Differentials
Von Willebrand disease (VWD)
SIGNS / SYMPTOMS
Family history is usually positive, including both females and males, due to an autosomal dominant pattern of inheritance.
Bleeding symptoms may be similar to mild congenital hemophilia, although patients with von Willebrand disease tend to have more mucosal bleeding symptoms.
INVESTIGATIONS
Diagnosis is based on various tests, including von Willebrand factor (VWF) antigen, VWF activity (ristocetin cofactor or collagen-binding assay), factor VIII assay, VWF multimers, and genetic testing for mutations within the VWF gene.
Most clinicians agree that VWF levels <30 international units/dL are consistent with a diagnosis of von Willebrand disease.[43] However, repeated testing is often needed to confirm the diagnosis because VWF levels may fluctuate with activity, concurrent illness, and inflammation, and can increase during pregnancy and during the use of hormonal therapy (oral contraceptive pill, hormone replacement therapy).
von Willebrand factor binding to factor VIII is defective in patients with type 2N von Willebrand disease, resulting in decreased levels of factor VIII activity (with normal VWF activity and antigen levels) suggestive of mild hemophilia A.
Type 2N von Willebrand disease (autosomal recessive) can be confirmed by genetic testing for mutation within the VWF gene encoding for the factor VIII binding domain or by von Willebrand factor-factor VIII binding assay.[62]
Platelet dysfunction
SIGNS / SYMPTOMS
Bleeding pattern is typically mucocutaneous and not musculoskeletal as in hemophilia.
INVESTIGATIONS
Platelet aggregation studies are the test of choice to diagnose platelet disorders.[46]
Closure time/bleeding time may be used as screening tests for platelet disorders. Results are, however, nonspecific.
Specific platelet agonists (adenosine diphosphate, epinephrine, collagen, ristocetin, and arachidonic acid) are used to assess platelet aggregation by measuring optical density.
Platelet electron microscopy can also be used to evaluate platelet ultrastructure, including delta granule content.
Deficiency of other coagulation factors (e.g., factor V, VII, X XI, or fibrinogen)
SIGNS / SYMPTOMS
Musculoskeletal bleeding is uncommon.
There have been cases of thrombosis reported in people with fibrinogen or factor VII deficiency.
Combined factor V and VIII deficiency may be mistaken for mild hemophilia A, but should be suspected when the prothrombin time and activated partial thromboplastin time are both prolonged, and/or there is parental consanguinity.
Combined factor V and factor VIII deficiency is an autosomal recessive bleeding disorder.
INVESTIGATIONS
Specific coagulation factor assays are needed to establish diagnosis.
Ehlers-Danlos syndrome
SIGNS / SYMPTOMS
Bleeding is primarily mucosal in origin.
Musculoskeletal bleeding is uncommon.
Skin hyperextensibility, joint laxity present.
INVESTIGATIONS
Diagnosis based on clinical findings, along with genetic testing and/or tissue biopsy.
Scurvy
SIGNS / SYMPTOMS
Bleeding is primarily mucosal in origin.
Musculoskeletal bleeding is uncommon.
History of a restricted diet, sepsis, HIV, critical illness, or pancreatitis may be present.
INVESTIGATIONS
Diagnosis based on clinical findings, along with a reduced serum vitamin C level.
Fabry disease
SIGNS / SYMPTOMS
Bleeding is primarily mucosal in origin.
Musculoskeletal bleeding is uncommon.
Typical skin lesions (angiokeratomas), pain in the extremities, renal and heart disease, typical ocular signs.
INVESTIGATIONS
Diagnosis based on clinical findings, along with genetic testing.
Child abuse
SIGNS / SYMPTOMS
Inconsistent history of how trauma occurred is typical.
Physical exam may show injuries in various healing stages or with an obvious pattern, bruises, inflicted burns, fractures.
INVESTIGATIONS
CBC may reveal anemia, which may be chronic in neglected or malnourished children.
Liver and pancreatic enzymes may be elevated if abdominal trauma.
Imaging may reveal abnormal x-rays with evidence of fractures, or abnormal brain or abdominal imaging due to bleeding.
Disseminated intravascular coagulation
SIGNS / SYMPTOMS
No differentiating signs/symptoms.
Underlying causal condition (e.g., acute promyelocytic leukemia) is present.
INVESTIGATIONS
Unlike in acquired hemophilia, platelet count is decreased.
Absence of factor VIII auto-antibodies.
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