ISSN:1424-8832    

DOI:10.1159/000217110

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217111

出版商:S. Karger AG    

年代:1994

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217112

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Von Willebrand disease, the most common congenital bleeding disorder in humans, is the consequence of quantitative and/or qualitative defects of von Willebrand factor, a protein necessary for platelet adhesion and thrombus formation at sites of vascular injury. Distinct molecular defects of von Willebrand factor are responsible for the heterogeneity of von Willebrand disease subtypes. A classification in four main groups, each characterized by distinctive pathogenetic features, represents the basis for a correct therapeutic approach to bleeding episodes in these patients.

ISSN:1424-8832    

DOI:10.1159/000217113

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The synthetic agent, l-deamino-8-D-arginine vasopressin (DDAVP), is generally regarded to be the treatment of choice for persons with type I von Willebrand disease (vWD), and may be useful in type IIA vWD as well. Several formulations of the drug are available, including a highly concentrated intranasal spray formulation which is ideal for home use. The degree of F VIII and vWF response to DDAVP varies among individuals, but is generally consistent in individual patients over time. Some have tachyphylaxis while others do not. While side effects are uncommon, DDAVP is a potent antidiuretic agent. Thus one should be aware of the possibility of hyponatremia and water intoxication if certain precautions are not observed.

ISSN:1424-8832    

DOI:10.1159/000217114

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Therapeutic plasma concentrates containing von Willebrand factor (vWF) lack the largest, most hemostatically active multimers. In order to evaluate whether this abnormality results from proteolysis during manufacturing, we have analyzed the subunit structure of vWF in 21 commercial products and found a marked reduction in the relative content of intact 225 kD subunit, paralleled by an increase in the proteolytic fragments normally present in plasma, particularly that of 176 kD. There was no heightened vWF fragmentation in blood-bank cryoprecipitate prepared from platelet-poor, single-donor plasma; in contrast, there was a marked degree of fragmentation in cryoprecipitate prepared from pooled plasmapheresis plasma representing the starting fraction for the production of commercial concentrates. In cryoprecipitate prepared experimentally from plasma containing varying numbers of platelets, the degradation of vWF was proportional to the platelet count but was greatly diminished by adding protease inhibitors to plasma. On the basis of these findings, we postulate that the loss of the largest vWF multimers in commercial concentrates results from the use of poorly centrifuged plasmapheresis plasma containing an excessive number of residual platelets and leukocytes.

ISSN:1424-8832    

DOI:10.1159/000217115

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

Four different virus-inactivated factor VIII concentrates (Haemate P, Behring; Profilate, Alpha, FVIII-VHP-vWF, CRTS), near-pure von Willebrand factor (Facteur Willebrand, CRTS) or one recombinant FVIII preparation (Recombinate, Baxter) were given to one or more patients with different forms of von Willebrand’s disease. Duke bleeding time, VIII:C, vWF:Ag, RCof activity, and the multimeric pattern of plasma vWF were monitored. Both Duke bleeding time and the multimeric pattern were normalized after treatment with Haemate P, FVIII-VHP-vWF, or Facteur Willebrand, and to a lesser extent after Profilate. Except in one case, the reduction in bleeding time lasted longer after Haemate P than after the other concentrates. Recombinate had no effect on primary hemostasis, and the half-life of VIII:C was very short. If prompt hemostasis is required, and when pharmacological correction of the defect is impossible, we recommend a concentrate containing both FVIII and the full complement of vWF multimers, but for prophylactic treatment pure von Willebrand factor may be use

ISSN:1424-8832    

DOI:10.1159/000217116

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

The virally inactivated pasteurized FVIII concentrate Haemate P contains nearly intact vWF multimers. It is currently the treatment of choice to achieve satisfactory hemostasis for moderate to severe vWD and for patients with variants of vWD that cannot be adequately treated with DDAVP or for whom DDAVP is contraindicated. Therefore, we treated patients with type la, type IIa, type IIb and type III vWD with Haemate P. A correction of the hemostatic defect was seen in all patients. The type of bleeding events included 24 gastrointestinal, 18 other mucosal, 5 central nervous system, 15 orthopedic and other. 28 dental surgical procedures, 9 operative deliveries, tonsillectomies, 17 orthopedic and 11 miscellaneous surgeries were performed under the cover of Haemate P.

ISSN:1424-8832    

DOI:10.1159/000217117

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In our center, 289 children with von Willebrand’s disease (vWD) have been diagnosed since 1982. The majority of cases (n = 198) were congenital vWD whereas 91 patients suffered from vWD induced by valproate (VPA). We overview bleeding episodes in 45 children and 64 operative procedures requiring therapeutic intervention. The aim of therapeutic and prophylactic procedures in vWD is correcting the hemostatic disorder and normalization of bleeding time. This can be achieved by application of Haemate P leading to an elevation of plasma levels of von Willebrand parameters together with normalization of bleeding time. In patients with vWD type I, DDAVP will be preferred if contraindications can be excluded and efficacy has been shown. Severe bleeding complications could be prevented in a total of 50 surgical procedures in children with vWD type I by prophylactic treatment with DDAVP or Haemate P. Two children initially treated with DDAVP had to be substituted with Haemate P in the follow-up because of continuous bleeding. In type IIa and type III vWD as well as in VPA-induced vWD, the use of Haemate P was essential for sufficient hemostasis in all bleeding and operations. We conclude that Haemate P provides effective bleeding prophylaxis and treatment in all types of vWD except platelet-typ

ISSN:1424-8832    

DOI:10.1159/000217118

出版商:S. Karger AG    

年代:1994

数据来源: Karger

摘要:

In clinical treatment practice of substitution therapy involving a plasma component, numerous aspects related to recipient’s safety are relevant to the physician. Since viral contaminants may be present in the donor blood, safety begins in the institution collecting raw plasma where donors are inquired about any unusual behavior that may potentially threaten safety. Other measures that could lead to exclusion of a donation are positive serological tests for HIV and hepatitis B and C. In this context, meticulously accurate logistics are mandatory. During the course of manufacture of plasma products, viral inactivation procedures have been adopted based on chemical and physical principles. The distinct effects of these depend on methodology and the types of virus in question. An important safety measure relates to establishing that the label value of content corresponds to the in vivo recovery of the reconstituted plasma derivative and, by inference, the clinical efficacy of the product. In patients deficient in plasma coagulation factors, treatment may trigger the development of functionally inhibiting alloantibodies against the factor needed for substitution which is a significant clinical complication. The reported incidences of such inhibitors have varied greatly. No clear relationship between their frequency and the type of concentrate used have been established. However, recent experience has shown an unexpected increase in inhibitors in a regional subset of previously stable patients when shifted from a dry-heat-inactivated concentrate to a pasteurized version of the same concentrate. Hence, the possible introduction of neoantigens is important. In the early era of concentrate use, side effects to treatment were often observed like alloimmune hemolytic anemia and various degrees of anaphylactoid reactions. With the appearance of concentrates of increased purity that contain less unwarranted proteins, side effects of this kind have been rare. In conclusion, safety of plasma derivatives by today’s standards is not a single entity, but a long chain of interdependent issues, each of which needs full attention to protect patients from mild and serious treatment complicati

ISSN:1424-8832    

DOI:10.1159/000217119

出版商:S. Karger AG    

年代:1994

数据来源: Karger