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:

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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

 
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Bedside

  • VBG - for rapid assessment of Hb and lactate

  • POCUS - if concerned about intraperitoneal haemorrhage

  • Urine Disptick - ? haematuria

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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

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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/

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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

  1. Guidelines for the Emergency Department Management of Individuals with Haemophilia 2019.

  2. Adults with Haemophilia and Related Bleeding Disorders, Acute treatment guidelines. National Haemophilia Council

  3. 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

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