Hemophilia A Clinical Presentation
- Author: Robert A Zaiden, MD; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP more...
For patients in whom hemophilia is suspected, inquire about any history of hemorrhage disproportionate to trauma, spontaneous hemorrhage, bleeding disorders in the family, concomitant illness (especially those associated with acquired hemophilia, such as chronic inflammatory disorders, autoimmune diseases, hematologic malignancies, and allergic drug reactions), and pregnancy.
For individuals with documented hemophilia, ascertain the type of deficiency (eg, factor VIII [FVIII], FIX, von Willebrand), degree of factor deficiency, known presence of inhibitors, and HIV/hepatitis status. For patients with mild-to-moderate disease, determine responsiveness to desmopressin acetate (DDAVP).
Signs and symptoms of hemorrhage include the following:
General - Weakness and orthostasis
Musculoskeletal (joints) - Tingling, cracking, warmth, pain, stiffness, refusal to use the joint (young children)
Central nervous system (CNS) - Headache, stiff neck, vomiting, lethargy, irritability, spinal cord syndromes
Gastrointestinal (GI) - Hematemesis, melena, frank red blood per rectum, abdominal pain
Genitourinary - Hematuria, renal colic, post-circumcision bleeding
Other - Epistaxis, oral mucosal hemorrhage, hemoptysis, dyspnea (hematoma leading to airway obstruction), compartment syndrome symptoms, contusions, excessive bleeding with routine dental procedures
Evidence of infectious disease includes the following:
Newborn boys with severe hemophilia may present with prolonged bleeding at circumcision. Easy bruising may occur at the start of ambulation or primary dentition. Older patients may have a history of hemarthroses and prolonged bleeding with surgical procedures, trauma, and dental extraction, and may have spontaneous bleeding in soft tissues.
A traumatic challenge relatively late in life may have to occur before mild or moderate hemophilia is diagnosed. Factors that elevate FVIII levels (eg, age, ABO blood type, stress, exercise) may mask mild hemophilia.
Weight-bearing joints and other joints are principal sites of bleeding in patients with hemophilia. 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 compression of the femoral nerve may occur.
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.
Acquired hemophilia due to an autoantibody in previously hemostatically normal individuals tends to affect elderly people who have comorbid conditions, but may also develop post partum. Persons with acquired hemophilia may experience extensive, often life threatening, bleeding before the condition is recognized.
In contrast to persons with severe inherited hemophilia A, in whom joint bleeding is common, patients with acquired hemophilia present with large intramuscular, retroperitoneal, limb, subcutaneous, genitourinary, gastrointestinal, or excessive postoperative or postpartum bleeding. Bleeding into an extremity can result in findings that are easily confused with deep vein thrombosis. Massive upper extremity bleeding can be precipitated by a simple venipuncture. Bleeding can develop at any site.
Postpartum acquired hemophilia usually comes to attention 2 to 5 months after delivery, when bleeding symptoms supervene. Rarely, the inhibitor may develop during pregnancy.
Systemic signs of hemorrhage include the following:
Organ system–specific signs and symptoms of hemorrhage include the following:
Musculoskeletal (joints) - Tenderness, pain with movement, decreased range of motion, effusion, and warmth
Central nervous system (CNS) - Abnormal neurologic exam findings, altered mental status, and meningismus
Gastrointestinal (GI) - Can be painless; hepatic/splenic tenderness, and peritoneal signs
Genitourinary - Bladder spasm/distension/pain and costovertebral angle pain
Other - Hematoma leading to location-specific signs (eg, airway obstruction, compartment syndrome)
Signs of infectious disease include the following:
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.
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 children grow and become more physically active, hemarthroses 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.
Petechiae usually do not occur in patients with hemophilia. The reason is that petechiae are manifestations of capillary blood leakage, which is typically the result of vasculitis or abnormalities in the number or function of platelets.
Hemophilia is classified according to clinical severity as mild, moderate, or severe (see Table 1, below). Patients with severe disease usually have less than 1% factor VIII (FVIII) activity and experience spontaneous hemarthrosis and soft-tissue bleeding in the absence of apparent precipitating trauma. Patients with moderate disease have 1-5% FVIII activity and bleed with minimal trauma. Patients with mild hemophilia have more than 5% factor 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|
Direct the examination to identify signs related to spontaneous bleeding, or bleeding with minimal challenge, in the joints, muscles, and other soft tissues. Observe the patient's posture. Examine the weight-bearing joints, especially the knees and ankles, and, in general, the large joints for deformities or ankylosis. Look for jaundice and other signs of liver failure (eg, cirrhosis), and for signs of opportunistic infections in patients who are HIV positive.
Pseudotumors are produced by a slow expansion of repeated hemorrhages in bone or soft tissues. They can be restricted by the fascial planes of a muscle, cause resorption of neighboring bone by pressure-induced ischemia, or develop under the periosteum, leading to erosion of the bony cortex. They develop slowly over months to years and often are asymptomatic, unless pressure on the nerves or vascular compromise occurs.
Pseudotumors contain a brownish material and can become infected. The buttock, pelvis, and thighs are common locations for a pseudotumor (see the images below).
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|Classification||Factor Activity, %||Cause of Hemorrhage|
|Mild||>5-40||Major trauma or surgery|
|Indication or Site of Bleeding||Factor level Desired, %||FVIII Dose, IU/kg*||Comment|
|Severe epistaxis; mouth, lip, tongue, or dental work||20-50||10-25||Consider aminocaproic acid (Amicar), 1-2 d|
|Joint (hip or groin)||40||20||Repeat transfusion in 24-48 h|
|Soft tissue or muscle||20-40||10-20||No therapy if site small and not enlarging (transfuse if enlarging)|
|Muscle (calf and forearm)||30-40||15-20||None|
|Muscle deep (thigh, hip, iliopsoas)||40-60||20-30||Transfuse, repeat at 24 h, then as needed|
|Neck or throat||50-80||25-40||None|
|Hematuria||40||20||Transfuse to 40% then rest and hydration|
|Laceration||40||20||Transfuse until wound healed|
|GI or retroperitoneal bleeding||60-80||30-40||None|
|Head trauma (no evidence of CNS bleeding)||50||25||None|
|Head trauma (probable or definite CNS bleeding, eg, headache, vomiting, neurologic signs)||100||50||Maintain peak and trough factor levels at 100% and 50% for 14 d if CNS bleeding documented†|
|Trauma with bleeding, surgery†||80-100||50||10-14 d|