A 50-year-old man with alcoholic cirrhosis and obesity presented to a local hospital with 1 week of generalized abdominal pain and distention, fatigue, and dark urine. In the emergency department, initial laboratory testing revealed platelets of 7 × 103/µL, white blood cell count 9.5 x 103/µL, hemoglobin 15.7 g/dL, INR 2.0, creatinine 1.1 mg/dL, total bilirubin 2.2 mg/dL, AST 235 U/L, and ALT 198 U/L. 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 113–161 × 103/µL in the 6 months prior to admission. He had received the Ad26.COV2.S COVID-19 vaccine 21 days prior to presentation.
Given the concern for VITT, PF4 antibody testing and abdominal Doppler ultrasound 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 OD. The patient was formally diagnosed with VITT and began treatment with argatroban and IVIG on the day of presentation.
The patient’s platelet trend and VITT treatments over his hospital course are depicted in Fig. 1. 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 × 103/µL 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 our 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 × 103/µL 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 × 103/µL on day 24. On day 24, the patient underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure, with successful recanalization of the portal vein.
As shown in Fig. 1, 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 × 103/µL 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 ~ 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. As shown in Fig. 1, 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 × 103/µL by day 42 (Fig. 1). 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 × 103/µL.
At outpatient hematology follow-up on day 49 after presentation, the patient’s platelet count had recovered to 124 × 103/µL, which is similar to his pre-VITT baseline.