Continuing Education Activity

Disseminated intravascular coagulation is a complex condition characterized by a widespread hypercoagulable state in small and large blood vessels that can lead to microvascular and macrovascular clotting and compromised blood flow, ultimately resulting in multiple organ dysfunction syndrome. Commonly, life-threatening illnesses accompany disseminated intravascular coagulation, presenting a challenge in diagnosis and management. 

This activity reviews the evaluation and management of disseminated intravascular coagulation and provides guidance on identifying underlying causes and implementing appropriate treatments tailored to individual patients. Additionally, the significance of recognizing disseminated intravascular coagulation in critically ill patients is highlighted, as its presence significantly impacts mortality rates, particularly in conjunction with sepsis or severe trauma. Further, this activity emphasises the importance of an interprofessional approach to caring for affected patients. Interdisciplinary collaboration ensures timely diagnosis, appropriate management, and ongoing monitoring, thereby enhancing the quality of care and outcomes for patients with disseminated intravascular coagulation.

Objectives:

• Identify the etiology of disseminated intravascular coagulation.

• Assess the clinical manifestations of disseminated intravascular coagulation.

• Implement management considerations for disseminated intravascular coagulation.

• Explain the importance of utilizing an interprofessional team to manage patients with disseminated intravascular coagulation.

Introduction

Disseminated intravascular coagulation (DIC) can be defined as a widespread hypercoagulable state that can lead to micro- and macrovascular clotting and compromised blood flow, ultimately resulting in multiple organ dysfunction syndrome or MODS. As this process begins consuming clotting factors and platelets in a positive feedback loop, hemorrhage can ensue, which may be the presenting symptom of a patient with DIC. Disseminated intravascular coagulation typically occurs as an acute complication in patients with underlying life-threatening illnesses such as severe sepsis, hematologic malignancies, severe trauma, or placental abruption. Determining the consequences of DIC and the overall mortality rate of DIC remains difficult as patients with this condition also have additional diagnoses that can cause many of the signs and symptoms consistent with DIC, particularly if they also have acute or chronic liver failure. While concomitant disease states can obscure a patient’s prognosis, mortality rates have been shown to double in patients who are septic or those with severe trauma if they also have DIC.[1][2][3][4][5]

Etiology

Multiple medical conditions can lead to the development of disseminated intravascular coagulation through a systemic inflammatory response or the release of procoagulants into the bloodstream. The pathological process of DIC has been estimated to occur in up to 30% to 50% of cases of severe sepsis, which is the most common cause of DIC. Classically, DIC has been associated with gram-negative bacteria sepsis, though the prevalence of this disorder in sepsis due to gram-positive organisms may be similar. Other causes of sepsis, including parasites, can also lead to DIC.

Up to 20% of patients with metastasized adenocarcinoma or lymphoproliferative disease also have DIC, in addition to 1% to 5% percent of patients with chronic diseases like solid tumors and aortic aneurysms. Obstetrical complications such as placental abruption, hemolysis, elevated liver enzymes, low platelet count (eg, hemolysis, elevated liver enzymes and low platelets [HELLP] syndrome), and amniotic fluid embolism have also been known to lead to DIC. Other causes of DIC include trauma, pancreatitis, malignancy, snake bites, liver disease, transplant rejection, and transfusion reactions. About 15.5% of cases of DIC have also been linked to complications occurring after surgery.[6][7][8][9][10][11]

Epidemiology

Because DIC is a complication of other medical diagnoses, the prevalence of DIC remains greater in higher acuity settings as opposed to lower acuity settings. Almost invariably, a severe or life-threatening diagnosis is associated with the disease. A 1996 study in Japan found that a diagnosis of DIC complicated about 1.0% percent of admissions to university hospitals. Similarly, a 1992 study showed that DIC complicated 12% of cases of acute lymphoblastic leukemia before starting chemotherapy, and DIC was detected in 78% of cases during remission induction. Furthermore, HELLP syndrome was associated with DIC in approximately 1 in 5 cases, according to a 1993 study. [12][13][14][15]

Pathophysiology

Also referred to as consumptive coagulopathy, DIC involves the homeostatic imbalance between coagulation and bleeding. Tissue factor (TF), which may be released into the circulation from vascular endothelial damage from trauma or certain cancer treatments, bacterial endotoxins, or cytokine exposure, activates coagulation factor VII to VIIa in the coagulation pathway. Via the extrinsic pathway, thrombin and fibrin are formed, forming clots in the circulation. As this process continues, thrombin and fibrin further impair the coagulation cascade through positive feedback loop stimulation and coagulation inhibitor consumption. Clotting factors, as a result, are consumed due to clotting, which can lead to excessive bleeding. Platelets may also become trapped and consumed during this process. Additionally, pathways, including the protein C system and antithrombin III, appear dysregulated in DIC. Furthermore, an increase in plasma activator inhibitor-1 (PAI-1) can prevent the inhibition of fibrinolysis.[5][11]

History and Physical

Components of a patient’s history that may be consistent with disseminated intravascular coagulation include a recent history of severe infections or trauma as well as hepatic failure, obstetric complications, and malignancy. A remote history of deep vein or arterial thrombosis may also suggest DIC. Patients may experience bleeding from multiple sites, including the gingiva, areas of trauma or surgery, the vagina, the rectum, or through devices such as urinary catheters. Symptoms such as hematuria, oliguria, and anuria may be seen if concomitant renal failure from DIC results. Likewise, end-organ damage to the lungs may lead to dyspnea and hemoptysis if pulmonary hemorrhage or pulmonary embolism occurs, and a patient may have a mental status change if either thrombi or hemorrhage to areas of the brain arise. A patient could also experience chest pain if arterial occlusion of a coronary artery develops. Regarding signs of DIC on physical exam, obvious bleeding or frank hemorrhage in various areas of the body may be noted. Skin lesions, including ecchymosis, hematomas, jaundice from liver failure, necrosis, and gangrene, may also arise. Excessive coagulation may lead to widespread purpura, petechiae, and cyanosis. A patient in DIC may also experience acute respiratory failure or neurological deficits based on the location of bleeding or clots.[11][16][17]

Evaluation

No single history, physical exam, or laboratory component can lead to a diagnosis of or rule out DIC; therefore, a combination of subjective, objective, and laboratory findings should be utilized. Laboratory findings suggestive of DIC include an increased prothrombin time (PT) and an increased partial thromboplastin time (PTT), as well as a decreased fibrinogen level as widespread activation and consumption of the clotting cascade occurs. The overall platelet count and hematocrit level may be reduced as well. Schistocytes or fragmented erythrocytes are also commonly seen on a peripheral blood smear. The presence of fibrin split products additionally has a high sensitivity but low specificity for DIC. A specific scoring system to assess for the presence of DIC was established in 2007. This score includes platelet count, fibrin markers such as D-dimer, PT, and fibrinogen level, with a score over 5 indicating a high likelihood for overt DIC.[18][19][20][21]

Treatment / Management

The treatment for DIC centers on addressing the underlying disorder that ultimately led to this condition. Consequently, therapies such as antibiotics for severe sepsis, possible delivery for placental abruption, and consideration for exploratory surgical intervention in trauma-related cases represent the mainstays of treatment for DIC. Platelet and plasma transfusions should only be considered in patients with active bleeding or a high risk of bleeding or those patients requiring an invasive procedure. A common threshold utilized for platelet transfusions in this patient population is less than 50 x 10⁹ platelets/L for actively hemorrhaging patients and 10-20 x 10⁹ platelets/L for those not actively bleeding but at high risk of future bleeding. Likewise, fresh frozen plasma, typically at 15 mL/kg to 30 mL/kg, and cryoprecipitate can be transfused to replenish coagulation factors. Prothrombin complex concentrate may also be considered; however, this formulation only contains some coagulation factors and will only mildly correct a patient’s hemostasis. Heparin may also become necessary if a patient has extensive clotting, as this medication may prevent further activation of the clotting cascade. Patients with DIC who are not actively bleeding should receive prophylactic anticoagulation with heparin or low molecular weight heparin (LMWH).[5][11][19][20][22]

Differential Diagnosis

The differential diagnosis for disseminated intravascular coagulation includes:

• Dysfibrinogenemia
• Hemolytic uremic syndrome
• Heparin-induced thrombocytopenia
• Immune thrombocytopenia (ITP)
• Thrombotic thrombocytopenic purpura (TTP)

Pearls and Other Issues

Disseminated intravascular coagulation can quickly lead to multiorgan failure and death, particularly if early recognition and treatment fail to occur. A high index of suspicion of this high-mortality disease in critically ill patients remains paramount to improve outcomes in patients with DIC.

Enhancing Healthcare Team Outcomes

The diagnosis and management of DIC are complex and challenging. The condition is best managed by an interprofessional team that could consist of a hematologist, surgeon, intensivist, infectious disease consultant, pathologist, and internist. The key is to address the underlying disorder that ultimately led to this condition developing. Consequently, therapies such as antibiotics for severe sepsis, possible delivery for placental abruption, and consideration for exploratory surgical intervention in trauma-related cases represent the mainstays of treatment for DIC. Platelet and plasma transfusions should only be considered in patients with active bleeding or a high risk of bleeding or those patients requiring an invasive procedure. Despite optimal treatment, DIC carries a very high mortality rate. Because DIC affects multiple organ systems, most survivors have a prolonged recovery period.[16][23]