Key points:
1. MGMT promoter methylation predicts response to alkylator treatment in IDH WT GBM, not in IDH mutant.
2. EGFR mutations in CNS disease have not been amenable to anti-EGFR treatment
3. ATRX loss to be a highly specific biomarker of astrocytic lineage
4. ATRX loss is mutually exclusive from 1p/19q co-deletion in oligodendroglioma
5. IDH WT has a worse prognosis
Reference:
1. https://www.sciencedirect.com/science/article/pii/S0716864017300603?via%3Dihub
Severe hemophilia - < 1% factor level
Moderate 1-5%
Mild 5-40%
Three types of prophylaxis
1. Primary: anyone with factor level <1% even before a bleed
2. Secondary: anyone with more than 1 bleed into a target joint irrespective of factor level
3. Continuous and intermittent: mild factor def with levels close to 5% rather than 40% prior to high impact activities, surgery etc
Choice of therapy
The bispecific monoclonal antibody emicizumab is approved for prophylaxis in adults and children (including newborns) who have hemophilia A with or without FVIII inhibitors.
Emicizumab is not derived from plasma and thus is not associated with infectious risk
It should not be used for acute bleeding.
It can be used for prophylaxis in patients with or without inhibitors.
It is a bispecific monoclonal antibody that scaffolds IXa and factor X bringing them together, a function normally carried out by factor 8.
