Recently, Warkenten has reported on limb gangrene in critically ill patients complicating sepsis or cardiogenic shock.60,61 These patients have DIC that is complicated by shock liver. Deep venous thrombosis with ischemic gangrene then develops, which can result in tissue loss and even amputation. The pathogenesis is hypothesized to be hepatic dysfunction leading to sudden drops in protein C and S plasma levels, which then leads to thrombophilia with widespread microvascular thrombosis. Therapy for purpura fulminans is controversial. Primary purpura fulminans, especially in those with postvaricella autoimmune protein S deficiency, has responded to plasma infusion titrated to keep the protein S level above 25%.51 Intravenous immunoglobulin has also been reported to help decrease the anti-protein S antibodies. Heparin has been reported to control the DIC and extent of necrosis.62 The starting dose in these patients is 5 to 8 units/kg/hr.2
Sick patients with secondary purpura fulminans have been treated with plasma drips, plasmapheresis, and continuous plasma ultrafiltration.62–66 Heparin therapy alone has not been shown to improve survival.66 Much attention has been given to replacement of natural anticoagulants such as protein C and antithrombin as therapy for purpura fulminans, but unfortunately randomized trials using antithrombin have shown mostly negative results.51,55,67–69 Trials using protein C concentrates have shown more promise in controlling the coagulopathy of purpura fulminans, but this is not widely available.63,70–72 Unfortunately, many patients will need debridement and amputation for their necrotic limbs, with one review showing approximately 66% of patients needing amputations.52
TRAUMA
Currently, the most common cause of acute DIC is trauma. The coagulation defects that occur in trauma patients are complex in origin and still controversial (including if even calling it DIC is appropriate!).73–76 The most common etiologies are
Generation of excess activated protein C leading to increased consumption of factor V and VIII and increased fibrinolysis;
Tissue damage leading to generation of excess thrombin generation;
Dilution of hemostatic factors by blood or fluid resuscitation; and
Activation of endothelial cells leading to generation of a prothrombotic surface and shedding of glycocalyx with antithrombotic properties.
Trauma patients are prone to hypothermia, and this can be the major complicating factor in their bleeding.77,78 Patients may be out “in the field” for a prolonged period of time and be hypothermic on arrival.79 Packed red cells are stored at 4°C, and the infusion of 1 unit can lower the body temperature by 0.16°C.80 Hypothermia has profound effects on the coagulation system that are associated with clinical bleeding.77,81,82 Even modest hypothermia can greatly augment bleeding and needs to be treated or prevented.
The initial management of the bleeding trauma patient is administration of red cells and plasma (FFP) in a 1:1 ratio. This has been shown by clinical studies to lessen the risk of exsanguination in the first 24 hours and to be associated with improved clinical outcomes.83,84 The basic set of coagulation tests should also be obtained to guide product replacement, especially as the bleeding is brought under control. Hypothermia can be prevented by several measures, including transfusing the blood through blood warmers. Devices are available that can warm 1 unit of blood per minute. An increasingly used technique is to perform “damage control” surgery. Patients are initially stabilized with control of damaged vessels and packing of oozing sites.85 Then the patient is taken to the intensive care unit to be warmed and have coagulation defects corrected.
For trauma patients at risk of serious bleeding, the use of tranexamic acid reduced all- cause mortality (relative risk 0.91), with death due to bleeding also being reduced (relative risk 0.85).86 There was no increase in thrombosis, but benefit was restricted to patients treated within 3 hours of the trauma. The dose of tranexamic acid was a 1-g bolus followed by a 1-g continuous infusion over 8 hours.
PREGNANCY-RELATED DIC SYNDROMES
Acute DIC of Pregnancy
Pregnancy can be associated with the rapid onset of severe DIC in 2 situations, abruption and amniotic fluid embolism.87,88 The separation of the placenta from the uterine wall creates a space for blood to occupy. Given the richness of the placenta in tissue factor, this leads to activation of coagulation both locally and systemically. Release of blood when this space reaches the vaginal opening can lead to rapid hemorrhage, further augmenting the coagulation abnormalities. Placental insufficiency can lead to fetal demise, which can also worsen the DIC. Management depends on the size of the abruption and the clinical status of both mother and fetus.87 For severe bleeding and DIC, blood product support is crucial to allow safe delivery. In pregnancy, the fibrinogen goal needs to be higher—200 mg/dL.89 For smaller abruption, close observation with early delivery is indicated.
