Presents with mucous membrane bleeding (eg epistaxis, ecchymoses, menorrhagia, and excessive bleeding with surgical or other invasive procedures esp post adenotonsillectomy). Not usually petechiae (more commonly associated with platelet function defects) but may be seen esp if aspirin/NSAID has been taken. Not usually haematomas (more characteristic of hemophilia) but may be seen if severe vWD. Menorrhagia is a frequent presentation in women.
vWD has been reported in association with hemorrhagic telangiectasia (Osler-Weber-Rendu) syndrome; so consider telangiectasias contributing eg recurrent epistaxis or gastrointestinal bleeding.
Diagnosis may be missed esp in mild vWD, because vWF levels are influenced by factors such as age, inflammation, stress, pregnancy, hormonal cycles, hypo- or hyperthyroidism, and various medications. Hence stress and inflammation due to illness (eg ruptured appendix) may reduce symptoms, whereas minor surgery in the nonstressed patient may be associated with severe bleeding! Family history should be positive, as VWD is mostly inherited in autosomal dominant fashion.
Although men and women are affected equally, women may be recognized more often because of menorrhagia and excessive bleeding with childbirth.
vWF binds platelets in plug formation. It is also a carrier for Factor VIII – without it factor VIII is lost from the circulation. Subtypes:
- Type 1 is the commonest and the mildest – simple deficiency.
- Type 2 is mutant vWF, so doesn’t work well. Type 2B binds platelets spontaneously leading to thrombocytopenia.
- Type 3 is total absence, factor VIII usually low (3-5% of normal) – severe, very rare (usually autosomal recessive).
Bleeding time is not particularly sensitive or specific. Prothrombin time is normal. APTT may be prolonged, depending on the impact on factor VIII. Specifc vWF antigen/activity tests (Ristocetin stimulates platelet aggregation in presence of vWF) available.
Desmopressin (DDAVP) is available in IV form and concentrated intranasal form (not the same as used for enuresis and diabetes insipidus!).
- IV desmopressin = 0.3 mcg/kg in 25-50 mL normal saline over 30 minutes.
- Intranasal desmopressin = 150 mcg (one puff) for under 50 kg and 300 mcg (two puffs) for those over 50 kg.
- Side effects are minimal and include facial flushing, headache, or mild increases in pulse rate or blood pressure that resolve when the infusion is slowed or discontinued. Rare cases of seizures and central nervous system injury that are associated with hyponatremia have been reported.
- In type 2B desmopressin may worsen platelet count.
Several vWF concentrates are available, with different ratios of vWF to Factor VIII – used to cover surgery. Maximal increase in VWF/FVIII occurs at 30 to 60 minutes, so time the infusion as close as possible to the surgical procedure. The response time varies between individuals and tachyphylaxis (ie reduction in effect) may occur with repeated doses of desmopressin. A trial to establish effectiveness (judged by vWF:RCo (Ristocetin) level) may be helpful.
For major surgery, give concentrate every 12 to 24 hours for 2 to 3 days to achieve levels of VWF greater than 40%. In patients who have decreased baseline VWF:RCo, levels should be measured daily and extra doses concentrate should be administered if tachyphylaxis occurs. In patients in whom FVIII:C levels also are decreased, FVIII:C should be monitored and maintained at a hemostatic level as recommended for hemophilia A. In Type 2B give platelets if low count.
Antifibrinolytics eg tranexamic acid are useful esp for oral/nasal mucosal bleeding. Can even be used topically (mouthwash).