Pediatric Factor XIII Deficiency Workup

  • Author: Helge Hartung, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Mar 9, 2011
 

Laboratory Studies

Screening tests

  • Results from standard hemostatic screening tests such as activated partial thromboplastin time (aPTT) and international normalized ratio (INR) assessments are normal in factor XIII (FXIII) deficiency.
  • Assessment of clot stability is the most common screening test for factor XIII deficiency.
  • The patient's plasma is incubated with thrombin with or without calcium for a sufficient period to allow formation of a stable clot; the formed clot is suspended in 5 mol/L urea, 2% acetic acid, or 1% monochloroacetic acid. Thrombin (without calcium) and acetic acid may provide the most sensitive combination.
  • In the presence of factor XIII, the clot is stable for more than 24 hours; in its absence, the clot dissolves in minutes to hours.
  • The qualitative test findings are positive in the absence of factor XIII; however, factor XIII levels as low as 1-3% may be sufficient to crosslink the fibrin, stabilizing the clot. Therefore, in patients with milder deficiencies or in patients who have recently received a transfusion, results of the clot stability assay may be normal.
  • A quantitative assay is required to confirm the diagnosis of factor XIII deficiency.

Functional assays

  • The 2 methods used to measure the enzymatic activity of factor XIII include measurement of synthetic amine incorporation into a fibrin clot, and measurement of ammonium ion release during the transglutaminase reaction.
  • Both assays are available as commercial kits.

Immunologic assays

  • Factor XIIIa and factor XIIIb antigen levels can be quantified by means of enzyme-linked immunosorbent assay (ELISA).
  • Patients with subunit A mutations have less than 2% of the reference range levels of A antigen.
  • The rare individuals with B subunit mutations have low B antigen levels, and, because of the shorter half-life of the A subunit in the absence of the B subunit, the A subunit antigen levels are also reduced.
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Imaging Studies

Appropriate imaging studies are required in the evaluation of suspected bleeding.

For instance, CT scanning or MRI of the brain is indicated in patients with a suspected CNS hemorrhage.

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Contributor Information and Disclosures
Author

Helge Hartung, MD  Attending Physician, Division of Hematology, Center for Cancer and Blood Disorders

Disclosure: Nothing to disclose.

Specialty Editor Board

Gary R Jones, MD  Associate Medical Director, Clinical Development, Berlex Laboratories

Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

James L Harper, MD  Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Helen SL Chan, MBBS, FRCP(C), FAAP  Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada

Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. Karimi M, Bereczky Z, Cohan N, Muszbek L. Factor XIII Deficiency. Semin Thromb Hemost. Jun 2009;35(4):426-38. [Medline].

  2. Anwar R, Minford A, Gallivan L, Trinh CH, Markham AF. Delayed umbilical bleeding--a presenting feature for factor XIII deficiency: clinical features, genetics, and management. Pediatrics. Feb 2002;109(2):E32. [Medline].

  3. Todd T, J Perry D. A review of long-term prophylaxis in the rare inherited coagulation factor deficiencies. Haemophilia. Nov 11 2009;[Medline].

  4. Anwar R, Miloszewski KJ. Factor XIII deficiency. Br J Haematol. Dec 1999;107(3):468-84. [Medline].

  5. Ariens RA, Lai TS, Weisel JW, Greenberg CS, Grant PJ. Role of factor XIII in fibrin clot formation and effects of genetic polymorphisms. Blood. Aug 1 2002;100(3):743-54. [Medline].

  6. Ichinose A. Physiopathology and regulation of factor XIII. Thromb Haemost. Jul 2001;86(1):57-65. [Medline].

  7. Ichinose A, Asahina T, Kobayashi T. Congenital blood coagulation factor XIII deficiency and perinatal management. Curr Drug Targ. 2005;6:541-549.

  8. Israels LG, Israels ED. Fibrinogen, factor XIII, and fibrinolysis. In: Mechanisms in Hematology. 3rd ed. Concord ON: Core Health Services, Inc; 2002:355-367.

  9. Jennings I, Kitchen S, Woods TA, Preston FE,. Problems relating to the laboratory diagnosis of factor XIII deficiency: a UK NEQAS study. J Thromb Haemost. Dec 2003;1(12):2603-8. [Medline].

  10. Lovejoy AE, Reynolds TC, Visich JE, Butine MD, Young G, Belvedere MA, et al. Safety and pharmacokinetics of recombinant factor XIII-A2 administration in patients with congenital factor XIII deficiency. Blood. Jul 1 2006;108(1):57-62. [Medline].

  11. Nugent DJ. Prophylaxis in rare coagulation disorders -- factor XIII deficiency. Thromb Res. 2006;118 Suppl 1:S23-8. [Medline].

 
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Activation of factor XIII (FXIII) by thrombin and calcium is a 2-step process. Thrombin cleaves an arginine-lysine bond in the A subunit and calcium causes dissociation of the B subunit, exposing the active site on the A subunit (XIIIa).
 
 
 
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