Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Factor XIII Deficiency Workup

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Perumal Thiagarajan, MD  more...
 
Updated: Jun 17, 2016
 

Laboratory Studies

The following routine tests are the first step in the evaluation of any bleeding disorder:

  • Activated partial thromboplastin time (aPTT)
  • Prothrombin time (PT)
  • Thrombin-clottable fibrinogen level
  • Platelet count
  • Bleeding time (after ascertaining that the patient was not on antiplatelet drugs for at least the preceding 5 d)

However, these tests cannot be used to screen for FXIII deficiency because the results would be within reference ranges in a patient with isolated severe FXIII deficiency,[3] and blood collection, transport, and storage may alter results for these initial screening tests.[94]

The next test performed is a qualitative screening test for severe FXIII deficiency that assesses clot solubility in 5M urea or 1% monochloroacetic acid. If the thrombin and Ca2+ -induced clot lyses within a few hours, severe FXIII deficiency is suggested provided fibrinogen levels are qualitatively and quantitatively within reference range. Excluding hypofibrinogenemia and dysfibrinogenemia is important, since these conditions cause false-positive results on the 5M urea solubility test. The thrombin-clottable fibrinogen test can be used to exclude hypofibrinogenemia and dysfibrinogenemia.

If the 5M urea solubility test demonstrates positive results, this finding should be confirmed by quantitating FXIII activity using a monodansylcadaverine or putrescine incorporation assay, which must be performed by laboratory personnel with expertise.

Thromboelastography (TEG) is an old method used to assess clotting and lysis of fresh whole blood, and it has been used as an early tool in the initial evaluation, and as a simple laboratory test, of the mechanical strength (effect of FXIII) of fibrin sealants.[95] However, TEG cannot supplant any of the qualitative or quantitative tests discussed in this section.

A sensitive assay used to quantitate FXIII activity is based on monitoring the amount of ammonia (NH3) released by using glutamate dehydrogenase and nicotinamide adenine dinucleotide phosphate during the transamidation reaction (cross-linking) by FXIII. Note the following:

  • Reportedly, this test is sensitive over a wide range of activities, from a low of 1 U/L (0.1%) to a high of 470 U/L (47%), with an impressive coefficient of variation (CV) of less than 8%, even at very low FXIII activity levels. Note that a low CV in the low range of FXIII activity is a desirable feature of assays of this enzyme. [96]
  • Compared to the cumbersome conventional quantitative amine incorporation assays, the newer method appears to be simple, rapid, and reproducible not only in the assessment of inherited or acquired reductions of FXIII activity levels but also in the ability to measure increased FXIII activity levels resulting from certain mutations. The test fulfills the need for a simpler method to quantify FXIII activity.
  • The same group also has published results of a simple, quick (2 h), 1-step, enzyme-linked immunoassay (ELISA) to determine the presence of the plasma tetramer (A 2 B 2). Results demonstrated high sensitivity and low CVs within batches and in day-to-day variations. [97]

Another sensitive colorimetric assay based on incorporation of 5-(biotinamido) pentylamine into fibrin/fibrinogen was compared to a photometric method based on ammonia release and an ELISA of FXIII subunit A to quantitate FXIII activity. The test was shown to be sensitive to both reductions and increases in activity; the increases resulted from the FXIII Val34Leu mutation.[4]

In addition, a2 PI and plasminogen activator inhibitor-1 assays should be performed to exclude abnormalities in the fibrinolytic pathway, which accelerate clot lysis.

Sodium dodecylsulfate polyacrylamide gel electrophoresis under reducing conditions has been used to assess the presence of cross-linked g or a chains of fibrin, which is a reflection of FXIII activity. The studies must be performed by laboratory personnel with special expertise.

If the presence of an inhibitor is suspected in a patient with a positive urea solubility test result, the next step is to repeat the urea solubility test with mixtures containing varying proportions of patient and normal plasma to differentiate between a deficiency or an inhibitor as the cause of a positive result. Since FXIII activity is present in serum, serum also may be substituted for plasma in the test.

Semiquantitation of the susceptibility of the fibrin clot to fibrinolysis can be obtained by adding iodine-125-labeled fibrinogen, tissue plasminogen activator, thrombin, and Ca2+ to the patient's plasma, with measurement of the time to 50% clot lysis. This method is useful in evaluating inhibitors but must be performed by laboratory personnel with special expertise.

See Lorand for a recent review of further details of the sequence of necessary testing to confirm the presence of a FXIII inhibitor.[87]

Acquired systemic disorders, including decompensated DIC and liver disease, require standard tests to confirm the diagnosis.

Caution is warranted in obtaining blood samples for any coagulation assays from heparinized central lines because of the effect of large amounts of heparin on any coagulation test that depends on thrombin generation.

Prenatal diagnosis is as follows:

  • Use of several diagnostic procedures has been well established in the evaluation of patients with FVIII and factor IX (FIX) deficiencies. In one case report, a short tandem repeat marker that was closely linked to subunit A was used antenatally to identify the presence of a severe bleeding disorder in a subsequent pregnancy in a family in which an older sibling had severe FXIII deficiency. [98]
  • Chorionic villous sampling at approximately 10-12 weeks of gestation or amniocentesis at 16-20 weeks of gestation can be performed to obtain fetal cells for DNA analysis or for linkage studies. If DNA analysis cannot be performed, fetal blood obtained by fetoscopy at approximately 20 weeks of gestation can be used. In general, these procedures carry risks ranging from a low of approximately 0.5% maternal-fetal complications to a high of approximately 1-6% fetal death for fetoscopy.
  • Perform these procedures only after intense genetic and obstetric counseling of the parents.

Perform liver function tests; kidney function tests; HIV-1 and HIV-2 antigen and antibody tests; hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D, and hepatitis E antigen/antibody levels; and other tests as needed.

Assess a-fetoprotein levels and other tumor markers as needed in patients with chronic hepatitis.

FXIII, which is involved in wound healing and angiogenesis, may be detectable by highly sensitive chemiluminescent ELISAs in tiny volumes of tear. This concept may provide a tool for monitoring FXIII subunit and complex levels in pathological conditions.[99]

Next

Imaging Studies

MRI, CT scan, and ultrasound have been used to localize, quantify, and serially monitor the location and response of bleeding to specific therapy. Perform other imaging tests as needed to diagnose associated diseases.

Previous
Next

Other Tests

Perform ECGs as needed.

Previous
Next

Procedures

Diagnostic amniocentesis, chorionic villous sampling, or fetoscopy may be performed during pregnancy. Perform other routine procedures when indicated. Perform arthrocentesis only when infection is suggested. Any invasive procedure requires the appropriate factor replacement.

When indicated, perform other procedures, such as colonoscopy, in persons without hemophilia. Evaluate persistent GI tract bleeding without an apparent cause using endoscopy and colonoscopy to exclude underlying lesions. Persistent genitourinary tract bleeding requires evaluation for nephrolithiasis, tumors, or obstruction. If a biopsy is needed, patients require replacement therapy prior to and following the procedure until the biopsy site has healed.

Invasive lifesaving procedures should be performed in patients with inhibitors only in concert with appropriate treatment.

Previous
 
 
Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Pere Gascon, MD, PhD Professor and Director, Division of Medical Oncology, Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona Faculty of Medicine, 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, Sigma Xi

Disclosure: Nothing to disclose.

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

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, MB, BCh, FRCPC, DTM&H Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

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

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: GSK Pharmaceuticals,Alexion,Johnson & Johnson Talecris,,Grifols<br/>Received honoraria from all the above companies for speaking and teaching.

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 Society for Clinical Investigation, Association of American Physicians, American Society for Biochemistry and Molecular Biology, American Heart Association, American Society of Hematology, 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.

References
  1. Shanbhag S, Ghosh K, Shetty S. Genetic basis of severe factor XIII deficiency in a large cohort of Indian patients: Identification of fourteen novel mutations. Blood Cells Mol Dis. 2016 Mar. 57:81-4. [Medline].

  2. Thakker S, McGehee W, Quismorio FP Jr. Arthropathy associated with factor XIII deficiency. Arthritis Rheum. 1986 Jun. 29(6):808-11. [Medline].

  3. McKenna R. Abnormal coagulation in the postoperative period contributing to excessive bleeding. Med Clin North Am. 2001 Sep. 85(5):1277-310, viii. [Medline].

  4. Wilmer M, Rudin K, Kolde H, et al. Evaluation of a sensitive colorimetric FXIII incorporation assay. Effects of FXIII Val34Leu, plasma fibrinogen concentration and congenital FXIII deficiency. Thromb Res. 2001 Apr 1. 102(1):81-91. [Medline].

  5. Laki K, Lóránd L. On the Solubility of Fibrin Clots. Science. 1948 Sep 10. 108(2802):280. [Medline].

  6. Duckert F, Jung E, Sherling DH. An undescribed congenital haemorrhagic diathesis probably due to fibrin stabilizing factor deficiency. Thromb Diath Haemorrh. 1960. 5:179.

  7. Duckert F. Documentation of the plasma factor XIII deficiency in man. Ann N Y Acad Sci. 1972 Dec 8. 202:190-9. [Medline].

  8. Laki K. Our ancient heritage in blood clotting and some of its consequences. Ann N Y Acad Sci. 1972 Dec 8. 202:297-307. [Medline].

  9. Reitsma PH. Genetic principles underlying disorders of procoagulant and anticoagulant proteins. Coleman RW, Hirsh J, Marder VJ, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 59-87.

  10. Loewy AG, McDonagh J, Mikkola H, et al. Structure and function of F XIII. Coleman RW, Hirsh J, Marder VJ, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 233-48.

  11. Cushman M, O'Meara ES, Folsom AR, Heckbert SR. Coagulation factors IX through XIII and the risk of future venous thrombosis: the Longitudinal Investigation of Thromboembolism Etiology. Blood. 2009 Oct 1. 114(14):2878-83. [Medline]. [Full Text].

  12. Hoppe B, Tolou F, Dörner T, Kiesewetter H, Salama A. Gene polymorphisms implicated in influencing susceptibility to venous and arterial thromboembolism: frequency distribution in a healthy German population. Thromb Haemost. 2006 Oct. 96(4):465-70. [Medline].

  13. Wells PS, Anderson JL, Rodger MA, Carson N, Grimwood RL, Doucette SP. The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?. Blood Coagul Fibrinolysis. 2006 Oct. 17(7):533-8. [Medline].

  14. Shafey M, Anderson JL, Scarvelis D, Doucette SP, Gagnon F, Wells PS. Factor XIII Val34Leu variant and the risk of myocardial infarction: a meta-analysis. Thromb Haemost. 2007 Apr. 97(4):635-41. [Medline].

  15. Shin JI, Lee JS. Severe gastrointestinal vasculitis in Henoch-Schoenlein purpura: pathophysiologic mechanisms, the diagnostic value of factor XIII, and therapeutic options. Eur J Pediatr. 2007 Nov. 166(11):1199-200; author reply 1201. [Medline].

  16. Shin JI, Lee JS. Could measurement of factor XIII level detect the vasculitic process of Henoch-Schönlein purpura without skin rash?. Acta Paediatr. 2008 Apr. 97(4):395. [Medline].

  17. Kuroda K, Tajima S. Proliferation of HSP47-positive skin fibroblasts in dermatofibroma. J Cutan Pathol. 2008 Jan. 35(1):21-6. [Medline].

  18. Ivaskevicius V, Biswas A, Loreth R, et al. Mutations affecting disulphide bonds contribute to a fairly common prevalence of F13B gene defects: results of a genetic study in 14 families with factor XIII B deficiency. Haemophilia. 2010 Mar 10. [Medline].

  19. Ichinose A. Factor XIII is a key molecule at the intersection of coagulation and fibrinolysis as well as inflammation and infection control. Int J Hematol. 2012 Apr. 95(4):362-70. [Medline].

  20. Schroeder V, Kohler HP. Factor XIII Deficiency: An Update. Semin Thromb Hemost. 2013 Sep. 39(6):632-41. [Medline].

  21. Lorand L. Factor XIII: structure, activation, and interactions with fibrinogen and fibrin. Ann N Y Acad Sci. 2001. 936:291-311. [Medline].

  22. Siebenlist KR, Meh DA, Mosesson MW. Plasma factor XIII binds specifically to fibrinogen molecules containing gamma chains. Biochemistry. 1996 Aug 13. 35(32):10448-53. [Medline].

  23. Greenberg CS, Shuman MA. The zymogen forms of blood coagulation factor XIII bind specifically to fibrinogen. J Biol Chem. 1982 Jun 10. 257(11):6096-101. [Medline].

  24. Mosesson M. Hereditary abnormalities of fibrinogen. Beutler E, Lichtman M, Coller BS, et al, eds. Williams Hematology. New York, NY: McGraw-Hill; 2001. 1659-71.

  25. Jenner L, Husted L, Thirup S, Sottrup-Jensen L, Nyborg J. Crystal structure of the receptor-binding domain of alpha 2-macroglobulin. Structure. 1998 May 15. 6(5):595-604. [Medline].

  26. Nagy B Jr, Simon Z, Bagoly Z, Muszbek L, Kappelmayer J. Binding of plasma factor XIII to thrombin-receptor activated human platelets. Thromb Haemost. 2009 Jul. 102(1):83-9. [Medline].

  27. Monteiro MR, Murphy EE, Galaria NA, Whitaker-Menezes D, Murphy GF. Cytological alterations in dermal dendrocytes in vitro: evidence for transformation to a non-dendritic phenotype. Br J Dermatol. 2000 Jul. 143(1):84-90. [Medline].

  28. Lorand L. Sol Sherry Lecture in Thrombosis : research on clot stabilization provides clues for improving thrombolytic therapies. Arterioscler Thromb Vasc Biol. 2000 Jan. 20(1):2-9. [Medline].

  29. Noguchi K, Ishikawa K, Yokoyama Ki, Ohtsuka T, Nio N, Suzuki E. Crystal structure of red sea bream transglutaminase. J Biol Chem. 2001 Apr 13. 276(15):12055-9. [Medline].

  30. Andersen MD, Kjalke M, Bang S, et al. Coagulation factor XIII variants with altered thrombin activation rates. Biol Chem. 2009 Dec. 390(12):1279-83. [Medline].

  31. Fox BA, Yee VC, Pedersen LC, et al. Identification of the calcium binding site and a novel ytterbium site in blood coagulation factor XIII by x-ray crystallography. J Biol Chem. 1999 Feb 19. 274(8):4917-23. [Medline].

  32. Casadio R, Polverini E, Mariani P, et al. The structural basis for the regulation of tissue transglutaminase by calcium ions. Eur J Biochem. 1999 Jun. 262(3):672-9. [Medline].

  33. Hevessy Z, Haramura G, Boda Z, Udvardy M, Muszbek L. Promotion of the crosslinking of fibrin and alpha 2-antiplasmin by platelets. Thromb Haemost. 1996 Jan. 75(1):161-7. [Medline].

  34. Moaddel M, Falls LA, Farrell DH. The role of gamma A/gamma ' fibrinogen in plasma factor XIII activation. J Biol Chem. 2000 Oct 13. 275(41):32135-40. [Medline].

  35. Weiss MS, Metzner HJ, Hilgenfeld R. Two non-proline cis peptide bonds may be important for factor XIII function. FEBS Lett. 1998 Feb 27. 423(3):291-6. [Medline].

  36. Jámbor C, Reul V, Schnider TW, Degiacomi P, Metzner H, Korte WC. In vitro inhibition of factor XIII retards clot formation, reduces clot firmness, and increases fibrinolytic effects in whole blood. Anesth Analg. 2009 Oct. 109(4):1023-8. [Medline].

  37. Lorand L, Urayama T, Atencio AC, Hsia DY. Inheritance of deficiency of fibrin-stabilizing factor (factor 13). Am J Hum Genet. 1970 Jan. 22(1):89-95. [Medline]. [Full Text].

  38. Anwar R, Gallivan L, Edmonds SD, Markham AF. Genotype/phenotype correlations for coagulation factor XIII: specific normal polymorphisms are associated with high or low factor XIII specific activity. Blood. 1999 Feb 1. 93(3):897-905. [Medline].

  39. Kangsadalampai S, Board PG. The Val34Leu polymorphism in the A subunit of coagulation factor XIII contributes to the large normal range in activity and demonstrates that the activation peptide plays a role in catalytic activity. Blood. 1998 Oct 15. 92(8):2766-70. [Medline].

  40. Saha N, Aston CE, Low PS, Kamboh MI. Racial and genetic determinants of plasma factor XIII activity. Genet Epidemiol. 2000 Dec. 19(4):440-55. [Medline].

  41. van Wersch JW, Vooijs ME, Ubachs JM. Coagulation factor XIII in pregnant smokers and non-smokers. Int J Clin Lab Res. 1997. 27(1):68-71. [Medline].

  42. Asahina T, Kobayashi T, Okada Y, et al. Studies on the role of adhesive proteins in maintaining pregnancy. Horm Res. 1998. 50 Suppl 2:37-45. [Medline].

  43. Asahina T, Kobayashi T, Okada Y, Goto J, Terao T. Maternal blood coagulation factor XIII is associated with the development of cytotrophoblastic shell. Placenta. 2000 May. 21(4):388-93. [Medline].

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

  45. Noll T, Wozniak G, McCarson K, et al. Effect of factor XIII on endothelial barrier function. J Exp Med. 1999 May 3. 189(9):1373-82. [Medline]. [Full Text].

  46. Cario E, Goebell H, Dignass AU. Factor XIII modulates intestinal epithelial wound healing in vitro. Scand J Gastroenterol. 1999 May. 34(5):485-90. [Medline].

  47. Naito M, Nomura H, Iguchi A, Thompson WD, Smith EB. Effect of crosslinking by factor XIIIa on the migration of vascular smooth muscle cells into fibrin gels. Thromb Res. 1998 May 1. 90(3):111-6. [Medline].

  48. Wozniak G, Noll T, Brunner U, Hehrlein FW. Topical treatment of venous ulcer with fibrin stabilizing factor: experimental investigation of effects on vascular permeability. Vasa. 1999 Aug. 28(3):160-3. [Medline].

  49. Catani MV, Bernassola F, Rossi A, Melino G. Inhibition of clotting factor XIII activity by nitric oxide. Biochem Biophys Res Commun. 1998 Aug 10. 249(1):275-8. [Medline].

  50. Bernassola F, Rossi A, Melino G. Regulation of transglutaminases by nitric oxide. Ann N Y Acad Sci. 1999. 887:83-91. [Medline].

  51. Huang QQ, Teng MK, Niu LW. Purification and characterization of two fibrinogen-clotting enzymes from five-pace snake (Agkistrodon acutus) venom. Toxicon. 1999 Jul. 37(7):999-1013. [Medline].

  52. Arocha-Pinango CL, Marval E, Guerrero B. Lonomia genus caterpillar toxins: biochemical aspects. Biochimie. 2000 Sep-Oct. 82(9-10):937-42. [Medline].

  53. Zavalova L, Lukyanov S, Baskova I, et al. Genes from the medicinal leech (Hirudo medicinalis) coding for unusual enzymes that specifically cleave endo-epsilon (gamma-Glu)-Lys isopeptide bonds and help to dissolve blood clots. Mol Gen Genet. 1996 Nov 27. 253(1-2):20-5. [Medline].

  54. Undas A, Brummel KE, Musial J, Mann KG, Szczeklik A. Simvastatin depresses blood clotting by inhibiting activation of prothrombin, factor V, and factor XIII and by enhancing factor Va inactivation. Circulation. 2001 May 8. 103(18):2248-53. [Medline].

  55. Finney S, Seale L, Sawyer RT, Wallis RB. Tridegin, a new peptidic inhibitor of factor XIIIa, from the blood- sucking leech Haementeria ghilianii. Biochem J. 1997 Jun 15. 324 ( Pt 3):797-805. [Medline].

  56. Lee SY, Chang SK, Lee IH, Kim YM, Chung SI. Depletion of plasma factor XIII prevents disseminated intravascular coagulation-induced organ damage. Thromb Haemost. 2001 Mar. 85(3):464-9. [Medline].

  57. Sidelmann JJ, Gram J, Jespersen J, Kluft C. Fibrin clot formation and lysis: basic mechanisms. Semin Thromb Hemost. 2000. 26(6):605-18. [Medline].

  58. Takahashi H, Isobe T, Horibe S, et al. Tissue transglutaminase, coagulation factor XIII, and the pro-polypeptide of von Willebrand factor are all ligands for the integrins alpha 9beta 1 and alpha 4beta 1. J Biol Chem. 2000 Aug 4. 275(31):23589-95. [Medline].

  59. Salge U, Daubner E, Heiden M, Sietz R. Factor XIII does not stimulate growth of human cultured tumor cells. Blood Coagul Fibrinolysis. 2000 Mar. 11(2):217-8. [Medline].

  60. Molnar P, Nemes Z. Hemangiopericytoma of the cerebello-pontine angle. Diagnostic pitfalls and the diagnostic value of the subunit A of factor XIII as a tumor marker. Clin Neuropathol. 1995 Jan-Feb. 14(1):19-24. [Medline].

  61. Adany R, Bardos H, Antal M, et al. Factor XIII of blood coagulation as a nuclear crosslinking enzyme. Thromb Haemost. 2001 May. 85(5):845-51. [Medline].

  62. Kallberg Y, Gustafsson M, Persson B, Thyberg J, Johansson J. Prediction of amyloid fibril-forming proteins. J Biol Chem. 2001 Apr 20. 276(16):12945-50. [Medline].

  63. Bajzar L, Manuel R, Nesheim ME. Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor. J Biol Chem. 1995 Jun 16. 270(24):14477-84. [Medline].

  64. Redlitz A, Tan AK, Eaton DL, Plow EF. Plasma carboxypeptidases as regulators of the plasminogen system. J Clin Invest. 1995 Nov. 96(5):2534-8. [Medline].

  65. Bajzar L, Nesheim ME, Tracy PB. The profibrinolytic effect of activated protein C in clots formed from plasma is TAFI-dependent. Blood. 1996 Sep 15. 88(6):2093-100. [Medline].

  66. Hoffman M, Monroe DM 3rd. A cell-based model of hemostasis. Thromb Haemost. 2001 Jun. 85(6):958-65. [Medline].

  67. HGMD. Human Gene Mutation Database at the Institute of Medical Genetics in Cardiff. Available at: http://www.uwcm.ac.uk//uwcm/mg/hgmd0.html. Accessed April 9, 2002. [Full Text].

  68. Attié-Castro FA, Zago MA, Lavinha J, et al. Ethnic heterogeneity of the factor XIII Val34Leu polymorphism. Thromb Haemost. 2000 Oct. 84(4):601-3. [Medline].

  69. Sharief LA, Kadir RA. Congenital factor XIII deficiency in women: a systematic review of literature. Haemophilia. 2013 Aug 28. [Medline].

  70. Mikkola H, Muszbek L, Laiho E, et al. Molecular mechanism of a mild phenotype in coagulation factor XIII (FXIII) deficiency: a splicing mutation permitting partial correct splicing of FXIII A-subunit mRNA. Blood. 1997 Feb 15. 89(4):1279-87. [Medline].

  71. Greenberg DL, Davie EW. Blood coagulation factors: their complementary DNAs, genes, and expression. Coleman RW, Hirsh J, Marder VJ, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 21-57.

  72. Kangsadalampai S, Yenchitsomanus P, Chelvanayagam G, Sawasdee N, Laosombat V, Board P. Identification of a new mutation (Gly420Ser), distal to the active site, that leads to factor XIII deficiency. Eur J Haematol. 2000 Oct. 65(4):279-84. [Medline].

  73. Koseki S, Souri M, Koga S, et al. Truncated mutant B subunit for factor XIII causes its deficiency due to impaired intracellular transportation. Blood. 2001 May 1. 97(9):2667-72. [Medline].

  74. Gomez Garcia EB, Poort SR, Stibbe J. Two novel and one recurrent missense mutation in the factor XIII A gene in two Dutch patients with factor XIII deficiency. Br J Haematol. 2001 Feb. 112(2):513-8. [Medline].

  75. Anwar R, Gallivan L, Trinh C, Hill F, Markham A. Identification of a new Leu354Pro mutation responsible for factor XIII deficiency. Eur J Haematol. 2001 Feb. 66(2):133-6. [Medline].

  76. Warner D, Mansfield MW, Grant PJ. Coagulation factor XIII and cardiovascular disease in UK Asian patients undergoing coronary angiography. Thromb Haemost. 2001 Mar. 85(3):408-11. [Medline].

  77. Canavy I, Henry M, Morange PE, et al. Genetic polymorphisms and coronary artery disease in the south of France. Thromb Haemost. 2000 Feb. 83(2):212-6. [Medline].

  78. Franco RF, Middeldorp S, Meinardi JR, van Pampus EC, Reitsma PH. Factor XIII Val34Leu and the risk of venous thromboembolism in factor V Leiden carriers. Br J Haematol. 2000 Oct. 111(1):118-21. [Medline].

  79. Catto AJ, Kohler HP, Coore J, Mansfield MW, Stickland MH, Grant PJ. Association of a common polymorphism in the factor XIII gene with venous thrombosis. Blood. 1999 Feb 1. 93(3):906-8. [Medline].

  80. Kohler HP. Role of blood coagulation factor XIII in vascular diseases. Swiss Med Wkly. 2001 Jan 27. 131(3-4):31-4. [Medline].

  81. Prata MJ, Miranda C, Rocha J, Amorim A. Allelic affinities between the F13A common gene products inferred by the analysis of an (AAAG)n STR polymorphism within the 5' untranslated region. Hum Hered. 2000 May-Jun. 50(3):189-93. [Medline].

  82. Hedner U, Ginsburg D, Lusher JM, High KA. Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia. Hematology Am Soc Hematol Educ Program. 2000. 241-265. [Medline].

  83. Coukos G, Rubin SC. Gene therapy for ovarian cancer. Oncology (Williston Park). 2001 Sep. 15(9):1197-204, 1207; discussion 1207-8. [Medline].

  84. Chandler WL, Patel MA, Gravelle L, et al. Factor XIIIA and clot strength after cardiopulmonary bypass. Blood Coagul Fibrinolysis. 2001 Mar. 12(2):101-8. [Medline].

  85. Holst FG, Hemmer CJ, Foth C, Seitz R, Egbring R, Dietrich M. Low levels of fibrin-stabilizing factor (factor XIII) in human Plasmodium falciparum malaria: correlation with clinical severity. Am J Trop Med Hyg. 1999 Jan. 60(1):99-104. [Medline].

  86. Matayoshi T, Omi T, Sakai N, Kawana S. Clinical Significance of Blood Coagulation Factor XIII Activity in Adult Henoch-Schönlein Purpura. J Nippon Med Sch. 2013. 80(4):268-78. [Medline].

  87. Lorand L, Velasco PT, Murthy SN, Lefebvre P, Green D. Autoimmune antibody in a hemorrhagic patient interacts with thrombin-activated factor XIII in a unique manner. Blood. 1999 Feb 1. 93(3):909-17. [Medline].

  88. Feinstein DI. Immune coagulation disorders. Coleman RW, Hirsh J, Marder VJ, et al, eds. Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 1003-20.

  89. Ahmad F, Solymoss S, Poon MC, Berube C, Sullivan AK. Characterization of an acquired IgG inhibitor of coagulation factor XIII in a patient with systemic lupus erythematosus. Br J Haematol. 1996 Jun. 93(3):700-3. [Medline].

  90. Tosetto A, Rodeghiero F, Gatto E, Manotti C, Poli T. An acquired hemorrhagic disorder of fibrin crosslinking due to IgG antibodies to FXIII, successfully treated with FXIII replacement and cyclophosphamide. Am J Hematol. 1995 Jan. 48(1):34-9. [Medline].

  91. Krumdieck R, Shaw DR, Huang ST, Poon MC, Rustagi PK. Hemorrhagic disorder due to an isoniazid-associated acquired factor XIII inhibitor in a patient with Waldenstrom's macroglobulinemia. Am J Med. 1991 May. 90(5):639-45. [Medline].

  92. Heinle K, Adam O, Rauh G. Factor XIII insufficiency in a patient with severe psoriasis vulgaris, arthritis, and infirmity. Clin Rheumatol. 1998. 17(4):346-8. [Medline].

  93. Lorand L. Acquired inhibitors of fibrin stabilization: a class of hemorrhagic disorders of diverse origins. Anticoagulants: Physiologic, Pathologic and Pharmacologic. CRC Press; 1994. 169-91.

  94. Dorgalaleh A, Kazemi A, Zaker F, Shamsizadeh M, Rashidpanah J, Mollaei M. Laboratory Diagnosis of Factor XIII Deficiency, Routine Coagulation Tests with Quantitative and Qualitative Methods. Clin Lab. 2016. 62 (4):491-8. [Medline].

  95. Glidden PF, Malaska C, Herring SW. Thromboelastograph assay for measuring the mechanical strength of fibrin sealant clots. Clin Appl Thromb Hemost. 2000 Oct. 6(4):226-33. [Medline].

  96. Karpati L, Penke B, Katona E, Balogh I, Vamosi G, Muszbek L. A modified, optimized kinetic photometric assay for the determination of blood coagulation factor XIII activity in plasma. Clin Chem. 2000 Dec. 46(12):1946-55. [Medline].

  97. Katona E, Haramura G, Karpati L, Fachet J, Muszbek L. A simple, quick one-step ELISA assay for the determination of complex plasma factor XIII (A2B2). Thromb Haemost. 2000 Feb. 83(2):268-73. [Medline].

  98. Killick CJ, Barton CJ, Aslam S, Standen G. Prenatal diagnosis in factor XIII-A deficiency. Arch Dis Child Fetal Neonatal Ed. 1999 May. 80(3):F238-9. [Medline]. [Full Text].

  99. Orosz ZZ, Katona E, Facsko A, Berta A, Muszbek L. A highly sensitive chemiluminescence immunoassay for the measurement of coagulation factor XIII subunits and their complex in tears. J Immunol Methods. 2010 Feb 28. 353(1-2):87-92. [Medline].

  100. Brooks M. FDA Clears Tretten for Coagulation Factor XIII Deficiency. Available at http://www.medscape.com/viewarticle/818264. Accessed: January 6, 2014.

  101. Inbal A, Oldenburg J, Carcao M, Rosholm A, Tehranchi R, Nugent D. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood. 2012 May 31. 119(22):5111-7. [Medline].

  102. Gootenberg JE. Factor concentrates for the treatment of factor XIII deficiency. Curr Opin Hematol. 1998 Nov. 5(6):372-5. [Medline].

  103. Green D. Spontaneous inhibitors to coagulation factors. Clin Lab Haematol. 2000 Oct. 22 Suppl 1:21-5; discussion 30-2. [Medline].

  104. Lorand L, Losowsky MS, Miloszewski KJM. Human factor XIII: fibrin stabilizing factor. Spaet T, ed. Progress in Hemostasis and Thrombosis. New York, NY: Grune & Stratton; 1980. Vol 5: 245-90.

  105. Abbondanzo SL, Gootenberg JE, Lofts RS, McPherson RA. Intracranial hemorrhage in congenital deficiency of factor XIII. Am J Pediatr Hematol Oncol. 1988 Spring. 10(1):65-8. [Medline].

  106. Green D, Sanders J, Wong C, et al. Coronary revascularization in the presence of an inhibitory antibody to factor XIII. Bull Intensive Crit Care. 1996. 3(3):14-6.

  107. Wiel E, Marciniak B, Wibaut B. [Recurrent hematomas and normal standard hemostasis tests]. Ann Fr Anesth Reanim. 1998. 17(1):61-4. [Medline].

  108. Kawamura A, Tamaki N, Yonezawa K, Nakamura M, Asada M. [Effect of factor XIII on intractable CSF leakage after a transpetrosal-approach operation: a case report]. No Shinkei Geka. 1997 Jan. 25(1):53-6. [Medline].

  109. Chamouard P, Grunebaum L, Wiesel ML, et al. Significance of diminished factor XIII in Crohn's disease. Am J Gastroenterol. 1998 Apr. 93(4):610-4. [Medline].

  110. Linskens RK, van Bodegraven AA, Schoorl M, Tuynman HA, Bartels P. Predictive value of inflammatory and coagulation parameters in the course of severe ulcerative colitis. Dig Dis Sci. 2001 Mar. 46(3):644-8. [Medline].

  111. Helio T, Wartiovaara U, Halme L, et al. Arg506Gln factor V mutation and Val34Leu factor XIII polymorphism in Finnish patients with inflammatory bowel disease. Scand J Gastroenterol. 1999 Feb. 34(2):170-4. [Medline].

  112. Burrows RF, Ray JG, Burrows EA. Bleeding risk and reproductive capacity among patients with factor XIII deficiency: a case presentation and review of the literature. Obstet Gynecol Surv. 2000 Feb. 55(2):103-8. [Medline].

  113. Kreilgaard L, Jones LS, Randolph TW, et al. Effect of Tween 20 on freeze-thawing- and agitation-induced aggregation of recombinant human factor XIII. J Pharm Sci. 1998 Dec. 87(12):1597-603. [Medline].

  114. Kreilgaard L, Frokjaer S, Flink JM, Randolph TW, Carpenter JF. Effects of additives on the stability of recombinant human factor XIII during freeze-drying and storage in the dried solid. Arch Biochem Biophys. 1998 Dec 1. 360(1):121-34. [Medline].

  115. Dickneite G, Metzner H, Nicolay U. Prevention of suture hole bleeding using fibrin sealant: benefits of factor XIII. J Surg Res. 2000 Oct. 93(2):201-5. [Medline].

  116. Inbal A, Oldenburg J, Carcao M, Rosholm A, Tehranchi R, Nugent D. Recombinant factor XIII: a safe and novel treatment for congenital factor XIII deficiency. Blood. 2012 May 31. 119(22):5111-7. [Medline].

  117. ARC. FDA-approved product circular for Pooled Plasma, Solvent-Detergent-Treated (PLAS+SD) manufactured by the American Red Cross and V.I. Technologies, Inc. 2000.

  118. ARC. PLAS+SD (pooled plasma, solvent-detergent treated). Monograph by the American Red Cross and V. I. Technologies, Inc. 1999. VIT-001A9/99:

  119. MediView Express. Recombinant therapy enhances safety and quality of life for hemophilia patients. Paper presented at: 53rd Annual Meeting of the National Hemophilia Foundation. November 16, 2001: Nashville, Tennessee.

  120. Rigas B, Hasan I, Rehman R, Donahue P, Wittkowski KM, Lebovics E. Effect on treatment outcome of coinfection with SEN viruses in patients with hepatitis C. Lancet. 2001 Dec 8. 358(9297):1961-2. [Medline].

  121. Azzi A, De Santis R, Morfini M, et al. TT virus contaminates first-generation recombinant factor VIII concentrates. Blood. 2001 Oct 15. 98(8):2571-3. [Medline].

  122. Bachmann F. Plasminogen-plasmin enzyme system. Colman RW, Hirsh J, George JN, et al, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Lippincott Williams & Wilkins; 2001. 275-320.

  123. Fergusson DA, Hebert PC, Mazer CD, et al. A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med. 2008 May 29. 358(22):2319-31. [Medline].

  124. Di Bisceglie AM. SEN and sensibility: interactions between newly discovered and other hepatitis viruses?. Lancet. 2001 Dec 8. 358(9297):1925-6. [Medline].

  125. Treisman GJ, Angelino AF, Hutton HE. Psychiatric issues in the management of patients with HIV infection. JAMA. 2001 Dec 12. 286(22):2857-64. [Medline].

  126. Urwin PJ, Mackenzie JM, Llewelyn CA, Will RG, Hewitt PE. Creutzfeldt-Jakob disease and blood transfusion: updated results of the UK Transfusion Medicine Epidemiology Review Study. Vox Sang. 2016 May. 110 (4):310-6. [Medline].

  127. Jackson GS, Burk-Rafel J, Edgeworth JA, Sicilia A, Abdilahi S, Korteweg J, et al. Population screening for variant Creutzfeldt-Jakob disease using a novel blood test: diagnostic accuracy and feasibility study. JAMA Neurol. 2014 Apr. 71 (4):421-8. [Medline].

 
Previous
Next
 
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.
Table. Some Features of the A and B Chains of Factor XIII
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
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.