What Is Causing This Young Man’s Sore Throat?

Answer: E. Spontaneous hemorrhage to the tongue base extending into the vallecula secondary to hemophila A

The patient received 4000 units of recombinant factor VIII and was prepped for an awake intubation for airway protection with nebulized lidocaine. He was intubated fiberoptically using sedatives only, without paralytics, with a 7.5-mm endotracheal tube. The patient continued factor replacement infusions twice daily in the intensive care unit (ICU). He was extubated on ICU day 2 and discharged 2 days later. He was subsequently lost to follow-up.

Discussion. While central nervous system hemorrhage is the most frequent emergent hemorrhagic event in patients with hemophilia, acute airway hemorrhage with obstruction is a life-threatening diagnosis that requires immediate recognition and treatment in patients with hemophilia.¹ While hemophilia is rare in the general population, results of a retrospective review of patients with classic hemophilia showed a 13% incidence of airway-compromising hemorrhage.²

Patients with hemophilia are classified based on their amount of native factor: severe (< 1% of normal), moderate (1%-5% of normal), and mild (> 5% to < 40% of normal).³ Mild disease is characterized as bleeding with major trauma or surgery; moderate disease is defined as bleeding that requires transfusion but does not result in hemodynamic instability; and severe disease is defined as spontaneous bleeding into joints or muscles.⁴ The target factor level for treatment depends largely on the site of bleeding. For example, the target factor level for hemarthrosis is 40% to 60%, compared with iliopsoas bleeds (80%-100%), and gastrointestinal or intracranial hemorrhages (100%).⁵

Factor VIII deficiency—also referred to as hemophilia A—can be treated with factor VIII, cryoprecipitate, 1-amino-8-D-arginine vasopressin (DDAVP) or fresh frozen plasma (FPP).⁶ Factor replacement can be calculated using this formula:

                                             Factor VIII (units) = weight (kg) × 0.5 × desired percentage of factor VIII level

In other words, 1 U/kg of factor VIII raises the circulating factor level by 2%.

Replacement for factor IX deficiency—commonly called hemophilia B—can be calculated using this formula:

                                                 Factor IX (units) = weight (kg) × desired percentage of factor IX level

In other words, 1 U/kg of factor IX raises the circulating factor level by 1%.

Specific factor replacement therapy may not be available at all institutions. FFP is more universally available, although it only contains about 1 U of both factor VIII and factor IX per mL of plasma.⁶ It is estimated that 1 unit of FFP (250 mL) has 200 to 300 U of factors VIII and IX, and 1 unit of cryoprecipitate contains 80 to 100 U of factor VIII. Cryoprecipitate contains no factor IX and should not be used for the treatment of hemophilia B.⁶

Deficiencies of factor IX may be treated with purified factor IX or FFP. Note that factor IX has twice the volume of distribution of factor VIII, and thus requires double the amount of factor IX replacement to raise factor levels by 1%. Using formula mentioned above, a patient with hemophilia A who weighs 70 kg would require 3500 U of factor VIII to increase his factor from 0 to 100%, while a patient with hemophilia B who weighs 70 kg would require 7000 U of factor IX.⁶ For life-threatening bleeds, the goal should be 100% replacement for several hours.⁷

Conclusions. Like much of medicine, this case hinges on proper history taking. It is often the parting line, “By the way, Doc...” that is crucial. As the physician is leaning on the doorknob, our patient casually mentioned he has hemophilia and has had a lack of care, which changes the whole scenario.