Normal hemostasis involves 13 coagulation factors, von Willebrand factor (VWF), platelets, and activation by the endothelial surface that is damaged. Clotting factor deficiencies result from a lack of hemostasis factors leading to abnormal bleeding. Cutaneous manifestations of such disorders may include petechiae, ecchymosis (bruising), and frank bleeding.
Disorders of hemostasis may be categorized as:
Primary hemostasis – Involving VWF, platelets, and the endothelium. Lack of these factors results in prolonged bleeding, petechiae, or easy bruising.
Secondary hemostasis – Involving the coagulation cascade and the 13 factors. Lack of these factors can result in more profound bleeding, such as hemarthroses, or bleeding into cavities and muscles.
VWF deficiency is the most common hereditary bleeding disorder, affecting approximately 1% of the general population. It is inherited as an autosomal dominant trait, although it can be acquired.
VWF is an important part of initial hemostasis and binds to the damaged endothelium and activates platelets. Additionally, VWF carries factor VIII, and a deficiency in VWF results in a relative deficiency in VIII (although it is quantitatively normal).
There are three classifications of von Willebrand disease (VWD):
Type 1 – a quantitative reduction (most common)
Type 2 – abnormal VWF
Type 3 – absent VWF (with many subtypes)
Symptoms of VWD may include prolonged bleeding, mucocutaneous bleeding, bullous hemorrhage on the buccal mucosa, epistaxis, menorrhagia, gastrointestinal bleeding, and postoperative hemorrhage.
Young patients with VWD may first present to the emergency room or pediatrician with bruising, and this can cause suspicion of physical abuse. Thus, while appropriate action regarding the suspicion of abuse is important, the workup can be challenging. Unusual bruising or injury, where abuse is denied, should involve consideration of a bleeding disorder, and it may also involve referral to a hematologist to exclude a clotting disorder.
ICD10CM: D68.0 – Von Willebrand's disease
SNOMEDCT: 128105004 – von Willebrand disorder
Differential Diagnosis & Pitfalls
The differential diagnosis of purpura or easy bruising can be divided into several categories of causation of similar symptoms.
Infectious – Viral, streptococcal, meningococcemia. Meningococcemia usually acutely erupts with petechiae throughout the body and quickly forms vesicles, bullae, and pustules that then become stellate purpura with a central dusky or gray hue. Viral includes a nonspecific widespread erythematous eruption where the patient does not look toxic.
Drug related – Erythematous macules and papules on the trunk that spread to the extremities. Rash blanches under pressure and is usually found 7-14 days after exposure to a medication.
Erythema nodosum – Erythematous, tender, deep-seated nodules and plaques, 2-5 cm, located on anterior shins, usually in women.
Immunoglobulin A vasculitis (formerly Henoch-Schönlein purpura) – Scattered palpable purpura distributed over ankles, knees, and buttocks bilaterally. May have associated abdominal or joint pain.
Capillary hemangioma – Telangiectatic, vasoconstricted patch. Not present at birth but arises within a few months and has deep red papules that involutes after a year.
Congenital dermal melanocytosis (formerly Mongolian spot) – Blue-gray spots that are evenly pigmented, located over the sacrococcygeal region, and tend to occur in infants or children of Asian or African descent. Generally present at birth.
Prominent facial veins
Connective Tissue Disorders
Ehlers-Danlos – Hypermobile joints; thin, soft, doughy skin that recoils. May have characteristic "fish mouth"-like scars or "cigarette paper"-like scars over extremities.
Scurvy – Corkscrew hairs, perifollicular purpura, bleeding gums, and broad areas of purpura and ecchymosis may be present.
Subconjunctival hemorrhage – Blood-red area of the conjunctiva that can cover a few millimeters or the whole eye. Associated with minor trauma, sneezing, eye rubbing, or straining.
Coining – Cultural practice showing linear erythematous patches with petechiae and ecchymosis, usually in parallel.
Cupping – 4- to 6-cm circular burns with central ecchymosis and petechiae.
Nonaccidental trauma (NAT) – It can be difficult to differentiate among a true coagulopathy, physical abuse, and accidental trauma. Accidental trauma usually occurs over bony prominences in mobile children, including knees and shins. Accidental bruises are small, between 10 and 15 mm. Signs concerning for NAT include bruises in infants younger than 9 months (as they are not cruising); ecchymosis on neck, face, torso, arms, buttocks, genitalia, lips, or earlobes; or evidence of an imprint from a weapon. An imprint in the shape of a hand, fingers, belt mark, iron, or electrical wires is more predictive of child abuse. Belt or electrical wire marks may be evenly spaced or curvilinear / arcuate. In NAT, bruises also tend to be grouped and larger. If fractures or subconjunctival hemorrhages or subdural hematomas are present and/or the parents have an inconsistent story, abuse is much more likely.