A previously healthy 53-year-old male was admitted to our emergency department on 2022-10-10 at 12:00 p.m. with fever, thrombocytopenia, and abnormal liver function.
The patient is a cook. In the past 20 years, he has smoked approximately 10 cigarettes a day and consumed approximately 80 grams of alcohol once a week. Before the onset of this disease, he had no underlying diseases, his annual check-ups had never indicated thrombocytopenia or abnormal liver function, he had never had any hepatitis or any surgery or any history of blood transfusion before and had not used any drugs or herbs recently.
Eight days prior, the patient displayed weakness and severe nausea without a clear cause. He started experiencing muscle aches all over his body, a 39  C body temperature, a gradual darkening of his urine to a coffee colour, yellow skin, and sclera staining 5 days prior. He visited the neighbourhood hospital. The results of the tests at that time revealed severe thrombocytopenia, abnormal liver function, and inflammation. His symptoms grew worse after 4 days of treatment with piperacillin sodium and tazobactam sodium for injection 4.5 g q8h, compound glycyrrhizin, reduced glutathione, transmetil, ursodeoxycholic acid, and interleukin-11, and he visited our emergency room.
At admission, he was conscious, able to answer questions clearly, his body skin and sclera depth yellow staining, and had no obvious haemorrhagic points or purpura on his body. He also had no obvious cardiopulmonary abnormalities, light tenderness in his xiphoid process, no enlargement of his liver or spleen, Murphy's sign (+), and no abnormalities in the nervous system physical examination. Urgent laboratory testing were as follows: PLT count 13 K/UL, Hb 104 g/L, Ret 52.4 K/UL, RBC count 3.47*10^6/UL, WBC count 10.94 K/UL, CRP 84.9 mg/L, ALT 288 U/L, AST 580 U/L, GGT 130 U/L, ALP 217 U/L, TB 15.76 mg/dL, DB 12.89 mg/dL, PT 14s, INR 1.22, and Cr 1.68 mg/dL. The direct Coombs test was negative, and the COVID-19 nucleic acid test was negative.
Therapies were initiated empirically with intravenous fluids. Glucocorticoids were given intravenously at a dose of 80 mg q12h and were combined with high-dose gamma globulin, meropenem 1 g q8h of anti-infection, ornithine aspartate and adenosine methionine for liver protection, and interleukin-11 to produce platelets. He also received 20 units of platelets and 300 mL of plasma.
On 2022-10-11 at 02:30, the patient suddenly displayed unconsciousness, an elevated heart rate, and limb convulsions, then developed decreased blood pressure and heart rate, and the carotid pulse was unreachable. Cardiopulmonary resuscitation was immediately performed. Approximately 1 minute later, the patient returned to sinus heart rate. After the rescue, we immediately performed blood tests on the patient, and the results showed that the levels of myocardial injury markers and blood potassium were normal. An urgent CT scan showed no obvious brain abnormalities, scattered cholecystitis or inflammation in the two lungs.
Ten hours later, laboratory test results were returned as follows: anti-HEV-IgM antibodies (1.3 S/CO) and anti-HEV-IgG antibodies (5.9 S/CO) were positive, whole blood metagenomics for pathogen detection failed to find any pathogens' DNA or RNA, anti-endothelial cell antibodies (AECA) +1:100. His laboratory tests did not support the diagnosis of hepatitis A or B or C, toxoplasmosis, Treponema pallidum, rubella, cytomegalovirus, herpesvirus and HIV. After a multidisciplinary discussion among doctors in the infectious, haematology and emergency departments, the preliminary diagnosis was 1. Acute hepatitis E; 2. Non-exclusion of haematological diseases; 3. Possibility of autoimmune liver disease; and 4. Cholecystitis. Considering the haematological diseases, we immediately performed bone marrow aspiration and biopsy and peripheral blood smear cell morphology analysis. We found more than 1% schistocytes on the peripheral blood smear (shown in Figure 1). On that day, his haemoglobin level was 8.3 g/dL, and schistocytes on the bone marrow smear were also found, suggesting microangiopathy haemolytic anaemia (MAHA). Laboratory results on 2022-10-10 were used to evaluate the patient via the PLASMIC score: peripheral blood platelet counts 13 K/UL (1 score), indirect bilirubin 2.87 mumol/L (1 score), no advanced cancer (1 score), no history of solid organ transplantation or stem cell transplantation (1 score), International Normalized Ratio (INR) 1.22 (1 score), and Cr 1.68 mg/dL (1 score), with 6 scores in total. It was suggested that the patient had a high risk of TTP. The patient's peripheral blood was sent for testing on 2022-10-12 to determine ADAMTS-13 activity and its inhibitor. The test results came back the following day, showing that ADAMTS-13 activity was 0% and ADAMTS-13 inhibitor was positive. The diagnosis of iTTP was clear. 
We started the primary treatment plan immediately, which included intravenous administration of rituximab 0.6 g once a week, 80 mg of glucocorticoids every 12 hours, and daily plasma exchange. The time between plasmapheresis was gradually increased throughout the course of the treatment, and the dosage of glucocorticoids was decreased from 80 mg q12h (for 6 days) to 40 mg q12h (for 5 days) to 20 mg q12h (for 7 days) to 30 mg qd (for 5 days) to 20 mg qd (at discharge). The patient gradually became conscious, his platelet counts gradually increased, while bilirubin, AST, ALT, and Cr gradually decreased, ADAMTS-13 activity recovered to 100%, and the ADAMTS-13 inhibitor returned negative on 2022-10-18.
The patient's platelet counts reached 254 K/UL on 2022-11-04 following the final plasma exchange and rituximab treatment on 2022-11-03, with a total of 12 plasma exchanges and 4 doses of rituximab. Liver function indicators were also much better than they were previously (shown in Figure 2). Schistocytes were still visible in peripheral blood smears that day, but they were considerably fewer than they had been earlier in the course of treatment. The patient was eligible for discharge and was discharged on 2022-11-05 with oral glucocorticoids (20 mg qd) and ursodeoxycholic acid. 
The patient underwent routine follow-up exams at the hospital over the course of the following five months, which revealed no anomalies.