Many clinical events can prompt the development of DIC in the critically ill patient, but the exact underlying trigger may not be identifiable (Box 27-1). There are, however, some commonly known conditions associated with the development of DIC.

The most common precipitating events for DIC are sepsis and trauma.¹ In sepsis, endotoxins serve as a trigger for activation of tissue factor and the extrinsic coagulation pathway. Metabolic acidosis and hypoperfusion associated with shock syndromes can result in increased formation of free radicals and damage to tissues. Tissue factor is activated, resulting in DIC.² Massive trauma or burns are frequently associated with DIC. Direct tissue damage activates the extrinsic coagulation pathway, and damage to endothelial surfaces activates the intrinsic pathway.² Obstetric emergencies, such as abruptio placentae, retained placenta, or incomplete abortion, are also associated with the development of DIC. Tissue factor is concentrated in the placenta, and damage or disruption of this structure can activate coagulation pathways, resulting in coagulopathy.³

Regardless of the cause, the common thread in the development of DIC is damage to the endothelium, which results in activation of the coagulation mechanism (Figure 27-1).¹ The extrinsic coagulation pathway plays a major role in the development of DIC. Direct damage to the endothelium results in the release of tissue factor and activation of this pathway. The secondary surge of thrombin formation as a result of activation of the intrinsic coagulation pathway leads to the massive disruption of the delicate balance that is hemostasis. Excessive thrombin formation results in rapid consumption of coagulation factors and depletion of regulatory substances—protein C, protein S, and antithrombin.⁴ With no checks and balances, thrombi continue to form along damaged epithelial walls, resulting in occlusion of the vessels. As occlusion reaches a critical level, tissue ischemia ensues, leading to further tissue damage and perpetuating the process. Eventually, end-organ function is affected by the ischemia, and failure is evident.¹

In response to the formation of clots, the fibrinolytic system is activated. As plasmin breaks down the fibrin clots, fibrin split products are released, and they act as anticoagulants.^2,3 Coupled with depletion of circulating clotting factors, activation of fibrinolysis results in excessive bleeding. The end result is shock and further tissue ischemia that aggravate end-organ dysfunction and failure. Death is imminent if this destructive cycle is not interrupted.⁵

Without question, the primary intervention in DIC is prevention. Being aware of the conditions that commonly contribute to the development of DIC and treating them vigorously and without delay provide the best defense against this devastating condition.2,4,6,8 After DIC is identified, maintaining organ perfusion and slowing consumption of coagulation factors are paramount to achieving a favorable outcome.^1,2

Multiple organ dysfunction syndrome (MODS) frequently results from DIC and exacerbates the underlying pathology. It is essential to prevent end-organ ischemia and damage by supporting blood pressure and circulating volume. Administration of intravenous fluids and inotropic agents, and, if overt hemorrhaging is evident, infusion of packed RBCs are appropriate interventions to replace blood volume and essential, oxygen-carrying RBCs.

In the presence of severe platelet depletion (<50,000/ mm³) and severe hemorrhage, platelet transfusions are often indicated.^4,6 However, caution must be used when administering platelets because antiplatelet antibodies may be formed. These antibodies may become activated during future platelet transfusions and elicit DIC.²

Replacement of clotting factors in the patient with DIC is thought by some authorities to perpetuate the coagulopathy; however, there is little scientific evidence to support this theory.¹ Fibrinogen levels less than 100 mg/dL indicate the appropriateness of administering cryoprecipitate. A prolonged PT indicates the need for fresh-frozen plasma.^2,4,6

Slowing consumption of coagulation factors by inhibiting the processes involved in clot formation is another strategy used in treating DIC. The use of heparin, particularly low-molecular-weight heparin, to prevent formation of future clots is controversial.⁵ It is contraindicated in patients with DIC associated with recent surgery or with gastrointestinal or central nervous system (CNS) bleeding. However, heparin has been beneficial in obstetric emergencies such as retained placenta or incomplete abortion, severe arterial occlusions, or MODS caused by microemboli.^2,6

The use of recombinant activated protein C is gaining popularity in treating DIC, especially in the setting of severe sepsis. Activated protein C acts as an anticoagulant and works to restore normal inhibition of coagulation pathways. However, it has been associated with an increased incidence of intracerebral bleeding and must be used with caution in patients with severely decreased platelets.^2,4

Thrombin production in DIC surpasses that of antithrombins and other regulatory factors that would normally be present to inactivate thrombin and its subsequent actions. The use of antithrombin III has recently been approved in the United States. Ongoing research is yielding mixed results in the treatment of DIC.⁴ One interesting area of research is the use of protease inhibitors. Protease molecules normally inhibit the conversion of fibrinogen to fibrin in the coagulation mechanism, but in DIC, this inhibitory mechanism is impaired. The introduction of protease inhibitors by intravenous infusion may be advantageous in arresting DIC.²

Immune-mediated HIT is a response to the administration of heparin therapy. It has been observed in 1% to 3% of patients treated with unfractionated heparin and has occurred after exposure to low-molecular-weight heparin (LMWH), although to a lesser degree.9 The disorder is characterized by severe thrombocytopenia during heparin therapy. Diagnostically it is identified by a platelet count less than 50,000/mm³ or at least a 50% decrease from the baseline platelet count from the initiation of therapy. Onset usually occurs 5 to 14 days from the first exposure to heparin, but the onset can occur within hours of a reexposure to heparin.^11–13 Depending on the source of the disorder, reported mortality rates are as high as 30%.⁹

The thrombocytopenia that occurs with immune-mediated HIT is related to the formation of heparin-antibody complexes. These complexes release a substance known as platelet factor 4 (PF4). PF4 attracts heparin molecules, forming immunogenic complexes that adhere to platelet and endothelial surfaces (Figure 27-2). Activation of platelets stimulates the release of thrombin and the subsequent formation of platelet clumps.¹²

Patients with immune-mediated HIT are at greater risk for thrombosis than bleeding. Vessel occlusion can result in the need for limb amputation, stroke, acute myocardial infarction, and even death.^10–12 The resultant formation of fibrin-platelet-rich thrombi is the primary characteristic of HIT that distinguishes it from other forms of thrombocytopenia and gives rise to its more descriptive name: white clot syndrome.¹⁰

Evidenced-based guidelines for the prevention and management of the patient with HIT are listed in the Evidence-Based Collaborative Practice Box on Treatment and Prevention of Heparin-Induced Thrombocytopenia.14 When a decrease in the platelet count is detected, heparin therapy should be discontinued immediately, and the patient should be tested for the presence of heparin antibodies.^11–14 If the original indication for heparin still exists or new thromboses occur, an alternative form of anticoagulation is usually necessary.¹⁴

Direct thrombin inhibitors (DTIs) are being used with increasing frequency to treat HIT. DTIs bind directly to the thrombin molecule, thereby inhibiting its action.¹⁴ Two such drugs are lepirudin and argatroban.⁹ Warfarin, although commonly used to treat deep vein thrombosis, is not indicated as a sole agent in treating HIT because of its prolonged onset of action. Studies have shown that the use of warfarin without concomitant use of DTIs can significantly increase the incidence of thrombosis in patients with HIT.⁹ Comparative information on these medications is provided in Table 27-4.^9,14

Although most often associated with the use of chemotherapeutic drugs, biological agents, and irradiation used in the treatment of malignant disorders, TLS can in rare instances occur spontaneously. The development of TLS has been linked to other pathophysiological conditions such as elevated WBC counts, large tumors, multiple organ involvement by malignancy, and renal insufficiency.18

The primary mechanism involved in the development of TLS is the destruction of massive numbers of malignant cells by chemotherapy or radiation therapy (Figure 27-3). Massive destruction of cells releases large amounts of potassium, phosphorus, and nucleic acids, leading to severe metabolic disturbances, such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia (Table 27-5). Vomiting, diarrhea, and other insensible fluid losses from fever or tachypnea also contribute to these electrolyte disturbances.¹⁷ Death of patients with TLS is most often caused by complications of renal failure or cardiac arrest.¹⁸

Detection and recognition of TLS is accomplished through assessment of clinical manifestations, evaluation of laboratory findings, and other diagnostic tests. Table 27-6 summarizes common findings in TLS.^17–19

Medical interventions are aimed at maintaining adequate hydration, treating metabolic imbalances, and preventing life-threatening complications.15–17 Administration of intravenous fluids may be necessary early in the course of treatment if inadequate hydration exists. The administration of isotonic saline (0.9% normal saline) reduces serum concentrations of uric acid, phosphate, and potassium.^16,17 The use of nonthiazide diuretics to maintain adequate urine output may be required. If renal failure occurs, hemodialysis should be considered.^16–18

Electrolytes and arterial blood gases are closely monitored. Dietary restrictions of potassium and phosphorus may be necessary. The goals in treating hyperuricemia are to inhibit uric acid formation and to increase renal clearance.¹⁷ This can be accomplished through the administration of sodium bicarbonate to increase the pH of the urine to above 7.0, which increases the solubility of uric acid, preventing subsequent crystallization. Allopurinol administration can also inhibit uric acid formation (see the Priority Medications Box on Allopurinol).¹⁶

If potassium levels rise dangerously, Kayexalate (sodium polystyrene sulfonate) may be given orally, or if the patient is unable to tolerate oral medications due to nausea and vomiting, rectal instillation may be used. If the patient is oliguric, glucose and insulin infusions may be given to facilitate lowering the potassium levels. A 10% solution of calcium gluconate may be administered to stabilize cardiac tissue membranes to prevent life-threatening dysrhythmias.²¹ Phosphorus-binding antacids can be used for treating hyperphosphatemia. Stool softeners may be necessary to treat the constipation often associated with the administration of these antacids. Calcium gluconate may be required to replace calcium, but it should be used judiciously.¹⁷