Bleeding & Haemophilias Flashcards
A mother brings her 4-year-old boy to see the GP. He has been at school and she has been called by his teacher as a result of an acutely painful knee. His knee has become very swollen and looks bruised. The teacher has asked him several times, but he denies any trauma and she tells the mother that she did not notice him injure his knee.
His mum reports to the doctor that she has noticed he bruises very easily.
The GP does not feel the history fits with abuse and decides to pursue other causes.
He requests a full blood count and clotting studies.
The full blood count appears to be normal. However, the clotting studies show an increased aPTT and a normal PT.
He requests clotting factor assays for factors VIII and IX.
The results show a deficiency of factor VIII.
What is the diagnosis?
Haemophilia A (Factor VIII deficiency)
explain haemophilia
The most common hereditary disease associated with life-threatening bleeding is Hemophilia. There are two primary types of Hemophilia:
Hemophilia A: This type is caused by mutations in the gene for factor VIII, an essential co-factor for factor IX. Hemophilia A is the most common type of hemophilia and is characterized by a deficiency of factor VIII. This deficiency impairs the blood’s ability to clot properly, leading to prolonged bleeding and potentially life-threatening bleeding episodes.
Hemophilia B: Hemophilia B, also known as Christmas disease, is caused by mutations in the gene for factor IX. It is less common than Hemophilia A but shares similar clinical features.
Here are some key points about Hemophilia:
Hemophilia is a hereditary disorder, meaning it is typically passed down from one generation to the next through specific genetic mutations.
It primarily affects males, as the genes responsible for the condition are located on the X chromosome. Females can be carriers of the gene but are usually not affected by the disorder itself.
Hemophilia can vary in severity. The extent of factor deficiency determines the severity of the condition, with mild, moderate, and severe forms.
Spontaneous mutations can occur, leading to the development of hemophilia in individuals without a family history of the condition.
Von Willebrand’s disease, as you mentioned, is another hereditary bleeding disorder, but it is not typically considered life-threatening. It is characterized by a deficiency or dysfunction of von Willebrand factor, which plays a crucial role in platelet adhesion and helps with blood clotting.
explain haemophilia A
Tendency Towards Easy Bruising: Individuals with Hemophilia A have a propensity to experience easy bruising due to impaired blood clotting.
Massive Hemorrhage After Trauma or Surgery: Hemophilia A individuals are at risk of severe bleeding, even after minor injuries or surgical procedures. This is because they lack sufficient factor VIII, a critical clotting factor.
Joints Are Susceptible: Hemophilia A patients are particularly prone to recurrent bleeding into joints, which can result in joint pain, swelling, and long-term joint damage. Weight-bearing joints, such as knees and ankles, are commonly affected.
Deformities: Repeated joint bleeding can lead to joint deformities over time, affecting an individual’s mobility and overall quality of life.
Prolonged aPTT and Normal PT: Hemophilia A is characterized by a prolonged activated partial thromboplastin time (aPTT), indicating an intrinsic pathway clotting abnormality. The prothrombin time (PT), measuring the extrinsic pathway, is typically normal in these patients.
Varying Clinical Severity: The severity of Hemophilia A varies based on the level of clotting factor VIII in the blood. The clinical severity is categorized as follows:
<1% clotting factor activity: Severe Hemophilia A
2-5% clotting factor activity: Moderately severe Hemophilia A
6-50% clotting factor activity: Mild Hemophilia A
Caused by Heterogeneity in Causative Mutations: Hemophilia A can be caused by a variety of mutations in the F8 gene, which is responsible for producing factor VIII. The specific genetic mutation and its impact on factor VIII production can vary among individuals, leading to differences in clinical presentation and severity.
explain the primary treatment approach for haemophilia A
In the case of Hemophilia A, which is characterized by a deficiency of factor VIII, the primary treatment approach is to replace the missing or deficient factor VIII. This is typically achieved through factor VIII concentrates, which are given as infusions to restore the clotting ability of the blood.
Factor VIII Replacement: Factor VIII concentrates contain the missing clotting factor and are administered intravenously. The goal is to increase the levels of factor VIII in the bloodstream, allowing for proper blood clotting. This treatment can be administered on-demand to address bleeding episodes or as a prophylactic measure to prevent bleeding.
However, it’s important to note that in some cases, individuals with Hemophilia A may develop inhibitors, which are autoantibodies that neutralize the infused factor VIII. This can make treatment more challenging, as higher doses of factor VIII or alternative treatments may be required.
Tranexamic Acid: Tranexamic acid is an antifibrinolytic medication that can be used to help prevent the breakdown of blood clots. It is sometimes used in combination with factor replacement therapy to manage bleeding episodes or as a prophylactic measure during surgical procedures or dental work. Tranexamic acid helps stabilize blood clots and reduce bleeding.
explain desmopressin
Desmopressin, also known by its brand name DDAVP (1-deamino-8-D-arginine vasopressin), is a synthetic analogue of antidiuretic hormone (ADH). One of its important clinical uses is to increase the release of von Willebrand factor (vWF) in the body.
vWF is a protein that plays a critical role in blood clotting, as it helps platelets adhere to damaged blood vessels and stabilize blood clots. People with von Willebrand disease, a bleeding disorder characterized by a deficiency or dysfunction of vWF, can benefit from desmopressin treatment.
When desmopressin is administered to individuals with von Willebrand disease or mild hemophilia A, it stimulates the release of stored von Willebrand factor from endothelial cells and can temporarily increase the levels of vWF in the bloodstream. This can help improve blood clotting and reduce the risk of bleeding, making it a valuable treatment option for some individuals with these bleeding disorders.
Desmopressin is typically administered by intravenous (IV) injection or nasal spray. It is an important part of the treatment regimen for those with mild to moderate von Willebrand disease or mild hemophilia A. However, it may not be effective for individuals with severe forms of these conditions or for those with inhibitors to factor VIII (in the case of Hemophilia A). Treatment plans should always be tailored to the specific needs and medical history of the patient under the guidance of a healthcare provider.
explain the key points regarding the diagnosis of Hemophilia A (Factor VIII deficiency) and Hemophilia B (Factor IX deficiency)
Hemophilia A (Factor VIII Deficiency):
Hemophilia A is a hereditary bleeding disorder caused by a deficiency of clotting factor VIII (FVIII).
It is diagnosed by measuring the levels of factor VIII in the blood.
The diagnosis is confirmed when factor VIII activity is significantly reduced, typically less than 1% of normal levels.
Hemophilia A is often diagnosed through specialized coagulation tests and genetic testing.
Hemophilia B (Factor IX Deficiency - Christmas Disease):
Hemophilia B, also known as Christmas disease, is another hereditary bleeding disorder.
It is caused by a deficiency of clotting factor IX (FIX).
The diagnosis involves measuring the levels of factor IX in the blood.
Hemophilia B is confirmed when factor IX activity is significantly reduced, typically less than 1% of normal levels.
Like Hemophilia A, the diagnosis of Hemophilia B is established through coagulation tests and genetic testing.
Both Hemophilia A and Hemophilia B are X-linked recessive disorders, which means they primarily affect males. Females can be carriers of the genes for these conditions but are typically not affected.
explain haemophilia B
Low Incidence: Hemophilia B is relatively rare, with an incidence of approximately 2 cases per 100,000 males.
Clinical Presentation: The clinical presentation of Hemophilia B is very similar to that of Hemophilia A (Factor VIII deficiency). Patients with Hemophilia B often experience a prolonged activated partial thromboplastin time (aPTT) but have a normal prothrombin time (PT). These laboratory findings indicate an intrinsic pathway clotting abnormality.
Treatment: The primary treatment for Hemophilia B is to replace the missing or deficient clotting factor IX. This is typically achieved through infusions of recombinant factor IX or plasma-derived factor IX concentrates. These treatments aim to increase the levels of factor IX in the bloodstream, allowing for proper blood clotting.
Hemophilia B can range in severity from mild to severe, depending on the level of factor IX activity in the blood. Patients with severe Hemophilia B may experience spontaneous bleeding episodes, while those with milder forms may have fewer bleeding episodes and may only require treatment during traumatic injuries or surgeries.
