F8 gene
OMIM#306700 https://omim.org/entry/306700
Also known as: Factor VIII deficiency
1. The disease:
A rare genetic haematological disorder characterized by spontaneous or prolonged haemorrhages due to factor VIII deficiency.
2. The symptoms:
In general, onset of bleeding anomalies occurs when affected babies start to learn to walk. Bleeding most often occurs in joints (hemarthroses) and muscles (hematomas), but any site may be involved following trauma or injury. Spontaneous haematuria is a frequent and highly characteristic sign of the disorder. However, newborns with haemophilia are at risk of intra- or extracranial haemorrhage and other bleeding complications. Lack of early signs or symptoms does not exclude the diagnosis.
- The severity of clinical manifestations depends on the extent of factor VIII deficiency in both males and females (in rare abnormal cases).
- If the biological activity of factor VIII is below 1 IU/dL, haemophilia is severe and manifests as frequent spontaneous haemorrhages and abnormal bleeding because of minor injuries or following trauma, surgery or tooth extraction (severe haemophilia A).
- If the biological activity of factor VIII is between 1 and 5 IU/dL, haemophilia is moderately severe with abnormal bleeding because of minor injuries or following trauma, surgery or tooth extraction but spontaneous haemorrhage is rare (moderately severe haemophilia A).
- If the biological activity of factor VIII is between 5 and 40 IU/dL, haemophilia is mild with abnormal bleeding because of minor injuries or following trauma, surgery or tooth extraction but spontaneous haemorrhage does not occur (mild haemophilia A).
3. Actions to take in case of early diagnosis:
- Correlation with other exams as prolonged coagulation times (activated partial thromboplastin time, aPTT), measuring factor VIII activity and antigen levels.
- Haemophilia is a lifelong disease requiring lifetime management and regular follow-up with a Haematology Center. Management is provided by multidisciplinary comprehensive haemophilia care centers.
- Replacement therapy consisting of administration of the missing factor VIII is the most straight forward treatment approach, using plasma-derived or recombinant factor VIII concentrates. Treatment may be administered after a haemorrhage or prophylactically, to prevent bleeding. The most frequent complication is the production of inhibitory antibodies against the administered coagulation factor.
- Agents/circumstances to avoid: Circumcision of at-risk males until hemophilia A is either excluded or treated with factor VIII concentrate regardless of severity; intramuscular injections; activities with a high risk of trauma, particularly head injury; cautious, if any, use of medications and herbal remedies that affect platelet function, including aspirin.
- Recently, bioengineered prolonged half-life factor VIII products and non-factor therapeutics such as emicizumab (a bispecific antibody that mimics the function of factor VIIIa) were approved. Emicizumab is approved for bleeding prophylaxis in hemophilia A with and without inhibitors. Other non-factor therapies and gene therapy are under development.
- Surgical interventions, most notably orthopaedic surgery, may be carried out but should be conducted in specialized centers.
- The pattern of inheritance is X-linked and genetic counselling should be offered to at-risk family members.