Hemolytic Uremic Syndrome

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamatand I'm Rahul Damania. We are coming to you from Children's Healthcare&nbsp;of Atlanta - Emory University School of Medicine.Welcome to our Episode of a 19 month old female with bloody stool, petechiae and no urine outputHere's the case presented by Rahul:A 19 month old previously healthy female was brought to the pediatric emergency department for blood in her stool. Patient was at daycare the previous day where she developed a low grade fever, congestion and URI symptoms along with non-bloody-non-bilious vomiting and diarrhea. Patient had a rapid COVID test which was negative and was sent home with instructions for oral hydration. That evening, patient began having vomiting/diarrhea which worsened. She was unable to retain anything by mouth and her parents also noted blood in her stool.Due to this, she was rushed to the Emergency Department. In the ED here, she was hypertensive for age BP of 124/103 mm Hg, febrile, and ill. Specks of blood were noted on the diarrheal stool in the diaper.On her physical exam she was noted to be pale with petechiae on neck and chest. Her abdomen was soft, ND, with some hyperactive bowel sounds, and no hepatosplenomegaly. The rest of her physical examination was normal.In the ED, initial labs were significant for WBC 19, Hgb 8.8, and Platelets 34. CMP was significant for BUN of 74mg/dL and Cr of 3.5mg/dL, Na 131 mmol/L, and K of 5.5mmol/L, Ca 8.3mg/dL (corrected for albumin of 2.2g/dL), Phosphorous 8.5 AST 413, and ALT of 227, LDH &gt; 4000. BNP was 142 and troponin negative. She was given 1 dose of CTX 50mg/kg and a 20cc/kg NS bolus. Stool PCR was sent. She was given labetalol for her hypertension, started on maintenance IV fluids and transferred to the PICU for further management.Rahul to summarize key elements from this case, this patient has:We have a 19-month old child withDiarrhea and emesis X 2 daysNo urine output for over 24 hoursBloody stoolPetechiae on the neck and chestAnemia and thrombocytopeniaAll of which bring up a concern for hemolytic uremic syndrome the topic of our discussion todayLet's transition into some history and physical exam components of this case.What are the key historical features in this child who presents with above?Bloody stool which alludes to an invasive diarrheaNo urine output and an ill appearing state which points to a systemic inflammatory condition and end organ dysfunction.Are there some red-flag symptoms or physical exam components which you could highlight?Presence of petechiae which are physical exam features of thrombocytopeniaHer pallor which is a physical exam sign of anemiaHypertension which is related to her renal dysfunctionTo continue with our case, the patient's labs were consistent with:AnemiaThrombocytopeniaElevated BUN and creatinineElevated serum LDHThe patient did not have hyperkalemia, or acidosis on initial presentationOK to summarize, we have a 19 month old girl with:Anemia, thrombocytopenia, and renal failure. This brings up the concern for Hemolytic uremic syndrome →Rahul Let's start with a short multiple choice question:A 2-year old boy is admitted to the PICU with acute respiratory failure secondary to pneumococcal pneumonia. On day # 3 of admission, the nurse reports the patient appears pale and has petechiae on his chest. The patient also has not had urine output for &gt; 12 hours and appears to be fluid overloaded. Of the following the lab findings would be most consistent with the above clinical findings in the patient?A) Elevation of serum haptoglobinB) Low serum lactate dehydrogenase (LDH)C) Negative Direct Coombs testD) Peripheral smear showing schistocytesThe correct answer is D-Peripheral smear showing schistocytes.Patient in the above case most likely has streptococcus pneumoniae associated hemolytic uremic syndrome commonly called as pneumococcal HUS, an uncommon condition, which accounts for 5% of all cases of HUS in children. A peripheral smear will show the presence of schistocytes (which consists of fragmented, deformed, irregular red blood cells). The schistocytes represent RBCs that are partially destroyed as they traverse through the blood vessels partially occluded by microthrombi. Smear may also show giant platelets due to the rapid platelet turnover from peripheral destruction. Because HUS is an intravascular hemolysis serum haptoglobin should be low. Serum LDH along with indirect bilirubin are typically elevated. The Direct Coombs test detects antibodies that coat RBCs and may allude to this pathology. In pneumococcal HUS where there is antigen-antibody interaction on RBC cell surface, the Direct Coombs test may be positive in 90% of the cases. A direct Coombs test is highly sensitive for pneumococcal HUS, but the degree of specificity is unclear.A few points which I want to highlight classically on board exams, schistocytes look like helmet cells on blood smear. Also, presence of COOMBs positivity in the setting of hemolysis think about autoimmune hemolytic anemia (AIHA).Rahul As you think about our case, what would be your differential?&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The following may sometimes be difficult to differentiate from HUSBacterial sepsis (History, clinical presentation with hemodynamic compromise and feature of distributive shock, fever with elevated WBC with neutrophil predominance, multiorgan presentation, source of infection, immunocompromised host etc)Disseminated intravascular coagulation (history of sepsis, drug, toxin eg snake venom, abnormal coagulation etc.)-In HUS the fibrinogen, PT, PTT are normal or slightly elevated and there is no active bleeding.Acute hemolysis from any other causes (drugs, toxins, warm-antibody, cold agglutinin disease, paroxysmal nocturnal hemoglobinuria etc.) -typical history, likely older patients, PNH post-viral in children.Hemophagocytic lymphohistiocytosis (HLH), acute macrophage activating syndrome (MAS), liver failure, TMA etc (good history, h/o JRA and other features may be helpful).Thrombotic thrombocytopenic purpura (older patient, neurological symptoms)The classic triad of hemolytic anemia, thrombocytopenia and renal failure is associated with hemolytic uremic syndrome can be seen on the spectrum of TTP — which adds fever and neurological symptoms to the diagnosis. In the pediatric population, TTP can be seen when children have acquired or congenital absence of ADAMS TS 13. Think of ADAMS TS 13 as a pair of scissors that cuts up vWF, an essential component of primary hemostasis. When you have a deficient or mutated ADAMS TS 13, which is a MMP, you end up having large vWF multimers which deposit in between endothelial cells which creates a consumptive thrombocytopenia and intravascular hemolysis. Pradip, do you mind building a framework between typical HUS versus Atypical HUS?<span...