High Risk/Low Prevalence: Hemophilia

Hemophilia is a clotting-factor deficiency in which history drives emergency care more than the initial exam, labs, or imaging. Intracranial, retroperitoneal, and joint bleeding can be occult, and early factor replacement should not wait for test results.

ED Approach to Hemophilia Bleeding

• History over initial testing: Acute management hinges on the bleeding history and mechanism, because exam findings can be normal early and labs should never delay indicated factor replacement.
• Early factor replacement: The mainstay is immediate clotting factor replacement based on suspected bleeding, with a target of 100% factor activity for major bleeds and 50% for minor bleeds.
• Major bleed locations: Treat bleeding in the CNS, retroperitoneum, throat, neck, eye, chest, or GI tract as major, and count rapidly expanding hemarthrosis with neurovascular compromise the same way.
• Head injury exception: A concerning head mechanism warrants factor concentrate first and imaging second, because spontaneous or traumatic intracranial hemorrhage may present with a normal early exam. We get into that sequencing in the episode.
• Low threshold for imaging: PECARN, the Canadian CT Head Rule, and Ottawa extremity rules do not apply in hemophilia; imaging decisions should follow the story and exam, not standard trauma tools.

Diagnosis, Dosing, and Inhibitors

• Hemophilia types and inheritance: Hemophilia A is factor VIII deficiency and Hemophilia B is factor IX deficiency; females can be symptomatic, and about one-third of cases arise from spontaneous mutation.
• Classic lab pattern limits: Suspected hemophilia may show an isolated prolonged aPTT with normal PT and platelets, but a normal aPTT does not exclude the disease.
• Mixing study clue: Correction after mixing points toward factor deficiency, while failure to correct suggests an inhibitor such as acquired hemophilia or treatment-related anti-factor antibodies.
• Headline replacement doses: To reach full correction, factor VIII concentrate is dosed at 50 U/kg and factor IX at 100 U/kg; if the baseline level is unknown, assume it is zero.
• Inhibitor rescue therapy: Breakthrough or recurrent bleeding despite factor raises concern for inhibitors, and recombinant factor VIIa becomes the safest first-line option for life- or limb-threatening hemorrhage.
• Medication pitfalls: Avoid drugs that impair platelet function or coagulation, especially aspirin, NSAIDs, anticoagulants, and antiplatelet agents; the practical exceptions come up in the chapter.

References:

1. Alblaihed L, et al. High risk and low prevalence diseases: Hemophilia emergencies. Am J Emerg Med. 2022;56:21-27. PMID: 35349958.
2. Kulkarni R, et al; Haemophilia Treatment Center Network Investigators. Sites of initial bleeding episodes, mode of delivery and age of diagnosis in babies with haemophilia diagnosed before the age of 2 years: a report from The Centers for Disease Control and Prevention's (CDC) Universal Data Collection (UDC) project. Haemophilia. 2009 Nov;15(6):1281-90. PMID: 19637999.
3. Plummer ES, et al. Prominent forehead hematomas ("goose-eggs") as an initial manifestation of hemophilia. J Pediatr. 2013 Dec;163(6):1781-3. PMID: 23968747.
4. Kitchens CS. Occult hemophilia. Johns Hopkins Med J. 1980 Jun;146(6):255-9. PMID: 7382250. PMID: 7382250
5. MASAC Document 257 - Guidelines for Emergency Department Management of Individuals with Hemophilia and Other Bleeding Disorders. Published 2019. Link.