in the form of fresh frozen plasma with heparin. We add 5 to 10 U/kg heparin
sodium to plasma before administration. Patients with peracute or chronic DIC with no secondary hemostatic abnormalities may
benefit from heparin treatment alone depending on antithrombin activity. Therefore, with few exceptions, systemic heparin
therapy is recommended for patients with DIC (Table 3). However, no single dosage can be recommended, and therapy should be tailored to the individual patient. Traditionally,
the four dose ranges for heparin sodium are1
Table 3. Clinical Forms of DIC and General Treatment Guidelines*
- Mini-dose: 5 to 10 U/kg given subcutaneously three times a day or added to plasma components 30 minutes before plasma administration
- Low-dose: 100 to 200 U/kg given subcutaneously three times a day
- Intermediate-dose: 300 to 500 U/kg given subcutaneously three times a day
- High-dose: 750 to 1,000 U/kg given subcutaneously or intravenously three times a day; this dose is rarely used in our clinic
and not recommended.
In our clinic, we routinely administer the low dose (100 to 200 U/kg) of heparin sodium in patients that have chronic DIC
without evidence of microvascular thrombosis. For patients with peracute DIC and normal clotting times, we recommend the intermediate
dose (300 to 500 U/kg) with the goal of prolonging the APTT one-and-one-half to two times normal baseline. During heparin
therapy in patients with peracute DIC, we recommend monitoring the APTT, not the activated clotting time. The APTT is prolonged
when any factor in the intrinsic and common pathway is decreased to less than 30% activity.17 A prolonged activated clotting time is seen with only more profound (> 30%) decreases in factor activity. Because of poor
sensitivity, it may be dangerous to use the activated clotting time for monitoring.
We recommend beginning at the lower dose and increasing the dose to the endpoint based on changes in platelet count and coagulation
times. In our experience, high-dose heparin is rarely justified and can be dangerous. In case of heparin overdosage, 1 mg
protamine sulfate can be given for each 100 U heparin to be inactivated.18 The protamine dose should be reduced by half for every 30 minutes lapsed since the last heparin administration.18 This dose should be given slowly intravenously at a rate not to exceed 50 mg over a 10-minute period.18 Administer protamine with caution because of the possibility of acute anaphylaxis.