Warfarin resistance: diagnosis and therapeutic alternatives.

Warfarin resistance is a rare phenomenon, and most of the related literature obtained in a MEDLINE search from 1964-1995 consists of case reports. Warfarin resistance may develop as a result of noncompliance, exogenous consumption of vitamin K, and concurrent ingestion of other agents known to decrease warfarin's effects. There are three documented cases of hereditary resistance and one case of loose documentation of hereditary resistance with confirmation of similar resistant patterns in family members. Data on two of the three cases may support the postulation that hereditary resistance may be caused by the presence of an abnormal receptor or enzyme that has an increased affinity for vitamin K. To date, this receptor or enzyme has not been identified. To assess a subtherapeutic dose response to oral anticoagulation, the clinician must consider many possible causes of resistance, such as noncompliance, drug interactions, laboratory error, or pharmacokinetic changes. Once these have been ruled out, it is possible to consider that a tissue resistance to warfarin may be responsible.

Effect of type III group B streptococcal capsular polysaccharide on invasion of respiratory epithelial cells.

Group B streptococcal (GBS) capsular polysaccharide is an important virulence factor, and its role in invasion of cultured respiratory epithelial cells was investigated. A type III GBS clinical isolate, COH1, and asialo and unencapsulated isogenic transposon capsule mutants of it were compared in an in vitro invasion assay. The results demonstrated that capsule attenuated the invasion process. Invasion was not affected when the A549 epithelial cells were preincubated with purified type III GBS capsular polysaccharide. Polyclonal type III GBS capsule antibody inhibited invasion by COH1 but did not affect invasion by the capsule mutants. Serotypes Ia, Ib, Ia/c, II, and III all invaded respiratory epithelial cells but demonstrated some strain variation in magnitude of invasion. These observations led us to conclude that type III capsular polysaccharide was not essential for invasion of respiratory epithelial cells by GBS and that bacterial factors other than capsule were responsible for respiratory epithelial cell invasion.