Guidelines
Guidelines Summary
Guidelines on the management of acute joint bleeds and chronic synovitis in hemophilia were issued by the United Kingdom Haemophilia Centre Doctors' Organisation in 2017. [74] Recommendations on hemostatic management of patients with hemophilia A without inhibitors were as follows:
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All patients with severe hemophilia A and other patients at risk of joint bleeding should be offered home treatment.
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The initial treatment of early and moderate bleeds should aim for a peak factor VIII (FVIII) of 50 to 60 IU dL −1. This is equivalent to 25 to 30 IU kg −1 for severe hemophilia A for standard and extended half-life products.
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Early bleeds often do not require a second infusion, and moderate bleeds often respond to a single infusion but may require up to 2 infusions.
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Children may require more frequent or higher doses, as they have a shorter factor half-life than adults.
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For joint-immobilizing bleeds, higher initial doses are recommended, which aim to raise the peak FVIII level to 60 to 80 IU dL −1. Doses should be administered every 24 hr until complete resolution of pain. For severe bleeds, more frequent administration may be required in the initial 48 hr with standard FVIII.
Recommendations for hemostatic management of patients with inhibitors to FVIII were as follows:
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Inhibitor patients should be encouraged to be on a home treatment program, and bleeds should be treated as early as possible.
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Activated prothrombin complex (aPCC) 50–100 μg kg −1 or recombinant factor VIIa (rFVIIa) 270 μg kg −1 as a single dose (or 90 μg kg −1 2–3 hourly) are equally acceptable treatments for joint or soft tissue bleeds with repeated doses as necessary. The frequency of infusion and duration of treatment should be determined by the clinical response.
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The total daily dose of aPCC should not exceed 200 IU kg −1.
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Tranexamic acid can be considered as adjunctive therapy to aPCC and rFVIIa.
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Sequential alternating treatment of aPCC and rFVIIa can be considered for the management of limb/life-threatening bleeds.
Media Gallery
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Coagulation pathway.
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The hemostatic pathway. APC = activated protein C (APC); AT-III = antithrombin III; FDP = fibrin degradation products; HC-II = heparin cofactor II; HMWK = high-molecular-weight kininogen; PAI = plasminogen activator inhibitor; sc-uPA = single-chain urokinase plasminogen activator; tc-uPA = two-chain urokinase plasminogen activator; TFPI = tissue factor pathway inhibitor; tPA = tissue plasminogen activator
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Structural domains of human factor VIII. Adapted from: Stoilova-McPhie S, Villoutreix BO, Mertens K, Kemball-Cook G, Holzenburg A. 3-Dimensional structure of membrane-bound coagulation factor VIII: modeling of the factor VIII heterodimer within a 3-dimensional density map derived by electron crystallography. Blood. Feb 15 2002;99(4):1215-23; Roberts HR, Hoffman M. Hemophilia A and B. In: Beutler E, Lichtman MA, Coller BS, et al, eds. Williams Hematology. 6th ed. NY: McGraw-Hill; 2001:1639-57; and Roberts HR. Thoughts on the mechanism of action of FVIIa. Presented at: Second Symposium on New Aspects of Haemophilia Treatment; 1991; Copenhagen, Denmark.
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Possible genetic outcomes in individuals carrying the hemophilic gene.
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Photograph of a teenage boy with bleeding into his right thigh as well as both knees and ankles.
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Photograph of the right knee in an older man with a chronically fused, extended knee following open drainage of knee bleeding that occurred many years previously.
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Photograph depicting severe bilateral hemophilic arthropathy and muscle wasting. The 3 punctures made into the left knee joint were performed in an attempt to aspirate recent aggravated bleeding.
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Radiograph depicting advanced hemophilic arthropathy of the knee joint. These images show chronic severe arthritis, fusion, loss of cartilage, and joint space deformities.
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Radiograph depicting advanced hemophilic arthropathy of the elbow. This image shows chronic severe arthritis, fusion, loss of cartilage, and joint space deformities.
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Photograph of a hemophilic knee at surgery, with synovial proliferation caused by repeated bleeding; synovectomy was required.
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Large amount of vascular synovium removed at surgery.
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Microscopic appearance of synovial proliferation and high vascularity. If stained with iron, diffuse deposits would be demonstrated; iron-laden macrophages are present.
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Large pseudocyst involving the left proximal femur.
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Transected pseudocyst (following disarticulation of the left lower extremity due to vascular compromise, nerve damage, loss of bone, and nonfunctional limb). This photo shows black-brown old blood, residual muscle, and bone.
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Dissection of a pseudocyst.
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Transected pseudocyst with chocolate brown-black old blood.
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Photograph of a patient who presented with a slowly expanding abdominal and flank mass, as well as increasing pain, inability to eat, weight loss, and weakness of his lower extremity.
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Plain radiograph of the pelvis showing a large lytic area.
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Intravenous pyelogram showing extreme displacement of the left kidney and ureter by a pseudocyst.
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Photograph depicting extensive spontaneous abdominal wall hematoma and thigh hemorrhage in an older, previously unaffected man with an acquired factor VIII inhibitor.
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Magnetic resonance image of an extensive spontaneous abdominal wall hematoma and thigh hemorrhage in an older, previously unaffected man with an acquired factor VIII inhibitor.
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Coagulation Cascade
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Tables
Table 1. Hemophilia Severity, Factor Activity, and Hemorrhage Type
Classification |
Factor Activity, % |
Cause of Hemorrhage |
Mild |
>5-40 |
Major trauma or surgery |
Moderate |
1-5 |
Mild-to-moderate trauma |
Severe |
< 1 |
Spontaneous |
Table 2. General Guidelines for Factor Replacement for the Treatment of Bleeding in Hemophilia
Indication or Site of Bleeding |
Factor level Desired, % |
FVIII Dose, IU/kg |
Comment |
Severe epistaxis; mouth, lip, tongue, or dental work |
20-50 |
10-25 |
Consider aminocaproic acid (Amicar), 1-2 d |
Joint (hip or groin) |
40 |
20 |
Repeat transfusion in 24-48 h |
Soft tissue or muscle |
20-40 |
10-20 |
No therapy if site small and not enlarging (transfuse if enlarging) |
Muscle (calf and forearm) |
30-40 |
15-20 |
None |
Muscle deep (thigh, hip, iliopsoas) |
40-60 |
20-30 |
Transfuse, repeat at 24 h, then as needed |
Neck or throat |
50-80 |
25-40 |
None |
Hematuria |
40 |
20 |
Transfuse to 40% then rest and hydration |
Laceration |
40 |
20 |
Transfuse until wound healed |
GI or retroperitoneal bleeding |
60-80 |
30-40 |
None |
Head trauma (no evidence of CNS bleeding) |
50 |
25 |
None |
Head trauma (probable or definite CNS bleeding, eg, headache, vomiting, neurologic signs) |
100 |
50 |
Maintain peak and trough factor levels at 100% and 50% for 14 d if CNS bleeding documented† |
Trauma with bleeding, surgery |
80-100 |
50 |
10-14 d |
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