The management of antenatal venous thromboembolism in the UK and Ireland: a prospective multicentre observational survey.

This prospective observational study reports on 126 women from 25 UK centres with image-proven antenatal venous thromboembolism (VTE), 62% deep vein thrombosis and 38% pulmonary embolism. Thrombophilia screening was of limited benefit except to identify antithrombin deficiency. Sixteen (13%) patients had previous VTE, all but one was related to previous pregnancy or combined oral contraceptive and 12 received no thromboprophylaxis in the index pregnancy, the other four thus received inadequate low molecular weight heparin (LMWH) doses.

The outcome of ambulatory DVT management using a multidisciplinary approach.

Low molecular weight heparins (LMWHs) have been demonstrated to be at least as safe and effective as unfractionated heparin (UFH) in the initial management of deep vein thrombosis (DVT). However, the effectiveness of using LMWH in the ambulatory management of DVT in a 'real-life' setting has yet to be evaluated. This multicentre retrospective study involving 697 patients considers the outcome data of patients under- going ambulatory DVT treatment with tinzaparin (Innohep(R), Leo Pharmaceuticals, Risborough, Buckinghamshire, UK).

Hereditary thrombophilia in a family with three independent protein S and C mutations. A cause of adverse perinatal outcome.

A non-related couple with two independent protein S and a protein C mutation had two of their three children suffering from severe thrombosis resulting in neonatal death of the firstborn. With prenatal testing an accurate prediction of phenotype was possible for the second child but the third infant was more severely affected than had been predicted from the genotype.

Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation.

Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency.

Detection and characterization of seven novel protein S (PROS) gene lesions: evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy.

The molecular genetic analysis of protein S deficiency has been hampered by the complexity of the protein S (PROS) gene and by the existence of a homologous pseudogene. In an attempt to overcome these problems, a reverse transcript-polymerase chain reaction (RT-PCR) mutation screening procedure was developed. However, the application of this mRNA-based strategy to the detection of gene lesions causing heterozygous type I protein S deficiency appears limited owing to the high proportion of patients exhibiting absence of mRNA derived from the mutation-bearing allele ("allelic exclusion").

Persistent polyclonal B-cell lymphocytosis.

We document a case of persistent lymphocytosis in which the characteristic binucleated circulating lymphocytes were shown immunologically to be polyclonal B-cells. Cytogenetic and molecular studies failed to show a clonal population. A review of the literature on this rare condition, persistent polyclonal B-cell lymphocytosis, highlights an association with the female sex, HLA-DR7 antigen, smoking and raised levels of IgM, all of which were present in our patient.

A novel point mutation (Val 297-->Met) in the serine proteinase domain of protein C in a patient with both venous and arterial thromboembolic disease.

A novel heterozygous GTG-->ATG (Val 297-->Met) substitution was detected in an individual with probable inherited protein C deficiency and both venous and arterial thrombotic disease. The lesion occurs in a highly conserved residue within the serine protease domain. In a molecular model of protein C, Met 297 makes unfavourable interactions with neighbouring residues suggesting that the mutant protein is unable to adopt a stable/functional conformation.