Hemophilia A and B: An Overview
LIFE-THREATENING HEMORRHAGE
Central Nervous System Bleeding
Most central nervous system (CNS) events, which involve bleeding inside the skull or spinal canal, are caused by trauma. CNS hemorrhage is the most common form of severe hemophilic trauma. However, since patients with hemophilia can experience bleeding even weeks after a minor head injury, a history of head trauma may be hard to determine, particularly in children. Spontaneous CNS bleeding in individuals with hemophilia is rare except when there has been a recent antecedent CNS hemorrhage (ie, a recurrent bleed at a previously injured site) or when there is an associated anatomic lesion that predisposes to acute hemorrhage (eg, aneurysm or arteriovenous malformation). Data from the Universal Data Collection Project of the U.S. Centers for Disease Control and Prevention indicates that predisposing risk factors for intracranial hemorrhage include HIV infection, presence of inhibitory antibodies, and age younger than 5 years or older than 51 years.16 Neonatal intracranial hemorrhage is most commonly due to birth trauma. Difficult vaginal deliveries (often requiring the application of forceps or vacuum extraction) are predisposing factors for intracranial hemorrhage in hemophilic newborns.
The site of intracranial CNS bleeding can be subdural, epidural, or intraparenchymal. Bleeding at any of these sites can cause rapidly deteriorating CNS brain function, associated brain swelling, and, in the most extreme circumstances, herniation of the brainstem and rapid death. If the bleeding is stopped with rapid clotting factor replacement, adverse clinical effects can be avoided. However, with intraparenchymal hemorrhage, even small hemorrhages can induce permanent structural and/or neurologic sequelae (in particular, if the anatomic site of the bleed is essential for routine brain function).17
,Throat and Neck Hemorrhage
An acute neck injury or a retropharyngeal hemorrhage induced by dental or oral surgical instrumentation can lead to a dissecting facial plane hematoma. This in turn can sometimes lead to compression and acute airway compromise. Bleeding from these injuries that is compressing or compromising the airway may require a rapid clinical response.18 The time from the injury until the trachea is compressed may be long, sometimes many hours. However, once the compression is sufficient to cause difficulty breathing, there may be a short amount of time to stop the bleeding and prevent complete respiratory obstruction.
MUCOCUTANEOUS BLEEDING
One of the common manifestations of hemophilia is oral bleeding. Tooth extraction poses a specific problem, and bleeding following extraction can be the first symptom that leads to the diagnosis of hemophilia. Bleeding after circumcision may also suggest the diagnosis. In 1 study cohort looking at sites of initial bleeding episodes in babies with hemophilia diagnosed before the age of 2 years, bleeding from circumcision and other iatrogenic causes tended to be most common in the neonatal period. Circumcision bleeding events occurred more often in infants with no family history (43%) as compared to those born to known maternal carriers (9.2%) or to mothers with some other family history of hemophilia (14.3%).19
Gastrointestinal (GI) bleeding occurs occasionally in hemophilia, and a wide spectrum of esophageal and GI bleeding may occur. A review of 41 episodes of GI bleeding in hemophilia patients who presented to 1 institution over 10 years implicated duodenal ulcer (22%), unknown site (22%), and gastritis (14%) as the most common sources.20 Mallory-Weiss syndrome has also been cited as a cause for upper GI bleeding in hemophilia patients.21
PRINCIPLES OF TREATMENT
Understanding the pathophysiology of hemophilia as well as the type and severity of hemophilia and the inhibitor status in an individual patient are paramount in the management of a patient with hemophilia. In the past, management mainly focused on the treatment of acute bleeding episodes (Table 2). With data showing the benefit of bleed prevention, the management of hemophilia now focuses on prophylaxis of bleeding episodes, which prevents chronic arthropathy and improves quality of life.
ACUTE BLEEDING EPISODES
Dosing of Factor VIII Products
Dosing for factor VIII concentrate is as follows: 1 IU of factor VIII concentrate per kg will increase the circulating factor VIII level by 2% (ie, patient weight in kg × 50 IU/kg = 100% correction). For example, a 30-kg patient requiring 100% correction of factor VIII needs an infusion of 1500 IU of factor VIII (30 kg × 50 IU/kg).
Dosing of Factor IX Products
Dosing for factor IX concentrate is as follows: 1 IU of factor IX concentrate per kg will increase the circulating factor IX level by 1% (ie, patient weight in kg × 100 IU/kg = 100% correction). For example, a 30-kg patient requiring 100% correction of factor IX needs an infusion of 3000 IU of factor IX (30 kg × 100 IU/kg). Higher doses (120 to 130 IU/kg) of the recombinant factor IX product BeneFIX (Pfizer) may be needed to reach the 100% circulating factor IX level.
