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Sections Factor XIII Deficiency
Overview
Presentation
- History
- Physical
- Causes
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DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
Media Gallery
Tables
References

Follow-up

Further Outpatient Care

Clinic-supervised outpatient care is an extremely important part of treatment. Complete annual physical examinations and laboratory testing for inhibitors, hepatitis, and HIV infection, as well as other tests, should be performed as needed. As in persons without hemophilia, routine care should be provided to patients with FXIII deficiency, including examination of stool for blood, rectal examination, colonoscopy, prostate-specific antigen determinations, mammography, and dental care. Physical therapy may be needed for the long-term care of affected joints. Prophylactic care includes vaccination for HAV^[128]and HBV and other routine vaccines.

Notify the local chapter of the National Hemophilia Foundation regarding the patient so that proper statistics can be provided to the appropriate agencies for adequate federal and state funding of patient care.

Provide counseling and classes to encourage questions and to help solve problems, such as possible ways to avoid transmission of HIV to an uninfected spouse and to children.^[129]

An appointment with a psychosocial worker at the time of counseling ensures that other psychological, social, and economic support is provided.

Further Inpatient Care

Patients should be hospitalized for serious complications, such as severe bleeding, or for major surgical procedures, all which require complex interdisciplinary care including pharmacy and laboratory support. Constant clinical evaluation and laboratory monitoring ensure adequacy of product replacement, pain relief, and other supportive care. The hematologist must be centrally involved to coordinate care.

Inpatient & Outpatient Medications

Patients should avoid acetylsalicylic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), and any over-the-counter herbal medications that can increase bleeding diathesis.

Transfer

If a qualified hematologist and laboratory personnel with expertise are available, patients may be cared for in a setting close to home. Laboratory testing provided by community hospitals has been improved by the existence of commercial referral laboratories.

Federal and state funding for programs may be available through a medical center. Costs of care are much higher at tertiary medical centers.

Deterrence/Prevention

Avoidance of high-risk activities (eg, boxing, motorbike riding) and NSAIDs reduces the frequency of bleeding.

Avoidance of alcohol helps protect liver function in patients with hepatitis.

Primary prophylaxis is the best way to prevent recurrent CNS bleeding, recurrent miscarriages or, rarely, recurrent joint bleeding. Joint replacement may be needed in the older patient with severe arthropathy.

Carcao et al reported that in patients with congenital FXIII A-subunit deficiency, prophylaxis with recombinant factor XIII-A2 (rFXIII-A2) provided sufficient hemostatic coverage for minor surgery without the need for additional FXIII therapy. Minor surgery was performed as long as 10 to 21 days after the last dose of rFXIII-A2.^[130]

HAV and HBV vaccines should be administered. Other routine vaccinations, such as those for influenza and pneumonia, should be provided as in other persons.

Complications

Recurrent CNS bleeding is a major problem requiring prophylactic transfusions. Infections, particularly HIV, AIDS, and chronic hepatitis, can lead to death. Interferon alfa has been used to treat chronic viral hepatitis. Multidrug cocktails are used to treat HIV/AIDS, but protease inhibitors can increase risk of bleeding. Some over-the-counter herbal remedies increase the risk of bleeding.

Viral safety in products derived from plasma is ensured through several techniques, ie, heating, pasteurization, SD treatment, and monoclonal antibody purification. These procedures currently free products from HIV and HCV (lipid-enveloped viruses) but do not solve the problem of transmission of non–lipid-enveloped viruses such as HAV, parvovirus B19, and other transfusion-transmitted viruses (TTV).

Even with recombinant products, a possibility exists of contamination with pathogens previously unknown, including new murine viruses. One report shows the presence of TTV in first-generation recombinant products, due to the use of human serum albumin that is contaminated with TTV.^[125]Thus, virus-induced illnesses of concern include hepatitis viruses A-E, GB virus C (or hepatitis G virus), the SEN family of viruses,^[124]and human herpesvirus 8,^[123]all of which constitute emerging pathogens related to transfusion-transmitted illnesses.

Potential transmission of prions causing Creutzfeldt-Jakob disease (CJD) or its variant form (vCJD) in recipients of blood products was a serious concern early in this century. However, no individual with hemophilia nor any other blood product recipient in the United States is known to have developed CJD. A United Kingdom study found that as of May 2015, no new cases of transfusion-associated vCJD had occurred since 2007 and there was no evidence of transfusion transmission of sporadic CJD.^[131]A sensitive and specific blood test for vCJD has been developed and has entered clinical use; it could be used to screen blood supplies.^[132]

The presence of inhibitors adds another layer of complexity when alloantibodies develop as a consequence of transfusion of blood products. Spontaneous disappearance is a typical feature of autoantibodies, presumably as a response to removal of the antigenic stimulus. Bleeding associated with inhibitors can be life threatening and requires complex care.

Severe economic and emotional problems occur as a result of the recurrent nature of the bleeding.

Complex psychiatric issues arise in the treatment of patients with HIV/AIDS.^[129]

Prognosis

Prognosis depends on the types of complications that develop, on the type of replacement product the patient has received, and on the viral infections that the patient has accumulated over the years. Newly diagnosed patients should, whenever possible, receive purer products to ensure maximum safety.

The presence of inhibitors in patients poses a serious therapeutic challenge, and, currently, surgery should be considered only as a lifesaving measure.

Patient Education

Encourage patients to register with the local chapter of the National Hemophilia Foundation and to attend educational seminars. Provide one-on-one discussions of issues with patients and family members. Early and complete genetic testing can help families plan future pregnancies.

For patient education information, see Bleeding Disorders.

Questions

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Media Gallery

Coagulation reactions leading to thrombin generation and activation of factor XIII.
Final steps in clot formation (from article: Factor XIII).
Activation of factor XIII and generation of insoluble cross-linked fibrin. Adapted from Lorand L. Ann N Y Acad Sci. 2001;936:291-311.
Postulated interaction between factor XIII and thrombin-activatable fibrinolytic inhibitor.
Cell surfaced–directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor–bearing (TF-bearing) cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation (from article: Factor XIII). Adapted from Hoffman and Monroe. Thromb Haemost. 2001;85(6):958-65.
Gene, messenger RNA, and protein for subunit A of factor XIII. Adapted from Reitsma PH. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Lippincott Williams & Wilkins; 2001:59-87 and from Roberts HR, Monroe DM III, Hoffman M. In: Williams Hematology. McGraw-Hill Professional; 2001:1409-34.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Elzbieta Klujszo, MD Head of Department of Dermatology, Wojewodzki Szpital Zespolony, Kielce

Disclosure: Nothing to disclose.

Pere Gascon, MD, PhD Professor and Senior Consultant, Division of Medical Oncology, Institute of Hematology and Medical Oncology, Hospital Clinic; Director, Laboratory of Molecular and Translational Oncology, University of Barcelona Faculty of Biology, Spain

Pere Gascon, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, New York Academy of Medicine, New York Academy of Sciences, Royal College of Surgeons of Edinburgh, Royal European Academy of Doctors, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Paul Schick, MD † Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Acknowledgements

Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Sections Factor XIII Deficiency
Overview
Presentation
- History
- Physical
- Causes
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DDx
Workup
Treatment
Medication
Follow-up
Questions & Answers
Media Gallery
Tables
References

Properties	A Chain	B Chain
Plasma FXIII	Has 2 A chains	Has 2 B chains
Plasma level	Approximately 15 mg/mL	Approximately 21 mg/mL
Chains are free in plasma	No. All bound to B chain and present as an A₂ B₂ tetramer	Yes. Excess B chain present in plasma as a B₂ dimer
Chain contains the catalytic site	Yes	No
Chain is the carrier protein	No	Yes
Chain acts as a brake on FXIII activation	No	Yes
Cellular FXIII	Has 2 A chains (A₂ dimer)	Has no B chains
Mutations can lead to decreased FXIII activity	Yes	Yes

Factor XIII Deficiency Follow-up

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