Deciphering sequela of multiple diseases.
A 75-year-old female with multiple comorbidities — stage IV lung cancer, hypertension, coronary artery disease and diabetes mellitus type 2 — presents with confusion and septic shock. She is febrile, tachycardic and hypotensive.
Her urinalysis is consistent with a significant urinary tract infection. Her serum labs also show leukocytosis, a normal hemoglobin with thrombocytopenia, normal creatinine, an elevated INR and decreased fibrinogen. Purpuric lesions are noted on the lower extremities. She starts to ooze from her IV sites. Which of the following medical conditions is most likely causing the external bleeding?
- Disseminated intravascular coagulation
- HELLP syndrome
- Hemolytic uremic syndrome
- Immune thrombocytopenia
- Thrombotic thrombocytopenic purpura
Correct answer: A. Disseminated intravascular coagulation (DIC)
DIC is a syndrome that involves widespread, unregulated activation of the coagulation system, presenting with elevated INR and D-Dimer and decreased platelet counts and fibrinogen level. The decreased fibrinogen level is what sets it apart from other bleeding disorders, a give-away in the stem. It can cause thrombotic/ischemic complications as well as internal and external hemorrhage.
DIC is associated with many different disease processes, with sepsis being the most common, as in the case patient. Other causes include malignancy, trauma, organ injury, pancreatitis, liver disease, pregnancy, envenomation, ARDS and transfusion reactions. DIC may be chronic and compensated or more acute.
Although it may present with hemorrhage, thrombosis, or both, certain disease entities tend to produce one more than the other. For example, patients with DIC from sepsis tend to present with ischemic/thrombotic complications. Patients with DIC from leukemia tend to display hemorrhagic complications.
Treatment is directed at the underlying cause. Blood products may be indicated when active bleeding is present, or anticoagulation when thrombotic complications develop. Tranexamic acid is only used in DIC thought to be caused by an acute hyperfibrinolytic response such as trauma or obstetric-related DIC, but should be given within three hours of the insult. TXA is not recommended in other forms of DIC.
Incorrect answer choices:
Hemolytic uremic syndrome, or HUS, (Choice C) is a syndrome of microangiopathic hemolytic anemia, renal failure, and thrombocytopenia. It primarily occurs in children and is usually preceded by a diarrheal illness. Atypical HUS may occur in adults and may be linked with streptococcal infection, Epstein-Barr virus or immunosuppressive/chemotherapeutic drugs. Treatment includes supportive care, hydration, transfusion as needed for anemia and hemodialysis as needed for renal failure.
Immune thrombocytopenia (ITP, previously idiopathic thrombocytopenic purpura, Choice D) is a disorder of immune-mediated platelet destruction. Antiplatelet antibodies attach to platelet surface glycoproteins and result in peripheral platelet destruction. Platelets may fall very low, but remaining platelets are functionally normal. Importantly, coagulation factors are not impacted, so the aPTT and PT should be normal (case reports to the contrary exist), as would be the levels of fibrinogen.
Thrombotic thrombocytopenic purpura (Choice E) classically presents with the pentad of fever, altered mental status, microangiopathic hemolytic anemia, renal pathology and thrombocytopenia. The case patient has several of these symptoms, but lacks the anemia and renal involvement. Additionally, the case patient has an elevated INR, and patients with TTP should have normal coagulation studies. TTP results from disordered function or low levels of ADAMTS-13, which cleaves damaged and unfolded von Willebrand factor.
Without ADAMTS-13, the unfolded von Willebrand factor forms large multimers, which then lead to intravascular thrombi. These intravascular thrombi cause ischemia as well as shear injury to RBCs. When the microthrombi are concentrated in the CNS they may lead to seizure, stroke, coma or focal neurologic deficits. Renal involvement is also common. TTP clots do not incorporate fibrin, so coagulation factors are not consumed, and thus these parameters should be normal. Treatment with plasmapheresis is very effective at achieving remission.
HELLP syndrome (Choice B) is a condition that can occur during pregnancy in the setting of preeclampsia. It is defined as Hemolysis, Elevated Liver Function tests and Low Platelets. It occurs between 20 weeks EGA up through four weeks postpartum. When this occurs during pregnancy, delivery is the only definitive treatment. Additionally, treatment with magnesium, and control of hypertension are also indicated.
REFERENCES:
Jecko Thachil; Disseminated Intravascular Coagulation: A Practical Approach. Anesthesiology 2016;125(1):230-236. doi: https://doi.org/10.1097/ALN.0000000000001123.
