eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Hemophilia, Overview: Follow-up

Author: Dimitrios P Agaliotis, MD, PhD, FACP, Consulting Staff, Department of Medicine, Baptist Health System
Coauthor(s): Robert A Zaiden, MD, Fellow, Department of Hematology and Medical Oncology, University of Florida at Jacksonville; Saduman Ozturk, PA-C, Physician Assistant, Bone Marrow Transplant Center, Florida Hospital Cancer Institute
Contributor Information and Disclosures

Updated: Nov 24, 2009

Follow-up

Further Inpatient Care

Hospitalizing patients with internal bleeding, with uncontrollable bleeding, and before elective surgery or other invasive procedures is advised.

Further Outpatient Care

• Monitor patients with hemophilia in an outpatient setting for bleeding episode frequency, use of home-administered replacement factors, dental status, and joint and muscle problems.
• If a patient has HIV seroconversion, arrange appropriate outpatient care at a specialty infectious disease clinic, monitor the patient's CD4 count, observe the patient for adverse effects of anti-HIV treatment, and monitor for and treat possible opportunistic infections.

Inpatient & Outpatient Medications

See Medication.

Transfer

Patients whose condition and bleeding are stabilized should be transferred to a specialized center for further treatment and monitoring because a multidisciplinary approach by specialists experienced in hemophilia may be required.

Deterrence/Prevention

• Prophylactic replacement of FVIII or FIX is used to maintain a measurable level at all times, with the goal of avoiding hemarthrosis and breaking the vicious cycle of repetitive bleeding and inflammation that results in destructive arthritis.¹⁴
  • This goal is achieved by administering factor 2-3 times a week.
  • The National Hemophilia Foundation has recommended the administration of primary prophylaxis, beginning at the age of 1-2 years.
• Carrier testing may prevent births of individuals with major hemophilia. This testing can be offered to women interested in childbearing who have a family history of hemophilia.
  • Carrier testing is valuable for women who are related to obligate carrier females or males with hemophilia.
  • Prenatal diagnosis is important even if termination of the pregnancy is not desired because a cesarean delivery may be planned or replacement therapy can be scheduled for the perinatal period.
  • Phenotypic and genotypic (ie, restriction fragment–length polymorphism) methods have advantages and disadvantages.
• Preimplantation genetic diagnosis has been used as a possible alternative to prenatal diagnosis in combination with in vitro fertilization to help patients avoid having children with hemophilia or other serious inherited diseases.^15,16,17
  • The genetic diagnosis is made by using single cells obtained during biopsy from embryos before implantation. For this, fluorescence in situ hybridization is used.
  • This technique circumvents pregnancy termination.
• In summary, data suggest that genetic correction of the hemophilias is feasible.
  • Future prospects for RNA repair, use of gene-modified endothelial progenitors, and gene-modified stem-cell therapy are being investigated.
  • Patients report decreasing bleeding episodes; this observation suggests that reasonable factor levels can be reached and encourage further research in this type of hemophilia treatment.
  • Gene transfer for the treatment of hemophilia requires a combination of vector delivery systems, animal models, and clinical models and/or studies to prove its practical utility.

Complications

• Infection is the most important complication of hemophilia therapy.
  • As many as 20,000 donors may contribute to a single lot of plasma-derived FVIII concentrate.
  • The preferred source of factor are recombinant preparations, which do pose a risk of transmitting infectious disease, which is still theoretically possible with plasma-derived concentrates.
  • Virally attenuated products have reduced the risk of hepatitis observed in most patients receiving early-developed products.
  • Products that are not heat treated result in 90% positivity rates for hepatitis B surface antibody and hepatitis C virus. Therefore, their use is not recommended (or generally available) for routine management.
  • More than 50% of patients with severe hemophilia who have used older products have elevations in liver enzyme levels.
  • Outbreaks of hepatitis A infection in Europe and the United States have prompted more vigorous monitoring of product safety than before.
  • HIV infection has been the most serious complication of hemophilia to date. In the United States, as many as 90% of adults with severe hemophilia are HIV-positive. HIV-associated immune thrombocytic purpura is an exceedingly serious complication in patients with hemophilia because it may result in lethal intracranial bleeding. Correct platelet counts to less than 50,000/mL. Steroids are of limited effectiveness, and intravenous immunoglobulin or anti-Rh(D) generally induces transient remissions. Anti-HIV medications and splenectomies may result in long-term improvement of thrombocytopenia.
• Allergic reactions are occasionally reported with the use of cryoprecipitate, fresh-frozen plasma (FFP), and factor concentrates. Premedication or adjustment of the rate of infusion may resolve the problem.
• Thrombosis or even acute myocardial infarctions have been encountered in patients using PCC products, especially patients with concurrent liver disease or those taking multiple doses, as during surgery. A highly purified FIX product that is preferred.
• The cost of treatment of an average adult patient is more than $100,000 per year.
  • Costs are increased for the treatment of patients with inhibitors.
  • The use of prophylactic factor has resulted in short-term increases in cost, though the long-term economic benefit of reducing the incidence of joint disease is expected to outweigh the initial expense.
• See also Mortality/Morbidity above.

Prognosis

• Prophylactic use of antihemophilic factors and early treatment with replacement therapy with factors that are safe from infections have dramatically improved the prognosis of patients regarding morbidity and mortality due to severe hemophilia.
• Factor concentrates have made home-replacement therapy possible, improving patients' quality of life.
  • In addition, dramatic gains in life expectancy occurred during the era of replacement therapy.
  • The life expectancy rose from 11 years or less for patients with severe hemophilia before the 1960s to more than 50-60 years by the early 1980s.
  • Viral complications occurred during the factor replacement era. See Morbidity/Mortality.
• Intracranial hemorrhages and hemorrhages of the soft tissue around vital areas, such as the airway or internal organs, remain the most important life-threatening complications.
  • The lifetime risk of intracranial bleeding is 2-8% and accounts for one third of deaths due to hemorrhage, even in the era of factor replacement.
  • The life expectancy of patients receiving inhibitors may be slightly shorter than that of patients not receiving inhibitors.
  • Approximately one quarter of children and adolescents with severe hemophilia aged 6-18 years have below-normal motor skills and academic performance and have more emotional and behavioral problems than others.¹⁸

Patient Education

• Patient and family education about early recognition of hemorrhage signs and symptoms is important to institute or increase the intensity of replacement therapy. This treatment helps prevent the acute and chronic complications of the disease that may vary from life-threatening events to quality-of-life–impairing events.
• In addition, educating patients or family members about factor replacement administration at home has greatly enhanced the quality of life of patients with severe hemophilia.
• Employing results from 67 male patients with hemophilia, including 53 with severe FVIII deficiency, Duncan et al assessed the efficacy of VERITAS-Pro (Validated Hemophilia Regimen Treatment Adherence Scale - Prophylaxis).¹⁹ The patient/parent questionnaire uses 6 subscales (time, dose, plan, remember, skip, communicate), each containing 4 items, to assess patient adherence to prophylactic hemophilia treatment. The authors validated their results by using subjective adherence ratings from patients and providers and by assessing through log entries the number of recommended infusions that were administered. The investigators found a strong correlation between adherence assessments derived from VERITAS-Pro scores and those obtained through the validation measures.
• Based on the above data, Duncan and colleagues stated that VERITAS-Pro is a better tool than a global or informal adherence rating is, concluding that it provides a quantified and validated means of assessing adherence from the patient's perspective, and that it delivers enough information to reveal specific nonadherence-related patient issues.
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Hemophilia.

Miscellaneous

Medicolegal Pitfalls

• See Differentials.
• Consider using state-of-the-art infection-safe factor replacement products instead of FFP when treating patients with hemophilia.
• Also see Deterrence/Prevention for information on carrier detection and prenatal diagnosis.

Special Concerns

• Pain management can be challenging in patients with severe hemophilia.
  • Acute bleeding in joints and soft tissues can be painful. This requires immediate analgesic relief.
  • Hemophilic chronic arthropathy is associated with pain. Narcotic agents have been used, but frequent use of these drugs may result in addiction. Nonsteroidal anti-inflammatory drugs may be used instead because their effects on platelet function are reversible and because these drugs can be effective in managing acute and chronic arthritic pain.
  • Avoid aspirin because of its irreversible effect on platelet function.
  • Other analgesics may include acetaminophen in combination with small amounts of codeine or synthetic codeine analogs.

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