[Von Willebrand disease--type 2N (case report)]. / Von Willebrandova choroba--typ 2N (kazuistika).

Isolated reduced coagulation activity of FVIII may be a manifestation of haemophilia A, carriership of haemophilia A, haemophilia A in a woman, acquired haemophilia A and type 2N of von Willebrand's disease. The authors were concerned with the cause of isolated reduction of the coagulation activity of factor VIII (19 IU/dl) in a 40-year-old woman with a history of excessive haemorrhage of the type of mild haemophilia A with a negative family history. The personal history, family history and laboratory examination suggested type (variant) 2N of von Willebrand's disease. For indirect evidence the authors used a therapeutic study where they investigated the effect of administration of a concentrate of coagulation factors VIII/von Willebrand's factor (1/2), 28 IU factor VIII/kg body weight, on the coagulation activity of factor VIII. They recorded a half-life prolonged to 53 hours as compared with controls where the half-life was less than 12 hours. The therapeutic study confirmed sufficient coagulation activity of factor VIII, the utilization of which improved as a result of administration of von Willebrand's factor. This investigation confirmed indirectly as the cause of reduced coagulation activity of factor VIII in the examined patient the assumed type (variant) 2N of von Willebrand's disease.

[A homozygous quantitative defect of alpha 2-antiplasmin in a family from central Slovakia]. / Homozygotný kvantitatívny defekt alfa2-antiplazmínu v rodine zo stredného Slovenska.

Alpha2-antiplasmin is the main inhibitor of plasma fibrinolytic system. An inborn defect of alpha2-antiplasmin was first described by Koie et al. in 1978 in connection with severe haemorrhage syndrome. The authors present a case report of 45 years old woman living in middle Slovakia with severe haemorrhagic syndrome started in childhood (epistaxis, skin and muscle hematomas, appendectomy with 6 weeks recovery, hardly manageable haemorrhage after teeth extractions, menorrhage, metrorrhage). Laboratory tests were negative for platelet function defects and coagulation system defects. Low level of alpha2-antiplasmin activity (10%) was detected with use of synthetic chromogenic substrate method and low amount (2%) with ELISA method. In asymptomatic daughter was decreased level of alpha2-antiplasmin (activity 51%, quantity 32%) detected. On the basis of patient history, laboratory investigations and comparison with published cases the haemorrhagic syndrome is considered to be an inborn homozygous quantitative defect of alpha2-antiplasmin. Detection of the defect in further haemorrhagic and risk situations (including laparotomy, multiple teeth extractions, obstetric surgery) led to following therapeutic measures: careful local care [by procedures], tranexamic acid in sufficient dose [4 g/day in continual i.v. infusion, or 4 x 1 g in 1/hour infusions, 4 x 1 g perorally], in sufficient duration [14 days by procedures]. Therapeutic approach after detection of the defect is efficient. (Tab. 2, Ref. 13.)

[Dominant beta-thalassemia alleles in the Czech and Slovak population (beta-thalassemia mutations in 112(T-A) and 121(G-T) codons and the unstable Hradec Králové hemoglobin or alpha 2 beta 2 115 (G17) Ala-Asp)]. / Dominantní beta-talasemické alely v ceské a slovenské populaci [beta-talasemické mutace v kodonech 112 (T-A) a 121 (G-T) a nestabilní hemoglobinová varianta Hradec Králové nebo alpha 2 beta 2 115 (G 17) Ala-Asp].

In four unrelated families of Czech and Slovak origin two nonsense dominant beta-thalassaemic alleles (CD 121 (G-T); CD 112 (T-A)) and in one family simple substitution in codon 115 (GCC-GAC) or alpha 2 beta 2 115 (G17) Ala-Asp HB-Hradec Králové were identified. Mutations in codons 112 and 115 were described for the first time. Phenotypic manifestation of beta-thal. intermedia was revealed in three families with CD 121 (G-T) and in a family with a mutation in CD 112, but the phenotypic manifestations differed markedly in individual subjects. Heinz bodies were detected in erythrocytes of the peripheral blood in two families. An exact explanation of phenotypic deviations in patients with the same mutation even within the same family were not obtained even in studies of alpha genes and the promoter area of the beta gene. The unstable variant of Hb-Hradec Králové is manifested in the mother and daughter by haemolytic anaemia with some traits of beta-thal. The authors discuss contemporary findings from the pathophysiology of recessive and dominant beta-thal. mutations and explain some of the phenotypic consequences. A relatively high incidence of dominant beta-thal. mutations in the Czech and Slovak Republic (4 of 12 families known world wide with a nonsense beta-thal. mutation in the 3rd exon) is explained by the absence of selective preference of these mutations in malaria infested areas as a result of serious clinical manifestations in heterozygotes. The haplotype in one of the families suggests a de novo origin of the mutation in CD 121.