Thrombocytopenia with and without thrombosis following COVID-19 vaccination: long-term management.

Background: Since administration of COVID-19 vaccines, there has been growing evidence of thrombotic and thrombocytopenic events following vaccination. However, there remains limited data on long-term management of these adverse hematologic events. Key Clinical Question: We report on 9 patients presenting with thrombocytopenia following COVID-19 vaccination, with 4 subsequently diagnosed with vaccine-induced thrombocytopenia and thrombosis (VITT) and 5 with immune thrombocytopenia. Clinical Approach: A retrospective chart review was completed for adults >18 years of age presenting to a tertiary care center with new-onset thrombocytopenia occurring 4 to 42 days following COVID-19 vaccination. Presenting symptoms, laboratory investigations, and response to treatment are described. Conclusion: Two of 4 patients with VITT developed refractory thrombocytopenia successfully treated with intravenous immunoglobulin, corticosteroids, and plasma exchange therapy. Patients with VITT remained on anticoagulation for at least 9 months due to persistently positive diagnostic tests. Four of 5 patients with immune thrombocytopenia received intravenous immunoglobulin and corticosteroids with good recovery. Patients who received a subsequent COVID-19 mRNA vaccine had no adverse hematologic effects.

Major bleeding during secondary prevention of venous thromboembolism in patients who have completed anticoagulation: a systematic review and meta-analysis.

BACKGROUND: The risk of major bleeding in patients who have completed anticoagulation therapy for unprovoked venous thromboembolism (VTE) is unknown. OBJECTIVE: To report the major bleeding and fatal bleeding rates in patients randomized to placebo or observation (i.e. no anticoagulation therapy) for the secondary prevention of recurrent VTE. PATIENTS AND METHODS: We performed a systematic review and meta-analysis of the literature to summarize the rates of major bleeding and fatal bleeding in patients randomized to placebo or observation during the secondary prevention of VTE. Unrestricted searches of MEDLINE (January 1, 1950 to August 31, 2013), Embase (January 1, 1980 to August 31, 2013), and the Cochrane Register of Controlled Trials using the OVID interface were conducted. Publications from potentially relevant journals were also searched by hand. We used a random-effects model to pool study results and I(2) testing to assess for heterogeneity. RESULTS: The analysis included 11 studies and 3965 patients who were followed for a median of 24 months. The overall pooled major bleeding rate was 0.45 per 100 patient-years (95% CI 0.29-0.64, I(2) = 0%), and the overall pooled fatal bleeding rate was 0.14 per 100 patient-years (95% CI 0.057-0.26, I(2) = 0%). CONCLUSIONS: Patients not receiving anticoagulant therapy for the secondary prevention of VTE experience major bleeding events, and this may have an impact on recommendations for extended treatment in this patient population.

FLI1 polymorphism affects susceptibility to cutaneous leishmaniasis in Brazil.

Mapping murine genes controlling cutaneous leishmaniasis (CL) identified Fli1 as a candidate influencing resistance to L. major and enhanced wound healing. We examine FLI1 as a gene controlling CL and mucosal leishmaniasis (ML) caused by L. braziliensis in humans. Intron 1 single nucleotide polymorphisms tagging promoter and enhancer elements were analysed in 168 nuclear families (250 CL; 87 ML cases) and replicated in 157 families (402 CL; 39 ML cases). Robust case-pseudocontrol logistic regression analysis showed association between allele C (odds ratio (OR) 1.65; 95% confidence interval 1.18-2.29; P=0.003) of FLI1_rs7930515 and CL in the primary sample that was confirmed (OR 1.60; 95% confidence interval 1.10-2.33; P=0.014) in the replication set (combined P=1.8 × 10(-4)). FLI1_rs7930515 is in linkage disequilibrium with the functional GAn microsatellite in the proximal promoter. Haplotype associations extended across the enhancer, which was not polymorphic. ML associated with inverse haplotypes compared with CL. Wound healing is therefore important in CL, providing potential for therapies modulating FLI1.

Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis.

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004