Severe factor XIII (FXIII) deficiency is a rare autosomal recessive coagulation disorder affecting one in two million individuals. The aim of the present study was to screen for and analyse F13B gene defects in the German population. A total of 150 patients presenting with suspected FXIII deficiency and one patient with severe (homozygous) FXIII deficiency were screened for mutations in F13A and F13B genes. Twenty-five individuals presented with detectable heterozygous mutations, 12 of them in the F13A gene and 13 of them in the F13B gene. We report on the genotype-phenotype correlations of the individuals showing defects in the F13B gene. Direct sequencing revealed 12 unique mutations including seven missense mutations (Cys5Arg, Ile81Asn, Leu116Phe, Val217Ile, Cys316Phe, Val401Glu, Pro428Ser), two splice site mutations (IVS2-1G>C, IVS3-1G>C), two insertions (c.1155_1158dupACTT, c.1959insT) and one in-frame deletion (c.471-473delATT). Two of the missense mutations (Cys5Arg, Cys316Phe) eliminated disulphide bonds (Cys5-Cys56, Cys316-Cys358). Another three missense mutations, (Leu116Phe, Val401Glu, Pro428Ser) were located proximal to other cysteine disulphide bonds, therefore indicating that the region in and around these disulphide bonds is prone to functionally relevant mutations in the FXIII-B subunit. The present study reports on a fairly common prevalence of F13B gene defects in the German population. The regions in and around the cysteine disulphide bonds in the FXIII-B protein may be regions prone to frequent mutations.

Resistance to activated protein C (APC resistance) is the most frequent inherited hypercoagulable state that represents a common risk factor for venous thrombosis [1]. This resistance is due to a G > A substitution in position 1691 of factor V (FV) gene which leads to the synthesis of an abnormal FV molecule (FV Leiden) where Arg 506, the first cleavage site of APC is replaced by Gln [2]. As a consequence FV Leiden heterozygotes experience a seven-fold increased risk of venous thromboembolism and homozygotes an 80-fold increased risk when compared with non-carrier [3]. Although there is a good correlation between the APC-ratio laboratory test and genotype for the Leiden mutation, a number of genotype/phenotype discrepancies have been observed. Among these is the so called pseudo-homozygous APC resistance. This condition is characterized by co-inheritance of the FV Leiden and FV null mutation on different alleles [4, 5]. Although partial FV deficiency could compensate for the thombotic defect, all of the very few cases reported so far are thrombophilic patients. Here we report a case of pseudo-homozygous FV Leiden associated with FV deficiency due to a null mutation in the FV gene.

INTRODUCTION:To evaluate the pregnancy-associated risk of venous thromboembolism and the risk of stillbirth and miscarriage a multicenter, retrospective and controlled study was conducted in women carrying the homozygous factor V Leiden mutation and in an agematched control group of women from the normal population.PATIENTS AND METHODS:In 64 homozygous (median age 44 years, range 21-75 years) and in 52 control women from five different centers data on venous thromboembolism and pregnancy outcome were obtained.RESULTS:The 64 homozygous women had in total 212 pregnancies, the 52 control women had 118 pregnancies. In homozygous women 65% of pregnancies ended with delivery of a viable infant, 15% with fetal loss (3.3% stillbirth, 12% miscarriage) and 20% by pregnancy termination. In the control women 75% of pregnancies ended with delivery of a viable infant, 12% with fetal loss (1.7% stillbirth, 10% miscarriage) and 13% by pregnancy termination. The differences were statistically not significant. Venous thromboembolism occurred significantly more often in the homozygous women, in 4.2% (9/212) during pregnancy and in 4.7% (10/212) after delivery or pregnancy termination. None of the control women had a thromboembolic episode.CONCLUSION:Our data indicate that women with homozygous factor V Leiden have a high probability for a favorable pregnancy outcome. The increased risk for venous thromboembolism during pregnancy and after delivery would favor heparin prophylaxis during and after pregnancy in women homozygous for factor V Leiden.