Hemophilia; Types, Causes, Symptoms, Diagnosis, Treatments

Hemophilia is not one disease but rather one of a group of inherited bleeding disorders that cause abnormal or exaggerated bleeding and poor blood clotting. The term is most commonly used to refer to two specific conditions known as hemophilia A and hemophilia B, which will be the main subjects of this article. Hemophilia A and B are distinguished by the specific gene that is mutated (altered to become defective) and codes for a defective clotting factor (protein) in each disease. Rarely, hemophilia C (a deficiency of Factor XI) is encountered, but its effect on clotting is far less pronounced than A or B.

There are two main types of haemophilia – haemophilia A, which occurs due to not enough clotting factor VIII, and haemophilia B, which occurs due to not enough clotting factor IX.They are typically inherited from one’s parents through an X chromosome with a nonfunctional gene.Rarely a new mutation may occur during early development or haemophilia may develop later in life due to antibodies forming against a clotting factor. Other types include haemophilia C, which occurs due to not enough factor XI, and parahaemophilia, which occurs due to not enough factor V.Acquired haemophilia is associated with cancers, autoimmune disorders, and pregnancy.Diagnosis is by testing the blood for its ability to clot and its levels of clotting factors.

Types

There are several types of haemophilia: haemophilia A, haemophilia B, haemophilia C, parahaemophilia, and acquired haemophilia A.

Haemophilia A – is a recessive X-linked genetic disorder resulting in a deficiency of functional clotting Factor VIII.

Hemophilia A results from too little of a plasma protein called factor VIII, which helps blood clot. The greater the deficiency, the more severe the symptoms.

• Mild hemophilia: 5% to 40% of the normal factor VIII level
• Moderate hemophilia: 1% to 5% of the normal factor VIII level
• Severe hemophilia: Less than 1% of the normal factor VIII level

Haemophilia B – is also a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX.

Haemophilia C – is an autosomal genetic disorder involving a lack of functional clotting Factor XI.Haemophilia C is not completely recessive, as heterozygous individuals also show increased bleeding.

The type of haemophilia known as parahaemophilia is a mild and rare form and is due to a deficiency in factor V. This type can be inherited or acquired.

A non-genetic form of haemophilia is caused by autoantibodies against factor VIII and so is known as acquired haemophilia A. Acquired haemophilia can be associated with cancers, autoimmune disorders and following childbirth.

Specific sites and types of bleeding are discussed below

• Hemarthrosis – (bleeding into the joints) is characteristic of hemophilia. The knees and ankles are most often affected. The bleeding causes distension of the joint spaces, significant pain, and over time, can be disfiguring. Over time, joint destruction occurs, and joint replacement surgeries can be required.
• Bleeding into the muscles  – may occur with hematoma formation (compartment syndrome).
• Bleeding from the mouth or nosebleeds –  may occur. Bleeding after dental procedures is common, and oozing of blood from the gums may occur in young children when new teeth are erupting.
• Bleeding from the gastrointestinal tract –  can lead to blood in the stool.
• Bleeding from the urinary tract  – can lead to blood in the urine (hematuria).
• 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.

Causes

Hemophilia types A and B are inherited diseases passed on to children from a gene located on the X chromosome. Females have two X chromosomes, while males have one X and one Y chromosome. A female carrier of hemophilia has the hemophilia gene on one of her X chromosomes. When a hemophilia carrier female is pregnant, there is a 50/50 chance that the hemophilia gene will be passed on. If the gene is passed on to a son, he will have the disease. If the gene is passed on to a daughter, she will be a carrier. If the father has hemophilia but the mother does not carry the hemophilia gene, then none of the sons will have hemophilia disease, but all of the daughters will be carriers.

In about one-third of the children with hemophilia, there is no family history of the disorder. It is believed that, in these cases, the disorder could be related to a new gene mutation. Tests are available to possible carriers to help determine whether or not they, in fact, carry the abnormal gene.

Symptoms

Hematomas

• These are characteristic of hemophilia (unusual in patients with platelet disorders).
• Patients with severe hematomas can have dissection (retropharyngeal/retroperitoneal).
• Muscle bleeding can lead to compartment syndromes.

Hemarthrosis

• Approximately 75% of hemophilia bleeding is joint‐related
• Joints are most commonly affected in the following order: knees, elbows, ankles, shoulders, wrists, and hips.
• Patients often have a target joint, resulting in a cycle of inflammation and rebleeding.
• If not treated quickly, hemarthrosis can result in chronic pain/joint destruction, and ultimately osteoporosis, bone cysts, and joint space narrowing.

Pseudotumors

• These tumors usually occur within the tendons or bones.

Hematuria

• Hematuria is often seen during the lifetime of a hemophiliac.
• Hematuria is usually from the renal pelvis.

Signs and symptoms of spontaneous bleeding include:

• Lengthy, uncontrollable bleeding — either heavy or oozing in nature — particularly after injury, immunizations or surgical or dental procedures
• Any signs of internal bleeding, such as a change in consciousness, alertness, or memory or difficulty breathing (note that these symptoms may also be signs of other medical problems unrelated to hemophilia)
• Excessive bleeding from the gums, tongue, or mouth following injury (seen particularly in infants and toddlers)
• Severe bleeding after tooth extractions or other invasive dental procedures
• Unexplained and excessive bleeding from cuts or injuries, or after surgery or dental work
• 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)
• 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

Diagnosis

A family history of bleeding disorders aids in diagnosing hemophilia. But certain tests help quantify the disease.

• Pronounced bruising at childbirth or bleeding with circumcision may suggest a case of severe hemophilia.
• A moderate case of hemophilia may become apparent during the toddler years when falls are common.
• A mild case may not become evident until adulthood when you need surgery.
• Blood tests can be performed if you have any reason to suspect hemophilia.
• Complete blood count (CBC)
• Prothrombin time (PT) and activated partial thromboplastin time (PTT). Both of these tests check how long it takes blood to clot.
• Factor VIII and factor IX tests, which measure levels of each of those proteins. Factor VIII is for hemophilia A. Factor IX is for hemophilia B, another type of hemophilia.

Severity

(percentage breakdown of overall hemophilia population by severity)

• Severe (factor levels less than 1%) represent approximately 60% of cases
• Moderate (factor levels of 1-5%) represent approximately 15% of cases
• Mild (factor levels of 6%-30%) represent approximately 25% of cases

Normal plasma levels of FVIII range from 50% to 150%. Levels below 50%, or half of what is needed to form a clot, determine a person’s symptoms.

• Mild hemophilia A-  6% up to 49% of FVIII in the blood – People with mild hemophilia Agenerally experience bleeding only after serious injury, trauma or surgery. In many cases, mild hemophilia is not diagnosed until an injury, surgery or tooth extraction results in prolonged bleeding. The first episode may not occur until adulthood. Women with mild hemophilia often experience menorrhagia, heavy menstrual periods, and can hemorrhage after childbirth.
• Moderate hemophilia A. 1% up to 5% of FVIII in the blood – People with moderate hemophilia A  tend to have bleeding episodes after injuries. Bleeds that occur without obvious cause are called spontaneous bleeding episodes.
• Severe hemophilia A.  <1% of FVIII in the blood – People with severe hemophilia A experience bleeding following an injury and may have frequent spontaneous bleeding episodes, often into their joints and muscles.

Treatment

• Giving a medicine called DDAVP (Octostim, desmopressin, or Stimate) may increase levels of Factor VIII (8) temporarily. But the medication will not be effective in severe cases of hemophilia or in hemophilia B.
• Aminocaproic acid  and tranexamic acid (Cyklokapron) assist your clotting by slowing down the ongoing destruction of clots. These medications are useful in oral bleeding in either hemophilia A or B.
• Immunizations may need to be given under the skin (subcutaneous) instead of in the muscle (intra muscular) to prevent deep muscle bleeds.
• Joint hemorrhages may require surgery and/or immobilization. Rehabilitation of the affected joint may include physical therapy and exercise to strengthen the muscles around the area.
• Your child’s doctor may also recommend the discontinuation of aspirin, and aspirin-containing products, since these products have been linked to bleeding problems.
• Blood transfusions may be necessary if significant blood loss has occurred.
• Proper dental hygiene is a preventive measure.
• Prophylactic self-infusion of factor VIII or IX can allow a child with hemophilia to lead a near normal lifestyle.
• Before surgery, including dental work, your child’s doctor may recommend factor replacement infusions to increase the child’s clotting levels prior to the procedures. Your child may also receive the specific factor replacement infusions during and after the procedure to maintain the clotting factor levels and to improve healing and prevention of bleeding after the procedure.

Other therapies may include

• Desmopressin (DDAVP) – In mild hemophilia, this hormone can stimulate your body to release more clotting factor. It can be injected slowly into a vein or provided as a nasal spray.
• Clot-preserving medications (anti-fibrinolytics – These medications help prevent clots from breaking down.
• Fibrin sealants  – These medications can be applied directly to wound sites to promote clotting and healing. Fibrin sealants are especially useful in dental therapy.
• Physical therapy – It can ease signs and symptoms if internal bleeding has damaged your joints. If internal bleeding has caused severe damage, you may need surgery.
• First aid for minor cuts – Using pressure and a bandage will generally take care of the bleeding. For small areas of bleeding beneath the skin, use an ice pack. Ice pops can be used to slow down minor bleeding in the mouth.
• Vaccinations – Although blood products are screened, it’s still possible for people who rely on them to contract diseases. If you have hemophilia, consider receiving immunization against hepatitis A and B.

References