Week of 19–25 October 2026¶
What is Quebec platelet disorder? How do you make the diagnosis, and what is the management?¶
Answer: Quebec platelet disorder (QPD) is a rare autosomal dominant bleeding disorder. It is caused by a tandem duplication of PLAU (the urokinase plasminogen activator gene) on chromosome 10. This leads to a platelet-dependent gain-of-function defect, with multiple-fold expression of uPA in megakaryocytes and platelets — causing local plasmin-mediated degradation of α-granules and accelerated platelet-localized clot lysis.
- Presentation: the hallmark is delayed bleeding after trauma, surgery, or dental procedures. Patients may have mild thrombocytopenia. PFA is usually normal; aggregation may show reduced epinephrine response. Platelet morphology is usually normal.
- Diagnosis: genetic testing.
- Treatment: antifibrinolytic therapy is the treatment of choice and the only known effective treatment. Unlike other inherited platelet function disorders, platelet transfusions are ineffective, as they do not correct the localized defect.
Source: Quebec platelet disorder: update on pathogenesis, diagnosis, and treatment
What is the rate of thrombosis in Glanzmann patients who are treated with rFVIIa?¶
Answer: Data are very limited, but rFVIIa appears to be safe, with a thrombosis rate lower than that reported when it is used for major bleeding.
This report summarizes data from the Glanzmann's Thrombasthenia Registry (GTR), published literature, and the Novo Nordisk safety database:
Overall efficacy rates were 79 and 88%, respectively, in patients treated for bleeding episodes or for the prevention of bleeding during surgery; effectiveness was generally similar across refractoriness/antibody status categories. Median dose per infusion of rFVIIa was close to that recommended for patients with GT (90 µg/kg).
- Thrombosis in Glanzmann: 1 of 133 patients in the GTR (a deep vein thrombosis, in a patient who also received platelets and other hemostatic treatment). The postmarketing safety database recorded 5 cases with thromboembolic events, 2 in patients aged ≥65 — spontaneous reports, so no rate can be calculated.
- Comparison — off-label use for life-threatening bleeding: in a pooled analysis of 35 placebo-controlled trials (Levi et al., NEJM 2010), arterial thromboembolic events occurred in 5.5% with rFVIIa vs 3.2% with placebo, rising to 9.0% vs 3.8% in those aged ≥65; venous events were similar (5.3% vs 5.7%).
Source: The Use of Recombinant Activated Factor VII in Patients with Glanzmann's Thrombasthenia
How do you prescribe and monitor antithrombin inhibitor therapy?¶
Answer: Fitusiran (siRNA) lowers antithrombin levels. It is approved in the USA for bleeding prophylaxis in people with hemophilia A or B, with or without inhibitors.
- Dosing: 50 mg every 2 months, to target antithrombin activity of 15–35%. Levels are checked at months 1, 3, 5, and 6, with adjustments made to maintain that level; lower the dose if <15%. The drug has a 6-month washout.
- Switching to fitusiran:
When changing from other products to fitusiran, the half-life of the previous product should be considered to ensure complete wash-out. For example:12 hours for recombinant FVIIa (rFVIIa), 48 hours for activated prothrombin complex concentrate (aPCC), 24 hours for standard half-life (SHL) factor VIII (FVIII) or factor IX (FIX) product. There is no data on changing from FVIII mimetic therapy or anti tissue factor inhibitor therapy to fitusiran. The complete washout period for emicizumab is six months.
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Treatment of breakthrough bleeding: dosing is significantly lower (MASAC table below). Real-world evidence is extremely limited; for surgical management, even less so.
Agent Recommended dose Repeat dosing Factor VIII 10 IU/kg (max: 20 IU/kg) Should not repeat in < 24 hours Factor IX (SHL) 20 IU/kg (max: 30 IU/kg) Should not repeat in < 24 hours Factor IX (EHL) 20 IU/kg (max: 30 IU/kg) Should not repeat in < 5 to 7 days aPCC 30 IU/kg (max: 50 IU/kg) Should not repeat in < 24 hours rFVIIa < 45 micrograms/kg Should not repeat in < 2 hours -
Adverse effects:
- Black box warning for thromboembolic events: 2.6% on the 80 mg once-monthly dose (not approved), vs 1.4% on the approved antithrombin-based dosing regimen.
- Counsel on gallbladder disease and hepatotoxicity: cholelithiasis and cholecystitis in 17% on the non-approved fixed-dose regimen, with 4% requiring cholecystectomy (3.8% gallbladder events on the approved regimen).
- Not recommended in hepatic impairment (Child-Pugh A–C).
Source: MASAC Document 295 — Recommendation on the Use and Management of Antithrombin Inhibitor
Do plasma emicizumab levels correlate with risk of bleeding?¶
Answer: No. In this real-world evidence (RWE) prospective study, there was no correlation.
Steady-state plasma emicizumab concentration did not correlate with total or spontaneous annualized treated bleed rate and annualized joint bleed rate or with patient age at enrolment, body weight, or body mass index. Dose capping at 150 mg/wk did not result in lower emicizumab concentrations in the 9 patients with body weight >100 kg.
— study abstract
- The authors call for reconsidering the minimum effective drug concentration, given the lack of correlation.
- In fact, in this study from a resource-limited setting, low-dose emicizumab was effective in preventing bleeding and improving QOL. ABR was comparable to full dose, from this very limited data set.
Source: Plasma emicizumab concentrations and bleeding rates in children and adults with severe hemophilia A