eMedicine Specialties > Pediatrics: General Medicine > Hematology

Inherited Abnormalities of Fibrinogen: Differential Diagnoses & Workup

Author: Sara J Israels, MD, FRCPC, Professor of Pediatric Hematology/Oncology, Section Head of Pediatric Hematology/Oncology/BMT, Department of Pediatrics and Child Health, University of Manitoba
Contributor Information and Disclosures

Updated: Feb 12, 2009

Differential Diagnoses

Consumption Coagulopathy
Factor XIII Deficiency

Other Problems to Be Considered

Congenital afibrinogenemia and dysfibrinogenemia with bleeding must be differentiated from other congenital clotting factor deficiencies. In addition, clinical conditions that result in acquired hypofibrinogenemia, such as consumptive coagulopathy, hepatic failure, and L-asparaginase therapy, or in acquired dysfibrinogenemia, such as liver disease and some neoplasms, should be excluded.

Dysfibrinogenemia with thrombosis must be differentiated from other causes of congenital or acquired thrombophilia.

Workup

Laboratory Studies

  • Screening tests: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are prolonged in afibrinogenemia and may be prolonged in dysfibrinogenemia. Thrombin time and reptilase time are more sensitive to abnormalities of fibrinogen than the PT or aPTT. Unlike the other tests listed, reptilase time is unaffected by heparin. A prolonged reptilase time, in the presence of a normal fibrinogen concentration, provides strong evidence of a dysfibrinogenemia.
  • Fibrinogen concentration: Fibrinogen levels are measured by either immunological assays or functionally as clottable protein. In afibrinogenemia, fibrinogen concentrations are low by either method, usually less than 0.1 g/L, and often undetectable in symptomatic individuals. In dysfibrinogenemia, a discrepancy may be found between fibrinogen measured in a functional assay (low) and fibrinogen measured immunologically (normal); however, in some dysfibrinogenemias, a concordant decrease in the 2 assays is observed.
  • Genotyping: Genotyping identification of the specific molecular defect may be useful in both afibrinogenemia and dysfibrinogenemia. Mutation analysis has not identified any correlation with phenotype or ethnic background. However, it can be useful in diagnosis confirmation, screening of relatives for carrier status, family counseling, and prenatal diagnosis.
  • Thrombophilia evaluation: Because dysfibrinogenemia is a rare cause of thrombosis (<1%), patients in whom dysfibrinogenemia is diagnosed in the setting of thrombosis should have a complete investigation for other risk factors, inherited and acquired, that may have contributed to the thrombotic event.

Imaging Studies

  • In the investigation of suspected bleeding, appropriate imaging studies (eg, brain CT scanning or MRI) may reveal the presence of suspected CNS hemorrhage.

More on Inherited Abnormalities of Fibrinogen

Overview: Inherited Abnormalities of Fibrinogen
Differential Diagnoses & Workup: Inherited Abnormalities of Fibrinogen
Treatment & Medication: Inherited Abnormalities of Fibrinogen
Follow-up: Inherited Abnormalities of Fibrinogen
Multimedia: Inherited Abnormalities of Fibrinogen
References
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References

  1. Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost. Jan 1995;73(1):151-61. [Medline].

  2. Asselta R, Duga S, Tenchini ML. The molecular basis of quantitative fibrinogen disorders. J Thromb Haemost. Oct 2006;4(10):2115-29. [Medline].

  3. Bolton-Maggs PH, Perry DJ, Chalmers EA, et al. The rare coagulation disorders--review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation. Haemophilia. Sep 2004;10(5):593-628. [Medline].

  4. Cunningham MT, Brandt JT, Laposata M, Olson JD. Laboratory diagnosis of dysfibrinogenemia. Arch Pathol Lab Med. 2002;126:499-505. [Medline].

  5. Martinez J. Congenital dysfibrinogenemia. Curr Opin Hematol. Sep 1997;4(5):357-65. [Medline].

  6. Parameswaran R, Dickinson JP, de Lord S, et al. Spontaneous intracranial bleeding in two patients with congenital afibrinogenaemia and the role of replacement therapy. Haemophilia. Nov 2000;6(6):705-8. [Medline].

  7. Peyvandi F, Haertel S, Knaub S, Mannucci PM. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. J Thromb Haemost. Jul 2006;4(7):1634-7. [Medline].

  8. Roberts HR, Stinchcombe TE, Gabriel DA. The dysfibrinogenaemias. Br J Haematol. Aug 2001;114(2):249-57. [Medline].

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Further Reading

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Keywords

afibrinogenemia, congenital afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, congenital dysfibrinogenemia, fibrinogen deficiency, fibrinogen abnormalities, clotting disorder, blood disorder, inherited abnormalities of fibrinogen, defective fibrinogen synthesis, venous thrombosis, factor XIII deficiency

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Contributor Information and Disclosures

Author

Sara J Israels, MD, FRCPC, Professor of Pediatric Hematology/Oncology, Section Head of Pediatric Hematology/Oncology/BMT, Department of Pediatrics and Child Health, University of Manitoba
Sara J Israels, MD, FRCPC is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Canadian Medical Association, Children's Oncology Group, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

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, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
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.

 
 
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