Von Willebrand s disease

Diabetes insipidus, hemophilia A, von Willebrand s disease, nodurnal enuresis... 

Devise a treatment plan for a patient with a specific variant of von Willebrand s disease. 

Type 1 patients unresponsive to desmopressin, patients with types 2 and 3 von Willebrand s disease, and major surgery patients require replacement therapy with plasma-derived intermediate- and high-purity factor VIII virus-inactivated factor VIII concentrates containing von Willebrand factor. 

Persons suffering from (the rarer) von Willebrand s disease lack both components of mature factor VIII complex (Figure 12.6). The severity of the resultant disease is somewhat dependent upon the level of intact factor VIII complex produced. Persons completely devoid of it (or expressing levels below 1 per cent of normal values) will experience frequent, severe and often spontaneous bouts of bleeding. 

Haemophilia A (classical haemophilia, often simply termed haemophilia) is an X-linked recessive disorder which is caused by a deficiency of factor VIII. Von Willebrand s disease is a related disorder, also caused by a defect in the factor VIII complex, as discussed below. 

Figure 9.9. Synthesis of factor VIII complex as occurs in healthy individuals, as illustrated in (a). In the case of persons suffering from haemophilia A, synthesis of factor VIILC is blocked (b), preventing constitution of an active factor VIII complex in plasma. Persons suffering from von Willebrand s disease fail to S5mthesize vWF(c). Although they can synthesize VIILC, this is rapidly degraded upon entering the blood dne to lack of its vWF stabilizing factor...

Desmopressin is sometimes used in mild Hemophilia A and Von Willebrand s disease. In December 2007, US drug regulators banned using desmopressin nasal sprays for treating bedwetting after two children died from hyponatremia. 

Because it is stable, desmopressin is preferred for treatments especially if pressor effects are not desired. The primary indication for therapy is central diabetes insipidus, a disorder that results when ADH secretion is reduced and that is characterized by polydipsia, polyuria, and dehydration. Desmopressin is also used to reduce primary nocturnal enuresis, or bedwetting, in children. It is useful in people with mild hemophilia A or with some types of von Willebrand s disease, in which von Willebrand s factor is present at low levels. In these cases, desmopressin is given when excessive bleeding occurs or before surgery to help reduce bleeding indirectly by increasing the amounts of coagulation factors. 

Contraindications HemophiliaAwithfactorVIII levels less than 5% hemophilia B severe type I, type HB, or platelet-type von Willebrand s disease... 

Von Willebrand s disease Assess levels of factor VIII coagulant, factor VIII antigen, and ristocetin cofactor skin bleeding time may also be helpful... 

Dosage form ReFacto is a sterile lyophifized powder for injection available in nominal dosage strengths of 250, 500, and 1000 international units (lU) per vial. Recombinate is formulated as a sterile lyophifized powder preparation of concentrated recombinant AHF for intravenous injection and is available in single-dose bottles which contain nominally 250, 500, and 1000 lU per bottle. The final product contains an insufficient quantity of von Willebrand Factor to have any clinically effect in patients with von Willebrand s disease. 

Desmopressin is also used for the treatment of coagulopathy in hemophilia A and von Willebrand s disease (see Chapter 34). 

Defects of platelet adhesion to subendothelium—these causing (a) the Bernard-Soulier syndrome, a rare, autosomal recessive trait which results in severe or even fatal hemorrhagic disease (b) von Willebrand s disease, which presents mucocutaneous problems of bruising, epistaxis, and gingival bleeding and (c) pseudo-von Willebrand s disease, in which platelets bind an increased amount of plasma vWF. 

A 55-year-old woman with Von Willebrand s disease was found comatose (44). She had received desmopressin as prophylaxis for bleeding several times before without problems. On this occasion she had also received ibuprofen as a pain killer. She was hyponatremic. 

There have been several reports of seizures in association with hyponatremia after intravenous administration of desmopressin to cover surgery in young children with congenital bleeding disorders such as mild hemophilia A or von Willebrand s disease (58-60). Hyponatremia and convulsions have occurred in children without congenital bleeding disorders who received desmopressin for urine concentration tests or to treat nocturnal enuresis (54,61,62). 

Holmberg L, Nilsson IM, Borge L, Gunnarsson M, Sjorin E. Platelet aggregation induced by l-desamino-8-D-arginine vasopressin (DDAVP) in Type IIB von Willebrand s disease. N Engl J Med 1983 309(14) 816-21. 

Ruggeri ZM, Mannucci PM, Lombardi R, Federici AB, Zimmerman TS. Multimeric composition of factor VlH/von Willebrand factor following administration of DDAVP implications for pathophysiology and therapy of von Willebrand s disease subtypes. Blood 1982 59(6) 1272-8. 

Garcia EBG, Ruitenberg A, Madrestsma GS, Hintzen RQ. Hyponatraemic coma induced by desmopresssin and ibu-profen in a woman with von Willebrand s disease. Haemophilia 2003 9 232-4. 

Chediak JR, Alban GM, Maxey B. von Willebrand s disease and pregnancy management during delivery and outcome of offspring. Am J Obstet Gynecol 1986 155(3) 618-24. 

Miller CH, Graham JB, Goldin LR, Elston RC, Genetics of classic von Willebrand s disease, I, Phenotype variation within families. Blood 1979 54 1 17-136. 

Bennett B, Oxnard SC, Douglas AS, et al. Studies on anti-haemophilic factor (AHF factor VIII) during labor in normal women, in patients woth premature separation of the placenta, and in a patient with von Willebrand s disease. J Clin Lab Med 1974 84 851-860. 

Tschopp TB, Weiss HJ, Baumgartner HR Decreased adhesion of platelets to subendothelium in von Willebrand s disease. J Lab Clin Med 83 296-300,1974... 

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