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].

• Prolonged Bleeding

  Clotting factor levels from 0.60 to 0.05 IU/mL were increasingly associated with prolonged bleeding from small wounds and prolonged bleeding after tooth extraction, tonsillectomy, and operations. [bloodjournal.org]

  Symptoms can include: Bleeding into joints with associated pain and swelling Blood in the urine or stool Bruising Gastrointestinal tract and urinary tract bleeding Nosebleeds Prolonged bleeding from cuts, tooth extraction, and surgery Bleeding that starts [nlm.nih.gov]

• Easy Bruising

  The main symptoms of hemophilia are excessive bleeding and easy bruising. Blood tests can tell if you have it. The main treatment is injecting the missing clotting factor into the bloodstream. [nlm.nih.gov]

  The major signs and symptoms of hemophilia are excessive bleeding and easy bruising. Excessive Bleeding The extent of bleeding depends on how severe the hemophilia is. [web.archive.org]

  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. [symptoma.com]

  Individuals affected by bleeding disorders may experience easy bruising, prolonged nosebleeds, heavy menstrual bleeding, and prolonged and spontaneous bleeding into joints, muscles, and organs. [hfmich.org]

• Spontaneous Hemorrhage

  If the biological activity of the coagulation factor is below 1%, the hemophilia is severe and manifests as frequent spontaneous hemorrhage and abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction (severe hemophilia [orpha.net]

  The clinical manifestation of AHA includes mostly spontaneous hemorrhages into skin, muscles and soft tissues, or mucous membranes. [doi.org]

• Neonatal Hemorrhage

  Rescue of fatal neonatal hemorrhage in factor V deficient mice by low level transgene expression. Thromb Haemost 2000; 83 (1) 70-77 41 Mann KG. How much factor V is enough?. Thromb Haemost 2000; 83 (1) 3-4 42 Duckers C, Simioni P, Spiezia L, et al. [doi.org]

• Subcutaneous Bleeding

  Subcutaneous bleeding (ecchymoses) is the most common manifestation of AH followed by muscle bleeding (hematoma), gastrointestinal (melena), genitourinary (hematuria), and retroperitoneal. Intracranial hemorrhage is rare, but can be fatal. [rarediseases.org]

• Pain

  METHODS: Pain and HRQoL were assessed via PRO instruments in US adult males with hemophilia A or B and a history of joint pain or bleeding. [ncbi.nlm.nih.gov]

  At first, the bleeding causes tightness in the joint with no real pain or any visible signs of bleeding. The joint then becomes swollen, hot to touch, and painful to bend. Swelling continues as bleeding continues. [web.archive.org]

  As more blood pools in it and swelling occurs, the joint feels tight, may be hot to the touch and becomes painful to bend. Children may hold or protect the affected joint, or start limping or crawling. [hemophilia.org]

• Swelling

  Swelling of the membrane around a joint. Pain, swelling, and redness of a joint. Pressure on a joint from swelling, which can destroy the joint. [web.archive.org]

  You may feel a warm prickly sensation before you develop pain and swelling in the joint. The degree of swelling does not match the severity of your bleeding. You may be bleeding significantly but show only a little swelling. [emedicinehealth.com]

  Bleeding that occurs in deep muscle can cause your limbs to swell. The swelling may press on nerves and lead to numbness or pain. Damage to joints. Internal bleeding may also put pressure on your joints, causing severe pain. [mayoclinic.org]

• Weakness

  Symptoms to be aware of include: painful headache, stiff neck, vomiting, sleepiness, changed behavior, sudden weakness or balance issues, difficulty walking, double vision, convulsions and seizures. [hemophilia.org]

  The signs and symptoms of bleeding in the brain include: Long-lasting, painful headaches or neck pain or stiffness Repeated vomiting Sleepiness or changes in behavior Sudden weakness or clumsiness of the arms or legs or problems walking Double vision [web.archive.org]

  In general, poor quality of life of patients was 13.1%, 42.9% weak-to-moderate, 38.1% moderate-to-good and 6% good. [ncbi.nlm.nih.gov]

  Signs and symptoms include: Painful, prolonged headache Repeated vomiting Sleepiness or lethargy Double vision Sudden weakness or clumsiness Convulsions or seizures When to see a doctor Seek emergency care if you or your child experiences: Signs or symptoms [mayoclinic.org]

• Anemia

  ichthyosis, infectious granuloma, iron deficiency anemia, leukemia, leukemic reticuloendotheliosis, macrocytic anemia, mongolianism, mongolism, mucoviscidosis, multiple myeloma, muscular dystrophy, myelogenous leukemia, neutropenia, pancreatic fibrosis [studysite.org]

  Here, we present the case of a term neonate who presented with worsening anemia in the setting of known hemolytic disease during the newborn period and was later found to have a spontaneous splenic rupture. [ncbi.nlm.nih.gov]

  The increased tendency to bleeding usually becomes noticeable early in life and may lead to severe anemia or even death. Large bruises of the skin and soft tissue are often seen, usually following injury so trivial as to be unnoticed. [britannica.com]

  A third risk to the hemophiliac client is the development of anemia due to excessive blood loss. Many years may go by before the body restores its necessary number of properly functioning blood cells. [massagemag.com]

• Pseudotumor

  […] intramuscular hematoma (pseudotumor) may lead to nerve compression iliacus hematoma may compress femoral nerve and presents with paresthesias in the L4 distribution leg length discrepancy due to epiphyseal overgrowth fractures due to generalized osteopenia [orthobullets.com]

  Pseudotumors Pseudotumors are collections of blood that are encapsulated like a cyst. They occur in soft tissues or bones following a prolonged bleeding episode. [rarebleedingdisorders.com]

  MD - This publication covers a wide range of orthopedic treatment issues, including hemophilic arthropathy, clinical considerations, diagnostic imaging, surgical and nonsurgical treatments, hemophilic synovitis, soft-tissue bleeding, the hemophilia pseudotumor [web.archive.org]

  If not managed properly it can lead to fibrosis and contractures with muscular atrophy and pseudotumor formation. Bleeding in to iliopsoas muscle is particularly notorious. [intechopen.com]

  Moreover, experts mentioned other haemophilia A complications in adults besides bleeding, such as foot ulcer or limb pseudotumor that may result in amputation prosthesis, wheelchairs use, technical help, and orthotics, which were not quantified in this [ojrd.biomedcentral.com]

• Tachypnea

  Signs of hemorrhage include the following: General: Weakness, orthostasis, tachycardia, tachypnea Musculoskeletal (joints): Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children) CNS: Headache, stiff neck, vomiting, lethargy, [emedicine.medscape.com]

• Dyspnea

  […] irritability, and spinal cord syndromes Gastrointestinal: Hematemesis, melena, frank red blood per rectum, and abdominal pain Genitourinary: Hematuria, renal colic, and post circumcision bleeding Other: Epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea [emedicine.medscape.com]

• Hemoptysis

  […] lethargy, irritability, and spinal cord syndromes Gastrointestinal: Hematemesis, melena, frank red blood per rectum, and abdominal pain Genitourinary: Hematuria, renal colic, and post circumcision bleeding Other: Epistaxis, oral mucosal hemorrhage, hemoptysis [emedicine.medscape.com]

• Vomiting

  Symptoms to be aware of include: painful headache, stiff neck, vomiting, sleepiness, changed behavior, sudden weakness or balance issues, difficulty walking, double vision, convulsions and seizures. [hemophilia.org]

  PATIENT CONCERNS: An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. [ncbi.nlm.nih.gov]

  The signs and symptoms of bleeding in the brain include: Long-lasting, painful headaches or neck pain or stiffness Repeated vomiting Sleepiness or changes in behavior Sudden weakness or clumsiness of the arms or legs or problems walking Double vision [web.archive.org]

  Signs of bleeding in the brain may include changes in behavior, excessive sleepiness, persistent headaches and neck pain, double vision, vomiting, and convulsions or seizures. Cleveland Clinic is a non-profit academic medical center. [my.clevelandclinic.org]

• Abdominal Pain

  PATIENT CONCERNS: An 8y7m-old Chinese boy presented with half a day of right sided abdominal pain, fever, nausea, and vomiting. [ncbi.nlm.nih.gov]

  Consider transfer when All children with Suspected intracranial haemorrhage Bleeding into neck/throat Forearm/calf bleed at risk of compartment syndrome Bleeding into hip or inguinal area (due to risk of iliopsoas haemorrhage) Undiagnosed abdominal pain [rch.org.au]

  Signs and symptoms of GI involvement include: • Fever • Abdominal distention and pain • Melena (bloody stool) • Hip flexion contracture (iliopsoas muscle spasm due to retroperitoneal hemorrhage) • Hematemesis (vomiting blood) • Low groin/abdominal pain [physio-pedia.com]

• Melena

  Signs and symptoms of GI involvement include: • Fever • Abdominal distention and pain • Melena (bloody stool) • Hip flexion contracture (iliopsoas muscle spasm due to retroperitoneal hemorrhage) • Hematemesis (vomiting blood) • Low groin/abdominal pain [physio-pedia.com]

  Genitourinary and gastrointestinal bleeding may respectively cause blood in the urine (hematuria) and black or bloody stools (melena, hematochezia). [rarediseases.org]

  tachycardia, tachypnea Musculoskeletal (joints): Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children) CNS: Headache, stiff neck, vomiting, lethargy, irritability, and spinal cord syndromes Gastrointestinal: Hematemesis, melena [emedicine.medscape.com]

• Hematemesis

  Signs and symptoms of GI involvement include: • Fever • Abdominal distention and pain • Melena (bloody stool) • Hip flexion contracture (iliopsoas muscle spasm due to retroperitoneal hemorrhage) • Hematemesis (vomiting blood) • Low groin/abdominal pain [physio-pedia.com]

  orthostasis, tachycardia, tachypnea Musculoskeletal (joints): Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children) CNS: Headache, stiff neck, vomiting, lethargy, irritability, and spinal cord syndromes Gastrointestinal: Hematemesis [emedicine.medscape.com]

• Hematochezia

  Genitourinary and gastrointestinal bleeding may respectively cause blood in the urine (hematuria) and black or bloody stools (melena, hematochezia). [rarediseases.org]

• Tachycardia

  The patient may have signs of pallor, fatigue, and tachycardia with excessive bleeding. [web.archive.org]

  Signs of hemorrhage include the following: General: Weakness, orthostasis, tachycardia, tachypnea Musculoskeletal (joints): Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children) CNS: Headache, stiff neck, vomiting, lethargy, [emedicine.medscape.com]

• Hypotension

  Precautions Injection contains benzyl alcohol as preservative and not recommended for use in newborns; rapid IV administration may induce hypotension, bradycardia, and/or arrhythmia; do not administer concomitantly with prothrombin complex concentrates [web.archive.org]

• Jaundice

  Look for jaundice, other signs of liver failure (eg, cirrhosis from viral infection), and signs of opportunistic infections in patients who are HIV seroconverted. [web.archive.org]

  Most people can safely return to work after the jaundice clears, even if their liver function test results aren’t quite normal. Acute viral hepatitis symptoms can range from minor flu-like illness to liver failure. [arizonahemophilia.org]

• Liver Tenderness

  Symptoms may include fatigue, nausea, vomiting, muscle and joint aches, liver tenderness and enlargement and/or weight loss. Hepatitis can be acute (lasting less than six months) or chronic. It occurs commonly throughout the world. [arizonahemophilia.org]

• Bleeding Gums

  […] helps avoid problems such as gum disease, which can cause bleeding. [nhs.uk]

  Spontaneous bleeding can cause the following: blood in the urine blood in the stool deep bruises large, unexplained bruises excessive bleeding bleeding gums frequent nosebleeds pain in the joints tight joints irritability (in children) The following symptoms [healthline.com]

  […] prone to frequent bleeding such as nosebleeds, bleeding gums, and excessive menstrual periods. [medicalnewstoday.com]

• Oral Bleeding

  Treatment of the bleeding caused by an injury or tooth extraction: For oral bleeding, it is advisable to use cyclocabron to prevent acute oral bleeding. It is used for only a short period (2-8 days). [moh.gov.sa]

  A severe hemophiliac should be evaluated at a hospital's emergency department for any bleeding whatsoever, because his or her blood will not clot adequately on its own in these situations: Oral bleeding Bleeding from skin that does not stop with simple [emedicinehealth.com]

  [citation needed] Treatment[edit] Cyklokapron (Tranexamic acid) In terms of haemophilia C medication cyklokapron is often used for both treatment after an incident of bleeding and as a preventive measure to avoid excessive bleeding during oral surgery [en.wikipedia.org]

• Purpura

  […] title=Category:Hemophilia&oldid=332489582 " Categorie : Congenital diseases and disorders Coagulation defects, purpura and other haemorrhagic conditions Categorie nascoste: Uses of Wikidata Infobox with no image Uses of Wikidata Infobox Uses of Wikidata [commons.wikimedia.org]

  Primary Hemostasis –> Platelet aggregation forms an initial plug (immediate) –> Deficiencies tend to cause superficial bleeds (i.e petechiae, ecchymosis, & purpura) Secondary Hemostasis –> Clotting Factors help support the plug (delayed) –> Deficiencies [rebelem.com]

  カテゴリ 血液疾患 階層分類 ヒト疾患 [BR: jp08402 ] 循環器系疾患 血液疾患 H00219 血友病 ICD-11 による疾患分類 [BR: jp08403 ] 03 Diseases of the blood or blood-forming organs Coagulation defects, purpura or other haemorrhagic or related conditions Coagulation defects Congenital or constitutional [genome.jp]

  Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood 2001; 98: 952-957. 84 Wiestner A. et al. Rituximab in the treatment of acquired factor VIII inhibitor. [doi.org]

  […] sites recruiting participants.[12] In 2017 a gene therapy trial on nine people with haemophilia A reported that high doses did better than low doses.[62][63] It is not currently an accepted treatment for haemophilia.[11] See also[edit] Coagulopathy Purpura [en.wikipedia.org]

• Arthritis

  /arthropathy, and knee/hip replacement among workers with hemophilia after multivariate adjustment, with hazard ratios (95% CI) of 4.60 (2.81-7.53), 4.03 (3.34-4.87), and 1.29 (1.10-1.41), respectively.Disorder of joints, hemophilia-related arthritis/ [ncbi.nlm.nih.gov]

  These joint hemorrhages culminate in a severe arthropathy, with signs of inflammation (as in rheumatoid arthritis) as well as degenerative damage (as. .. [content.nejm.org]

  Bleeding in the joints causes pain and, if not treated, can lead to arthritis. Bleeding in the brain, a very serious complication of hemophilia, requires emergency treatment. The main symptoms of hemophilia are excessive bleeding and easy bruising. [nlm.nih.gov]

• Joint Deformity

  People with less severe hemophilia may have bleeding in a joint if they fall or are injured. If joint bleeds are not promptly and adequately treated, joint deformity can occur. Bleeding in a joint can cause scarring in the joint. [webmd.com]

  Insufficient or incorrect treatment of recurrent hemarthroses and hematomas leads to motor impairment with severe disability associated with stiffness, joint deformation and paralysis. [orpha.net]

• Contusion

  […] red blood per rectum, and abdominal pain Genitourinary: Hematuria, renal colic, and post circumcision bleeding Other: Epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea (hematoma leading to airway obstruction), compartment syndrome symptoms, and contusions [emedicine.medscape.com]

• Arthralgia

  The most common adverse reactions reported (incidence ≥10%) were injection site reactions, headache, and arthralgia. [fda.gov]

  In pooled data from the phase III HAVEN programme (n=373), the most common adverse reactions occurring in 10% or more of people treated with Hemlibra were injection site reactions (20%), joint pain (arthralgia; 15%) and headache (14%). [roche.com]

  143 145 19 236 543 Most common adverse events — no. of participants (%) † Injection-site reaction ‡ 9 (25) 7 (20) 2 (12) 20 (32) 38 (25) Upper respiratory tract infection 4 (11) 4 (11) 0 8 (13) 16 (11) Nasopharyngitis 2 (6) 6 (17) 0 10 (16) 18 (12) Arthralgia [doi.org]

• Joint Swelling

  Clinical Assessment of Joints Clinical examination of joints, with assessment of swelling, strength, range of motion, pain, and gait, was performed semiannually, as previously described, and videotaped for central review at study entry, midpoint, and [doi.org]

  Some patients develop chronic synovitis with joint swelling caused by synovial inflammation and hypertrophy but without clear cartilage damage, whereas others develop hemophilic arthropathy with significant osteochondral damage without synovitis.20 Hemophilic [hematologyandoncology.net]

• Epistaxis

  Recurrent, heavy nosebleeds, or epistaxis, without apparent cause are another symptom. Minor cuts that don’t clot or that stop and then start again also can occur. [hemophilia.org]

  Menorrhagia was predominant (13.6%) followed by epistaxis (9%), gingivorrhagia (9%), and prolonged bleeding after tooth extraction (9%). [ncbi.nlm.nih.gov]

  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. [symptoma.com]

  […] patients Factor Level: Option A: The patient knows their factor level Option B: Patient Does Not Know their factor level ( If the patient does not know their factor level assume 0% ) Severity of Bleed Mild to Moderate –> Soft Tissue, Muscle, Hemarthrosis, Epistaxis [rebelem.com]

  These medications may be particularly helpful for managing bloody noses (epistaxis), heavy menstrual bleeding, and after dental procedures for patients with bleeding disorders.They may be used alone or together with DDAVP or factor replacement therapy [danafarberbostonchildrens.org]

• Hematuria

  Hematuria is frequent in hemophilia. Hematuria in hemophilia is generally considered benign and manageable with conservative therapy; however, severe hematuria requiring surgical therapy has rarely been reported. [ncbi.nlm.nih.gov]

  Spontaneous hematuria is a fairly frequent and highly characteristic sign of the disorder. [orpha.net]

  Blood in the urine ( hematuria ) commonly occurs with hemophilia. However, it can also occur in people without hemophilia. Many people will have microscopic blood in urine, not visible with the naked eye. [emedicinehealth.com]

• Urogenital Bleeding

  Specific symptoms can include nosebleeds (epistaxis), bruising throughout the body, solid swellings of congealed blood (hematomas), blood in the urine (hematuria) and gastrointestinal or urogenital bleeding. [rarediseases.org]

• Headache

  Symptoms to be aware of include: painful headache, stiff neck, vomiting, sleepiness, changed behavior, sudden weakness or balance issues, difficulty walking, double vision, convulsions and seizures. [hemophilia.org]

  The signs and symptoms of bleeding in the brain include: Long-lasting, painful headaches or neck pain or stiffness Repeated vomiting Sleepiness or changes in behavior Sudden weakness or clumsiness of the arms or legs or problems walking Double vision [web.archive.org]

  The most common adverse reactions reported (incidence ≥10%) were injection site reactions, headache, and arthralgia. [fda.gov]

• Intracranial Hemorrhage

  However, as he suffered from intracranial hemorrhage at the age of 1 year, he underwent first ITI at the age of 1 year. Unfortunately, this failed to reduce the level of the inhibitor, and this strategy was stopped after 2 years. [ncbi.nlm.nih.gov]

  Brain bleeds, or intracranial hemorrhage (ICH), are serious. They can occur spontaneously or after trauma. [hemophilia.org]

  Intracranial hemorrhage is a life-threatening hemorrhage with a lifetime risk of 2-8%, accounting for one third of deaths due to hemorrhage. [web.archive.org]

  Patients bleed into tissues (eg, hemarthroses, muscle hematomas, retroperitoneal hemorrhage) following minimal trauma; fatal intracranial hemorrhage may occur. [msdmanuals.com]

• Seizure

  Symptoms to be aware of include: painful headache, stiff neck, vomiting, sleepiness, changed behavior, sudden weakness or balance issues, difficulty walking, double vision, convulsions and seizures. [hemophilia.org]

  […] symptoms of bleeding in the brain include: Long-lasting, painful headaches or neck pain or stiffness Repeated vomiting Sleepiness or changes in behavior Sudden weakness or clumsiness of the arms or legs or problems walking Double vision Convulsions or seizures [web.archive.org]

  Signs of bleeding in the brain may include changes in behavior, excessive sleepiness, persistent headaches and neck pain, double vision, vomiting, and convulsions or seizures. Cleveland Clinic is a non-profit academic medical center. [my.clevelandclinic.org]

  Signs and symptoms include: Painful, prolonged headache Repeated vomiting Sleepiness or lethargy Double vision Sudden weakness or clumsiness Convulsions or seizures When to see a doctor Seek emergency care if you or your child experiences: Signs or symptoms [mayoclinic.org]

• Lethargy

  Signs and symptoms include: Painful, prolonged headache Repeated vomiting Sleepiness or lethargy Double vision Sudden weakness or clumsiness Convulsions or seizures When to see a doctor Seek emergency care if you or your child experiences: Signs or symptoms [mayoclinic.org]

  Symptoms of brain bleeding can include headaches, vomiting, lethargy, behavioral changes, clumsiness, vision problems, paralysis, and seizures. Medical history and blood tests are key to diagnosing hemophilia. [medicalnewstoday.com]

  Other signs of internal bleeding include: red or tea-colored urine (pee), called hematuria black or bloody feces (poop) blood in vomit after a head injury, headache, vomiting, lethargy (sleepiness), or seizures Diagnosis Few babies are diagnosed with [kidshealth.org]

  Intracranial hemorrhage (bleeding into the brain or skull) can lead to symptoms such as nausea, vomiting, and/or lethargy, and can lead to death. Increased bleeding after surgery or trauma is characteristic of hemophilia. [medicinenet.com]

• Irritability

  If bleeding occurs frequently and you don't receive adequate treatment, the irritation may lead to destruction of the joint or to the development of arthritis. Infection. [web.archive.org]

  […] bleeding from cuts or injuries, or after surgery or dental work Many large or deep bruises Unusual bleeding after vaccinations Pain, swelling or tightness in your joints Blood in your urine or stool Nosebleeds without a known cause In infants, unexplained irritability [mayoclinic.org]

  Spontaneous bleeding can cause the following: blood in the urine blood in the stool deep bruises large, unexplained bruises excessive bleeding bleeding gums frequent nosebleeds pain in the joints tight joints irritability (in children) The following symptoms [healthline.com]

  This can present clinically as impaired movement, posturing, or irritability in the male infant. Other sites of bleeding include mucosal surfaces and the central nervous system, the latter carrying particularly devastating consequences. [ajmc.com]

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.

• Prothrombin Time Normal

  [citation needed] In both haemophilia A and B, there is spontaneous bleeding but a normal bleeding time, normal prothrombin time, normal thrombin time, but prolonged partial thromboplastin time. [en.wikipedia.org]

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.