Essay 18- Coagulation disorder- classification. Hemophilia A and B
Classification of coagulation disorders
Hereditary
- Hemophilia (A+B)
- VWD
Acquired
- Vitamin K deficiency
- Coagulation disorder of liver disease
- Fibrinolytic defects
- DIC
Hemophilia A
Definition
- Hemophilia encompasses a group of inherited disorders that alter blood coagulation.
- Classical hemophilia (AKA hemophilia A), is a hereditary hemorrhagic disorder resulting from a congenital deficit of factor VIII that manifests as protracted and excessive bleeding either spontaneously or secondary to trauma
Etiology
- An X-linked, recessive hemorrhagic trait or gene induces Hemophilia A
- Manifests as a congenital absence or decrease in plasma clotting Factor VIII
- Factor VIII is a pro-coagulation cofactor and robust initiator of thrombin that is essential for the generation of adequate amounts
of fibrin to form a platelet-fibrin plug at sites of endothelial disruption
- Female Hemophilia A gene carriers will transmit the gene to 50% of their male offspring, who will inherit the disorder.
- Female carriers do not manifest symptoms of Hemophilia A but may have lower than usual quantities of Factor VIII.
- Male Hemophilia A patients do not transmit hemophilia to male offspring, but their female offspring will carry the hemophilia gene
Pathophysiology
- When the vascular endothelium sustains an injury, the hemostatic process initiates the coagulation cascade to restore vascular integrity and prevent further bleeding.
- Platelet activation occurs at the site of vascular rupture initiating promulgation of clotting factors and fibrin formation, resulting in a platelet-fibrin plug to inhibit further bleeding
- Factor VIII provides essential enhancement of thrombin generation and promulgation of fibrin formation to inhibit further bleeding.
- It also adheres to von Willebrand factor to protect it from proteolytic degradation
Symptoms
- Severe hemophilia often manifests in the first months of life, whereas mild or moderate hemophilia will present later in childhood or adolescence
- When baby starts to walk (1 year old)
- Hemarthrosis
- Deep muscle hematomas
- Intracranial bleeding without major trauma
- Prolonged oozing or renewed bleeding after it initially stops
- Unexplained GI bleeding or hematuria
- Menorrhagia
- Prolonged bilateral nosebleeds
- Excessive bruising
Diagnosis
- Known family history
- Clinical signs
- Lab tests:
- APTT abnormal
- Factor VIII clotting assay
- PTT is prolonged
- Low levels of factor VIII
- Prenatal- CVS and amniocentesis
Treatment
- Administration of recombinant factor VIII replacement
- Immune tolerance therapy
- Tranexamic acid, epsilon aminocaproic acid, and management of factor VIII inhibitors
- Desmopressin- provides alternative means of increasing plasma factor VIII level