Sex: M
Vaccine: COVID19, COVID19
Symptoms: Platelet factor 4, Portal vein thrombosis, Thrombocytopenia
Clinical narrative: Vaccine-induced thrombotic thrombocytopenia; THROMBOCYTOPENIA; PORTAL VEIN THROMBOSIS; PROGRESSIVE HEPATIC ENCEPHALOPATHY; ASTERIXIS; ACUTE LIVER FAILURE; This spontaneous report was received from from a literature article :This report concerned a 50 year-old male. The patient's height and weight were not reported. The patient received COVID-19 vaccine Ad26.CoV2.S (suspension for injection, intramuscular, batch number and expiry date not reported), once in total on an unspecified date for prophylactic vaccination. No concomitant medications were reported. This patient with alcoholic cirrhosis and obesity presented to a local hospital 21 days after vaccination with a 1 week history of generalized abdominal pain and distention, fatigue and dark urine. In the emergency department, initial laboratory testing revealed platelets of 7 x 10*3/uL, white blood cell count 9.5 x 10*3/uL, hemoglobin 15.7 g/dL, international normalized ratio (INR) 2.0, creatinine 1.1 mg/dL, total bilirubin 2.2 mg/dL, aspartate aminotransferase (AST) 235 U/L, and alanine aminotransferase (ALT) 198 U/L (normal ranges not reported). Fibrin D-dimer was elevated at 23.64 mg/L; FEU and fibrinogen was normal at 211 mg/dL. Computed tomography (CT) imaging revealed cirrhotic liver disease, increasing ascites, and possible thrombi in the portal and hepatic veins. He did not have recent heparin exposure. His baseline platelet count was 113 to 161 x 10*3/uL in the 6 months prior to admission. Given the concern for VITT, platelet factor 4 (PF4) antibody testing and abdominal Doppler ultrasound scans were ordered. Abdominal ultrasonography confirmed complete thrombosis of the right portal vein and partial thrombus in the main portal vein. IgG-specific PF4/polyanion antibody ELISA testing (LIFECODES, Immucor) was positive at 1.578 optical density (OD). The patient was formally diagnosed with VITT and began treatment with argatroban and IVIG on the day of presentation. The patient received IVIG 1 g/kg on days 1 and 2 of admission with 125 mg of intravenous methylprednisolone on day 2. Due to persistent thrombocytopenia, oral prednisone was initiated on day 7 at 120 mg daily on a prolonged taper, with a small but transient increase in his platelet count to 21 x 10*3/uL by day 12. However, on day 14, he developed progressive hepatic encephalopathy and asterixis concerning for acute liver failure. Repeat abdominal Doppler ultrasound on day 15 revealed progression of his portal vein thrombosis despite therapeutic argatroban. On day 16, the patient was transferred to the authors' medical center for consideration of orthotopic liver transplantation. After arrival, the patient was switched to intravenous bivalirudin for anticoagulation and ADAMTS13 functional testing confirmed normal activity. Due to worsening thrombocytopenia to 9 x 10*3/uL despite IVIG and high-dose steroids, the patient received his first dose of rituximab on day 17, followed by two additional doses of IVIG 1 g/kg. P-selectin expression assay (Versiti, Inc.) was performed on day 19 and was negative, with 8% activity with 30 mcg of PF4 and 0% activity with 30 mcg of PF4 and 100 U of heparin. The patient had a robust but again transient response to IVIG, with a maximum platelet count of 72 x 10*3/uL on day 24. On day 24, the patient underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure, with successful recanalization of the portal vein. The patient's platelet count continued to downtrend after day 24. A single unit of platelets was given on day 26 to determine if the patient was platelet-responsive, but there was no response and the patient reached a nadir of 24 x 10*3/uL on day 31. A repeat CT of the abdomen on day 31 demonstrated an intact TIPS with complete resolution of the previous portal vein thrombosis. With no other apparent causes of persistent thrombocytopenia, refractory VITT was considered and a repeat anti-PF4/polyanion ELISA (polyspecific IgG/IgA/IgM, LIFECODES, Immucor) on day 32 was positive at 2.063 OD. Given a persistently positive ELISA, the decision was made to pursue TPE. TPE was performed using the Spectra Optia (TerumoBCT) instrument via an internal jugular dialysis catheter. In each procedure, 6.0 L of plasma (equivalent to approximately 1.1 times the patient's total plasma volume) was exchanged using 100% donor plasma as replacement fluid with intravenous calcium gluconate. After the first TPE on day 32, the polyspecific anti-PF4/polyanion ELISA was reduced to 1.010 OD. Given persistent thrombocytopenia, the decision was made to pursue serial TPE until the PF4 became negative. The PF4 decreased to 0.452 OD after the second TPE on day 36, and then decreased to negative at 0.347 OD after the third TPE on day 37. TPE was generally uncomplicated, apart from a febrile non-hemolytic reaction after the second TPE that did not recur with premedication. The patient had a robust improvement in his platelet count after the three TPE procedures, with a platelet count rising to 57 x 10*3/uL by day 42. A repeat PF4 ELISA on day 42 continued to be negative at 0.267 OD. As the patient's clinical status had significantly improved after the TIPS procedure, with resolution of hepatic encephalopathy and improvement in liver function, the patient was switched to subcutaneous fondaparinux for anticoagulation and was discharged from the hospital on day 44 with a platelet count of 68 x 10*3/uL. At outpatient hematology follow-up on day 49 after presentation, the patient's platelet count had recovered to 124 x 10*3/uL, which was similar to his pre-VITT baseline. The action taken with COVID-19 vaccine Ad26.CoV2.S was not applicable. The patient recovered from vaccine-induced thrombotic thrombocytopenia, thrombocytopenia, portal vein thrombosis, and progressive hepatic encephalopathy, was recovering from acute liver failure, and the outcome of asterixis was not reported. This report was serious (caused/prolonged hospitalization).; Sender's Comments: V0: This case concerns a 50-year-old male with a history of alcoholic cirrhosis, obesity, and baseline platelet count of 113-161x10^3/ul in the prior 6 months who was hospitalized for vaccine induced thrombotic thrombocytopenia (VITT), involving portal vein thrombosis, and resulted in acute liver failure with associated progressive hepatic encephalopathy 21 days after vaccination. He presented to the emergency department with abdominal pain, and dark urine. He was noted to have a platelet count of 7x10^3/uL, AST 235U/L, ALT 198U/L, total Bilirubin 2.2 mg/dL, D-dimer 23.64mg/L, and normal fibrinogen. CT revealed a cirrhotic liver and possible thrombus in the portal and hepatic veins. An anti-PF4 ELISA was positive at 1.578 OD. Treatment included IVIG, argatroban, steroids, and later bivalrudin. The platelet count did not improve, the patient developed progressive hepatic encephalopathy and an ultrasound showed progression of the thrombus. Rituximab was added 17 days after admission. He underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure, with successful recanalization of the portal vein 24 days after admission. A repeat anti-PF4 was 2.063 despite treatment and it was decided to use therapeutic plasma exchange 32 days after admission. The anti-PF4 decreased decrease and became negative by 37 days after admission. The patient was discharged 44 days after admission with a platelet count of 68x10^3/uL and resolved hepatic encephalopathy. On follow-up, 49 days after admission, the platelet count was 124x10^3/uL. Based on evolving knowledge of Thrombosis with Thrombocytopenia Syndrome (TTS, per definition from Brighton Collaboration-BC), the low platelet count and temporal relationship to vaccination, the event of VITT with portal vein thrombosis is assessed to have a plausible relationship with vaccination. The hepatic failure and hepatic encephalopathy are likely secondary to the VITT although the underlying cirrhosis may also have contributed.