Managing Hemophilia in the ED: All Bleeding Stops Eventually

Authors: Amber Fiutko, MD (EM Resident Physician, Cook County Health & Hospitals System) and Neeraj Chhabra, MD (EM Attending Physician, Department of Emergency Medicine, Cook County Health & Hospitals System; Assistant Professor of Emergency Medicine, Rush Medical College) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case

A 16-year-old male with severe hemophilia A (factor VIII deficiency) presents to the Emergency Department lacerations to his bilateral forearms. He has wrapped the wounds in compression dressings; however, there is significant strikethrough of all bandages and the wounds continue to actively bleed when undressed. How should his bleeding be controlled?

Types of Hemophilia

Hemophilia is an X-linked deficiencyof clotting factors that is more prevalent in male patients.Deficiencies of factor VIII (hemophilia A) or factor IX (hemophilia B) are the predominant forms of hemophilia (with A more common than B). While the majority of patients with hemophilia will have congenital hemophilia, some may acquire hemophilia. Acquired hemophilia, most commonly due to Factor VIII antibody, can be caused by a variety of factors; it may be associated with the post-partum period, autoimmune diseases, malignancy (especially lymphoproliferative disorders), and use of certain medications, particularly antibiotics and anticonvulsants.  These patients may present with a range of bleeding disorders from easy bruising to hemarthrosis to life-threatening hemorrhage.  It is important to recognize bleeding complications early and treat them aggressively in the ED.

Many patients who have been diagnosed with hemophilia are trained to administer additional doses of factor when experiencing bleeding. Therefore, these patients frequently only present to the ED when episodes of bleeding are persistent or severe. At times, patients may also present if unable to obtain venous access for factor administration, particularly in pediatric or geriatric populations. Although commonly diagnosed in pediatric age groups, patients with mild to moderate factor deficiency may present later in life, so it is important to consider in those with uncontrolled or severe episodes of bleeding.2

Severity

In patients with hemophilia A or B, the severity of disease correlates with percentage of factor activity. A patient functionally will have normal clotting activity with >50% factor activity. Mild factor deficiency ranges from 5-40% of factor activity, moderate from 1-5% of factor activity, and a patient will have severe deficiency if less than 1% factor activity is present.Factors VIII and IX are located in the intrinsic pathway and will affect the aPTT, but not the PT, platelets, or bleeding time.

Indications for factor replacement

Evaluate the severity of bleeding to determine the amount of factor replacement required. For mild to moderate bleeding, including soft tissue bleeding, muscular bleeding, hemarthrosis, or epistaxis, replace up to 50% of factor. For severe bleeding, including intracranial, gastrointestinal, any bleeding around the neck or airway that could lead to airway compromise, or major trauma, replace up to 100% of factor.2

How to Replace Factor

In hemophilia A, every 1 U/kg of factor VIII replacement increases the factor activity by 2%.For example, 25U/kg of factor VIII replacement will lead to a 50% correction and should be used in cases of mild to moderate bleeding. For severe bleeding in a patient with hemophilia A, give 50U/kg of factor replacement to achieve 100% correction.

In hemophilia B, every 1 U/kg of factor IX increases the factor activity by 1%.For example, 50U/kg of factor IX will yield a 50% correction for mild to moderate bleeds, and 100U/kg will yield a 100% correction for severe bleeds.

Ideally, use the factor the patient takes at home to reduce development of inhibitors. Remember, these patients probably know their disease better than you do.

If a patient does not know their own factor activity, assume that it is 0% for purposes of correction.

Other Options

Although factor replacement is the first-line option, there are other treatment options if factor is not available:

  • Cryoprecipitate contains 80-100 units of factor VIII per single donor bag and can be used to replace factor in patients with hemophilia A. It has no role in hemophilia B.6
  • DDAVP is recommended for acute bleeding in patients with mild hemophilia A. It increases factor VIII by 3-5x by promoting release of endogenous factor VIII. The recommended dose is 0.3 mcg/kg/dose IV, and onset is approximately 30 minutes, with peak action at 90-100 minutes.3, 7
  • FFP is another option for hemophilia A, however, there is only 1 unit of factor/mL of FFP, and complete replacement of factor activity requires a large volume.6
  • PCC can be used as it contains factors II, VII, IX, and X, though there are potentially thrombogenic side effects.3
  • TXA is recommended for mucosal bleeds and stabilized clot formation. The recommended dose is 10 mg/kg IV or 25 mg/kg PO.8

Hemophilia with inhibitors

Some patients with hemophilia may develop antibodies or inhibitors to exogenous factor. Options in these scenarios include NovoSeven (recombinant factor VIIa) or FEIBA (factor eight inhibitor bypassing agent). Activated factor VII directly activates factor X, bypassing the need for factors VIII and IX. Be aware that both recombinant factor VIIa and FEIBA contain activated clotting factors and a risk for thrombogenic effects.2,9

Case Conclusion

The patient received 25 U/kg of his own exogenous factor VIII for a correction of 50%. Hemostasis was achieved within 30 minutes allowing for irrigation and repair of his wounds. Upon follow up for suture removal, the patient stated that the wounds remained hemostatic following the initial ED visit. He had continued to use his normal factor dosing following the ED visit and did not require additional extra doses.

Clinical Pearls

  • Replace factor with a patient’s own exogenous factor whenever available.
  • For MSK bleeds and epistaxis, replace up to 50% of factor. For severe bleeds, replace 100% of factor.
  • Each U/kg of factor VIII in hemophilia A increases factor by 2%Each U/kg of factor IX in hemophilia B increases factor level by 1%.
  • Aim for 50% correction in moderate bleeds and 100% correction for severe.
  • Cryoprecipitate, DDAVP, and FFP can be used as second-line agents in hemophilia A.
  • TXA can be useful for mucosal bleeding.
  • Patients with inhibitors may require recombinant factor VIIa or FEIBA.

 

References / Further Reading

  1. Delgado, Julio, et al. “Acquired Haemophilia: Review and Meta-Analysis Focused on Therapy and Prognostic Factors.” British Journal of Haematology, vol. 121, 2003, pp. 21–35., doi:10.1046/j.1365-2141.2003.04162.x.
  2. Singleton, Tammuella, et al. “Emergency Department Care for Patients with Hemophilia and Von Willebrand Disease.” The Journal of Emergency Medicine, vol. 39, no. 2, Aug. 2010, pp. 158–165., doi:10.1016/j.jemermed.2007.12.024.
  3. Bhat, Rahul, and Whitney Cabey. “Evaluation and Management of Congenital Bleeding Disorders.” Emergency Medicine Clinics of North America, vol. 32, no. 3, Aug. 2014, pp. 673–690., doi:10.1016/j.emc.2014.04.009.
  4. Hemphill, Robin R. “Hemophilias and von Willebrand’s Disease.” Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e Eds. Judith E. Tintinalli, et al. New York, NY: McGraw-Hill, 2016, http://accessmedicine.mhmedical.com.ezproxy.rush.edu/content.aspx?bookid=1658&sectionid=109444198.
  5. Kulkarni, Roshni, and J. Michael Soucie. “Pediatric Hemophilia: A Review.” Seminars in Thrombosis and Hemostasis, vol. 37, no. 07, 2011, pp. 737–744., doi:10.1055/s-0031-1297164.
  6. Bansal, Deepak, et al. “Approach to a Child with Bleeding in the Emergency Room.” The Indian Journal of Pediatrics, vol. 80, no. 5, 27 Dec. 2012, pp. 411–420., doi:10.1007/s12098-012-0918-2.
  7. Nolan, B., et al. “Desmopressin: Therapeutic Limitations in Children and Adults with Inherited Coagulation Disorders.” British Journal of Haematology, vol. 109, no. 4, 24 Dec. 2001, pp. 865–869., doi:10.1046/j.1365-2141.2000.02067.x.
  8. Noble, Sarah, and Jaydeep Chitnis. “Case Report: Use of Topical Tranexamic Acid to Stop Localised Bleeding.” Emergency Medicine Journal, vol. 30, no. 6, 25 July 2012, pp. 509–510., doi:10.1136/emermed-2012-201684.
  9. Gouw, Samantha C., et al. “Factor VIII Products and Inhibitor Development in Severe Hemophilia A.” New England Journal of Medicine, vol. 368, no. 3, 17 Jan. 2013, pp. 231–239., doi:10.1056/nejmoa1208024.

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