Chapter 109. Disorders of Platelets and Vessel Wall (Part 9)

von Willebrand Disease vWD is the most common inherited bleeding disorder. Estimates from laboratory data suggest a prevalence of approximately 1%, but data based on symptomatic individuals suggest that it is closer to 0.1% of the population. vWF serves two roles: (1) as the major adhesion molecule that tethers the platelet to the exposed subendothelium; and (2) as the binding protein for FVIII, resulting in significant prolongation of the FVIII half-life in circulation. The platelet-adhesive function of vWF is critically dependent on the presence of large vWF multimers, while FVIII binding is not. Most of the symptoms of vWD...
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Chapter 109. Disorders of Platelets and Vessel Wall (Part 9) Chapter 109. Disorders of Platelets and Vessel Wall (Part 9) von Willebrand Disease vWD is the most common inherited bleeding disorder. Estimates fromlaboratory data suggest a prevalence of approximately 1%, but data based onsymptomatic individuals suggest that it is closer to 0.1% of the population. vWFserves two roles: (1) as the major adhesion molecule that tethers the platelet to theexposed subendothelium; and (2) as the binding protein for FVIII, resulting insignificant prolongation of the FVIII half-life in circulation. The platelet-adhesivefunction of vWF is critically dependent on the presence of large vWF multimers,while FVIII binding is not. Most of the symptoms of vWD are platelet-likeexcept in more severe vWD when the FVIII is low enough to produce symptomssimilar to those found in Factor VIII deficiency (hemophilia A). vWD has been classified into three major types, with four subtypes of type2 (Table 109-2). By far the most common type of vWD is type 1 disease, with aparallel decrease in vWF protein, vWF function, and FVIII levels, accounting forat least 80% of cases. Patients have predominantly mucosal bleeding symptoms,although postoperative bleeding can also be seen. Bleeding symptoms are veryuncommon in infancy and usually manifest later in childhood with excessivebruising and epistaxis. Since these symptoms occur commonly in childhood, theclinician should particularly note bruising at sites unlikely to be traumatizedand/or prolonged epistaxis requiring medical attention. Menorrhagia is a commonmanifestation of vWD. Menstrual bleeding resulting in anemia should warrant anevaluation for vWD and, if negative, functional platelet disorders. Frequently,mild type 1 vWD first manifests with dental extractions, particularly wisdom toothextraction, or tonsillectomy. Table 109-2 Laboratory Diagnosis of von Willebrand Disease Type aPTT vWF vWF FVIII Multimer Antigen Activity Activity 1 Nl or down down down Normal up distribution, decreased in quantity2A Nl or down down down Loss of up down high and intermediate MW multimers2Ba Nl or down down down Loss of up down high MW multimers2M Nl or down down down Normal up down distribution, decreased in quantity2N up up Nl or Nl or down Normal down b down b down distribution 3 up up down down down Absent down down down a Usually also decreased platelet count. b For type 2N, in the homozygous state, FVIII is very low; in theheterozygous state, only seen in conjunction with type 1 vWD. Abbreviations: aPTT, activated partial thromboplastin time; vWF, vonWillebrand factor; F, Factor; Nl, normal; MW, molecular weight. Not all patients with low vWF levels have bleeding symptoms. Whetherpatients bleed or not will depend on the overall hemostatic balance they haveinherited, along with environmental influences and the type of hemostaticchallenges they experience. Although the inheritance of vWD is autosomal, manyfactors influence both vWF levels and bleeding symptoms. These have not allbeen defined but include blood type, thyroid hormone status, race, stress, exercise,and hormonal (both endogenous and exogenous) influences. Patients with type Oblood have vWF protein levels about one-half those of patients with AB bloodtype; in fact, the normal range for patients with type O blood overlaps that usuallyconsidered diagnostic for vWD. A mildly decreased vWF level should perhaps beviewed more as a risk factor for bleeding than as an actual disease.