Appendix B

Suggested treatment for spontaneous and traumatic bleeding episodes in high-risk patients

Clinical situation	Treatment
Intracerebral hemorrhage	rFVIIa: 15–30 µg/kg every 4–6 h for a minimum of 3 days or continuous infusion as described under major surgery. Tranexamic acid: initially 10 mg/kg i.v. ttd. then given orally at 20 mg/kg ttd. for a total of 3-7 days.
Subarachnoidal hemorrhage	rFVIIa: 15–30 µg/kg every 4–6 h until aneurism is clipped/coiled or for a minimum of 3 days or continuous infusion as described under major surgery. Tranexamic acid: Application in subarachnoidal hemorrhage is controversial. Consider 1g i.v. immediately at diagnosis repeated every 6 hours until aneurism is clipped/ coiled or for a maximum of 72 hours [1].
Subdural hemorrhage	rFVIIa: 15–30 µg/kg every 4–6 h for a minimum of 6 doses or continuous infusion as described under major surgery. Tranexamic acid: initially 10 mg/kg i.v. ttd. then given orally at 20 mg/kg t.i.d. for a total of 3-7 days.
Major traumatic bleeds	rFVIIa: 15–30 µg/kg every 4–6 h until bleeding is stopped or continuous infusion as described under major surgery. Tranexamic acid: initially 10 mg/kg i.v. ttd. then given orally at 20 mg/kg t.i.d. for a total of 3-7 days.
Hemarthrosis	rFVIIa: 15–30 µg/kg every 4–6 h for a minimum of 3 doses. Tranexamic acid: initially 10 mg/kg i.v. ttd. then given orally at 20 mg/kg ttd. for a total of 3-7 days.
Muscle hematoma	rFVIIa: 15–30 µg/kg every 4–6 h for a minimum of 3 doses. Tranexamic acid: 10 mg/kg i.v. ttd. or 20 mg/kg p.o, ttd. for a total of 3-7 days.
Subcutaneous hematoma	Tranexamic acid: 20 mg/kg ttd. orally for a total of 3-7 days. rFVIIa: In gross hematomas consider a single dose of 15–30 µg/kg, repeated if needed after 4-6 hours.
Superficial cutaneous bleeding	Tranexamic acid: Locally applied 4 times daily, and/or 20 mg/kg ttd. p.o. for a total of 3-7 days.
Epistaxis	Tranexamic acid: 20 mg/kg ttd. p.o. for a total of 3-10 days [2]. rFVIIa: In gross bleeding consider a single dose of 15–30 µg/kg, repeated if needed after 4-6 hours. Alternatively, one single dose of 60 µg/kg [3].
Gum bleeds	Tranexamic acid: Mouthwash four times daily for a total of 3-7 days or 20 mg/kg ttd. orally for a total of 3-7 days. rFVIIa: Consider a single dose of 15–30 µg/kg, repeated if needed after 4-6 hours. Alternatively, one single dose of 60 µg/kg [3].
Upper gastrointestinal bleeds	rFVIIa: 15–30 µg/kg every 4–6 h at least until gastroscopy or for a minimum of 3 doses. Tranexamic acid: Consider 10 mg/kg i.v. ttd. or 20 mg/kg p.o t.i.d. for a total of 3-7 days.
Lower gastrointestinal bleeds	rFVIIa: 15–30 µg/kg every 4–6 h until coloscopy or for a minimum of 3 doses. Tranexamic acid: Consider 10 mg/kg i.v. ttd. or 20 mg/kg p.o ttd. for a total of 3-7 days.
Menorrhagia	Oral contraceptives with estrogen/hormonal intrauterine devices. Tranexamic acid: 20 mg/kg ttd. orally on days with heavy bleeding. rFVIIa: Consider a single dose of 15–30 µg/kg, repeated if needed after 4-6 hours.
Upper urinary tract bleeds	rFVIIa: 15–30 µg/kg every 4–6 h for a minimum of 3 doses.
Lower urinary tract bleeds	rFVIIa: 15–30 µg/kg every 4–6 h for a minimum of 3 doses. Tranexamic acid: Consider 10 mg/kg i.v. ttd. or 20 mg/kg p.o. ttd. for as short a time period as possible.

1.

Hillman J, Fridriksson S, Nilsson O, Yu Z, Säveland H, Jakobsson K-E. Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: A prospective randomized study. Journal of Neurosurgery 2002;97:771–8. doi:10.3171/jns.2002.97.4.0771.

2.

Petruson B. Epistaxis A clinical study with special reference to fibrinolysis. Acta Oto-Laryngologica 1974;77:1–73. doi:10.3109/00016487409129566.

3.

Mariani G, Konkle BA, Ingerslev J. Congenital factor VII deficiency: therapy with recombinant activated factor VII – a critical appraisal. Haemophilia 2006;12:19–27. doi:10.1111/j.1365-2516.2006.01180.x.