Canada, 26 August 2021, Patriquin et al, New England Journal of Medicine
Three patients with VITT who had positive results on PF4 SRA after ChAdOx1 nCoV-19 vaccination had persistent thrombocytopenia and progressive thrombosis despite initial treatment. At presentation, the d-dimer level in each patient was above the upper limit of quantification of the assay used for measurement.
Patient 1, a previously healthy 45-year-old woman, was admitted 11 days after vaccination with a left renal infarct, bilateral adrenal hemorrhage, subsegmental pulmonary emboli, and right vertebral artery and left internal carotid artery thromboses. The platelet count was 53,000 per cubic millimeter, the activated partial thromboplastin time (aPTT) 40.1 seconds, the international normalized ratio (INR) 1.3, the fibrinogen level 322 mg per deciliter, and the d-dimer level greater than 35,200 μg per liter fibrinogen equivalent units (FEU). The optical density on PF4 ELISA was 2.38.
Patient 2, a previously healthy 46-year-old woman, presented 10 days after vaccination with cerebral venous sinus thrombosis involving the transverse, sigmoid, and superior sagittal sinuses. The platelet count was 16,000 per cubic millimeter, the aPTT 31 seconds, the INR 1.3, the fibrinogen level 120 mg per deciliter, and the d-dimer level greater than 44,000 μg per liter FEU. The optical density on PF4 ELISA was 2.06.
Patient 3, a 48-year-old woman who had had breast cancer several years earlier, presented 16 days after vaccination with thrombosis of the left subclavian artery, thoracic and abdominal aorta, and right internal iliac artery. Arterial thrombi with ischemia and cyanosis was also present in the left leg. One dose of intravenous heparin was given. No recurrence of cancer was found. The platelet count was 37,000 per cubic millimeter, the aPTT 24.5 seconds, the INR 1.2, the fibrinogen level 100 mg per deciliter, and the d-dimer level greater than 9999 μg per liter FEU. The optical density on PF4 ELISA was 2.28.
Therapeutic plasma exchange was initiated (with full plasma for Patients 1 and 3 and half plasma and half albumin for Patient 2). Argatroban treatment was monitored closely before, during, and after the exchanges, and only minimal aPTT variation was found, with no attributable bleeding. Patients 1 and 2 recovered despite their severe presentation. Patient 1 received rituximab after the fifth therapeutic plasma exchange. The platelet count for Patient 2 did not improve until IVIG (0.5 g per kilogram of body weight) was given after therapeutic plasma exchanges 4 through 7. Patient 3 underwent above-knee amputation, but therapeutic plasma exchange most likely prevented more extensive resection. No further thromboses occurred.
VITT that is unresponsive (refractory) to initial treatment requires urgent additional intervention. Because VITT is IgG-mediated, antibody removal or neutralization is plausibly effective, although further study is needed, since therapeutic plasma exchange with the use of plasma as replacement fluid would not elevate IgG to inhibitory levels.4 We suggest consideration of therapeutic plasma exchange for thrombocytopenia and thrombosis that does not begin to abate after 5 days, continuing until platelet normalization. Earlier intervention could be considered.