If you work long enough in the ED it is likely that you will see a child with hemophilia presenting to the ED. You may even have known ahead of time that they were coming. Regardless you definitely need to get moving when these patients arrive in your department – and if you remember “factor first” you’ll be keeping the most important treatment consideration in mind. Know also, that there are no consensus guidelines or treatment algorithms, so the purpose of this post is to help you think systematically before these patients arrive.
Just because children have hemophilia it doesn’t mean they won’t roll out of bed, or lacerate their chin on the corner of a coffee table, or take a tumble on their way to AP Biology class. Many of these patients receive regular factor infusions and have complex management regimens. Others will have a history of hemophilia but no bleeding risk at all. It can be overwhelming to try to parse this all out in the ED – and there’s time for that – just not initially. Give factor first if the patient warrants it, and come back to learn the interesting details of their disease later. These patients always need to be a triage priority as well.
|Hemophilia A||X-Linked recessive disease. Deficiency of factor VIII. 1/5,000 males. 80% of all hemophilia patients. One-third have severe disease.||IV Factor VIII|
|Hemophilia B||X-Linked recessive disease. Deficiency of factor IX. 1/30,000 males. 60% have severe disease.||IV Factor IX|
|Von Willebrands||The most common bleeding disorder in the US. Only 10% of lab-defined vWD have clinical disease. Multiple subtypes. Deficit in amount/function of vWF.||Von Willebrand Factor or desmopressin|
The three most common diseases that will present to the ED are Hemophilia A, Hemophilia B, and Von Willebrands. The hemophilias are further subcategorized by severity. You should at the very least know (if you can) the severity of hemophilia or sub-type of von Willebrands. The presence of inhibitors can increase the risk of significant bleeding. These inhibitors, well inhibit, clotting factors, and develop over time occurring more often in children with certain genetic risk factors and in those who get lots of factor treatment early on in life. A third of hemophilia A patients have them compared with 6.5% of hemophilia B. The presence of inhibitors means you may need to give more factor or a “bypass agent.”In general per Schwartz et al.;
Severe – Multiple bleeding episodes per month, usually in joints and soft tissues. can also have spontaneous bleeds
Moderate – Typically bleed 4 to 6 times per year, generally with mild trauma
Mild – May only hemorrhage with surgery or significant trauma
Let’s take a look at some of the ways these patients will present to the ED in a little bit of detail, and how to treat them. I’ll include a table of factor dosing recommendations at the end. Note that I won’t specifically state which factor to give. Also, in general Von Willebrand treatment is categorized as either desmopressin responsive versus not. Patients that are desmopressin responsive can get it IV or intranasally. Otherwise they can get von Willebrand’s factor concentrates IV.
Don’t prioritize labs over the administration of factor. Early factor treatment helps decrease total factor requirement and length of hospitalization. Access a central line if they have one and check with local recommendations on which labs to get. In general a CBC and type and screen are needed. Specific factor levels and coags are necessary only if Hematology asks for them.
This is the most common bleeding symptom in hemophiliacs. They will complain of mild pain in the joint, at least initially, that progresses to more significant pain, swelling, redness and decreased range of motion. The ankles, elbows and knees are the most common joints. Hemarthosis is usually clinically apparent and unless you suspect a fracture you don’t need to get plain radiographs. Ultrasound is sensitive as well. But most patients don’t need imaging at all.
The treatment is early factor administration, ice, a compression bandage, and acetaminophen +/- opioids for pain management. Don’t give NSAIDs, as they can add an anti platelet effect. Corticosteroids don’t have evidence for their use. Joint aspiration is not recommended. Many patients can be managed at home after a single dose in the ED. Experienced parents may want to manage this at home.
This is the second most common bleeding problem seen in patients with hemophilia who present to the ED. Treatment, is of course IV factor and acetaminophen +/- opiates. The main complication of note is compartment syndrome. Nerve compression is also worrisome.
Iliopsoas hemorrhage is important to call out specifically, since patients can lose A LOT of blood. Patients can have a combination of thigh, hip, abdomen and/or groin pain. The long term risk is development of a devastating hip flexion contracture. Patients can also end up with femoral nerve paresthesias. Iliopsoas hemorrhage occurs without warning. Factor treatment goals are higher than those of other muscle bleeds. Patients are admitted, and placed on strict bed rest followed by 7-14 days of inpatient treatment. If you need imaging help MRI is preferred, but ultrasound and CT can be used as well.
The prevalence is estimated to be 1/50 in children with hemophilia and can have devastating consequences. The most common risk factors for ICH are severe hemophilia, the presence of inhibitors, and a history of trauma. Per Witmer et al. only drowsiness and a history of loss of consciousness predicted intracranial hemorrhage in hemophiliacs. Altered mental status is predictive, but normal mental status can’t exclude the possibility of ICH.
You should have the lowest possible threshold to give factor when there is a history of head trauma. Ideally it should be given with in 6-hours. Give factor BEFORE imaging. Head CT is quick and readily available to identify bleeding, but you should not apply the PECARN clinically important traumatic brain injury clinical decision rule to hemophiliacs as it does not apply. MRI may better identify posterior fossa bleeding in these patients.
In vWD there are no consensus guidelines for when to obtain head imaging. This is when knowing which type (types 2N or 3 are more at risk as they are more like hemophilia) can help. Any child with an abnormal Neuro exam or depressed mental status after a head injury should be imaged.
This is less often seen in hemophiliacs, and may represent another process rather than hemophilia itself. Treatment is IV factor, appropriate resuscitation, IV PPI, and consultation with GI. Kids with significant hemorrhage are admitted.
This is also more rarely seen. Treatment is IV factor, and aggressive rehydration with fluids at least at a rate 1.5 times maintenance. Interestingly, antifibrinolytic agents (TXA) can precipitate renal thrombi.
Nose and oral mucosal bleeds
Direct pressure, oxymetolazone spray (to the nose) and of course early administration of factor. Antifibrinolytic agents tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) have been utilized in these situations as well.
Minor bruises, wounds, and lacerations
Give factor, then repair as you normally would. Soft tissue injuries (big bruises) may also occur in conjunction with muscle bleeds. Ultrasound, MRI or CT can help make the diagnosis.
Treatment consists of both factor as well as hormonal contraceptives. Otherwise speak early with Hematology and Gynecology if you are worried.
There are many different types of replacement factor. Two of the more common ones in use include Advate and Benefix. I remember which is for which because AdvATE = factor EIGHT / and BenfIX = IX factor 9! Just like units of blood, factor can come in odd aliquots. It is also SUPER expensive, so wasting it is not an option. If Hematology recommends 25 Units/kg and the available Advate is 24 Units/kg its OK not to order more. In general, in order to be respectful of cost round up to the nearest number of vials.
With that said, hematologists can generally predict how much each unit of Factor will increase plasma levels – Per Schwartz. “In general, 1 unit/kg of factor VIII will increase factor VIII in the recipient’s plasma by 2% (0.02 IU/ mL), whereas 1 unit/kg of factor IX will increase the factor IX in the recipient’s plasma by 1% (0.01 IU/mL).” Always consult with Hematology regarding specific dosing and goals.
For severe bleeds (without an inhibitor) the following general dosing considerations are a good starting point:
- Hemophilia A initial dose of factor VIII 50 units/kg
- Hemophilia B initial dose of factor IX of 100 units/kg
For less significant bleeds – for instance hemarthroses – lower factor doses may be recommended
- Hemophilia A initial dose of factor VIII 25 units/kg
- Hemophilia B initial dose of factor IX 50 units/kg
And finally, key questions you should always ask in the ED…
- Which bleeding disorder does the child have?
- Is the disease severe, moderate, or mild?
- Does the patient have an inhibitor?
- What is the dose and specific factor/medicine that the patient needs to get?
- Did the patient bring their home-dose of factor with them?
- Do they have a port or other type of existing access?
Di Michele D, Neufeld EJ. Hemophilia: a new approach to an old disease. Hematol Oncol Clin North Am. 1998;12(6):1315- 1344.
Di Michele D. Inhibitor treatment in haemophilias A and B: inhibitor diagnosis. Haemophilia. 2006;12(Suppl 6):37-42.
Labarque V, Stain AM, Blanchette V, et al. Intracranial haem- orrhage in von Willebrand disease: a report on six cases. Heamophilia. 2013;19(4):602-606.
Melchiorre D, Linari S, Innocenti M, et al. Ultrasound detects joint damage and bleeding in haemophilic arthropathy: a proposal of a score. Haemophilia. 2011;17(1):112-117.
Nagel K, Pai MK, Paes BA, et al. Diagnosis and treatment of intracranial hemorrhage in children with hemophilia. Blood Coagul Fibrinolysis. 2013;24(1):23-27.
Oren H, Yaprak I, Irken G. Factor VIII inhibitors in patients with hemophilia A. Acta Haematologica. 1999;102(1):42-46.
Schwartz et al. Hemophilia And Von Willebrand Disease In Children: Emergency Department Evaluation And Management. EB Medicine, 2015.
Witmer C, Presley R, Kulkarni J, et al. Associations between intracranial haemorrhage and prescribed prophylaxis in a large cohort of haemophilia patients in the United States. Br J Haematol. 2010;152(2):211-216.
Witmer CM, Raffini LJ, Manno CS. Utility of computed tomography of the head following head trauma in boys wth haemophilia. Haemophilia. 2007;13(5):560-566.