Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 569

The first principle of managing DIC should be toward resuscitation of the patient to achieve adequate oxygenation, blood pressure, circulation, and renal perfusion. Once resuscitation is complete, aggressive treatment of the DIC's underlying precipitating cause should be addressed. Most frequently, this is sepsis, and aggressive broad‐spectrum antibiotic therapy is necessary following the taking of appropriate microbiological samples. A few causes of disseminated malignancy, such as acute promyelocytic leukaemia and hormone‐responsive breast and prostatic carcinoma, may also be amenable to treatment, but the prognosis in DIC secondary to disseminated malignancy is usually poor; indeed, mortality overall remains high at 25–75% in various series.

There is considerable controversy about the place of blood product support in DIC. Clearly, red cells and platelet support, together with plasma product support, are indicated in actively bleeding patients. In patients who are not actively bleeding or requiring surgical or other intervention, the use of transfused clotting factors and platelets only makes the microvascular thrombosis worse unless the underlying precipitating factors have been treated. However, once these issues have been addressed, if the patient is bleeding, it is appropriate to transfuse red cells to achieve a haemoglobin level of above 10 g l⁻¹ or haematocrit above 30%, to transfuse platelets to achieve a platelet count of >80 × 10⁹ l⁻¹, to transfuse FFP (10–15 ml kg⁻¹) to correct the PT and APTT to no more than 10% prolonged above the upper limit of normal, and to increase the fibrinogen to >1 g l⁻¹ through the appropriate use of cryoprecipitate (cryoprecipitate is particularly rich in fibrinogen) or fibrinogen concentrate. Following blood product intervention, the clotting screen should be repeated to assess the response to therapy and the need for additional future therapy.

In DIC due to sepsis, there is now evidence that depletion of the natural anticoagulant pathway proteins such as antithrombin, protein C, and protein S contributes to microvascular thrombosis, the systemic inflammatory response, and a poorer prognosis. It is not clear if replacement of natural anticoagulants is of therapeutic benefit, but several trials have been published, especially with antithrombin concentrate, with inconclusive results.

The use of heparin is even more controversial.^8,9 There are no adequate controlled trials to support its use, and although it would appear logical to use an anticoagulant in a condition where the major morbidity and mortality are due to thrombosis, the use of a systemic anticoagulant in patients either with active bleeding or at high risk of catastrophic bleeding is problematic. Furthermore, there are considerable problems in determining the dose and duration of treatment and monitoring heparin therapy in the presence of severely prolonged clotting times. As heparin works by potentiating the activity of antithrombin, which is usually severely depleted in DIC, its efficacy is uncertain. Fibrinolytic therapy with tranexamic acid is contraindicated in DIC unless the trigger mechanism is hyperfibrinolysis, and the use of aprotinin, prostacyclin, and antiplatelet drugs remains controversial and unproven. There is evidence that human recombinant activated FVIIa may be useful in uncontrolled life‐threatening haemorrhage, but it should be recognized that the product is not licensed for this indication; and its use in systemic bleeding disorders outside of haemophilia and platelet disorders is associated with a significant increase in arterial thrombotic events, particularly heart attacks and cerebrovascular accidents.