Presented by Rob Klever, MD
15 year-old female with a past medical history for asthma, who presents to the ED for a headache, myalagias and anorexia of two days duration. She states that her headache is constant, located bilaterally frontal and of aching quality, relieved by laying down, worsened with movement and has intermittent photophobia. She reports last week that she a had a ‘stuffy nose’ and had one episode of diarrhea and vomiting.
Her grandmother states that took her to the pediatrician five days ago who diagnosed her with viral illness and gave her a prescription for amoxicillin that she took for two days then stopped because she had felt better before developing the headache.
Patient states that she as a mildly sore neck, but no stiffness. Pt reports feeling malaised.
Patient denies any fevers, chills, nausea, vomiting, cough, congestion, wheezing, shortness of breath, chest pain, weakness, numbness or tingling in any of her extremities, constipation, diarrhea then the aforementioned week before, changes in bowel or bladder habits.
Asthma, currently well controlled on no medications.
Medications: Albuterol prn
Patient states that several people in her church youth group have been sick lately, but denies any recent travel.
She lives at home with her grandmother and does well at school as a sophomore.
She denies any alcohol, tobacco and drug use.
She reports no sexual history and states last menstrual period was two weeks ago lasting normal duration and volume.
Positive for migraine headaches, negative for sickle cell and diabetes.
VS: Temp: 36.6C; HR 84; RR 24; BP 109/71; Wt 69.4 kilo
General: 15 year female who appears stated age.
Eyes: PERRLA, EOMI, sclera icteric, conjuctiva pale, fundoscopic exam shows sharp disc margins, no evidence of papillaedema.
Ears: TM clear
Tonsils: tonsils bilaterally 1+; no evidence of erythema, edema or exudates
Neck: soft, supple, no evidence of meningsmus. No Kernig’s or Brudzinki’s sign present. Trachea midline.
Cardiac: RRR s1,s2; no m/r/g
Lungs: CTA B
Abdomen: soft, NTND, no evidence of HSM, no rebound, no guarding
Extremities: Patient moves all extremities spontaneously, normal muscle strength and tone.
Neuro exam: Patient has normal gait and station; patient has normal strength and reflexes in all 4 extremities. CN II thru XII intact.
Skin: Warm, dry and well perfused. Good skin turgor. No evidence of rashes, petechiae or bruises. There is palmar pallor present.
Initial Lab Values:
CBC: WBC: 13.0; H/H 4.1/13.4; Plt 8
UA: Cloudy, Amber, SG 1.014, pH 5.5, 3+ Blood, 1+ protein, negative nitrite, trace leukocyte esterase, > 100 RBCs, 5-10 WBC, 2-5 RBC casts, 2+ bacteria
Urine β-HcG: Negative
1) Given the history and initial lab values, what is the most likely diagnosis?
a. Urosepsis with associated DIC
b. Idiopathic Thrombocytopenic Purpura
c. Viral Meningitis caused by Parvovirus B19
d. Catastrophic anti-phospholipid syndrome
e. Thrombotic Thrombocytopenic Purpura
2) What lab test do you want to order to confirm the diagnosis?
a. Aerobic and Anaerobic Blood Cultures
b. Hemoglobin Electrophoresis
c. Lumbar Puncture
d. Peripheral Smear
e. PT/PTT/INR; D-dimer; Fibrinogen, Fibrinogen Split Products
3) What is your initial ED management?
a. Transfusion of pRBCs and Platelets
b. High dose prednisone, pRBCs, FFP while awaiting Plasma Exchange Transfusion
c. Early Goal Directed Therapy (Fluids, Antibiotics, pRBCs)
d. Early intubation, Dialysis, Fluid Bolus, Platelets, Steroids, Broad-spectrum antibiotics
e. Give methylprednisolone and IVIG
There is spectrum of TTP-HUS that involves a pentad of the following: microangiopathic hemolytic anemia (100%), thrombocytopenia (100%), renal insufficiency ((88%) with gross hematuria (15%)), fluctuating neurologic abnormalities AMS (36%) confusion, generalized headaches, altered mental status, focal deficits (12%), seizures (16%), visual disturbances, and coma, and fever (60%); with the understanding of that TTP has more neurologic findings and an adult disease with HUS has more renal and pediatric involvement. It is a MEDICAL EMERGENCY and a CLINICAL DIAGNOSIS and you cannot wait for the other lab tests to come back before implementing treatment. Without plasma exchange, mortality is greater than 90%. Most cases of TTP arise from deficiency or inhibition of the enzyme ADAMTS13, which is responsible for cleaving large multimers of von Willebrand factor (vWF). Treatment is aimed at reducing circulating antibodies against ADAMTS13 and to replenish blood levels of the enzyme via plasma exhange. There are two exceptions to the general recommendation of plasma exchange in TTP-HUS: Post-diarrheal HUS in children and cancer chemotherapy or transplantation. Physical exam could show fever, hypertension, purpura, jaundice (ie, hemolysis), neurologic deficits (eg, altered mental status, seizure) and splenomegaly or be normal
In the emergency department after making the diagnosis you should begin looking for underlying causes such as pregnancy, cancers, medications including mitomycin C, cyclosporine, oral contraceptive, quinine, and ticlopidine.
1) E. TTP
Given the fact that the patient has a hemolytic (scleral icterus) anemia (palmar and conjuctival pallor (Hgb 4.1), a severe thrombocytopenia (platelets of 8), acute renal insufficiency (Creatinine 1.5) and an neurologic abnormality (headache). She meets 4/5 criteria for TTP-HUS. This is an emergency and you would be amiss to not have this as number one on your differential. She does not have fever or a white count and has relatively normal vital signs, therefore she is not uroseptic. ITP does not have the hemolytic anemia that she has. The patient very well could have viral meningitis towards the top of your differential, but Parvovirus B19 causes a pancytopenia and she has a normal white count. Catastrophic anti-phospholipid syndrome would present similar to this as it causes widespread microvascular and macrovascular changes and this should be on your differential as it is often confused with TTP-HUS. It would be too early to tell as the first lab value to help differentiate PTT (normal value in HUS-TTP and elevated in anti-phospholipid syndrome) is not back yet. Fortunately, the initial ED management is the same.
2) A. Peripheral Smear
Peripheral blood smear from a patient with a microangiopathic hemolytic anemia with marked red cell fragmentation. The smear shows multiple helmet cells (small black arrows), other fragmented red cells (large black arrow); microspherocytes are also seen (blue arrows). The platelet number is reduced; the large platelet in the center (red arrow) suggests that the thrombocytopenia is due to enhanced destruction. Courtesy of Carola von Kapff, SH (ASCP).
- Although there are a plethora of blood tests you should send off, the test that is most likely to confirm the diagnosis is a peripheral blood smear. This test will come back as soon as you or the hematologist looks at it and will change your diagnosis.
- Tests that I sent off for Heme/Onc
CBC Anemia, low platelet count, normal WBC or increased with normal differential
Electrolytes Elevated BUN/Cr
UA Blood in urine, RBC casts
LFTs elevated indirect Bilirubin/ total Bilirubin
Reticulocyte count Increased
LDH/Uric Acid Severely Elevated
ADAMTS-13 Increased activity
DIC panel Fibrinogen and FSPs normal
Coombs’ Test (direct and indirect) Negative
Hemoglobin Electrophoresis Normal
Immunoglobulins A, G, E, M Elevated IgG
Epstein-Barr Panel Normal
Lupus Panel Normal
3) B. High dose prednisone, pRBCs, FFP while awaiting Plasma Exchange Transfusion
- The initial management, while awaiting definitive treatment (Plasma Exchange Transfusion) is high dose prednisone 1 to 2 mg/kg.
- Transfusion of pRBCs is indicated in those with angina, CHF, mental status changes and hypoxia
- Transfusion of FFP is indicated if there is an anticipated delay in arranging Plasma Exchange (i.e., transferring to a tertiary care center)
- Supportive care is always indicated
- DO NOT, under any circumstances GIVE PLATELETS! This is a consumptive coagulopathy and giving platelets will make it worse. EGDT. Methylprednisolone and IVIG are indicated for ITP.
Patient’s Hospital Course:
Patient was admitted to the MICU for Plasma Exchange Transfusion 1.5 times plasma volume twice daily. The patient neurological status fluctuated and she had neuroimaging done that was negative for any acute neurological process. A renal ultrasound showed normal renal architecture.
The patient’s clinical condition improved on day of admission #3, then her mental status deteriorated again on day #5, where repeat imaging was done and the MRI showed multiple focus of infarct with the largest focus in the posterior medial aspect of the right temporal lobe. A cardiac echo was done and showed no evidence of thrombus.
On hospital day 8 the patient became febrile and IV Ceftriaxone IV was started and cultures were sent. The femoral pheresis catheter was replaced with an IJ catheter on day 9 the blood and urine cultures grew E. coli sensitive to Ceftriaxone.
The patient platelet count slowly recovered over the next few days but was still below 150 so it was decided that the patient received steroids (Decadron 36 mg PO q12h).
The patient remained on therapy for E. Coli urosepsis for 10 days, showed much clinical improvement and her platelet count raised above 150 on hospital day #18.
On hospital day #20 the patient developed abdominal pain and elevated BP, so steroids were discontinued with clinical improvement.
The patient was discharged on hospital day #22 with pheresis QOD as an outpatient.
The patient had her R IJ catheter removed on post-ED visit day #56. The patient is doing better with no relapse as of post-ED visit day #85.
- CLINICAL DIAGNOSIS of a MEDICAL EMERGENCY!
- MAHA, TCP, fever, neuro, renal
- Rarely all five are present (1/3)
- Don’t give platelets.
- Transfer out as soon as possible with steroids and FFP hanging.
This case discussion presented by Rob Klever, MD