Pediatric Von Willebrand Disease 

Updated: Feb 05, 2019
Author: Suchitra S Acharya, MD, MBBS; Chief Editor: Hassan M Yaish, MD 

Overview

Background

Although referred to as a single disease, von Willebrand disease (VWD) is in fact a family of bleeding disorders caused by an abnormality of the von Willebrand factor (VWF). von Willebrand disease is the most common hereditary bleeding disorder.[1, 2]

The condition was first described by Erik Adolf von Willebrand in 1926, who called it pseudohemophilia because of the fact that his first patient was a female. It took several decades before the actual nature of this bleeding disorder was understood. von Willebrand disease is a congenital bleeding disorder characterized by a lifelong tendency toward easy bruising, frequent epistaxis, and menorrhagia.

Pathophysiology

von Willebrand disease is due to an abnormality, either quantitative or qualitative, of the von Willebrand factor, which is a large multimeric glycoprotein required for normal platelet adhesion. It also functions as the carrier protein for factor VIII (FVIII).[3]  As such, von Willebrand factor functions in both primary (involving platelet adhesion and platelet plug formation) and secondary (involving FVIII) hemostasis. In primary hemostasis, von Willebrand factor attaches to platelets by its specific receptor to glycoprotein Ib on the platelet surface and acts as an adhesive bridge between the platelets and damaged subendothelium at the site of vascular injury. In secondary hemostasis, von Willebrand factor protects FVIII from degradation and delivers it to the site of injury.

von Willebrand factor is composed of dimeric subunits that are linked by disulfide bonds to form complex multimers of low, intermediate, and high molecular weights. The small multimers function mainly as carriers for FVIII.

High–molecular weight multimers have higher numbers of platelet-binding sites and greater adhesive properties. Each multimeric subunit has binding sites for the receptor glycoprotein Ib on nonactivated platelets and the receptor glycoprotein IIb/IIIa on activated platelets. This facilitates both platelet adhesion and platelet aggregation, making high molecular weight multimers most important for normal platelet function. See the image below.

Structure and domains of von Willebrand factor. Structure and domains of von Willebrand factor.

von Willebrand disease types

von Willebrand disease can be classified into 3 main types.

Type 1 von Willebrand disease

Type 1 von Willebrand disease, which accounts for 70-80% of cases, is characterized by a partial quantitative decrease of qualitatively normal von Willebrand factor and FVIII. An individual with type 1 von Willebrand disease generally has mild clinical symptoms, and this type is usually inherited as an autosomal dominant trait; however, penetrance may widely vary in a single family. In addition, clinical and laboratory findings may vary in the same patient on different occasions. Typically, a proportional reduction in von Willebrand factor activity, von Willebrand factor antigen, and FVIII is observed in type 1 von Willebrand disease.[4]

Type 2 von Willebrand disease

Type 2 disease accounts for 15-20% of von Willebrand disease cases. It is a variant of the disease with primarily qualitative defects of von Willebrand factor. Type 2 von Willebrand disease can be either autosomal dominant or autosomal recessive.[5] Of the four described type 2 von Willebrand disease subtypes (ie, 2A, 2B, 2M, 2N), type 2A  is by far the most common.

Type 2A von Willebrand disease is inherited as an autosomal dominant trait and is characterized by normal-to-reduced plasma levels of factor VIIIc (FVIIIc) and von Willebrand factor. Analysis of von Willebrand factor multimers reveals a relative reduction in intermediate and high molecular weight multimer complexes. The multimeric abnormalities are commonly the result of in vivo proteolytic degradation of the von Willebrand factor. The ristocetin cofactor activity is greatly reduced, and the platelet von Willebrand factor reveals multimeric abnormalities similar to those found in plasma.

Type 2B von Willebrand disease is also an autosomal dominant trait. This type is characterized by a reduction in the proportion of high molecular weight von Willebrand factor multimers, whereas the proportion of low–molecular weight fragments are increased. Patients with type 2B von Willebrand disease have a hemostatic defect caused by a qualitatively abnormal von Willebrand factor and intermittent thrombocytopenia. This is a gain of function mutation in the von Willebrand factor causing spontaneous binding to platelets and rapid clearance of both platelets and high molecular weight von Willebrand factor multimers. The abnormal von Willebrand factor has an increased affinity for platelet glycoprotein Ib.

The platelet count may fall further during pregnancy, in association with surgical procedures, or after the administration of desmopressin acetate (DDAVP). Although some investigators found DDAVP to be clinically useful in persons with type 2B von Willebrand disease , studies directed at excluding the 2B variant should be completed before DDAVP is used. Measurements of FVIIIc and von Willebrand factor in plasma vary; however, studies involving the use of titered doses of ristocetin reveal that aggregation of normal platelets is enhanced and induced by unusually small amounts of the drug (low dose ristocetin induced platelet aggregation assay- LD- RIPA).

In patients with the rare type 2M von Willebrand disease, laboratory results are similar to those of certain patients with type 2A von Willebrand disease. Type 2M von Willebrand disease is characterized by a decreased platelet-directed function that is not due to a decrease of high–molecular weight multimers. Laboratory findings show decreased von Willebrand factor activity, although von Willebrand factor antigen, FVIII, and multimer analysis are found to be within reference range. This is caused by a defect in the von Willebrand factor gene that produces decreased or absent binding to platelet glycoprotein Ib and is autosomal dominant in inheritance. The ratio of von Willebrand factor ristocetin cofactor activity to the von Willebrand factor antigen is usually less than 0.5-0.7 (as in types 2A and 2B). Normal multimers distinguish type 2M from types 2A and 2B.

Type 2N von Willebrand disease is also rare and is characterized by a markedly decreased affinity of von Willebrand factor for FVIII because of a genetic mutation in the factor VIII binding region of von Willebrand factor; this results in FVIII levels being reduced to usually around 5-15% of the reference range, with a half life of about 2 hours only. Other von Willebrand factor laboratory parameters (ie, von Willebrand factor antigen, ristocetin cofactor activity) are usually normal. The FVIII-binding defect in these patients is inherited in an autosomal recessive manner. Male patients type 2N–like findings are frequently mistaken for having mild hemophilia A. For this reason, type 2N von Willebrand disease should be considered in patients with FVIII deficiency (mild FVIII deficiency) and a bleeding disorder that is not clearly transmitted as an X-linked disease, as well as in patients who respond incompletely to hemophilia A therapy. Unfortunately, the confirmatory test, which is a specific assay of FVIII binding to von Willebrand factor for type 2N von Willebrand disease, is not routinely available, likely resulting in an underestimation of the true frequency of this subtype.[6]

Type 3 von Willebrand disease

Type 3 von Willebrand disease is the rarest and most severe form of the condition. The disease is inherited as an autosomal recessive trait, and symptomatic patients are homozygous or combined heterozygous. Type 3 von Willebrand disease is characterized by marked deficiencies of both von Willebrand factor and FVIIIc (2-10%) in the plasma, the absence of von Willebrand factor from both platelets and endothelial cells, and a lack of response to DDAVP. Type 3 von Willebrand disease is also characterized by severe clinical bleeding, which is characteristic of both the primary hemostatic defects (superficial and mucous membrane bleeds) and the secondary hemostatic defects (joint and muscle bleeds) and is inherited as an autosomal recessive trait. Consanguinity is common in kindreds with this variant. Multimeric analysis of the small amount of von Willebrand factor present yields variable results, in some cases revealing only small multimers, if any.

Epidemiology

Frequency

United States

von Willebrand disease is estimated to affect about 1% of the population.[7]

International

Prevalence worldwide is estimated at 0.9-1.3%.

Mortality/Morbidity

The morbidity in individuals with von Willebrand disease varies. Many children with von Willebrand disease are asymptomatic. Some of these children have cutaneous and/or mucous membrane bleeding (eg, easy bruising, epistaxis).

Menorrhagia is a common symptom in females with von Willebrand disease. It occurs in more than 50% of women with von Willebrand disease and may be the only clinical manifestation of the disease.

The rare type 3 von Willebrand disease can manifest with severe bleeding symptoms similar to those of mild to moderate hemophilia A (eg, hemarthrosis, intramuscular bleeding).

A Swedish study, by Holm et al, found that compared with controls, patients with von Willebrand disease had a higher risk of hospitalization associated with cardiovascular disease (CVD; 1.3 fold) but a lower risk of CVD-linked mortality (0.4 fold). According to the investigators, this suggests that von Willebrand factor deficiency protects against arterial thrombosis even in the presence of atherosclerosis.[8]

Race

No influence of ethnicity on the prevalence of von Willebrand disease has been reported.

Sex

von Willebrand disease affects males and females in equal numbers.

Age

von Willebrand disease is a congenital bleeding disorder and can be diagnosed at any age.

 

Presentation

History

Many children with von Willebrand disease (VWD) are asymptomatic and are diagnosed as a result of a positive family history or during routine preoperative screening. Some children may have completely normal screening and yet bleed at procedures in areas with increased fibrinolysis, such as the mouth (ie, tonsillectomy). Importantly, remember that a wide variation in clinical manifestations is observed, even for members of the same family.

The diagnosis of von Willebrand disease can be challenging and depends on an accurate personal and family bleeding history, as well as demonstration of a low von Willebrand factor (VWF) level.[9, 10]

The history may reveal the following:

  • Increased or easy bruising

  • Recurrent epistaxis

  • Menorrhagia

  • Postoperative bleeding (particularly after tonsillectomy or dental extractions): Medical records of 99 patients younger than 18 years with von Willebrand disease who underwent tonsillectomy were compared with 99 patients without von Willebrand disease in the same age group; subjects were matched for age, year of surgery, type of surgery, and indication for surgery.[11] The study concluded that children with von Willebrand disease have a postoperative bleeding rate similar to that of a matched group. However, the sample size was insufficient to eliminate any clinically important difference between the two groups.

  • Family history of a bleeding diathesis - Bleeding from wounds, gingival bleeding, postpartum bleeding

A study by Bowman et al reported that the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease [MCMDM-1 VWD]) Bleeding Questionnaire, as modified into the Pediatric Bleeding Questionnaire, has a strong negative predictive value in addressing bleeding symptoms.[12]

A study by Sanders et al found that out of 113 children with von Willebrand disease (type 1, type 2, or type 3), 44% experienced pediatric-specific bleeding (any of the following: umbilical stump bleeding, cephalohematoma, cheek hematoma, conjunctival bleeding, postcircumcision bleeding, postvenipuncture bleeding). The study also found that children with type 2 or 3 von Willebrand disease had greater frequency of any bleeding, epistaxis, and oral cavity bleeding than did those with type 1 disease, with this frequency linked to von Willebrand factor levels.[13]

Physical

The physical examination findings may be normal, but the following may be present:

  • Increased bruises

  • Mucosal bleeding

Causes

von Willebrand disease is caused by an inherited defect that results in a deficiency or dysfunction of von Willebrand factor. The gene for von Willebrand factor is on the short arm of chromosome 12. It spans approximately 180 kilobases (kb) and is composed of 52 exons. Exons range in size from 40 base pairs (bp) to 1.4 kb. Various point mutations, insertions, and deletions at the von Willebrand factor locus have been described.

In some cases, von Willebrand disease is believed to result from other pathologic processes; however, because of the relatively high prevalence of von Willebrand disease, its concomitant occurrence with other disease states may be coincidental.

Nevertheless, acquired forms of von Willebrand disease can be observed in the following conditions:

  • Wilms tumor

  • Congenital heart disease[14]

  • Systemic lupus erythematosus

  • Angiodysplasia, telangiectasia, connective tissue disorders

  • Seizure disorders treated with valproic acid

  • Hypothyroidism

A meta-analysis by Sahebkar et al of randomized, controlled trials indicated that high-intensity statin therapy can significantly reduce von Willebrand factor antigen levels. This was particularly found in studies lasting 12 weeks or more, with simvastatin and pravastatin showing the greatest lowering effect.[15]  

 

DDx

Diagnostic Considerations

Other platelet function abnormalities, such as Glanzmann thrombasthenia, storage pool defects, and acquired abnormal platelet function due to medication (eg, aspirin, long-term nonsteroidal anti-inflammatory drug [NSAID] use); hyperextensibility syndromes

Differential Diagnoses

 

Workup

Laboratory Studies

Screening tests

Screening tests for von Willebrand disease (VWD) include the following:

  • Complete blood count (CBC)
  • Template bleeding time
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)

Complete blood count (CBC)

Assess platelet number and morphology, which should be normal in most patients with von Willebrand disease, except those with type 2B von Willebrand disease who may have thrombocytopenia.

Template bleeding time

Because it is reasonably well standardized, the template bleeding time is used as a screening test for primary hemostasis. The reference range for the bleeding time in children is longer than that of adults. Results of the bleeding time are affected by many technical factors, such as the direction of the incision and the skill of the technician. Although a bleeding time outside of the reference range may suggest a defect in hemostasis, it is not diagnostic. Similarly, a bleeding time within the reference range does not exclude the presence of such a defect.

Although neither sensitive nor specific for von Willebrand disease, template bleeding time is outside of the reference range in about 50% of patients with type 1 von Willebrand disease. Patients with von Willebrand disease types 2A, 2B, 2M, and 3 often have prolonged bleeding times.

The template bleeding time has largely been replaced by automatic platelet function analyzers (PFAs), such as the PFA-100, the results from which are frequently normal except in the more severe types of von Willebrand disease.

Prothrombin time (PT)

PT is within the reference range in von Willebrand disease.

Activated partial thromboplastin time (aPTT)

Approximately 25% of patients with type 1 von Willebrand disease have aPTT results outside of the reference range. These results may be caused by concurrent deficiencies of other clotting factors in addition to, or rather than, factor VIII (FVIII). The aPTT should be outside of the reference range in patients with severe von Willebrand disease or type 2N von Willebrand disease in whom circulating FVIII levels are very low. Because aPTT and the template bleeding time are insensitive tests for von Willebrand disease, add von Willebrand factor (VWF) activity to the screening tests performed for patients with suspected bleeding disorders (see below).

Specific assays

Specific assays include the following:

  • von Willebrand factor levels
  • FVIII activity
  • von Willebrand factor activity (ristocetin cofactor)
  • von Willebrand factor antigen

von Willebrand factor levels

von Willebrand factor levels vary and can be influenced by numerous factors, including stress, inflammation, and blood type. Individuals with type O blood have lower values of von Willebrand factor levels on average, whereas those with type AB blood have higher values of von Willebrand factor.

Day-to-day variation in von Willebrand factor levels is a normal occurrence in the same individual; therefore, a single level within the reference range does not exclude the diagnosis of von Willebrand disease. Also, estrogen levels increase von Willebrand factor and may affect results in adolescent females and women with menorrhagia. Therefore, in the presence of significant bleeding symptoms, testing to rule out von Willebrand disease may need to be repeated several times.

FVIII activity

FVIII activity is variably decreased.

von Willebrand factor activity (ristocetin cofactor)

Ristocetin is an antibiotic that causes von Willebrand factor to bind to and, subsequently, to activate platelets. In the ristocetin cofactor assay, platelets from individuals who are healthy, standard concentrations of ristocetin, and varying quantities of patient or control plasma are used. In individuals who are healthy, platelets rapidly agglutinate in response to ristocetin; however, the presence of plasma von Willebrand factor is necessary for the reaction to occur. The degree of platelet agglutination is proportional to the concentration of von Willebrand factor in the plasma. Several variations of this assay have been developed. Because the result of this assay reflects the functional activity of von Willebrand factor, it is usually called the von Willebrand factor activity. It is variably decreased in von Willebrand disease.

von Willebrand factor antigen

The total plasma concentration of von Willebrand factor protein is measured by one of several assays. The Laurell rocket immunoelectrophoresis technique measures the amount of von Willebrand factor protein in the plasma, whereas radioimmunoassays and enzyme-linked immunoabsorbent assays reflect the number of von Willebrand factor–binding sites. These tests determine the total amount of von Willebrand factor antigen in the plasma but do not reflect its molecular structure and, hence, may be normal in von Willebrand disease variants with abnormal multimers. Therefore, von Willebrand factor antigen is variably decreased.

Multimer analysis

In multimer analysis to determine the physical structure of von Willebrand factor (ie, whether high–molecular-weight multimers are present), plasma is electrophoresed through agarose gel. The presence or absence of high–molecular-weight von Willebrand factor is used to classify von Willebrand disease. Absence or decreased levels of high–molecular-weight von Willebrand factor multimers is consistent with type 2 von Willebrand disease. Further analysis of von Willebrand factor subunits has been performed with sophisticated electrophoretic techniques, resulting in the description of many type 2 variants.

ACOG statement

The American College of Obstetricians and Gynecologists states that von Willebrand disease “and other inherited and acquired disorders of coagulation and hemostasis should be considered in the differential diagnosis of all patients being evaluated for heavy menstrual bleeding, regardless of age,” with the disease commonly being the source of bleeding problems, including heavy menstrual bleeding, in women and adolescent females.[16]

However, a study by Jacobson et al reported that of 23,888 postpubertal girls and adolescents identified, using a national claims database, with heavy menstrual bleeding, only 8% (and only 16% with severe heavy menstrual bleeding) were screened for von Willebrand disease.[17] .

As previously stated, testing on multiple occasions may be needed to confirm the diagnosis of von Willebrand disease, given the influence of estrogen, stress, and inflammation on von Willebrand factor levels.

Other Tests

In some laboratories, platelet von Willebrand factor analysis is performed. Gene analysis can also be performed for diagnosis.

 

Treatment

Medical Care

Evidence-based guidelines for the diagnosis and management of von Willebrand disease (VWD) have been established.[18, 19]

Minor bleeding problems in patients with von Willebrand disease, such as bruising or a brief nosebleed, may not require specific treatment. For more serious bleeding, medications that can raise the von Willebrand factor (VWF) level and, thereby, limit bleeding are available. The goal of therapy is to correct the defect in platelet adhesiveness (by raising the level of effective von Willebrand factor) and the defect in blood coagulation (by raising the factor VIII [FVIII] level). In recent years, desmopressin (1-deamine-8-D-arginine vasopressin [DDAVP]) has become a mainstay of therapy for most patients with mild von Willebrand disease. At appropriate doses, DDAVP causes a 2-fold to 5-fold increase in plasma von Willebrand factor and FVIII concentrations in individuals who are healthy and patients who are responsive. DDAVP can be used to treat bleeding complications or to prepare patients with von Willebrand disease for surgery.

In general, a patient's responsiveness to DDAVP prior to its use for these purposes can be determined. Once determined, such responsiveness is generally consistent in patients over time and within families. In patients with serious bleeding, prompt treatment is important in order to decrease the possibility of complications.

Remember that in type 2B von Willebrand disease, DDAVP may cause a paradoxical drop in the platelet count and should not be used in a therapeutic setting without prior testing to see how the patient responds. Some other forms of type 2 von Willebrand disease may not be responsive to DDAVP either.

Consultations

Consult a pediatric or adult hematologist.

Activity

No evidence suggests that extensive activity restrictions are necessary for most patients with mild type 1 von Willebrand disease. Patients with more severe forms of von Willebrand disease should follow guidelines developed for patients with severe hemophilia, including considering a prophylactic regimen in patients with severe type 3 who are active or have repeated bleeding.

 

Medication

Vasopressin analogues

Class Summary

Desmopressin is a synthetic analogue of antidiuretic hormone. It is considered the primary treatment for bleeding in individuals with mild von Willebrand disease (VWD). It works by causing release of von Willebrand factor (VWF) from endothelial storage sites.

Desmopressin can be administered intravenously, intranasally, or subcutaneously. The dose for hemostasis is approximately 15 times the dosage used to treat individuals with diabetes insipidus. The regular intranasal preparation (0.1 mg/mL), which is used to treat persons with diabetes insipidus, is too dilute to elicit a hemostatic response. A high-concentration intranasal preparation (ie, Stimate 1.5 mg/mL) has been licensed and has shown a similar response as the intravenous form.

The higher concentration intranasal preparation allows home treatment for bleeding symptoms; however, experience with its use in the surgical setting is limited. Most experience in treating individuals with von Willebrand disease is with intravenous infusion, with which the response is rapid (ie, peak von Willebrand factor levels in approximately 45-90 min of infusion). Doses may be repeated at intervals of 12-24 hours for continued bleeding or for postoperative use. Desmopressin has also been administered subcutaneously with a favorable response.

Desmopressin (Stimate)

Increases cellular permeability of collecting ducts, resulting in reabsorption of water by kidneys.

Test patients for response prior to usage in a bleeding episode. A 2-fold to 5-fold increase in VWF and FVIII commonly is obtained after treatment.

The higher concentration of desmopressin (ie, Stimate 1.5 mg/mL) is prescribed for VWD to provide an adequate dose.

Plasma products

Class Summary

For patients with Type 1 von Willebrand disease who do not respond to desmopressin, and for individuals with the rare types 2A, 2B or Type 3 von Willebrand disease, plasma-derived factor VIII (FVIII) concentrates that contain von Willebrand factor in high molecular weight can be used. The product used must contain von Willebrand factor in the high–molecular weight form to be effective. However, most available FVIII concentrates do not contain sufficient von Willebrand factor to be used in von Willebrand disease. Cryoprecipitate contains multimeric von Willebrand factor; however, concerns about possible virus transmission have led many clinicians to choose FVIII products that contain multimeric von Willebrand factor and have undergone viral inactivation processes.

Only a minority of currently available FVIII products contain von Willebrand factor; the protein has been eliminated from the others. In general, the dosage of cryoprecipitate or von Willebrand factor to be used is calculated on the basis of ristocetin cofactor  units. Other blood products are rarely required for patients with von Willebrand disease. Rarely, platelet transfusion may benefit patients with type 3 von Willebrand disease or platelet-type von Willebrand disease who do not respond to von Willebrand factor–containing concentrates or cryoprecipitate.

Antihemophilic factor/von Willebrand Factor Complex, human (Alphanate, Humate-P, Wilate)

Some FVIII concentrates (eg, Humate-P, Alphanate, Wilate) also contain VWF in high molecular weight form. These concentrates are especially useful in types 2B and 3 vWD.

Alphanate is indicated to prevent excessive bleeding for surgical and invasive procedures in vWD in cases in which desmopressin is either ineffective or contraindicated. It is not indicated for patients with severe vWD (ie, Type 3) undergoing major surgery.

Humate-P is indicated for treatment and prevention of spontaneous and trauma-induced bleeding episodes for patients with mild-to-moderate or severe vWD. A recombinant VWF concentrate (Vonvendi) has been recently  licensed  for use in VWD for Type 2 and 3 disease

Aminocaproic acid (Amicar)

Inhibits fibrinolysis via inhibition of plasminogen activator substances and, to a lesser degree, through antiplasmin activity. Main problem is that the thrombi that forms during treatment are not lysed and effectiveness is uncertain. Has been used to prevent recurrence of subarachnoid hemorrhage (SAH). Useful in mucous membrane bleeding.

Antifibrinolytic agents

Class Summary

Antifibrinolytic agents inhibit the breakdown of blood clots, in that way encouraging blood clotting.

Tranexamic acid oral (Lysteda)

Tranexamic acid is another antifibrinolytic agent that can be used for bleeding in areas with high fibrinolytic activity, such as the mouth, nose, and uterus. It is contraindicated for hematuria. Because tranexamic acid is available in pill form, adolescents can benefit from this drug. It has been approved by the US Food and Drug Administration (FDA) for use in heavy menstrual bleeding.

 

Follow-up

Inpatient & Outpatient Medications

The following may be used in patients with von Willebrand disease (VWD):

  • Epsilon amino caproic acid (Amicar)

    • Inhibition of fibrinolysis

    • Useful in mucous membrane bleeding

    • Dose: 100 mg/kg/dose orally every 4-6 hours

Deterrence/Prevention

Avoid medications with known antiplatelet effects. Although aspirin is rarely taken by children, over-the-counter compounds containing acetylsalicylic acid often are used by adolescents. Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) are reversible cyclooxygenase inhibitors and may cause intestinal bleeding. The risks of these and other medicines with antiplatelet effects should be considered in light of the severity of the von Willebrand disease. Provide patients with von Willebrand disease a list of prescription and nonprescription medications to avoid. This list should include the following:

  • Over-the-counter medications

    • Aspirin

    • Ibuprofen

    • Naproxen

    • Antihistamines

    • Ethanol

  • Antiplatelet agents

    • Dipyridamole

    • Ticlopidine

    • Prescription nonsteroidal anti-inflammatory compounds

  • Antimicrobials

    • High-dose penicillins

    • Cephalosporins

    • Nitrofurantoin

    • Hydroxychloroquine

  • Cardiovascular medications

    • Propranolol

    • Furosemide

    • Calcium channel blockers

    • Quinidine

  • Others

    • Caffeine

    • Tricyclic antidepressants

    • Phenothiazines

    • Valproate

    • Heparin

Prognosis

Individuals with von Willebrand disease have a lifelong tendency toward easy bruising, frequent epistaxis, and menorrhagia.

Patient Education

Patients should avoid medications with antiplatelet activity. Mild activity restrictions may be necessary.

For patient education information, see eMedicineHealth's Skin Conditions and Beauty Center, as well as the patient education article Bruises.

 

Questions & Answers

Overview

What is pediatric von Willebrand disease (VWD)?

What is the pathophysiology of pediatric von Willebrand disease (VWD)?

What is the pathophysiology of type 3 pediatric von Willebrand disease (VWD)?

What is the pathophysiology of type 1 pediatric von Willebrand disease (VWD)?

What is the pathophysiology of type 2 pediatric von Willebrand disease (VWD)?

What is the prevalence of pediatric von Willebrand disease (VWD) in the US?

What is the global prevalence of pediatric von Willebrand disease (VWD)?

What is the mortality and morbidity associated with pediatric von Willebrand disease (VWD)?

What are the racial predilections of pediatric von Willebrand disease (VWD)?

What are the sexual predilections of pediatric von Willebrand disease (VWD)?

At what age is pediatric von Willebrand disease (VWD) diagnosed?

Presentation

How is pediatric von Willebrand disease (VWD) diagnosed?

Which clinical history findings are characteristic of pediatric von Willebrand disease (VWD)?

Which physical findings are characteristic of pediatric von Willebrand disease (VWD)?

What causes pediatric von Willebrand disease (VWD)?

What conditions are associated with acquired pediatric von Willebrand disease (VWD)?

DDX

Which conditions are included in the differential diagnoses of pediatric von Willebrand disease (VWD)?

What are the differential diagnoses for Pediatric Von Willebrand Disease?

Workup

Which tests are used to screen for pediatric von Willebrand disease (VWD)?

Which specific assays are performed in the workup of pediatric von Willebrand disease (VWD)?

What is the role of CBC count in the screening of pediatric von Willebrand disease (VWD)?

What is the role of template bleeding time in the screening of pediatric von Willebrand disease (VWD)?

What is the role of prothrombin time (PT) in the screening of pediatric von Willebrand disease (VWD)?

What is the role of activated partial thromboplastin time (aPTT) in the screening of pediatric von Willebrand disease (VWD)?

What is the role of von Willebrand factor levels in the workup of pediatric von Willebrand disease (VWD)?

Which findings on factor VIII (FVIII) activity are characteristic of pediatric von Willebrand disease (VWD)?

What is the role of von Willebrand factor activity (ristocetin cofactor) in the workup of pediatric von Willebrand disease (VWD)?

What is the role of von Willebrand factor antigen in the workup of pediatric von Willebrand disease (VWD)?

What is the role of multimer analysis in the workup of pediatric von Willebrand disease (VWD)?

What are the ACOG guidelines for the evaluation of pediatric von Willebrand disease (VWD)?

What is the role of genetic analysis in the workup of pediatric von Willebrand disease (VWD)?

Treatment

How is pediatric von Willebrand disease (VWD) treated?

Which specialist consultations are beneficial to patients with pediatric von Willebrand disease (VWD)?

Which activity modifications are used in the treatment of pediatric von Willebrand disease (VWD)?

Follow-up

What is the role of epsilon amino caproic acid (Amicar) in the treatment of pediatric von Willebrand disease (VWD)?

Which medications should be avoided by patients with pediatric von Willebrand disease (VWD)?

What is the prognosis of pediatric von Willebrand disease (VWD)?

What is included in patient education about pediatric von Willebrand disease (VWD)?

Medications

Which medications in the drug class Antifibrinolytic agents are used in the treatment of Pediatric Von Willebrand Disease?

Which medications in the drug class Plasma products are used in the treatment of Pediatric Von Willebrand Disease?

Which medications in the drug class Vasopressin analogues are used in the treatment of Pediatric Von Willebrand Disease?