The patient is a middle-aged female with a remote past medical history of idiopathic thrombocytopenic purpura as a teenager status post splenectomy who presents to a community emergency department (ED) for abdominal pain. She reports one day of left lower quadrant (LLQ) abdominal pain which was described as sharp, stabbing, and worsened with any movement. She has nausea but no emesis, diarrhea, constipation, or genitourinary symptoms. She is status post hysterectomy without vaginal bleeding. She has never had similar pain in the past.
Past Medical History: ITP, hypothyroidism
Past Surgical History: Hysterectomy, splenectomy
Medications: Levothyroxine, multivitamin
Vital Signs: T 100.6°F BP 85/40 P 115 RR 29 SaO2 99% on room air
Physical Exam: Physical exam reveals a tearful, ill-appearing female in mild respiratory distress with some associated tachypnea. She has diffusely scattered petechiae and hemolacria (blood-tinged tears). She is tachycardic without an appreciable murmur. Her capillary refill is delayed at six seconds. Pulmonary exam reveals bibasilar crackles. Her abdomen is tender in the LLQ without rebound or guarding. Her extremities are cold, and her pulses are weak throughout. Neurologic examination is grossly intact without focal deficits.
VBG: pH 7.15/ pCO2 47/ pO2 28/ BE -12.1 Lactate: 15.00 WBC: 9.6 Hgb: 16.5 Plt: Detected only in clumps
Na: 139 K: 3.3 Cl: 95 HCO3: 15 BUN: 28 Cr: 2.87 Glu: 48
Alk Phos: 195 AST: 179 ALT: 93 T. Bili: 1.9 I. Bili: 1.1 INR: 2.5 PTT: 145.5 seconds D-dimer: >20.00 Fibrinogen: 61 mg/dL
Urinalysis: High protein, 2 RBC, 3 WBC, negative ketones
Chest X-ray: Bibasilar opacification.
CT Chest: Groundglass opacification of dependent portions of upper and lower lobes concerning for pulmonary hemorrhage.
CT Abdomen and Pelvis: Retroperitoneal stranding around bilateral adrenal glands concerning for adrenal hemorrhage.
The patient was evaluated and treated promptly and aggressively given signs of both septic shock as well as disseminated intravascular coagulation (DIC). She was given broad spectrum antibiotics with cefepime and vancomycin. In addition, she was resuscitated with three liters of intravenous fluids in the ED. Nonetheless, her metabolic acidosis worsened and she remained hypotensive. Given her refractory hypotension, a right femoral central line was placed and a norepinephrine drip was started. She received a dextrose bolus and was treated with dextrose containing maintenance fluids for her hypoglycemia. Her respiratory status slowly worsened in the ED so she was intubated for expected clinical course given her profound acidosis. CT scan revealed pulmonary as well as adrenal hemorrhage concerning for Waterhouse-Friderichsen syndrome, a syndrome characterized by severe DIC with adrenal hemorrhage often associated with meningococcemia. Given refractory hypotension, hypoglycemia, and likely adrenal insufficiency secondary to hemorrhage, she was also treated with stress dose steroids. Ultimately, she was transferred to the medical intensive care unit and had a complicated, prolonged hospital course. The cause of her profound sepsis was found to be Streptococcus pneumoniae bacteremia.
Disseminated intravascular coagulation is a disorder of simultaneous systemic activation of coagulation and fibrinolysis, which can lead to both microvascular thrombi as well as hemorrhage. This can quickly lead to multi-system organ dysfunction, as seen in the above patient. DIC is not a primary illness, but rather secondary to a clinical condition involving systemic inflammation, with sepsis, malignancy, or trauma being the most common causes. Other less common causes of DIC include heat stroke, crush injuries, vascular abnormalities, crotalid envenomation, ABO incompatibility, preeclampsia, and fat embolism. Sepsis, trauma, surgery, and solid organ malignancy each make up approximately 20% of cases of DIC. However, this is a relatively uncommon illness, seen in only 1% of total admissions in a retrospective, observational study of over 100,000 patients. While meningococcemia is the most common cause of DIC leading to Waterhouse-Friderichsen syndrome in adults, Pseudomonas aeruginosa was found to be the most common pathogen in children. Additionally, there have been reports of DIC secondary to Streptococcus pneumoniae, Neisseria gonorrhoeae, Escherichia coli, Haemophilus influenzae, and Staphylococcus aureus.
Regardless of the cause, DIC results from diffuse activation of coagulation and fibrinolysis. This is typically triggered by exposure of tissue factor, a potent activator of the clotting cascade, to the systemic circulation. This may be in response to massive cytokine release, as in sepsis, or from direct vascular damage from trauma or surgery. Because of the underlying illness, there is a lack of localization and regulation of coagulation which results in systemic activation of the clotting cascade. This leads to diffuse microvascular thrombosis which can compromise perfusion and lead to organ dysfunction. As clotting factors are consumed, the process can lead to concomitant bleeding, making treatment particularly complicated.
The diagnosis of DIC is often suspected clinically and confirmed with laboratory data. All patients with evidence of severe systemic illness and shock in addition to physical exam findings suggestive of coagulopathy should be evaluated for DIC. Patients in the ED will typically be in the acute, decompensated phase of illness. Therefore, they will most commonly present with findings of increased bleeding. Providers should have a high index of suspicion for DIC in patients with ongoing oozing from trauma and procedure sites, petechiae, purpura, significant bruising, or refractory epistaxis. Often, severe bleeding can even be seen from simple peripheral line placement. In addition, these patients will likely display signs of shock, including but not limited to decreased capillary refill, cool extremities, altered mental status, tachypnea, or tachycardia.
Given that DIC occurs secondarily to another illness, a careful history and exam is crucial to identification and management. Providers should elicit any infectious symptoms that could result in sepsis, recent traumatic injuries, and current or prior cancer history. If a cause is not readily apparent, further questioning is required as treatment is centered around identification of the underlying disorder.
To confirm the diagnosis of DIC, emergency providers should order laboratory studies that highlight the underlying pathophysiology of the illness. In DIC, the coagulation cascade is activated but unregulated. The unregulated clotting cascade causes microthrombi that are formed by cleavage of fibrinogen into fibrin to form platelet/fibrin clots. This process consumes the body’s coagulation factors, and with a lack of platelets or coagulation factors, the intrinsic and extrinsic coagulation cascades are unable to control bleeding. Therefore, studies obtained at the initial presentation in the emergency department should evaluate for fibrinolysis with “fibrin split products.” These include fibrinogen levels, D-dimer, prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT). A complete blood count (CBC) should be sent to evaluate for anemia and thrombocytopenia, as well as a peripheral smear to evaluate for evidence of microangiopathic hemolytic anemia. Figure 1 shows what these lab tests will typically reveal in acute, decompensated DIC.
The International Society for Thrombosis and Haemostasis Subcommittee recognizes a published scoring system to help identify DIC (Figure 2). In order to utilize this score, the patient must have an identified underlying disorder that is known to be a s s o c i a t e d with DIC asdiscussed previously. The score can then be calculated by using the results of the above labs. A score of less than five is not suggestive of DIC, while a score greater than or equal to five is indicative of overt DIC. Additionally, there is an association between higher scores and increasing mortality. This score is 91% sensitive and 97% specific for DIC and provides a way to risk stratify critical patients with higher scores.
If the etiology of DIC is not discovered on the history and physical examination, emergency providers should broaden the work-up to identify the principal disorder as indicated. For example, pregnancy testing should be performed in females of child-bearing age. Consideration of malignancy work-up may be warranted if suggested by the history. All patients with DIC should have blood cultures obtained due to the strong association with sepsis. Imaging is not mandatory but should be obtained if clinically indicated by the presenting symptoms, as in the previously described case.
Treatment for DIC in the ED is primarily supportive and aimed at treating the underlying illness to eliminate the stimulus for coagulopathy. These patients are often critically ill and may require an advanced airway, aggressive intravenous fluid resuscitation, and vasopressor support as needed. Frequently, broad spectrum antibiotic coverage is indicated, and this can be expanded to fungal/viral coverage based on the patient's clinical presentation. Delivery of the fetus is indicated if DIC is secondary to a pregnancy-related complication.
As DIC can increase the risk of both thrombosis as well as bleeding, use of blood products is controversial. There is a lack of evidence on when to use these, so treatment is largely based on consensus opinion. With the best available evidence, coagulopathy should be reversed in the case of active bleeding, recent trauma, or need for urgent or emergent surgery. Fresh-frozen plasma or prothrombin complex concentrate can be used to correct an elevated INR. Vitamin K should also be administered to those with active bleeding and an elevated INR. Platelet transfusion should be initiated for platelet count less than 10,000 or less than 50,000 with active bleeding. Cryoprecipitate should be transfused for fibrinogen levels less than 100 mg/dL.
Despite aggressive treatment, severe DIC has a mortality rate of greater than 75% which typically results from multi-system organ failure. Early recognition and aggressive resuscitation is therefore imperative in the ED. These patients should be admitted to the ICU for continued resuscitation as well as the high morbidity and mortality associated with this condition. Due to the complex nature of their coagulopathy, these patients would benefit from an early hematology consult. Additional consulting services may be indicated depending on the underlying etiology of the patient’s DIC.
In summary, DIC is a pathologic activation of the coagulation cascade that can result in concomitant thrombosis and bleeding. Management of this critical illness begins in the ED, making identification and initial stabilization of such patients a crucial responsibility for emergency providers. While mortality remains high, proper ED care can help optimize patient outcomes.
Authored by Isaac Shaw, MD
Posted by Matthew Scanlon, MD
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