Bleeding disorders

• Severe liver disease (eg, cirrhosis, fulminant hepatitis, acute fatty liver of pregnancy) may disturb hemostasis by impairing clotting factor synthesis. Because all coagulation factors are made in the liver (by hepatocytes and hepatic sinusoidal endothelial cells), both the prothrombin time (PT) and partial thromboplastin time (PTT) are prolonged in severe liver disorders. Occasionally, decompensated liver disease also causes excessive fibrinolysis and bleeding due to decreased hepatic synthesis of alpha 2-antiplasmin.
• Haemophilia A is caused by mutations in the factor VIII gene, whilst haemophilia B is caused by mutations in the factor IX gene. Both genes are mapped to the X chromosome and are passed down in a recessive fashion, so males with a single mutation will have the disease, whilst females, with two X chromosomes, will be carriers for the disease.
• Occasionally, haemophilia can be acquired due to the formation of autoantibodies targeting factor VIII or IX, or as a result of malignancy.
• There are three types of hemophilia that are caused by genetic mutations in clotting factor genes and can be passed on from parent to child. Hemophilia A is a deficiency in factor VIII, hemophilia B is a deficiency in factor IX, and hemophilia C is a deficiency in factor XI.
• All types of hemophilia affect the intrinsic pathway.
• Von willibrand factor is a blood glycoprotein that promotes hemostasis and platelet adhesion. Von Willebrand disease is the most common bleeding disorder and is characterized by a deficiency in von Willebrand factor due to an autosomal dominant genetic mutation. The von Willebrand factor is mostly involved in primary hemostasis where it helps platelets stick together. The factor also plays a role in secondary hemostasis by helping stabilize factor VIII.
• Von Willebrand disease is a common entity in which the associated deficiency of factor VIII is frequently insufficient to prolong the PTT. Patients who have normal initial test results, along with symptoms or signs of bleeding and a positive family history, should be tested for von Willebrand disease by measuring plasma von Willebrand factor (VWF) antigen, ristocetin cofactor activity (an indirect test of VWF function), VWF multimer pattern, and factor VIII levels.
• Vitamin K is involved in essential processes such as blood clotting, bone metabolism, and cardiovascular health. Vitamin K is a cofactor required to make factors II, VII, IX, and X functional. Therefore, vitamin K deficiency affects all three pathways. The absence of vitamin K in the human body can result in a spectrum of complications, including bleeding disorders, impaired bone development, and potential cardiovascular risks.
• Vitamin K deficiency can occur due to various factors, such as insufficient consumption of vitamin K-rich foods, including leafy greens and fermented products, which can be a primary cause. Certain medical conditions that affect fat absorption, such as celiac disease or inflammatory bowel diseases, can impede vitamin K absorption. Furthermore, prolonged use of antibiotics can disrupt the gut bacteria responsible for synthesizing vitamin K. Medications that interfere with vitamin K metabolism, such as blood thinners, can also contribute to deficiency.
• Drugs that increase bleeding risk:

  Anticoagulants

  Antiplatelets

  NSAIDs

  SSRIs

  SNRIs
• Hemophilia affects:

  ·       A – Deficient factor VIII

  ·       B – Deficiency in factor IX

  ·       C – Factor XI

  ·       All affect intrinsic pathway
• Von Willibrand disease:

  ·       Cannot stabilise factor VIII

  ·       No platelet adhesion
• Vitamin K deficiency:

  Can’t make factors

  ·       II

  ·       VII

  ·       IX

  ·       X

  ·       Affects all three pathways
• Hemophilia management

  Prophylaxis:

  ·       Prophylactic factor infusions

  ·       Avoid competitive contact sports and unnecessary manual labour

  ·       Vaccinated against hepatitis A and hepatitis B

  Acute bleeds:

  ·       Factor infusions, fresh frozen plasma or cryoprecipitate

  ·       Haematomas and haemarthroses require analgesic treatment – not NSAIDs or opiates

  ·       Mild haemophilia A patients with desmopressin (DDAVP), which stimulates von Willebrand factor (vWF), which in turn promotes factor VIII activity

  Genetic counselling
• Von Willibrand disease management

  Non-concentrate therapies tranexamic acid and desmopressin or concentrates containing either high purity VWF alone or intermediate purity concentrates containing FVIII-VWF.
• Vitamin K deficiency management

  Oral dose vitamin K1 or subcutaneous injection, IV administration for severe bleeding.

  In newborns prophylaxis typically involves administering 0.5 to 1 mg of vitamin K1 via intramuscular injection within the first hour of birth.