Haemophilia
Introduction
Haemophilia is a disorder of coagulation caused primarily by a deficiency in a circulating plasma protein. Haemophilia A and B are the most common severe inherited coagulation disorders. Haemophilia rarely occurs as a result of a spontaneous mutation. Much more commonly it is a hereditary X linked recessive disorder meaning females are typically asymptomatic carriers of the gene, while males suffer from the disease. Most boys will present towards the end of the first year of life, with almost 40% of cases presenting in neonates.
Haemophilia A is caused by Factor VIII deficiency and has a frequency of 1 in 5000 male births.
Haemophilia B is caused by Factor IX deficiency and has a frequency of 1 in 30000 male births.
The two are clinically indistinguishable from each other, and specific factor testing is required to identify the specific type of haemophilia
The disorder is graded as severe, moderate or mild depending on factor levels with severity often remaining constant within a family:
Complications of Haemophilia
Bleeding post operatively
Bleeding after minor or major trauma
Spontaneous bleeds into joints, muscles and soft tissue. Some of these bleeds may be life threatening ie if they are intracranial, GI or in the neck/throat causing airway compromise.
Inhibitors- ie antibodies to FVIII of FIX develop in 5-20% of cases and may reduce or completely inhibit the effect of treatment .
Treatment of patients with haemophilia relies on either the replacement of missing factors or, for those with mild Factor VIII deficiency, stimulating the body to secrete additional clotting factor from intracellular stores.
Clinical Features
Symptoms
Excessive bruising
Bleeding gums
Excessive bruising or bleeding out of proportion to degree of trauma/injury
Pain secondary to bleeding into joints or muscles
Haematuria
Signs
Joints and muscles are most common site of haemorrhage
Haemarthrosis, haematomas
Bleeding can also occur in abdomen, retroperitoneum or CNS
Therefore the patient may present in haemorrhagic shock, with an acute abdomen or with acute neurological findings
Mucocutaneous bleeding
GI bleed, epistaxis, bleeding gums
Differential Diagnosis
DDx for Coagulopathy
In paediatric population, especially in first presentations, be suspicious for non accidental injury in any child that presents with bleeding or bruising that is out of proportion to trauma described
Bleeding due to platelet disorder
Disorders of platelet production (thrombocytopaenia)
Drugs (alcohol, chemotherapy, valproate)
bone marrow replacement e.g. malignancy, fibrosis
bone marrow aplasia
B12 deficiency
Increased loss or consumption of platelets
Splenic sequestration
Autoimmune thrombocytopaenia e.g. ITP, HIV, Lymphoproliferative disorders
Disseminated intravascular coagulation (DIC)
Thrombotic thrombocytopaenia (TTP)
Sepsis
Disorders of platelet function
Congenital = Von-Willebrand disease
Acquired = medications (Aspirin, clopidogrel), Uraemia, myeloproliferative disorder (essential thrombocytopaenia)
Bleeding due to clotting factor abnormalities
Congenital
Haemophilia
Other clotting factor disorders (v rare)
Acquired deficiency of clotting factors
Liver Disease
Vit K inhibition (warfarin) or deficiency
Inhibition of factors (DOAC)
DIC
DDx for acutely swollen joint
Trauma
ligamentous, meniscal, boney injury
Infection
septic arthritis, gonococcal infection, lyme disease, mycobacteria
Crystal arthropathies
gout, pseudogout
Rheumatic Disease
rheumatoid arthritis, reactive arthritis, psoriatic arthritis, SLE, sarcoidosis
Tumour
Osteoarthritis and overuse syndromes
Clinical Investigations
Bedside
VBG - for rapid assessment of Hb and lactate
POCUS - if concerned about intraperitoneal haemorrhage
Urine Disptick - ? haematuria
Laboratory
FBC - assessment of Hb
Coagulation - assess PT/APTT levels
Factor levels can also be checked on this specimen if haematology request same
U&E, LFT, CRP
Group and crossmatch
Radiology
X-ray of involved joint
looking for joint effusion indicating haemarthrosis,
underlying fracture secondary to trauma
evidence of recurrent/chronic haemarthrosis
CT scanning based on clinical presentation
Management
All registered patients with bleeding disorders in Ireland should have a registration card which shows their diagnosis on the front and the contact details for their comprehensive care centre (i.e SJH, CUH, GUH or Our Ladies Children’s Hospital Crumlin) on the back
Contact the patient’s CCC immediately to confirm the diagnosis, blood levels and haemostatic treatment of choice. The local Haematology service should also be informed as they will need to co-ordinate local treatment stocks and give local advice and support
Treatment guidelines are available online for all of the bleeding disorders. These give step-by-step guidance for managing these patients and for reconstituting and administering haemostatic treatments and advice on pain management - http://www.nationalhaemophiliacouncil.ie/home/
Indications for Factor Replacement
Suspected bleeding into a joint or muscle
Any significant injury to the head, neck, mouth or eyes or evidence of bleeding in these areas
Any new or unusual headache
Severe pain or swelling at any site
All open wounds requiring surgical closure, wound adhesive or steri strips
History of an accident or trauma that may result in internal bleeding
Any invasive procedure or surgery
GI bleeding leading to moderate or severe anaemia
Heavy menstrual bleeding leading to moderate to severe anaemia or volume instability
Indications for Admission
Disposition decisions should be made in conjunction with haematology
In general, patients presenting with the following conditions/ bleeding sites require admission:
Head injury/ intracranial haemorrhage
Spinal cord
Neck/tongue/throat
GI bleed/ intra-abdominal
Psoas haemorrhage
Blunt trauma
Tight soft tissue bleeds
Bleeding into hip/inguinal area
Occular
Persistent haematuria
Severe persistent Epistaxis
References
Guidelines for the Emergency Department Management of Individuals with Haemophilia 2019.
Adults with Haemophilia and Related Bleeding Disorders, Acute treatment guidelines. National Haemophilia Council
Lissauer T, Carroll W. Illustrated textbook of Paediatrics Fifth Edition. 2018. Elsevier
This blog was written by Dr Sarah Daubras and was last updated in Feb 2021