Hemophilia

Last reviewed: 27 Aug 2022
Last updated: 04 Aug 2022

Summary

Definition

History and exam

Key diagnostic factors

  • history of recurrent or severe bleeding
  • bleeding into muscles
  • prolonged bleeding following heel stick or circumcision
  • mucocutaneous bleeding
  • hemarthrosis
  • pseudotumor
  • intracranial bleeding
More key diagnostic factors

Other diagnostic factors

  • excessive bruising/hematoma
  • fatigue
  • menorrhagia and bleeding following surgical procedures or childbirth (female carriers)
  • extensive cutaneous purpura (acquired hemophilia)
  • gastrointestinal bleeding and hematuria
  • distended and painful abdomen
  • pallor, tachycardia, tachypnea, or hypotension
Other diagnostic factors

Risk factors

  • family history of hemophilia (congenital hemophilia)
  • male sex (congenital hemophilia)
  • age >60 years (acquired hemophilia)
  • autoimmune disorders, inflammatory bowel disease, diabetes, hepatitis, pregnancy and postpartum period, malignancy, monoclonal gammopathies, use of certain drugs (acquired hemophilia)
More risk factors

Diagnostic investigations

1st investigations to order

  • activated partial thromboplastin time (aPTT)
  • plasma factor VIII and IX assay
  • mixing study
  • CBC
  • prothrombin time (PT)
  • plasma von Willebrand factor assay
  • plasma factor V, VII assay
  • plasma factor XI, XII assay
  • closure time/bleeding time and platelet aggregation studies
  • serum liver aminotransferases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT])
  • plain x-rays of specific bony sites
  • prenatal factor VIII or IX mutation analysis by amniocentesis or chorionic villus sampling (CVS)
More 1st investigations to order

Investigations to consider

  • head or neck CT
  • head or neck MRI
  • abdominal ultrasound or abdominopelvic CT scan
  • esophagogastroduodenoscopy or colonoscopy
  • blood factor VIII or IX mutation analysis
  • plasma factor VIII or IX inhibitor screen
  • Bethesda assay/modified Bethesda assay (on plasma sample)
More investigations to consider

Treatment algorithm

INITIAL

life-threatening/limb-threatening bleed

ACUTE

congenital: nonlife-threatening bleed into joint or muscle

congenital: nonlife-threatening bleed into urinary tract

congenital: nonlife-threatening nasal or oral bleeding

acquired

ONGOING

inhibitors to factor VIII or IX

no VIII/IX inhibitors: severe hemophilia

no VIII/IX inhibitors: mild-moderate hemophilia with recurrent bleeds into single joint

Contributors

Authors

Man-Chiu Poon, MD, FRCP (C), FACP

Professor Emeritus

Departments of Medicine, Pediatrics and Oncology

Cumming School of Medicine

University of Calgary

Calgary

Canada

Disclosures

M-CP has been an ad hoc speaker for Bayer, Novo Nordisk, and Pfizer; attended advisory board meetings of Bioverativ/Sanofi, CSL Behring, KVR Pharmaceuticals, Novo Nordisk, Octapharma, Pfizer, Roche, and Takeda; received grant funding from Bayer and CSL Behring; and undertaken contract research for Novo Nordisk.

Adrienne Lee, MD, FRCP (C)

Clinical Assistant Professor

Department of Medicine

Cumming School of Medicine

University of Calgary

Calgary

Canada

Disclosures

AL declares that she has no competing interests.

Acknowledgements

Professor Poon and Dr Lee would like to gratefully acknowledge Dr Nigel S. Key, Dr Paul Giangrande, Dr Nidra I. Rodriguez, and Dr W. Keith Hoots, the previous contributors to this topic.

Disclosures

NSK has undertaken paid consultancy for Baxter Biosciences, Novo Nordisk, CSL Behring, and Bayer. He has received grant funding from Baxter. PG has undertaken paid consultancy and/or received lecture fees from the following companies involved in hemophilia care: Bayer, CSL Behring, NovoNordisk, Pfizer/ BPL, Octapharma, Biogen Idec, and Biotest. NSK, NIR, and WKH are authors of reference(s) cited in this topic.

Peer reviewers

Louis Aledort, MD

The Mary Weinfeld Professor of Clinical Research in Hemophilia

Mount Sinai School of Medicine

New York

NY

Disclosures

LA declares that he has no competing interests.

Christoph Pechlaner, MD

Associate Professor of Medicine

Innsbruck Medical University

Innsbruck

Austria

Disclosures

CP declares that he has no competing interests.

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