Hemophilia

Hemophilia A and B are sex-linked (X chromosome) recessive disorders. Hemophilia A is a clotting factors VIII (FVIII) deficiency affecting one in every 5,000–10,000 male births. Hemophilia B is a clotting factor IX (FIX) deficiency which has a an occurrence of approximately one per 30,000–50,000 male births. Both factors as involved in the intrinsic coagulation pathway leading to an increase in activated partial thromboplastin time (aPPT). The hallmark of hemophilic bleeding  is hemarthroses. The penetrance determines the patient’s baseline clotting factor level which determines the severity of symptoms, and frequency of bleeding episodes. Both disorders are classified into three categories according to the coagulation factor activity: severe (<1%), moderate (1–5%), and mild (>5% to <40%).

The main objective when a patients presenting to the ED with bleeding symptoms is to elevate the circulating levels of the deficient clotting factor as soon as possible. “Major bleeding” (ie life threatening) includes: head trauma with potential intracranial hemorrhage, throat/neck hemorrhage with potential airway obstruction, brisk intra-abdominal or retroperitoneal hemorrhage, bleeding into a closed space such as a large muscle leading to a compartment syndrome, and post-traumatic or post-surgical bleeding. Most patients and their family are trained in administration and dosing, it is recommended that their recommendations be followed and if available the patients clotting factor concentrates be utilized. The desired FVIII of FIX level is 30–50% for minor/moderate bleeding, and 80–100% for severe/life-threatening hemorrhage.

Hemophilia A:

  • Purified FVIII concentrate
    • Minor bleed: 25 IU/kg
    • Major bleed: 50 IU/kg loading dose which may be followed by continuous infusion of 3 IU/kg/h for 24 h or 25 IU/kg q 12 h until hemostasis achieved
  • Cryoprecipitate: Use only if concentrate factors not available. 10 bags initially, check FVIII level. Pediatric dosing is 1 bag/6 kg body weight. Each unit of FVIII/kg results in a 2% rise in plasma FVIII.
  • Desmopressin acetate (DDAVP) can be used for baseline FVIII levels > 10%. Only for known responders.

Hemophilia B:

  • Purified FIX concentrate
    • Minor bleed: 40 IU/kg
    • Major bleed: 80–100 IU/kg loading dose, 50 IU/kg every 18–24 h until full hemostasis
  • Fresh Frozen Plasma: Use only when FIX concentrates are not available. 15 mL/kg initially, check FIX level. Hemostatic concentration of FIX is difficult secondary to volume overload.

Patient with inhibitors to factor concentrates (occurs 20-30% to FVIII and <5% to FXI)

  • “Low responding” inhibitor (<5 BU): 2-3 times the standard factor dose. In some cases, elevation of factor levels is best obtained by administering a large bolus dose, followed by continuous infusion of factor concentrate.
  • “High responding” inhibitors (> 5 BU): bypassing agents include FEIBA-VH and NovoSeven should be used.
Singleton T, Kruse-Jarres R, Leissinger C. Emergency department care for patients with hemophilia and von Willebrand disease. J Emerg Med. 2010 Aug;39(2):158-65. Epub 2008 Aug 30
Berntorp E, Shapiro AD. Modern haemophilia care. Lancet. 2012 Apr 14;379(9824):1447-56. Epub 2012 Mar 27.
 

About these ads
This entry was posted in Hematology. Bookmark the permalink.

One Response to Hemophilia

  1. 40yearoldpremed says:

    Excellent post. I am studying this very topic in my A&P II class right now. Thank you for all of your very relevant information.

Leave a Reply

Please log in using one of these methods to post your comment:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s