hemostasis. These disorders can be inherited, acquired, or caused by certain drugs that adversely affect hemostasis. The various disorders will be discussed according to whether they are the result of coagulation disorders, platelet dysfunction, or platelet quantity. A deficiency in factor VIII results in hemophilia A, and a deficiency in factor IX causes hemophilia B. Hemophilia appears in one of every 10,000 male live births and is X-linked, meaning that the gene for the disease is on the X chromosome. Males born to a woman who is a carrier for hemophilia have a 50% chance of developing the disease. Hemophilia A is the more common type, occurring in 85% to 90% of cases, with hemophilia B occurring in 10% to 15% of cases (Rojas et al., 2022). Hemophilia’s continued presence in the gene pool is accounted for by variations in severity and the gene’s frequency of mutation. Factors VIII and IX are both required for the activation of factor X in the coagulation cascade that forms the fibrin clot. Clinically, patients with hemophilia A or B will bruise easily, experience spontaneous muscle and joint hemorrhage, and bleed excessively following trauma and surgical procedures. The two types of hemophilia are clinically indistinguishable, and severity is determined by residual circulating factors. Nonspontaneous mild hemophilia results in delayed-onset bleeding after trauma or surgery. Moderate hemophilia is characterized by bleeding into muscles and into joint spaces following minor trauma or surgery. The most life-threatening form is severe hemophilia, which results in spontaneous bleeding internally and within joint spaces (Regling et al., 2023). Of the inherited coagulation disorders, von Willebrand disease (vWD) is the most common and occurs in 1% of the general population, affecting males and females equally (i.e., it is not a sex-linked disorder). The von Willebrand factor (vWF) is a glycoprotein that is produced by endothelial cells and aids in platelet adhesion and factor VIII activation. This disease falls into three types. Type 1 is the most common and is inherited as an autosomal dominant gene. Deficient vWF results in unbound factor VIII being destroyed. Factor VIII is associated with hemophilia A; therefore, patients with vWD might show signs and symptoms similar to hemophilia A. In type 1 disease, there is a partial deficiency of vWF. Type 2 variants (2A, 2B, 2N, 2M) are characterized by various qualitative defects in vWF. Type 3, the most severe type, is inherited as an autosomal recessive gene leading to severe vWF deficiency (Corrales- Medina et al., 2023). Clinically, children with vWD will exhibit bruising and nosebleeds resulting from diminished platelet adhesion. Serious bleeding can occur in these patients after surgical procedures or trauma. People with severe forms of vWD will likely have a family history of recurrent mucosal bleeds. Patients with vWD tend to have a prolonged activated partial thromboplastin time (aPTT), normal prothrombin time (PT), and normal platelet count, but prolonged bleeding time. A measurement of the von Willebrand factor can be done to confirm the disease. The intrinsic pathway in the coagulation cascade is measured by partial thromboplastin time (PTT), and the extrinsic pathway is measured by PT. The INR is the standard used to report PT values (Corrales- Medina et al., 2023; Punjadath et al., 2022). doses or continuous infusion. For patients with mild hemophilia, a factor VIII promoter called desmopressin acetate can be enough to raise the level of factor VIII for adequate hemostasis for minor surgical procedures (Little et al., 2018). A serious complication of factor replacement therapy is the potential development of inhibitors as the
yet related processes: The coagulation cascade and the platelet activation pathway. An insult to the endothelial (interior) layer of blood vessels exposes the glycoprotein tissue factors to the circulating blood, setting off the coagulation cascade. A succession of proteolytic events (breakdown of proteins) and activations of soluble enzymes takes place. The cascade can start out on one of two paths, depending on the nature of the insult. The intrinsic pathway starts with damage to the endothelial surface of blood vessels, leading to activation of factor X. The extrinsic, or tissue factor, pathway is initiated via trauma such as a cut from a sharp object, and activation of factor VII. The pathways of the cascade converge when factor X becomes activated. This factor causes transformation of prothrombin into thrombin. Thrombin initiates the activation of fibrin and also catalyzes the cross-linking of fibrin in the formation of the hemostatic plug that acts as a powerful local platelet activator. (See Figure 1.) Figure 1: Coagulation Cascade
Note. From Western Schools, @2019. In the platelet activation pathway, damage to the endothelial lining initiates adhesion of platelets to numerous adhesive proteins stored in endothelial cells. Derived from megakaryocytes, platelets are the smallest cells in the circulating blood. They possess surface receptors that modulate their adhesion and activation. Platelets contain membrane phospholipase C that is activated to form diglyceride. In turn, diglyceride is converted to arachidonic acid, a substrate for prostaglandin synthase. The prostaglandin is required for ADP-induced aggregation and release that induces platelet adhesion. Bleeding disorders are conditions that alter the ability of blood vessels, platelets, and coagulation factors to maintain Medical considerations/current medical therapies Treatments for hemophilia include intravenous replacement of factor VIII (for hemophilia A) or IX (for hemophilia B) that are prepared using recombinant factor concentrates or purified plasma. Prior to surgical procedures, patients receive factor concentrate to raise their plasma concentrations, and they continue to receive intermittent
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