Type of hemorrhage Factor replacement guidance Additional management • Life-threatening hemorrhage • Severe head injury • CNS bleed or nerve compression • Major trauma • Throat/neck swelling • Intra-abdominal/GI bleed 100% factor correction; may Appropriate intensive care consider continuous Head imaging factor infusion depending Additional imaging studies on injury (FVIII) or q12hr dosing (FIX) Major bleed/procedure 50–100% initial factor correction and will likely • Hemarthrosis need repeated doses • Iliopsoas or thigh bleed • Compartment syndrome (forearm/calf) • Periodontal surgery • Major surgery Rest, ice, compression, elevation No weight bearing Non-NSAID pain control Measurements may be helpful to check for enlargement Minor bleed/procedure • Expanding SQ bleed • Muscle • Fracture • Tooth extraction/filling • Mild/moderate trauma • Sutures 25–50% factor correction; may need repeated doses Fractures require factor replacement at least until swelling subsides (at least days and generally 5–7 days) Rest, ice, compression, elevation No weight bearing Non-NSAID pain control Measurements may be helpful to check for enlargement Minimal bleeding • Epistaxis • Subcutaneous bleed • Mouth/tongue laceration • Abrasions/lacerations (no sutures) Factor replacement typically Hold pressure/cold not needed compress Consider antifibrinolytic agent Measurement of bruise may be helpful to check for enlargement Hematuria Factor replacement only if (painless/nontraumatic) fails all conservative measures Increase fluid intake PO/IV Exclude infectious etiology Bed rest Steroids (0.5–1 mg/kg/day) × days if persists after 24 hrs of increased hydration Antifibrinolytic medications contraindicated Emicizumab is a recombinant, humanized, bispecific monoclonal antibody that mimics part of the cofactor function of activated factor VIII promoting improved hemostasis in individuals with FVIII deficiency with or without inhibitors It is indicated for prophylaxis in both adults and children and is administered subcutaneously typically weekly Emicizumab is not indicated for bleed treatment It may provide adequate hemostasis for minor procedures; however, major surgeries or trauma will require additional hemostatic agents For patients without inhibitors, FVIII replacement using conventional dosing strategies is appropriate For patients with inhibitors, rFVIIa is the bypassing agent of choice as several severe adverse events have occurred with concomitant use of activated prothrombin complex concentrate (aPCC) FEIBA (Factor Eight Inhibitor Bypassing Agent) Emicizumab interferes with routine coagulation assays such as aPTT and FVIII activity assays These tests should not be sent or used to inform clinical decision making about a patient’s level of hemostasis CNS Bleed/Head Injury All major head injuries require evaluation by a physician and immediate treatment with a goal of correction to 100% factor activity level A pathway for the management of head trauma in patients with hemophilia is avaliable at https://www.chop.edu/clinical-pathway/hemophilia-with-head-trauma-clinical-pathway For patients with minor trauma without any symptoms or external evidence of injury, or the child with mild hemophilia, replacement therapy may not be required Any child with moderate or severe hemophilia needs careful attention to the type of trauma and bleeding history for the physician to decide whether to use replacement therapy A CT scan of the head is indicated for patients with hemophilia if there is any sign of trauma (e.g., hematoma), history of falling downstairs or from crib/changing table, hitting the head on a hard surface or corner, altered mental status, vomiting, or focal neurologic changes There should be a low threshold to perform a CT scan on patients with prior history of head bleed even if the mechanism of injury seems minor Children with seemingly insignificant trauma may develop the first obvious signs of intracranial bleeding several days later when concern has diminished For patients with mild to moderate hemophilia, imaging is indicated for any clinical features concerning for neurologic injury such as lethargy, vomiting, or focal neurologic changes For children with indeterminate presentations (e.g., mild mechanism of injury and normal neurologic examination), consideration of imaging versus observation is based on the severity of the hemophilia combined with usual management strategies for pediatric head trauma If the trauma is mild (e.g., a light bump on the forehead), patients may be observed at home for the usual signs of intracranial hemorrhage or increased intracranial pressure Ruling out intracranial hemorrhage does not exclude the possibility of a concussion Persistent symptoms after an intracranial bleed have been excluded warrant follow-up with the patient’s primary provider and specialists as indicated Emergent or Major Surgery The indications for surgery are similar to those for children without coagulation disorders, provided an appropriate correction of clotting abnormalities is planned When the need for surgery has been definitively established, correction up to 100% should be given and the aPTT should be measured to ensure its normalization Throat or Neck Swelling For bleeds of the neck muscles, careful evaluation of airway patency is essential Pressure on the airway from a fascial bleed of the neck may become life threatening, requiring steps to ensure airway patency such as endotracheal intubation, in addition to correction of the factor level to 100% Complete airway obstruction may also result from extensive bleeding in the tongue Early anticipation of the need to secure the airway is essential in these presentations Compartment Syndrome If there is concern for nerve compression or vascular insufficiency in a child with a muscle or soft tissue bleed, immediate intervention is important Compartment syndrome is a limb-threatening event Imaging of the affected area and consultation with orthopedics is necessary Iliopsoas or Thigh Hemorrhage Retroperitoneal bleeds can be life threatening and may present with lower abdominal pain A mass is sometimes palpable deep in the pelvis, and sensation in the distribution of the femoral nerve may be diminished Loss of the psoas shadow may be seen on an abdominal radiograph, and a hematoma may be demonstrated by ultrasonography The hemoglobin level should be measured initially and, if bleeding persists, at regular intervals thereafter Hematuria When the child with hemophilia develops hematuria or flank tenderness after trauma, a more aggressive approach to diagnosis and treatment is required Perform ultrasound, CT, or MRI as soon as possible to look for subcapsular or intrarenal bleeding or an obstructive clot at the pelvic–ureteral junction To prevent parenchymal damage and deterioration of renal function, administer replacement therapy to achieve a level of 70% to 100% immediately Atraumatic, painless hematuria generally does not require replacement therapy, but rest and hydration are key Management of Patients with Inhibitors The treatment of bleeding episodes in the child with hemophilia and alloantibodies (i.e., inhibitors) against the missing or diminished factor is challenging and should be managed in conjunction with a hematologist especially for those hemophilia A patients on emicizumab prophylaxis Options for treatment depend on the clinical scenario and inhibitor titer Possible therapies include massive doses (100 to 200 units/kg) or continuous infusion of factor product, aPCCs such as FEIBA, or rFVIIa [NovoSeven]) Hemophilia B patients with inhibitors are at risk of severe allergic reaction/anaphylaxis when receiving factor; FEIBA is contraindicated in this setting because it contains factor IX Factor IX inhibitor complexes can precipitate and eventually cause nephrotic syndrome and renal failure Clinical Indications for Discharge or Admission Severe, life-threatening bleeding events require monitoring for CNS or airway complications Hemarthrosis may require hospitalization for immobilization and elevation of limb, pain control, or serial examinations Minor or moderate bleeds including some hemarthroses and superficial muscle bleeds can usually be managed on an outpatient basis VON Willebrand Disease CLINICAL PEARLS AND PITFALLS DDAVP is a good therapeutic option for patients with type disease who have previously demonstrated response to a DDAVP challenge DDAVP is generally ineffective for those with subtypes of type and type disease and can exacerbate symptoms in patients with type 2B disease by accelerating platelet clearance Patients with type VWD typically manifest a clinical phenotype similar to patients with severe hemophilia Current Evidence VWD is the most common inherited bleeding disorder affecting about 1% of the population; however, only a small fraction of patients manifest bleeding symptoms VWF plays a key role in coagulation by facilitating platelet aggregation and adhesion and serving as a carrier molecule for factor VIII There are three main types of VWD: Type is a deficiency of VWF, type subtypes are functional defects associated with VWF, and type is an absence of VWF The vast majority of patients with VWD have type 1, inherited in an autosomal dominant pattern with variable expressivity and penetrance Clinical Considerations Clinical Recognition The sites of bleeding in VWD (types and 2) resemble the mucocutaneous bleeding found in patients with platelet disorders such as bruising, epistaxis, oral bleeding, GI bleeding, and menorrhagia Joint and deep muscle bleeding is unusual except in cases of children affected by type VWD Since the most common type of VWD is a dominant ... observation is based on the severity of the hemophilia combined with usual management strategies for pediatric head trauma If the trauma is mild (e.g., a light bump on the forehead), patients may be