WORKUP	Section 5 of 10
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Lab Studies:

• Never delay indicated coagulation correction pending diagnostic testing.

• Hemoglobin/hematocrit

• Assess blood loss.

• Expect normal range or low values.

• Prothrombin time (PT)

• Extrinsic coagulation pathway screen

• Normal range expected

• Activated partial thromboplastin time (aPTT)

• Intrinsic pathway screen

• Elevated values expected

• May be normal range in mild disease

• Platelet count

• Assess bleeding.

• Expect normal range.

• Factor VIII level

• Assess percentage activity (normal 50-150%).

• Expect severe disease with less than 1%, moderate disease with 1-5%, and mild disease with greater than 5%.

• Factor VIII inhibitors

• Assess presence.

• Assess anamnestic response to factor VIII.

• Expect low titer (0-10 Bethesda U) or high titer (>10 Bethesda U).

Imaging Studies:

• Early and aggressive imaging is indicated, even with low suspicion for hemorrhage, after coagulation therapy is initiated.

• Head CT scan (noncontrast): Assess spontaneous or traumatic hemorrhage.

• Body CT scan

• Perform with or without intravenous (IV) and/or oral contrast.

• Perform as indicated by clinical suspicion and anatomical location.

• Assess spontaneous or traumatic hemorrhage.

• MRI

• Head and spinal column

• Further assessment of spontaneous or traumatic hemorrhage

• X-ray for joint assessment

• Of limited value in acute setting of hemarthrosis

• Chronic degenerative joint disease often present

• Special studies (as clinically indicated)

• Angiography

• Nucleotide bleeding scan

	TREATMENT	Section 6 of 10
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Prehospital Care:

• Rapid transport to definitive care is the mainstay of prehospital care.

• Prehospital care providers should do the following:

• Apply aggressive hemostatic techniques.

• Assist patients capable of self-administered factor therapy.

• Gather focused historical data if the patient is unable to communicate.

Emergency Department Care:

• Use aggressive hemostatic techniques.

• Correct coagulopathy immediately. Never delay indicated coagulation correction pending diagnostic testing.

• Include a diagnostic workup for hemorrhage.

• If possible, draw blood for the studies listed above, including 2 blue top tubes to be spun and frozen for factor and inhibitor assays.

Consultations:

• Hematologist/blood bank/pathologist

• Others as indicated by hemorrhagic complications

	MEDICATION	Section 7 of 10
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Factor VIII is the treatment of choice for acute or potential hemorrhage. Recombinant factor VIII concentrate is the preferred source of factor VIII. The factor VIII activity level should be corrected to 100% of normal for potentially serious hemorrhage (eg, CNS, trauma related, GI, genitourinary [GU], epistaxis) and to 30-50% of normal for minor hemorrhage (eg, hemarthrosis, oral mucosal, muscular). One unit of factor VIII is the amount of factor VIII in 1 mL of plasma (1 U/mL or 1%). The volume of distribution of factor VIII is that of plasma, approximately 50 mL/kg. The difference between the desired factor VIII activity level and the patient's native factor VIII activity level can be calculated by simple subtraction and expressed as a fraction (eg, 100% - 5% = 95% or 0.95).

To find the number of units of factor VIII needed to correct the factor VIII activity level, use the following formula:

Units factor VIII=(weight in kg)(50 mL plasma/kg)(1 U factor VIII/mL plasma)(desired factor VIII level minus the native factor VIII level)

As an example, an 80-kg individual diagnosed with hemophilia with known 1% factor VIII activity level presents to the ED with a severe upper GI bleed. The correct dose of factor VIII to administer to the patient would be calculated as follows:

Units factor VIII = (80 kg)(50 mL/kg)(1 U factor VIII/mL)(.99) = 3960

The next dose should be administered 12 hours after the initial dose and is one half the initial calculated dose. Minor hemorrhage requires 1-3 doses of factor VIII. Major hemorrhage requires many doses and continued factor VIII activity monitoring with the goal of keeping the trough activity level at least 50%. Continuous infusions of factor VIII may be considered for major hemorrhage.

Other medicinal adjuncts to factor VIII (eg, DDAVP, antifibrinolytics) often are useful in achieving hemostasis and can lessen the need for factor VIII infusion.

	MISCELLANEOUS	Section 9 of 10
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Medical/Legal Pitfalls:

• Failure to administer indicated coagulation correction promptly pending diagnostic testing

• Failure to monitor the results of treatments administered

• Failure to administer prophylactic factor VIII replacement, which is indicated prior to invasive procedures (eg, lumbar puncture [LP], tooth extraction)

• Failure to recognize the remote risk of viral infection from blood products

Special Concerns:

• Inhibitors

• Inhibitors are antibodies that neutralize factor VIII and can render replacement therapy ineffective.

• They are found more commonly in patients with moderate to severe hemophilia (up to 30% of those with severe disease) who have received significant amounts of replacement therapy.

• Inhibitors can rarely develop in individuals without hemophilia (eg, elderly persons, pregnant women) and occasionally are responsive to immunosuppressive therapy (eg, prednisone).

• Recent treatments with the anti-inhibitor coagulant complex factor VIII inhibitor bypassing activity (FEIBA) have shown promise.

• Immune tolerance strategies in those with identified inhibitors also have been successful.

• Assuming no anamnestic response, low-titer inhibitors occasionally can be overcome with high doses of factor VIII.

• High-titer inhibitors have been treated with variable success using porcine factor VIII, factor IX complex concentrates, recombinant factor VIII, and exchange plasma pheresis.

• Combination therapy with activated prothrombin complex concentrate and recombinant factor VIIa has been used with caution in the inpatient setting.

• Early hematology consultation for management of this type of patient is essential.