Page 2331 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 139 Disseminated Intravascular Coagulation 2073

BOX 139.3 Mainstays of Supportive Treatment of Disseminated Intravascular Coagulation
Modality Details Expectations/Rationale
Treating the underlying Dependent on the primary diagnosis Inhibit or block the complicating pathologic mechanism of
disorder disseminated intravascular coagulation (DIC) in parallel
with the response (if any) of the disorder
Antithrombotic agents Prophylactic heparin to prevent venous Risk of thromboembolism is increased in critically ill
thromboembolic complications patients, trauma patients, or patients with cancer
(Low dose) therapeutic heparin in case of Prevent fibrin formation; tip the balance within the
confirmed thromboembolism or if clinical microcirculation toward anticoagulant mechanisms and
picture is dominated by (micro) vascular physiologic fibrinolysis; allow reperfusion of the skin,
thrombosis and associated organ failure kidneys, and brain
Transfusion Infuse platelets, plasma and fibrinogen Bleeding should diminish and stop over the course of hours
(cryoprecipitate) if there is overt bleeding or a Platelet count, coagulation tests and fibrinogen should
high risk of bleeding return toward normal
Anticoagulant factor Recombinant human activated protein C may be Restore anticoagulation in microvascular environment and
concentrates effective in sepsis and DIC (24 µg/kg/h for 4 may have antiinflammatory activity
days); Currently withdrawn from the market Latest trials were negative.
Fibrinolytic inhibitors Tranexamic acid (e.g., 500–1000 mg q8–12 h or May be useful if there is (hyper) fibrinolysis
ε-aminocaproic acid 1000–2000 mg q8–12 h) Bleeding ceases, but there is a risk of microvascular
thrombosis and renal failure

THERAPY Cryoprecipitate (if available) can be used to rapidly raise the levels
of fibrinogen, von Willebrand factor, and factor VIII levels in patients
Management of patients with DIC depends on vigorous treatment with DIC, particularly when there is bleeding and the fibrinogen level
of the underlying disorder to alleviate or remove the inciting injurious is less than 1 g/L. Cryoprecipitate has at least four- to fivefold more
cause. For sepsis-induced DIC, treatment includes aggressive use of fibrinogen in each milliliter than fresh-frozen plasma. Nonetheless,
intravenous organism-directed antibiotics and source control (e.g., by fresh-frozen plasma contains sufficient amounts of fibrinogen to treat
surgery or drainage). Other examples of vigorous treatment of the mild to moderate hypofibrinogenemia.
underlying condition include cancer surgery or chemotherapy, uterus
evacuation in patients with abruptio placentae, resection of aortic
aneurysm, and debridement of crushed tissue in the case of trauma. Anticoagulant Treatment
In addition to intensive support of vital functions, supportive treat-
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ment aimed at the coagulopathy may be helpful (Box 139.3), as Heparin therapy in patients with DIC remains controversial. Experi-
outlined later. mental studies have shown that heparin can at least partly inhibit
activation of coagulation in DIC. However, clinical trials have failed
to demonstrate a beneficial effect of heparin on clinically important
Platelet and Plasma Transfusion outcome events in patients with DIC and the safety of heparin is
debatable in those at risk for bleeding. A large trial in patients with
Low levels of platelets and coagulation factors may increase the risk severe sepsis showed a small but nonsignificant benefit of low dose
of bleeding. However, plasma or platelet transfusion should not be heparin on 28-day mortality in patients and no major safety
instituted on the basis of laboratory results alone; it is only indicated concerns. 25
in patients with active bleeding and in those requiring an invasive There is general consensus that administration of heparin is benefi-
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procedure or at risk for bleeding complications. The presumed cial in some categories of DIC, such as metastatic cancer, purpura
efficacy of treatment with plasma, fibrinogen concentrate, cryopre- fulminans, and aortic aneurysm (prior to resection). Heparin also is
cipitate, or platelets is not based on the results of randomized con- indicated for treating thromboembolic complications in large vessels
trolled trials. Nonetheless, transfusion of these products is rational in and before surgery in patients with chronic DIC. Heparin administra-
bleeding patients or in patients at risk of bleeding who have significant tion may be helpful in patients with acute DIC when intensive blood
depletion of these hemostatic factors. The suggestion that administra- component replacement fails to improve excessive bleeding or when
tion of blood components might “add fuel to the fire” has never been thrombosis threatens to cause irreversible tissue injury (e.g., acute
proven in clinical or experimental studies. cortical necrosis of the kidney or digital gangrene).
Replacement therapy for thrombocytopenia consists of 5 to 10 U Heparin should be used cautiously in these conditions. In patients
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platelet concentrate to raise the platelet count to 20–30 × 10 /L and with chronic DIC because of metastatic cancer or aortic aneurysm,
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to 50 × 10 /L in patients requiring an invasive procedure. continuous infusion of unfractionated heparin (500 to 750 U/hour
One of the major challenges of infusion of fresh-frozen plasma in without a bolus) has been advocated. If no response is obtained within
patients with DIC who are bleeding is the propensity of the added 24 hours, higher dosages can be used. In hyperacute DIC cases, such
volume, which is necessary to correct the coagulation defect, to as amniotic fluid embolism, septic abortion, and purpura fulminans,
exacerbate the capillary leak syndrome. This increases the risk of intravenous bolus injection of 5000 to 10,000 U heparin may be given
causing or worsening pulmonary edema and, by extension, predis- simultaneously with replacement therapy with blood products. Some
poses to ARDS and induces ascites. Coagulation factor concentrates, experts, however, recommend against administration of a bolus dose
such as prothrombin complex concentrate, may partially overcome of heparin under these circumstances. A heparin infusion of 500 to
this obstacle, but these concentrates do not contain essential factors, 1000 U/hour may be necessary to maintain the benefit until the
such as factor V. Moreover, caution is advocated with the use of underlying disease responds to treatment. Aside from these consider-
prothrombin complex concentrates in DIC because they can contain ations, current guidelines recommend universal thromboprophylaxis
trace amounts of activated coagulation factors, which may worsen the with low doses of heparin or LMWH in critically ill patients. 6
coagulopathy. Specific deficiencies of coagulation factors, such as Theoretically, the most logical anticoagulants to use in DIC would
fibrinogen, may be corrected by administration of purified coagula- be those directed against TF. Potential agents include recombinant
tion factor concentrates. TFPI, inactivated factor VIIa, and recombinant NAPc2, a potent and