Coagulation Mechanism

The coagulation mechanism consists of 13 factors that work together through a series of feedback loops to achieve hemostasis (Table 38-1 and Fig. 38-1). Depending on the initial triggering event, the extrinsic or intrinsic coagulation pathway is intiated.^1,2 The extrinsic pathway begins when vascular injury occurs, resulting in release of tissue factor and activation of coagulation factor VII. The intrinsic pathway is activated when the damaged subendothelium comes into direct contact with circulating blood. In this contact phase, proteins activate additional coagulation factors (XII, XI, IX, and VIII).¹ At this point, the two pathways converge into a common pathway, and prothrombin and fibrinogen are converted to their active forms, resulting in clot formation.^3,4

Clot Formation

Platelets are activated by the arrival of thrombin at the site of injury (Fig. 38-2). Local platelets change shape, become sticky, and begin to aggregate along the vessel wall. Activated platelets undergo degranulation, releasing several factors to assist in clot formation. Serotonin and histamine, two potent vasoconstrictors, help limit blood loss while the clot is forming. The prostaglandin thromboxane A₂ (TXA₂) contributes to vasoconstriction and promotes further platelet degranulation. Adenosine diphosphate (ADP) recruits platelets by increasing adherence and degranulation,^2,3 and the process continues.

At the convergence of the intrinsic and extrinsic pathways, factor X is converted into its active form, thereby enabling the conversion of prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin. Strands of fibrin form and radiate around the newly formed clot, essentially creating a net in which platelets, red blood cells (RBCs), and white blood cells (WBCs) are trapped.¹ The clot is further secured to the site as platelet actomyosin causes it to contract and consolidate.²

Regulatory Mechanisms

Under normal conditions, feedback systems prevent the coagulation process from spinning out of control. Prostacyclin I₂ (PGI₂) is a prostaglandin released from damaged endothelial cells. It counteracts the effects of TXA₂, serotonin, and histamine through vasodilation and inhibition of platelet degranulation.1–3 Another means of regulating clot formation is through inhibition of enzymes necessary for activation of coagulation factors along the intrinsic and extrinsic pathways, preventing the conversion of prothrombin to thrombin. The most important of these regulators is antithrombin III; however, protein C and protein S also play a role in thrombin inhibition.⁵

Fibrinolysis

The process of fibrinolysis promotes dissolution and remolding of the clot to promote repair of the vessel wall and maintain flow through the vessel lumen (Fig. 38-2D). Fibrinolysis begins as soon as the fibrin clot is formed. Circulating plasminogen, a precursor to the powerful enzyme plasmin, binds to fibrin and is trapped within the newly formed clot. The injured epithelial wall releases tissue-type plasminogen activator (tPA), which converts plasminogen to its active state, plasmin. The plasmin begins to digest the fibrin, rapidly breaking down the clot.^2,4 When fibrin is broken down, the fibrin degradation products released act as anticoagulants.

Etiology

Many clinical events can prompt the development of DIC in the critically ill patient, but the exact underlying trigger may not be identifiable (Box 38-1). There are, however, some commonly known conditions associated with the development of DIC.

Sepsis, particularly that caused by gram-negative organisms, can be identified as the culprit in as many as 20% of cases, making it the most common cause of DIC. In this instance, 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. 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.³ Obstetric emergencies, such as abruptio placenta, 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.⁷

Pathophysiology

Regardless of the cause, the common thread in the development of DIC is damage to the endothelium that results in activation of the coagulation mechanism (Fig. 38-3).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.⁵ 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.3,7 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.⁸

Assessment and Diagnosis

Favorable outcomes for patients with DIC depend on accurate and timely diagnosis of the condition. Realization of the role underlying pathology plays, recognition of clinical manifestations, and assessment of appropriate laboratory values are key steps in this process.

Medical Management

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.3,6,7,9 After DIC is identified, maintaining organ perfusion and slowing consumption of coagulation factors are paramount to achieving a favorable outcome.^1,3

Multiple organ dysfunction syndrome (MODS) frequently results from DIC and exacerbates the underlying pathology.⁸ 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 (less than 50,000/mm³) and severe hemorrhage, platelet transfusions are often indicated.5,6 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.³

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.^3,5,6

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 (LMWH), to prevent formation of future clots is controversial.⁶ 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.^3,6 Inhibitors such as aminocaproic acid may be used in conjunction with heparin.^3,6

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.3,5

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.⁵ 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.³

Nursing Management

Nursing management of the patient with DIC incorporates a variety of nursing diagnoses (Box 38-2). Assessment and monitoring are the primary weapons in the critical care nurse’s arsenal against DIC. Knowing the diseases and conditions that are most often associated with DIC and understanding the pathophysiologic mechanisms involved enables the critical care nurse to anticipate its development and intervene quickly. Nursing interventions include supporting the patient’s vital functions, initiating bleeding precautions, providing comfort and emotional support, and maintaining surveillance for complications.

Etiology

Onset of thrombocytopenia often follows a viral infection, pregnancy, administration of certain medications (e.g., heparin, thiazide diuretics, chemotherapeutic agents), malignancies, splenomegaly, blood transfusions, or alcoholism.¹² Regardless of the precipitating condition, the development of thrombocytopenia occurs by means of one of four mechanisms: 1) decreased platelet production; 2) increased platelet destruction; 3) splenic sequestration of platelets; and 4) platelet dilution.¹⁰ The most common form of thrombocytopenia seen in the critical care unit is immune thrombocytopenic purpura (ITP).¹¹

Pathophysiology

In ITP, lymphocytes produce antibodies that begin to destroy existing platelets. The cause of this autoimmune response is unknown.¹³ With insufficient platelets available, the normal coagulation pathways are disrupted. Inadequate hemostasis ensues, and bleeding results. Although life-threatening gastrointestinal or intracerebral bleeding can occur, the bleeding seen in ITP does not result in deep visceral hemorrhage and hematoma.¹⁰

Assessment and Diagnosis

ITP is characterized by the gradual onset of signs and symptoms.¹³ The diagnosis is primarily based on findings in the patient’s history and physical examination.