Introduction: Female hemophilia is an intriguing rare disorder and few larger reports on its genetic etiology are available. While historically the diagnosis was satisfactorily reached by factor VIII activity assays, the clinical and potentially therapeutic heterogeneity of female hemophilia calls for comprehensive molecular diagnosis in each case. Currently, the genetic investigations are not a part of routine, state-funded, diagnostics in Poland, and thus molecular epidemiological data are missing. Aim: We set out to perform a comprehensive genetic analysis of Polish females with hemophilia A. Patients/methods: Eighteen females with hemophilia A (including 2 with severe and 5 with moderate hemophilia phenotype) consented for genetic diagnostics. To establish F8 mutations, we used next-generation sequencing of a panel of genes associated with hematological disorders, standard assays for recurrent intragenic F8 inversions and MLPA when deletions were suspected. When appropriate we also used karyotyping, genomic microarrays and X chromosome inactivation assays. Results: While abnormally skewed X-chromosome inactivation combined with a F8 variant on the active allele was, as expected, the most common genetic etiology, a number of other genetic scenarios were unraveled. This included: misdiagnosis (molecular diagnosis of vWd), Turner syndrome, compound heterozygosity and androgen insensitivity syndrome (a phenotypical 46,XY female with a novel androgen receptor gene mutation). We report 3 novel F8 mutations. Conclusion: Every case of female hemophilia warrants full genomic diagnostics, as this may change the diagnosis or reveal broader morbidity than a coagulation disorder (Turner syndrome, androgen insensitivity, or cardiovascular morbidity that we described previously in a SHAM syndrome carrier).

Home treatment and prophylaxis are standard of care in severe hemophilia, but data in its outcome in Poland is scarce. In particular, the available data on adherence to the prophylaxis in hemophilia is limited; no research was conducted in Poland on this topic despite consistently growing access to prophylactic treatment. We present a large national study on this topic and discuss barriers to effective prophylaxis regimen, which can improve effectiveness of hemophilia treatment in clinical practice.

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Von Willebrand disease (VWD), is the most common hereditary bleeding disorder (HBD) and affects approximately 1-2% of the population. Type 1 accounts for 70-80% of all cases and involves partially reduced levels of functional VWF. It is usually manifested by mild to moderate mucocutaneous bleeding. A 63-year-old patient with multivessel coronary artery disease and diagnosed with Von Willebrand's disease type 1 after a previous NSTEMI infarction (10 days earlier) was admitted to the cardiac surgery department for a planned CABG procedure. The coagulation factor values on admission to the ward were successively (VIII 15%; VWF: Ag 12%). Coronary angiography revealed MV CAD. The patient was consulted with the HEART Team. The decision was made to qualify the patient for CABG using the OPCAB technique. A detailed plan for securing the haemostasis was established. Haemate P 500/1200 and 1000/2400, a lyophilized concentrate of humans VIII and von Willebrand Factors, were secured. During surgery, LITA-LAD and Ao-RCA bridges were performed using Medtronic Starfish® Heart Positioners. In the post-operation period, no complications were noted. Plasma levels of VIII and VW factors were measured daily and antihemorrhagic prophylaxis was given accordingly to measured values. The patient was discharged on the eighth day after surgery in good condition, with the haematological recommendations. Currently, there are no guidelines for the management of patients with Von Willebrand's disease undergoing cardiac surgery. Incorrectly conducted pharmacotherapy may result in an elevated level of VW factor and additional exposure to the occurrence of acute coronary syndromes and heart attacks.