Author: Ashley Phipps, MD (EM Chief Resident, UTSW / Parkland Memorial Hospital // Edited by: Jennifer Robertson, MD, MSEd and Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital)

Case

A 67 year-old male presents to the emergency department (ED) for fevers, nausea, vomiting, and severe epigastric pain for the past 2 days. The patient has a history of alcoholism, hypertension, and diabetes. On exam, he is ill-appearing, tachycardic, and mildly tachypneic. Laboratory studies and a computed tomography (CT) abdomen/pelvis are obtained showing a lipase of 316 and pancreatic stranding making pancreatitis the most likely diagnosis. Other notable laboratories studies include leukocytosis to 22,000/microliter (uL), thrombocytopenia to 42,000/uL, hyperglycemia to 351, and a mild transaminitis. His nurse tells you that there is blood oozing around his intravenous (IV) sites. Being an astute clinician, you recognize that this patient is critically ill, and you begin to worry about disseminated intravascular coagulation (DIC).

Background

DIC is an acquired coagulation syndrome that results in excessive clotting and clotting factor consumption, with subsequent severe bleeding in severely ill patients. Many different conditions can lead to DIC (table 1); however, the mechanism for DIC is the same in each case. In DIC, the coagulation cascade is activated and its control mechanism is lost. This leads to the formation of thrombin clots that are then deposited in capillaries and small vessels. The large amount of thrombin and fibrin clot deposition has three big consequences. First, the excessive clotting effectively consumes the body’s store of clotting factors and platelets. Next, the clot deposition in the microcirculation leads to hemolysis as red blood cells attempt to pass through. Lastly, the counter-regulatory system, the fibrinolytic system, also gets activated and starts dissolving the clots. At this point, clotting factors are depleted and significant bleeding can ensue. (1)

Table 1. Known causes of DIC

Infection (bacterial, viral, & fungal) Trauma Pregnancy complications (placental abruption, intrauterine fetal demise, amniotic fluid embolus, HELLP syndrome) Acute Respiratory Distress Syndrome (ARDs) Acute liver failure Pancreatitis Malignancy (most common in leukemia), chemotherapy Vasculitis Envenomation (rattlesnakes, vipers) Transfusion reactions

Clinical Presentation

The clinical presentation will vary based on the precipitating cause. Patients can present with hypercoagulation, hyperfibrinolysis, or a mixed picture of both. If hypercoagulation predominates, clinical presentation can include signs of end-organ failure or gangrene in small vascular beds such as the fingers or toes. This is the most common initial presentation of DIC in septic patients. Contrastingly, if bleeding predominates, the patient may have petechiae or large ecchymosis, hematuria or hematochezia, or oozing from IV sites and any other sites of trauma. This is the most common presentation of DIC in patients with trauma, malignancy, pregnancy, or liver failure related illnesses. (2)

Diagnostic Studies

In all severely ill patients, especially those with symptoms or signs of DIC, coagulation laboratories studies should be obtained. These include platelet count, prothrombin time (PT), and fibrinogen. Additional tests including d-dimer, fibrin degradation products, activated partial thromboplastin time (aPTT), clotting time, and specific factor assays can be helpful. (1) DIC is often associated with several characteristic laboratory findings, shown in Table 2. This disease differs from other coagulation disorders in the degree and number of laboratory abnormalities.

Table 2. Laboratory abnormalities in DIC

Platelet count ↓ PT (INR) ↑ Fibrinogen ↓ (can be elevated in early DIC) D-dimer ↑ Fibrin degradation products ↑ aPTT ↑ Clotting time ↑ Specific factor assays ↓ (especially Factor II, V, VII, X)

Several scoring systems exist to determine the likelihood of DIC as well as prognosis (2). For example, the International Society on Thrombosis and Haemostasis has a scoring system that gives points for the degree of thrombocytopenia, degree of elevation in the d-dimer, degree of prolongation of the PT, and if the fibrinogen level is low or not. If that score is greater than or equal to 5, the presentation is consistent with DIC. (3) This score was then validated in a prospective study looking at 217 intensive care patients at an academic center resulting in a sensitivity of 91% and specificity of 97%. The study also showed a strong correlation between DIC and 28-day mortality (4), further illustrating how important it is to start treatment for DIC in the emergency department if it is suspected.

Treatment: What can we do about it?

1. Treat the underlying disease. For most cases, DIC will resolve on its own if the underlying condition is appropriately treated (5).

2. If bleeding is the main problem and there is continuing active bleeding or a high risk for more bleeding:

Lab Abnormality Treatment Hgb <7 or active significant bleeding on exam PRBCs (packed red blood cells) Platelets <50,000 Platelets PT >1.5 or fibrinogen <100 FFP (fresh frozen plasma) Vitamin K Trauma-related bleeding TXA (tranexamic acid)

The dosing for transfusions will vary based on the exact lab values and presentation. For platelet transfusion, the platelet count should rise by 5,000/uL for each unit of platelets (6). For FFP, the initial recommended dose is 15 cc/kg (2).

If the patient cannot tolerate large volumes of fluid, small volume PCC (prothrombin complex concentrate) can be substituted for FFP. However, giving only PCC will not replenish all of the needed clotting factors, especially factor V and fibrinogen. Thus, cryoprecipitate should also be given to help replenish the patient’s depleted fibrinogen. (6)

Some patients in DIC will also continue to have low fibrinogen levels that are refractory to FFP administration. These patients require concomitant cryoprecipitate (7).

Disposition for all of these patients should be to an intensive care unit (ICU). However, depending on how long it takes to get the patient out of the ED and into the ICU, it is important to keep in mind that the DIC labs should be repeated every six hours in critically ill patients and after any interventions (7).

3. If hypercoagulation is the main problem, consider therapeutic doses of low molecular weight heparin. A small randomized control study showed this was superior to using unfractionated heparin. The predominately hyperfibrinolytic patients are also at increased risk for venous thromboembolism and should be started on prophylactic anticoagulation with low molecular weight heparin as soon as the bleeding risk is mitigated. (5)

Case Resolution

You reassess the patient and notice that he indeed is continuing to ooze from his two IV sites. You also notice petechiae on his lower extremities. Concerned for DIC, you immediately start treating the patient’s underlying condition of pancreatitis and a urinary tract infection. The patient is made nil per os (NPO) and given IV fluids, antiemetics, and analgesia. His hyperglycemia is controlled after fluids are started. He has known thrombocytopenia and the rest of his DIC labs show an INR of 1.8, a low fibrinogen level, and an elevated d-dimer. The patient is given two units of platelets, 15 cc/kg FFP, 10 mg IV Vitamin K and is admitted to the ICU laboratory tests are frequently checked and he is given blood products as needed. On day two, the patient begins to improve and by day eight, the patient is discharged home.

Summary

DIC is an important clinical entity seen in critically ill patients. Laboratories studies may demonstrate low platelets, an elevated INR, an elevated d-dimer, and low fibrinogen levels. Rapid identification and treatment of the underlying cause as well as supplementation with blood products is important to reduce mortality in these patients.

References/Further Reading

Tintinalli JE et al. Acquired bleeding disorders: disseminated intravascular coagulation. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 2011; 7. Wada H, Matsumoto T, Yamashit Y. Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. J Intensive Care. 2014; 2(1):15. Taylor FB, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001; 86: 1327-30. Bakhtiari K, Meijers JC, de Jonge E, Levi M. Prospective validation of the International Society of Thrombosis and Haemostasis scoring system for disseminated intravascular coagulation. Crit Care Med. 2004; 32(12): 2416-21. Wada H, et al. Guidance for diagnosis and treatment of disseminated intravascular coagulation from harmonization of the recommendations from three guidelines. J Thrombosis & Haemostasis. 2013; 11: 761-7. Levi M, Opal SM. Coagulation abnormalities in critically ill patients. Crit Care. 2006; 10(4): 222. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009; 145(1): 24-33.