Hemophilia

Genetics and mechanism of development

Hemophilia is inherited in an X-linked (recessive) manner. Females play the primary role in preserving and transmitting the pathological gene. They act as asymptomatic or mildly symptomatic carriers (conducers) and transmit the mutant X chromosome to half of their sons, who inevitably develop the disease. Meanwhile, daughters have a 50% chance of becoming new carriers. Interestingly, despite having a healthy second X chromosome, some heterozygous female carriers may also exhibit signs of hemostatic dysfunction.

The pathogenesis is based on a critical failure in the intrinsic pathway of blood clotting — the process of thromboplastin formation is impaired. A key clinical feature of the disease is the occurrence of specifically delayed, rather than immediate, bleeding following trauma. This is because the patient's own platelet count and function are completely normal. Immediately after vascular injury, the primary (platelet) hemostatic link successfully activates, forming a temporary primary plug. However, due to a defect in plasma factors, a full-fledged fibrin clot is not created, and the primary thrombus rapidly lyses. As a result, severe coagulopathic bleeding begins after some time.

Clinical presentation and complications

Clinical manifestations vary depending on the child's age. In newborns, the disease may manifest as prolonged bleeding from the umbilical cord stump, extensive cephalhematomas, and slightly later, prolonged bleeding during the teething period. For older children, large hematomas on the trunk and extremely painful intra-articular hemorrhages, known as hemarthroses, are most characteristic. In general, a hematoma bleeding type is typical for the disorder.

Persistent hemorrhages lead to severe complications:

• Articular: frequent recurrent hemarthroses trigger a cascade of changes leading to the development of secondary rheumatoid arthritis.
• Bone: blood entering bone tissue provokes the formation of foci of aseptic necrosis.
• Tissue and neurological: massive hematomas in intermuscular and interfascial spaces can mechanically compress peripheral nerve trunks, provoking paresis, as well as disrupt the function of vital internal organs.

Classification and diagnosis

The severity of the clinical course directly correlates with the residual concentration of antihemophilic factor (FVIII or FIX) in the blood:

• Severe degree: factor level < 1%.
• Moderate degree: activity ranging from 1% to 5%.
• Mild degree: factor concentration is from 5% to 40%.

Diagnostic workup is based on three data blocks: evaluation of a burdened family history, analysis of specific coagulogram abnormalities, and exclusion of other hemostatic disorders. The coagulogram records prolongation of overall blood clotting time and aPTT (activated partial thromboplastin time), as well as a decrease in plasma clotting factor concentrations. At the same time, parameters of the vascular-platelet link (bleeding time, platelet count, endothelial capillary fragility tests) remain normal, which is critically important for differential diagnosis.

Principles of therapy

The mainstay of management for such patients is lifelong replacement therapy with specific clotting factor concentrates (vWF/FVIII). The preparations must be highly purified and undergo mandatory virus inactivation. A crucial rule: physicians strongly discourage frequent switching of product brand names to minimize the risk of antibody development and inhibitor hemophilia.

The following treatment strategies are distinguished:

1. Prophylactic treatment (priority): regular infusions (in severe forms, up to 3 times a week) to maintain factor activity at the 5% level. This prevents spontaneous bleeding and disability.
2. Home therapy: immediate administration of a hemostatic agent at the first signs of bleeding or trauma. Requires training for parents and the child.
3. On-demand therapy: strictly intravenous bolus administration of a freshly prepared solution immediately after reconstitution once a hemorrhagic episode has already developed.

Treatment of hemarthroses requires a separate algorithm. In the acute period, strict limb immobilization for 3–5 days is indicated. Joint puncture is performed to aspirate accumulated blood and lavage the cavity. To suppress inflammation, glucocorticosteroids are injected intra-articularly. At the rehabilitation stage, massage, physiotherapy, and exercise therapy (physical therapy) are mandatory to restore function.

Class and exam questions

What else to study on this topic

• Features of hemophilia manifestation in the neonatal period
• Differential diagnosis of hemophilia based on coagulogram parameters
• Algorithm for managing acute hemarthrosis and arthritis prevention
• Pathogenesis of the development of inhibitor hemophilia
• Principles of home therapy and patient education

Other topics in "Chapter 10. Diseases of the Blood and Blood-Forming Organs"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.