Disseminated Intravascular Coagulation

GENERAL THERAPY

The best way to treat DIC is to treat the underlying cause that is driving the thrombin generation.^1,2,4,30,31 Fully addressing the underlying cause may not be possible or may take time, and in the meantime it is necessary to disrupt the cycle of thrombosis and/or hemorrhage. In the past, there was concern about using factor replacement due to fears of “feeding the fire,” or perpetuating the cycle of thrombosis. However, these concerns are not supported by evidence, and factors must be replaced if depletion occurs and bleeding ensues.³²

Transfusion therapy of the patient with DIC is guided by the 5 laboratory tests that reflect the basic parameters essential for both hemostasis and blood volume status:^33,34 hematocrit, platelet count, prothrombin time-INR, aPTT, and fibrinogen level. Decisions regarding replacement therapy are based on the results of these laboratory tests and the clinical situation of the patient (Table 3). 

The transfusion threshold for a low hematocrit depends on the stability of the patient. If the hematocrit is below 21% and the patient is bleeding or hemodynamically unstable, packed red cells should be transfused. Stable patients can tolerate lower hematocrits and an aggressive transfusion policy may be detrimental. ^35–37 In DIC, due to both the bleeding and platelet dysfunction, keeping the platelet count higher than 50,000 cells/μL is reasonable.^33,38 The dose of platelets to be transfused should be 6 to 8 platelet concentrates or 1 plateletpheresis unit. In patients with a fibrinogen level less than 150 mg/dL, transfusion of 10 units of cryoprecipitate is expected to increase the plasma fibrinogen level by 150 mg/dL. In patients with an INR greater than 2 and an abnormal aPTT, 2 to 4 units of fresh frozen plasma (FFP) can be given.³¹ For an aPTT greater than 1.5 times normal, 4 units of plasma should be given. Elevation of the aPTT above 1.8 times normal is associated with bleeding in trauma patients.³⁹ Patients with marked abnormalities, such as an aPTT increased 2 times normal, may require aggressive therapy with at least 15 to 30 mL/kg (4–8 units for an average adult) of plasma.⁴⁰

The basic 5 laboratory tests should be repeated after administering the blood products. This allows one to ensure that adequate replacement therapy was given for the coagulation defects. Frequent checks of the coagulation tests also allow rapid identification and treatment of new coagulation defects in a timely fashion. A flow chart of the test and the blood products administered should also be maintained. This is important in acute situations such as trauma or obstetrical bleeding.

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In theory, since DIC is the manifestation of exuberant thrombin production, blocking thrombin with heparin should decrease or shut down DIC. However, studies have shown that in most patients heparin administration has led to excessive bleeding. Currently, heparin therapy is reserved for patients who have thrombosis as a component of their DIC.^2,41,42 Given the coagulopathy that is often present, specific heparin levels instead of the aPTT should be used to monitor anticoagulation.^43,44

SPECIFIC DIC SYNDROMES

SEPSIS/INFECTIOUS DISEASE

Any overwhelming infection can lead to DIC.⁴⁵ Classically, it was believed that gram-negative bacteria can lead tissue factor exposure via production of endotoxin, but recent studies indicate that DIC can be seen with any overwhelming infection.^46,47 There are several potential avenues by which infections can lead to DIC. As mentioned, gram-negative bacteria produce endotoxin that can directly lead to tissue factor exposure, resulting in excess thrombin generation. In addition, any infection can lead to expression of inflammatory cytokines that induce tissue-factor expression by endothelium and monocytes. Some viruses and Rickettsia species can directly infect the vascular endothelium, converting it from an antithrombotic to a prothrombotic phenotype.⁴⁸ When fighting infections, neutrophils can extrude their contents, including DNA, to help trap organisms. These neutrophil extracellular traps (NETS) may play an important role in promoting coagulopathy.^49,50 The hypotension produced by sepsis leads to tissue hypoxia, which results in more DIC. The coagulopathy in sepsis can range from subtle abnormalities of testing to purpura fulminans. Thrombocytopenia is worsened by cytokine-induced hemophagocytic syndrome.

As with all forms of DIC, empiric therapy targeting the most likely source of infection and maintaining hemodynamic stability is the key to therapy. As discussed below, heparin and other forms of coagulation replacement appear to be of no benefit in therapy.

PURPURA FULMINANS

DIC in association with necrosis of the skin is seen in primary and secondary purpura fulminans.^51,52 Primary purpura fulminans is most often seen after a viral infection.⁵³ In these patients, the purpura fulminans starts with a painful red area on an extremity that rapidly progresses to a black ischemic area. In many patients, acquired deficiency of protein S is found.^51,54,55 Secondary purpura fulminans is most often associated with meningococcemia infections but can be seen in any patient with overwhelming infection.^56–58 Post-splenectomy sepsis syndrome patients and those with functional hyposplenism due to chronic liver diseases are also at risk.⁵⁹ Patients present with signs of sepsis, and the skin lesions often involve the extremities and may lead to amputations. As opposed to primary purpura fulminans, those with the secondary form will have symmetrical ischemia distally (toes and fingers) that ascends as the process progresses. Rarely, adrenal infarction (Waterhouse-Friderichsen syndrome) occurs, which leads to severe hypotension.⁴⁵