Paediatrics: von Willebrand disease

von Willebrand disease

von Willebrand factor (vWF) functions as the carrier protein for factor VIIIC, protecting it from degradation, which facilitates platelet adhesion to damaged endothelium. Deficiency in vWF leads to reduced factor VIII activity and impaired platelet function.

·  Von Wi;;ebrand disease (vWD) is an inherited bleeding disorder due to deficiency or abnormal function of vWF.

·  Incidence 71:5000.

·  M = F.

There are three main subtypes:

·  Type I: autosomal dominant. 70% of cases. Mild–moderate severity.

·  Type II: autosomal dominant or recessive. 25% of cases. Mild–moderate severity. In Type IIb there is usually thrombocytopenia.

·  Type III: autosomal recessive. Almost complete absence of vWF. <5% cases. Severe.

Presentation

Presentation is very variable. Type III usually has severe mucosal bleed-ing, but when FVIII level is very low picture is similar to haemophilia A. Other types may vary from virtually asymptomatic to easy bruising with associated excessive bleeding from dental surgery, trauma, surgery, and menorrhagia (always screen for vWD in any female with menorrhagia or iron deficiency s to menorrhagia).

Investigations

APTT is usually ‘rise’(if factor VIII activity is low); PT n; platelet count usu-ally normal except in Type IIb; PFA i; factor VIIIC d; vWF antigen levels reduced and function d.

Note: vWF is an acute phase protein, as is FVIII, and may be raised to normal immediately after birth and following trauma, illness, or traumatic venepunc-ture (hence difficult to make a diagnosis of mild vWD in a child!).

Management

·  Avoid NSAIDs and IM injections.

·  Minor bleeding may respond to local pressure or tranexamic acid (locally with mouthwash or systemically 20–25mg/kg tds for 74–5 days).

·  More significant bleeds or minor surgery may respond to DDAVP (avoid if type IIB as further reduces platelet count).

·  Severe bleeding or severe disease requires virally-inactivated plasma-derived factor VIII concentrate combined with vWD factor (no recombinant product currently available). Manage as for severe haemophilia A.

Complications

Mainly occur in undiagnosed cases. May be profoundly anaemic s to chron-ic blood loss and iron deficiency. If receiving plasma derived products there is the risk of viral infection or exposure to new variant Creutzfeldt–Jakob disease (nvCJD). Acute joint involvement is rare except in type III. In severe disease, complications are otherwise similar to haemophilia A.

Prognosis

Patients with type I and II disease rarely have severe bleeds and generally have normal life expectancy and quality of life, especially in men (no peri-ods). Severity seems to improve with age, but also knowledge about how to manage bleeds improves with age. Even those with type III, if properly managed, should normal have life expectancy.

Other congenital clotting factor deficiencies

·Deficiency of every coagulation factor exists, but most are very rare.

·All have autosomal recessive inheritance.

·The most common defects are those of fibrinogen (e.g. dysfibrinogenaemia or hypofibrinogenaemia) and specific deficiency of factors VII, II prothrombin, V, XI, XIII, and X. Factor XII deficiency results in prolonged APTT, but no bleeding tendency.

In general, the severity of bleeding tendency varies from that of mild haemophilia to a familial bruising tendency. Most patients present with bleeding after surgery (circumcision, trauma, or dental extraction) rather than spontaneous bleeding or haemarthrosis. Can rarely present as cord haemorrhage in the neonatal period—usually caused by FXIII deficiency. Congenital afibrinogenaemia is clinically the most severe, and haemor-rhagic manifestations usually appear within the first 2yrs of life. Patients with this condition require weekly IV infusions of fibrinogen.

Depending on specific deficient factor, PT and/or APTT will be increased (XIII deficiency excepted). Generally, any boy with unexplained bleeding in infancy or as a toddler with isolated raised APTT must be considered to have haemophilia until proven otherwise. Unless bleeding is catastrophic, send blood for urgent factor assays and treat with appropriate factor rather than FFP, unless in extremis.

Acquired haemorrhagic disorders

·Haemorrhagic disease of the newborn. Due to vitamin K deficiency.

·  rare early presentation occurs within 24hr of life with serious bleeding, including intracranial haemorrhage (mothers may be completely vitamin K deficient);

·  more classical presentation occurs in first week of life in breast-fed infants with GI bleeding, widespread bruising, occasionally intracranial haemorrhage;

·  late presentation occurs after the first week of life, again in breast-fed infants, and usually associated with a variety of diseases that compromise or reduce the availability of vitamin K, e.g. cystic fibrosis with diarrhoea, alpha1 antitrypsin deficiency, liver diseases.

·Coagulation factor deficiencies secondary to liver disease.

·DIC.