Hemophilia, which is usually hereditary, is characterized by a deficiency or dysfunction of coagulation protein factor VIII (hemophilia A), IX (hemophilia B), or XI (hemophilia C).1 This disorder is defined by impaired blood clotting, which leads to prolonged bleeding and a hemorrhagic diathesis affecting soft tissue, joints, and muscles. The symptomatology of hemophilia generally correlates with the severity of the clotting factor deficiency:2

–     Patients with mild hemophilia (factor level >5% to <40% of normal) often have prolonged bleeding after major trauma or surgery. Spontaneous bleeding may occur occasionally.

–     In moderate hemophilia (factor level 1% to 5% of normal), bleeding usually occurs after trauma, injury, dental work, or surgery. Recurrent joint bleeds may affect up to 25% of patients.

–    In severe hemophilia (factor level <1% of normal), spontaneous bleeding occurs often. Bleeding from the nose, gums, joints, and muscles is frequent. Affected people bruise easily.

Severe hemophilia usually manifests in the first few months of life; however, some children may not have bleeding symptoms until they begin to crawl and walk. Mild or moderate hemophilia can present later in childhood or during adolescence.

Because hemophilia is generally inherited as an X-linked recessive trait, severe forms affect mainly males. However, female carriers may have some manifestations, such as menorrhagia, dysmenorrhea, perimenopausal bleeding, joint complications, and bleeding after childbirth.3–5

Joint Bleeding

The most frequent manifestation (70%-80%) of severe hemophilia is spontaneous intra-articular bleeding.5 The incidence increases with age, from a mean of 21% of all hemorrhages in children 1 to 6 years of age, to 50% in those 10 to 17 years old, and to 60% in persons aged 18 to 65 years.6

Hemarthrosis (haemarthrosis) is a bleeding into joint spaces. human anatomy. Two knee joint: healthy and with injury
Credit: Getty Images

The symptoms usually begin with paresthesia, mild pain, and progressive swelling in the affected joint. The ankles are most frequently affected, followed by the elbows and knees. Less commonly, the shoulder, wrist, and hip joints can be affected.

Bleeding into joints of the fingers or other small joints is relatively infrequent in hemophilia. In contrast, involvement of the small joints is common in rheumatoid arthritis.2 A single joint in which 3 or more spontaneous bleeds occur within 6 consecutive months is considered a “target-joint.”.

Muscle Hemorrhage

Between 10% and 20% of bleeding complications in hemophilia occur within the muscles.5 Spontaneous hemorrhage occurs in the lower legs, gluteal muscles, iliopsoas muscle, and muscles of the forearms, often as a result of injury or a sudden stretch.5,7 These bleeds are generally associated with pain and/or swelling and loss of movement, with tension and tenderness on palpation.

Almost 50% of children with severe hemophilia will have a muscle bleed or hematoma at 6 to 8 months of age, when physical activity increases.7

Iliopsoas hematoma is one of the most common muscular hematomas in patients with haemophilia and can lead to a life-threatening situation if left untreated.5,8 Symptoms may include pain in the thigh, hip, groin, and/or lower back; tenderness in the lower abdomen; and paresthesia due to femoral nerve compression.

Central Nervous System and Intracranial Hemorrhage

The most dreaded bleeding complication in hemophilia is intracranial bleeding. This may occur as early as the neonatal period (1%–4% of cases) and can cause permanent neurologic sequelae.7 Extracranial bleeds, such as subgaleal bleed and cephalohematoma, can be part of the initial presentation.

Most cases of intracranial and extracranial hemorrhage result from traumatic deliveries, particularly those in which forceps, vacuum extraction, or fetal scalp monitors are used. In children and adults, intracranial bleeding usually follows trivial trauma, although it may also be spontaneous. Affected patients can present with falls, confusion, lethargy, meningismus, and coma in severe cases.1

Individuals with a spinal hematoma may present with the sudden onset of severe back pain, paresthesia, or radiculopathies.1

Gastrointestinal/Abdominal Hemorrhage

Occult abdominal bleeding may occur spontaneously or with trauma, involving organs such as the liver, spleen, and kidneys.5 Characteristic symptoms are abdominal pain, especially over the hepatic or splenic area; abdominal distension; melena, hematemesis, and hematochezia (rectal passage of fresh blood); costovertebral angle tenderness; and bladder spasms, suprapubic tenderness, and hematuria.1 In a patient with liver disease, the first sign of gastrointestinal bleeding may be hepatic encephalopathy, whch develops as the failing liver cannot process the high protein load of gastrointestinal bleeding.

Throat and Neck Bleeding

Local disease, trauma, and severe coughing may be causes of throat or neck bleeding, which usually presents as pain or swelling.5 If the bleeding is severe, it can lead to sometimes life-threatening obstruction of airflow.

Similarly, thoracic bleeds may occur spontaneously or following trauma and cause chest pain, shortness of breath, and hemoptysis.1

Oral Hemorrhage

The most common causes of bleeding in the mouth are dental extraction, periodontal disease, and trauma caused by tooth brushing and food abrasion.5,9 Gum bleeding is a sign of inflammatory gum disease (gingivitis) and can be prevented and treated in people with hemophilia. Other, less frequent causes of oral bleeding may include self-injury and shedding of deciduous teeth.

References

1.  Mehta P, Reddivari AKR. Hemophilia. StatPearls. Published January 2021. Accessed July 27, 2021.

2.  Blanchette VS, Srivastava A. Definitions in hemophilia: resolved and unresolved issues. Semin Thromb Hemost. 2015;41(8):819-825. doi:10.1055/s-0035-1564800

3.  Page D. Comprehensive care for hemophilia and other inherited bleeding disorders. Transfus Apher Sci. 2019;58(5):565-568. doi:10.1016/j.transci.2019.08.005

4.  Bryant P, Boukouvala A, McDaniel J, Nance D. Hemophilia A in females: considerations for clinical management. Acta Haematol. 2020;143(3):289-294. doi:10.1159/000503889

5.  Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1-158. doi:10.1111/hae.14046

6.  Fischer K, Collins P, Björkman S, et al. Trends in bleeding patterns during prophylaxis for severe haemophilia: observations from a series of prospective clinical trials. Haemophilia. 2011;17(3):433-438. doi:10.1111/j.1365-2516.2010.02450.x

7.  Peyvandi F, Garagiola I, Young G. The past and future of haemophilia: diagnosis, treatments, and its complications. Lancet. 2016;388(10040):187-197. doi:10.1016/S0140-6736(15)01123-X

8.  Balkan C, Kavakli K, Karapinar D. Iliopsoas haemorrhage in patients with haemophilia: results from one centre. Haemophilia. 2005;11(5):463-467. doi:10.1111/j.1365-2516.2005.01123.x9.  Zaliuniene R, Peciuliene V, Brukiene V, Aleksejuniene J. Hemophilia and oral health.Stomatologija. 2014;16(4):127-131.

Reviewed by Debjyoti Talukdar, MD, on 8/10/2021.