Deterioration of vaccine-induced immune thrombotic thrombocytopenia treated by heparin and platelet transfusion: Insight from functional cytometry and serotonin release assay.

We report a case of a 62-year-old man who developed cerebral venous sinus thrombosis with subarachnoid hemorrhage and concomitant thrombocytopenia, which occurred 13 days after ChAdOx1 nCov-19 injection. The patient died in the intensive care unit after heparin infusion and platelet transfusion. The key clinical purpose of this case report is to better understand how to confirm vaccine-induced immune thrombotic thrombocytopenia (VITT). VITT diagnosis was made using 14C-serotonin release and flow cytometry evaluating activation and platelet microvesicles on washed platelets. Four control patients were examined: a patient with heparin-induced thrombocytopenia (HIT), two patients with thrombotic events without thrombocytopenia after ChAdOx1 nCov-19 or BNT162b2, and a patient with suspected HIT and an excluded diagnosis. We evidenced in the VITT case a high level of IgG anti-platelet factor 4-heparin antibodies associated with a high level of platelet activation in the absence of heparin. Conversely, the functional assays were negative in the patients with thrombosis without thrombocytopenia.

Genotype-Phenotype Relationships in a Large French Cohort of Subjects with Inherited Protein C Deficiency.

Inherited protein C (PC) deficiency caused by mutations in the PROC gene is a well-known risk factor for venous thromboembolism. Few studies have investigated the relationship between PROC genotype and plasma or clinical phenotypes. We addressed this issue in a large retrospective cohort of 1,115 heterozygous carriers of 226 PROC pathogenic or likely pathogenic mutations. Mutations were classified in three categories according to their observed or presumed association with type I, type IIa, or type IIb PC deficiency. The study population comprised 876 carriers of type I category mutations, 55 carriers of type IIa category mutations, and 184 carriers of type IIb category mutations. PC anticoagulant activity significantly influenced risk of first venous thrombosis (p trend < 10-4). No influence of mutation category on risk of whole or unprovoked thrombotic events was observed. Both PC anticoagulant activity and genotype significantly influenced risk of venous thrombosis. Effect of detrimental mutations on plasma phenotype was ambiguous in several carriers, whatever the mutation category. Altogether, our findings confirm that diagnosing PC inherited deficiency based on plasma measurement may be difficult but show that diagnosis can be improved by PROC genotyping.