Hemophilia

Study guide:

Definitions:  

Hemophilia is an X-linked disorder, inherited in a recessive pattern. Hemophilia A and B are the two main types. Males are affected more than females, due to disease mood of transition through X chromosome, X-linked recessive (keep in mind that females have two X chromosome that decrease chance of having the disease).

Deficiency of the clotting factor VIII and IX are the causes of Hemophilia A and B, respectively.

Epidemiology:

  • Hemophilia A : affects 1 in 5,000 male births. About 400 babies are born with hemophilia A each year.

  • Hemophilia B : It constitutes 20% of the total Hemophilia cases. occurring in 1 out of 20,000 babies.

  • Hemophilia C and Hemophilia D: no clear statistics about the diseases’ prevalence.

There are three ways to get this disorder:

  • Inherited (X-linked recessive) Figure 1-2

  • Spontaneous mutations

  • Acquired immunological defects

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Figure 1: The image shows one example of how the hemophilia gene is inherited. In this example, the father doesn't have hemophilia (that is, he has two normal chromosomes—X and Y). The mother is a carrier of hemophilia (that is, she has one hemophilia gene on one X chromosome and one normal X chromosome).

Hemophilia A

  • It is an X-lined disorder caused by the deficiency of clotting factor VIII.

  • It is the most common type of Hemophilia.

Hemophilia B

  • It is also known as Christmas disease.

  • Hemophilia B occurs due to the deficiency of clotting factor IX.

  • It is less common that Hemophilia A.

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Figure 2 :The image shows one example of how the hemophilia gene is inherited. In this example, the father has hemophilia (that is, he has the hemophilia gene on the X chromosome). The mother isn't a hemophilia carrier (that is, she has two normal X chromosomes).

Hemophilia C

  • It also occurs due to the deficiency of factor XI.

  • The symptoms are few and mild in intensity.

  • It is not transmitted in an X-link recessive pattern, so both the sexes are equally susceptible to the disease.

Hemophilia D

  • Hemophilia D occurs due to the deficiency of clotting factor XII

Classification of Pediatric Hemophilia:

  • Mild: The concentration of the clotting factor (VIII or IX) is 5–40 %

  • Moderate: 1–5 % of the clotting factors are available for the clotting mechanism

  • Severe: < 1 % of the clotting factors are present for the cascade

Symptoms and Signs of Pediatric Hemophilia (table 1)

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1.    Haemarthrosis: ‘Haem’ is blood and ‘arthrosis’ stands for joints, ‘bleeding in the joint spaces’.

  •        It is a specific sign of the disease.

  •        Ankles and knees are more commonly affected than the smaller joints.

  •        Repeated bleeding can lead to joint destruction.

2.    Bleeding into muscles: Hematoma formations can even lead to compartment syndrome.

3.    Gastrointestinal tract bleeding: A small peptic ulcer cannot be healed and lead to continuous bleeding.

4.    Urinary tract bleeding: It can present as hematuria.

5.    Intracranial bleeds: Symptoms such as:

  •         a headache, lethargy, nausea and vomiting start to appear.

  •         It needs immediate treatment.

6.    Bleeding after trauma and surgery: It is a common scenario in hemophilia children.

Diagnosis of Pediatric Hemophilia:

​There are three main steps of diagnosis. It is important to go step-wise as the warning signs can be missed.

1.    Examination:

After taking a detailed history of the patient, go towards the general physical and systemic examination. All the systems should be examined in details.

  • Neurological: Look for any abnormal findings, altered mental status, and signs of meningism

  • Musculoskeletal: Joint tenderness, warmth, swelling, and limited range of motions

  • Gastrointestinal: Examine for hepatic tenderness, splenic, and signs of peritonitis

  • Genitourinary: Bladder distensions, irritation, and tenderness of costovertebral angles

  • Other signs of airway obstruction and compartment syndrome should also be checked.

2.    Laboratory Investigations:

  • Complete blood cells CBC count and hemoglobin levels

  • Bleeding Time (BT) to test for platelet function

  • Clotting time (CT)

  • Coagulation studies:

    • PT (Prothrombin time)

    • and APTT (Activated Partial Thromboplastin Time)

  • Factor VIII, IX, and vWF (Von Willebrand factor) Assays

  • Testing for infections like hepatitis or AIDS

  • Genetic Testing

Differentiation between Hemophilia A and B and von Willebrand disease on lab tests table 2.

3.    Radiological Investigations

  • Head CT to look for a hemorrhage

  • MRI brain

  • Ultrasound for signs of effusions in the joint spaces

Management of Pediatric Hemophilia (table 3)

General approach:

  • Advise avoiding the trauma

  • Do not use aspirin

  • Immunization against infectious diseases like hepatitis

  • Genetic counseling

Specific treatment:

  • Factor IX concentrates (Hemophilia B)

  • Factor VIII concentrates (Hemophilia A)

  • If the concentrates are not available, then consider these options:

    • Whole blood

    • Fresh frozen plasma

    • Cryoprecipitate

  • Synthetic vasopressin analog, Desmopressin Acetate

  • Antifibrinolytics: Aminocaproic Acid and Tranexamic acid

  • Monoclonal antibodies (Rituximab)

  • Analgesics (acetaminophen)

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Overview of management:

References:

  1.  Pediatric Hemophilia — Pathophysiology and Types . 2018 Lecturio GmbH.

  2. Mayo Clinic Staff. 2014. “Diseases and Conditions: Hemophelia.” Available at: http://www.mayoclinic.org/diseases-conditions/hemophilia/basics/definition/con-20029824

  3. Schrader, John, 2015. “Hemophilia.” ResearchGate. Available at: https://www.researchgate.net/publication/284761902_Hemophilia.

  4. World Federation of Hemophilia. 2012. “Guidelines for the Management of Hemophelia.” Available at: https://www1.wfh.org/publication/files/pdf-1472.pdf.

  5. Way of Inheritance - https://www.nhlbi.nih.gov/health-topics/hemophilia

  6. Table of the symptoms - https://www.kokilabenhospital.com/health/healthtip/symptomsofhemophila.html

  7. Table of the symptoms - https://www.uspharmacist.com/article/hemophilia-review

  8. Management Table - https://www.uspharmacist.com/article/hemophilia-review

 

First author: 

Abdullah Al tamimi


Reviewed by: 

Ahmad Aldayel

Abdulrahman Alhassan


Format Editor:  

Noura Abdullah Alsubaie.