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Hemophilia B Clinical Presentation

  • Author: Robert A Zaiden, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
 
Updated: Mar 11, 2016
 

History

Hemophilia is suggested by a history of hemorrhage disproportionate to trauma or of spontaneous hemorrhage, or a family history of bleeding problems. Concomitant illness may include chronic inflammatory disorders, autoimmune diseases, hematologic malignancies (acquired form), and allergic drug reactions.

For individuals with documented hemophilia, inquire regarding the type of deficiency (eg, VIII, IX, von Willebrand), percent factor deficiency, known presence of inhibitors, and HIV/hepatitis status.

Approximately 30-50% of patients with severe hemophilia present with manifestations of neonatal bleeding (eg, after circumcision). Approximately 1-2% of neonates have intracranial hemorrhage. Other neonates may present with severe hematoma and prolonged bleeding from the cord or umbilical area or at sites of blood draws or immunizations.

After the immediate neonatal period, bleeding is uncommon in infants until they become toddlers, when trauma-related soft-tissue hemorrhage occurs. Young children may also have oral bleeding when their teeth are erupting. Bleeding from gum and tongue lacerations is often troublesome because the oozing of blood may continue for a long time despite local measures.

As physical activity increases in children, hemarthrosis and hematomas occur. Chronic arthropathy is a late complication of recurrent hemarthrosis in a target joint. Traumatic intracranial hemorrhage is a serious life-threatening complication that requires urgent diagnosis and intervention.

With mild disease, hemorrhage is most likely to occur with trauma or surgery. A traumatic challenge relatively late in life may have to occur before mild or moderate hemophilia is suspected.

Signs of hemorrhage include the following:

  • General - Weakness and orthostasis
  • Musculoskeletal (joints) - Tingling, cracking, warmth, pain, stiffness, and refusal to use joint (children)
  • CNS - Headache, stiff neck, vomiting, lethargy, irritability, and spinal cord syndromes
  • GI - Hematemesis, melena, frank red blood per rectum, and abdominal pain
  • Genitourinary - Hematuria, renal colic, and postcircumcision bleeding
  • Other - Epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea (hematoma leading to airway obstruction), compartment syndrome symptoms, and contusions

Joint and muscle hemorrhage are the most common manifestations of moderate and severe hemophilia. Petechiae usually do not occur in patients with hemophilia because they are manifestations of capillary blood leaking, which is typically the result of vasculitis or abnormalities in the number or function of platelets.

Signs of infectious disease include the following:

  • HIV/AIDS-related symptoms
  • Hepatitis-related symptoms

The principal sites of bleeding in patients with hemophilia are as follows. Bleeds affect weight-bearing joints and other joints. The muscles most commonly affected are the flexor groups of the arms and gastrocnemius of the legs. Iliopsoas bleeding is dangerous because of the large volumes of blood loss and because of compression of the femoral nerve.

In the genitourinary tract, gross hematuria may occur in as many as 90% of patients. In the GI tract, bleeding may complicate common GI disorders. Bleeding in the CNS is the leading cause of hemorrhagic death among patients with hemophilia.

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Physical Examination

Systemic signs of hemorrhage include the following:

  • Tachycardia
  • Tachypnea
  • Hypotension
  • Orthostasis

Organ system–specific signs of hemorrhage include the following:

  • Musculoskeletal (joints) - Tenderness, pain with movement, decreased range of motion, swelling, effusion, and warmth
  • CNS - Abnormal neurologic exam findings, altered mental status, and meningismus
  • GI - Can be painless; hepatic/splenic tenderness and peritoneal signs
  • GU - Bladder spasm/distension/pain, costovertebral angle pain
  • Other - Hematoma leading to location-specific signs (eg, airway obstruction, compartment syndrome)

Signs of infectious disease include the following:

  • HIV/AIDS-related signs
  • Hepatitis-related signs

Direct the examination to identify signs related to bleeding in the joints, muscles, and other soft tissues that has occurred spontaneously or after minimal challenge. Observe the patient's stature. Examine the weight-bearing joints, especially the knees and ankles, and, in general, the large joints for deformities or ankylosis. Look for jaundice, other signs of liver failure (eg, cirrhosis from viral infection), and signs of opportunistic infections in patients who are HIV seroconverted.

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Clinical Classification

Hemophilia is classified according to the clinical severity as mild, moderate, or severe (see Table 1, below). Patients with severe disease usually have less than 1% factor activity. It is characterized by spontaneous hemarthrosis and soft tissue bleeding in the absence of precipitating trauma. Patients with moderate disease have 1-5% factor activity and bleed with minimal trauma. Patients with mild hemophilia have more than 5% factor VIII (FVIII) activity and bleed only after significant trauma or surgery.

Table 1. Severity, Factor Activity, and Hemorrhage Type (Open Table in a new window)

Classification Factor Activity, % Cause of Hemorrhage
Mild >5-40 Major trauma or surgery
Moderate 1-5 Mild-to-moderate trauma
Severe < 1 Spontaneous, hemarthrosis
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Contributor Information and Disclosures
Author

Robert A Zaiden, MD Assistant Professor, Division of Hematology/Oncology, Department of Medicine, University of Florida at Jacksonville College of Medicine

Robert A Zaiden, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Acknowledgements

Dimitrios P Agaliotis, MD, PhD, FACP Consulting Staff, Department of Medicine, Baptist Health System

Disclosure: Nothing to disclose.

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians

Disclosure: Nothing to disclose.

Emmanuel C Besa, MD Professor, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Gary D Crouch, MD Associate Professor, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology

Disclosure: Nothing to disclose.

Brendan R Furlong, MD Clinical Chief, Department of Emergency Medicine, Georgetown University Hospital.

Brendan R Furlong is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Mary A Furlong, MD Associate Professor and Program/Residency Director, Department of Pathology, Georgetown University School of Medicine

Mary A Furlong, MD is a member of the following medical societies: United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

William G Gossman, MD Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Consulting Staff, Department of Emergency Medicine, Creighton University Medical Center

William G Gossman, MD is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Lawrence F Jardine, MD, FRCPC Associate Professor, Department of Pediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario; Head, Section of Pediatric Hematology and Oncology, Children's Hospital of Western Ontario; Associate Scientist, Child Health Research Institute

Lawrence F Jardine, MD, FRCPC is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Canadian Medical Protective Association, Children's Oncology Group, College of Physicians and Surgeons of Ontario, Hemophilia and Thrombosis Research Society, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada

Disclosure: Baxter Honoraria Consulting; Bayer Honoraria Consulting; Novartis Honoraria Speaking and teaching

Adonis Lorenzana, MD Consulting Staff, Department of Pediatric Oncology, St John Hospital and Medical Center

Adonis Lorenzana, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Saduman Ozturk, PA-C Physician Assistant, Bone Marrow Transplant Center, Florida Hospital Cancer Institute

Disclosure: Nothing to disclose.

Ronald A Sacher, MB, BCh, MD, FRCPC Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

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

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching

Hadi Sawaf, MD Director, Pediatric Hematology Oncology, Van Elslander Cancer Center; Clinical Assistant Professor, Wayne State University School of Medicine

Hadi Sawaf, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Society of Hematology

Disclosure: Novartis Honoraria Speaking and teaching; Novartis Consulting fee Speaking and teaching; Ariad Honoraria Speaking and teaching; Celgene Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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Coagulation Cascade
Table 1. Severity, Factor Activity, and Hemorrhage Type
Classification Factor Activity, % Cause of Hemorrhage
Mild >5-40 Major trauma or surgery
Moderate 1-5 Mild-to-moderate trauma
Severe < 1 Spontaneous, hemarthrosis
Table 2. General Guidelines for Factor Replacement for the Treatment of Bleeding in Hemophilia B
Indication or Site of Bleeding Factor level Desired, % FIX Dose, IU/kg* Comment
Severe epistaxis; mouth, lip, tongue, or dental work 20-50 20-50 Consider aminocaproic acid (Amicar), 1-2 d
Joint (hip or groin) 40 40 Repeat transfusion in 24-48 h
Soft tissue or muscle 20-40 40 No therapy if site small and not enlarging (transfuse if enlarging)
Muscle (calf and forearm) 30-40 40 None
Muscle deep (thigh, hip, iliopsoas) 40-60 40-60 Transfuse, repeat at 24 h, then as needed
Neck or throat 50-80 50-80 None
Hematuria 40 40 Transfuse to 40% then rest and hydration
Laceration 40 40 Transfuse until wound healed
GI or retroperitoneal bleeding 60-80 60-80 None
Head trauma (no evidence of CNS bleeding) 50 50 None
Head trauma (probable or definite CNS bleeding, eg, headache, vomiting, neurologic signs) 100 100 Maintain peak and trough factor levels at 100% and 50% for 14 d if CNS bleeding documented
Trauma with bleeding, surgery 80-100 100 10-14 d
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