Management of Hemophilia

Patient Guideline Summary

Publication Date: August 3, 2020

Last Updated: March 3, 2023

Objective

This patient summary means to discuss key recommendations from the World Federation of Hemophilia for the management of hemophilia.

Overview

Hemophilia is a hereditary bleeding disorder mainly affecting males. There are two main types (A and B) representing two different mutations among the genes that control blood clotting.
Hemophilia is caused by a non-functioning gene on the X chromosome. Since females have two X chromosomes, they are far less likely to have severe disease.
- There are other inherited bleeding disorders, the most common of which is Von Willebrand disease (VWD).
We will use the abbreviation CFCs throughout this summary to refer to clotting factor concentrates.
Symptoms include easy bruising, painful spontaneous bleeding into muscles, skin, joints, the brain, and the digestive tract, and an inability of blood to clot and stop the bleeding.
This patient summary focuses on international standards for the quality care of patients with hemophilia.

Diagnosis

Laboratory diagnosis and testing

Because some treatments differ, it is important to identify the type of hemophilia:
- Hemophilia A: deficiency of coagulation factor VIII (FVIII)
- Hemophilia B: deficiency of coagulation factor IX (FIX)
It is also important to identify “inhibitors” — antibodies that neutralize clotting factors —because they may require a different treatment using bypassing agents.
Women with one non-functioning gene are called “carriers.” Carriers may have symptoms and complications and are often misdiagnosed.
All blood relatives of a patient with hemophilia should be screened for abnormal genes.
Blood clotting is a complex interaction of multiple factors, all of which are important in managing bleeding disorders. A finely tuned balance between too little and too much clotting is crucial to successful treatment.

Treatment

Ideal requirements for comprehensive hemophilia care:

Prevention is the standard of care for all severe bleeding disorders and some less severe cases.
Prophylaxis (prevention) requires lifelong regular testing and replacement of needed clotting factors or substitutes.
Less severe cases can often be treated as bleeding events occur.
Lifelong 24/7 care
National patient registry to support research and assure accurate data for each patient.
Continuing research
Medical specialists in bleeding disorders
- physical therapist, psychosocial counselor, laboratory specialist, pain specialist, and physicians for all related specialties
Multidisciplinary teams available to each patient
The facilitated transition from pediatric to adult care
Patient self-management
- Education
- Record keeping
- Lifestyle changes
Recognition and home management of bleeds and common complications
- first-aid measures
- storage, preparation, and administration of CFCs and/or other treatment products
- dosage calculation
- venipuncture (or access through a central venous catheter) and self-infusion/self-injection
- aseptic techniques to prevent infection
- proper storage and disposal of needles/sharps
- handling of blood spills.
Available, safe, and effective treatment supplies:
- clotting factor concentrates (CFCs),
- coagulation inhibitors
- non-factor hemostatic agents
  - emicizumab (Hemlibra) (prophylactic subcutaneous humanized bispecific antibody mimicking activated factor VIII)
  - desmopressin (DDAVP)
  - antifibrinolytic agents (tranexamic acid or epsilon amino-caproic acid [EACA]
  - non-factor agents in development
  - emerging therapies

Vascular access

Preventive treatment often requires a surgically implanted device that can deliver medications at home and immediately in emergencies.
- At other times, injections into the skin or a vein can be adequate.

Concerns
Sites of bleeding in hemophilia

Serious	Joints (hemarthrosis Muscles, especially deep compartments (iliopsoas [low back], lower leg, forearm) Mucous membranes of the mouth, nose, and genitourinary tract
Life-threatening	Intracranial (brain) Neck/throat Gastrointestinal

Site of bleeding	Approximate frequency
Joints • More common in hinged joints: ankles, knees, elbows • Less common in multi-axial joints: shoulders, wrists, hips	70%-80%
Muscles	10%-20%
Other sites (major bleeds)	5%-10%
Central nervous system	Less than 5%

Surgery of any kind must be carefully planned and done with scrupulous attention to a patient’s blood clotting balance.
- All blood clotting tests must be brought to normal by adding any that are deficient.
- In addition, strict attention must be paid to the increased risk of venous thrombosis and pulmonary embolism (unwanted clotting) that accompanies most surgical procedures.
  - Mechanical rather than medicinal methods of preventing blood clots are highly preferred — early ambulation, compression leg wraps or stockings, and devices that automatically move legs and ankles to keep blood flowing briskly

Comorbidities

Cardiovascular

Foremost among medical conditions that complicate bleeding disorders are those that involve the cardiovascular system (heart and blood circulation). This is because blood clots cause strokes, heart attacks, and loss of blood supply to any part of the body.
Therefore, drugs like aspirin that reduce clotting are the first choice of prevention for these events. Such drugs increase the risk of bleeding.
Expertise is the only solution to this dilemma.

Pregnancy

Pregnancy, especially giving birth, is fraught with bleeding risks and should therefore be managed by a team of experts.

Aging

Conditions that can complicate the management of bleeding disorders, especially cardiovascular risks, are more common in the elderly.

Transfusion-transmitted infections

Because clotting factor concentrates come from donors, the risk of infection is constant.
More non-factor treatments like emicizumab are being developed and will help to alleviate this problem. But for now, viral-inactivated plasma-derived or recombinant CFCs, when available, are preferred over cryoprecipitate and fresh frozen plasma (FFP) that cannot assure sterility.

The complexity of the clotting system has given rise to a large number of treatments, each tailored to specific bleeding conditions. An optimum treatment plan will depend on all the factors present in each patient and will change with time and circumstances.

Abbreviations

CFCs: Clotting Factor Concentrations
DDAVP: 1-deamino-8-D-arginine Vasopressin
EACA: Epsilon Amino-caproic Acid
FFP: Fresh Frozen Plasma
VWD: Von Willebrand Disease

Source Citation

Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, Carcao M, Mahlangu J, Ragni MV, Windyga J, Llinás A, Goddard NJ, Mohan R, Poonnoose PM, Feldman BM, Lewis SZ, van den Berg HM, Pierce GF; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020 Aug;26 Suppl 6:1-158. doi: 10.1111/hae.14046. Epub 2020 Aug 3. Erratum in: Haemophilia. 2021 Jul;27(4):699. PMID: 32744769.

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.