Hemophilia

Hemophilia presents at birth or during childhood as episodes of uncontrollable bleeding from wounds and injuries. Several episodes of frequently occurring bleeding from gums, nose (epistaxis), etc and easy bruising are characteristic findings. Petechiae are characteristically absent. There is massive hemorrhage following trauma. Bleeding into joints, particularly as a result of trauma, is a common finding and is known as hemarthrosis. Hemophilic arthrosis is associated with acute pain during bleeding episodes and the presence of chronic pain caused by arthritic complications of repeated bleeding into joints [9].

Laboratory Tests:

• Complete blood count
• Prothrombin time
• Activated partial thromboplastin time (APTT)
• INR and clotting factors assay
• Screening transfusion-associated diseases like HIV
• Blood hematocrit and serum ferritin levels

Imaging

Imaging studies are not required for diagnosing hemophilia. However, in case of hemarthrosis, radiography and CT scans may be performed to visualize the hematoma.

Test results

A competent history is generally sufficient to suspect hemophilia and the diagnosis can be confirmed with the help of laboratory tests. The subtype of this disease is also determined to begin appropriate treatment.

Prophylactic treatment

Prophylactic treatment may be begun right after a child has been diagnosed of hemophilia. It can be started at as young as the first year of age. Prophylaxis, which includes administration of FVIII (or FIX) in regular doses of carefully calculated amounts, has been shown in many studies to prevent or at least reduce the progression of damage to target sites, such as joints [10].

Pharmacological treatment

Previously fresh frozen plasma and cryoprecipitate were used to treat this condition but now various concentrates of FVIII/FIX are available and have become the treatment of choice. Inhibitors of antibodies against FVIII/FIX can also be given as adjunct therapy to promote optimum effect of the administered FVIII/FIX. Although replacement therapy with plasma-derived or recombinant FVIII is proven to be life-saving for patients with Hemophilia A , such therapy is a life-long treatment rather than a cure for the disease [3]. Administration of desmopressin or DDAVP, instead of FVIII is an effective treatment for mild to moderate hemophilia.

Hemophilia persists for life. It does not necessarily progress or worsen, but it tends to stay all the same. Treatment and appropriate management can help reduce bleeding episodes and promote a long, healthy life. Mortality is associated with hemorrhage and chronic systemic infections like that from HIV or Hepatitis virus. Indeed, AIDS is the most common cause of death in patients with severe hemophilia [8].

Hemophilia A results from an insufficiency of clotting factor VIII (FVIII) [3]. The insufficiency of the factor could be due to point mutations in factor VIII that may impair the proper function of the clotting protein or due to an inversion in the X chromosome that leads to complete loss of production of FVIII.

Hemophilia B is also an X-linked recessive disorder which results in decreased production or, in severe cases, complete absence of clotting factor IX. This disease is also known as Christmas disease, after the first patient identified with this condition. It is also due to mutations in the gene controlling the FIX or the X chromosome itself.
Acquired hemophilia is a very rare idiopathic subtype of this disease and it usually occurs in immunocompromised patients.

Incidence

According to the World Federation of Hemophilia, the ratio of hemophilia A is 1:10,000 live births and 1:50,000 live births for hemophilia B. Hemophilia A is the most common X-linked disease in the world.

Age

Hemophilia is an inherited disorder so it usually presents at birth or early life. Acquired hemophilia occurs in immunocompromised patients so it can occur at any age.

Sex

Hemophilia is an X-linked disorder so it is much more common in males than in females. However, females are usually asymptomatic or mildly symptomatic carriers. A study revealed that 5 out of a group of 55 mild hemophiliacs were females [4].

Hemophilia A

Hemophilia A is a heritable disorder characterized by deficiency of clotting factor VIII (FVIII), which predisposes patients to bleeding events [5]. It is the most common type, accounting to 80% of hemophilia cases. FVIII acts directly on FIX in the intrinsic pathway of the coagulation cascade to enable clotting and a deficiency of FVIII will lead to an inability of this pathway to proceed, resulting in bleeding dyscrasias.

Hemophilia B

Hemophilia B is an X-linked genetic disease caused by mutation of the gene for clotting factor IX (FIX). It has an incidence of approximately 1 every 30,000 male births in all populations and ethnic groups. It may lead to spontaneous bleeding episodes in severe cases which may be life threatening. If it is left untreated, most patients die from bleeding complications before they reach 25 years of age [6].

Acquired hemophilia

Acquired hemophilia is an extremely rare bleeding disorder caused by autoantibodies against factor VIII (FVIII), in patients without any previous history of hemophilia. Spontaneous bleeding in various sites of the body is the most common clinical presentation of this condition [7]. It is usually idiopathic but it can be associated with adverse drug reactions or vascular disease.

Classification based on severity

On the basis of how severe the disease is, it can be classified into 3 subtypes:

• Mild hemophilia: FVIII/FIX between 6% and 50% of normal levels.
• Moderate hemophilia: FVIII/FIX between 1% and 5% of normal levels.
• Severe hemophilia: FVIII/FIX less than 1% of normal levels.

The disease itself cannot be prevented from occurring, however, its prognosis can be significantly altered with the aid of medication and joint-strengthening exercise. Prophylactic treatment can also help reduce bleeding episodes.

Hemophilia is a hematological disorder characterized by a partial or complete deficiency of clotting factors VIII or Christmas factor (FIX) [2]. It is an X-linked recessive disorder that presents as profuse bleeding and hematoma formation due to an inability to clot blood. Hemophilia itself is not very common but its first type, called Hemophilia A, is the world’s most common X-linked coagulation disorder.

Definition

Hemophilia is an inherited disease that results in an inability of the blood to properly clot.

Cause

It is due to mutations in the genes or chromosome controlling the clotting factors (factor VIII and factor IX). Due to mutations, a deficiency of clotting factor VIII, resulting in hemophilia A, or factor IX, resulting in hemophilia B, occur. As a consequence of this deficiency, the blood fails to coagulate after trauma, injuries and even the regular wear and tear of the body.

Signs and symptoms

The disease presents as profuse bleeding and massive swelling particularly of joints after trauma. Other symptoms include frequent episode of bleeding from gums, nose and mild cuts, and easy bruising.

Diagnosis

Hemophilia can be easily confused with severe deficiency of vitamin K or another bleeding disorder called von Willebrand disease. Diagnosis is made based on the history, clinical examination and laboratory tests.

Treatment

Treatment includes lifelong administration of FVIII/FIX depending upon the subtype, or other similarly acting drugs like desmopressin. Gene therapy can also be performed.

1. Castaldo G et al: Hemophilia A: molecular insights. Clin Chem Lab Med 45:450,2007 
2. Lobet S, Hermans C, Lambert C. Optimal management of hemophilic arthropathy and hematomas. J Blood Med. 2014 Oct 17;5:207-18. 
3. Fomin ME, Togarrati PP, Muench MO. Progress and challenges in the development of a cell-based therapy for hemophilia A. J Thromb Haemost. 2014 Oct 8. 
4. Venkateswaran L, Wilimas JA, Jones DJ, Nuss R. Mild hemophilia in children: prevalence, complications, and treatment. J Pediatr Hematol Oncol. Jan-Feb 1998;20(1):32-5
5. Ferreira AA, Leite IC, Bustamante-Teixeira MT, Guerra MR. Hemophilia A in Brazil - epidemiology and treatment developments. J Blood Med. 2014 Sep 23;5:175-84. 
6. Miguelino MG, Powell JS. Clinical utility and patient perspectives on the use of extended half-life rFIXFc in the management of hemophilia B. Patient Prefer Adherence. 2014 Aug 8;8:1073-83. 
7. Rattanathammethee T1, Norasetthada L, Tantiworawit A, Rattarittamrong E, Hantrakool S, Chai-Adisaksopha C. Acquired hemophilia A in the HIV-infected patient: a case report and literature review. Blood Coagul Fibrinolysis. 2014 Sep 25 
8. Chorba TL, Holman RC, Strine TW, Clarke MJ, Evatt BL. Changes in longevity and causes of death among persons with hemophilia A. Am J Hematol. Feb 1994;45(2):112-21 
9. Humphries TJ, Kessler CM. Managing chronic pain in adults with haemophilia: current status and call to action. Haemophilia. 2014 Oct 2.  
10. Berntorp E, Astermark J, Björkman S, Blanchette VS, Fischer K, Giangrande PL, et al. Consensus perspectives on prophylactic therapy for haemophilia: summary statement. Haemophilia. May 2003;9 Suppl 1:1-4.