Last reviewed: 6 Nov 2021
Last updated: 31 Oct 2019



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
  • intracranial bleeding

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

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, postpartum, or malignancy (acquired hemophilia)

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)

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)

Treatment algorithm



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

Clinical Professor

Departments of Medicine, Pediatrics and Oncology

Cumming School of Medicine

University of Calgary




M-CP has been an ad hoc speaker for Bayer, Novo Nordisk, and Pfizer; attended advisory board meetings of Biogen Idec, Baxalta/Shire, CSL Behring, Novo Nordisk, Octapharma, Pfizer, and Roche; received grant funding from CSL Behring and Bayer; 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




AL declares that she has no competing interests.


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.


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



LA declares that he has no competing interests.

Christoph Pechlaner, MD

Associate Professor of Medicine

Innsbruck Medical University




CP declares that he has no competing interests.

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