Inherited bleeding disorder due to familial type 2 platelet cyclo-oxygenase deficiency.

Inherited platelet cyclo-oxygenase (COX) deficiency is a rare bleeding disorder. We report here the first case of familial type 2 platelet COX deficiency responsible for a moderate bleeding phenotype. The propositus was admitted in the emergency department for major epistaxis following treatment with aspirin. Epinephrine closure time is very sensitive to drugs which inhibit COX but the test was normal in patients with inherited COX deficiency. This clinical and biological data suggest that the anti-platelet effect of aspirin may be dependent on mechanisms other than the inhibition of COX. Thrombin generation test confirmed mild bleeding phenotype in patients with COX deficiency as they had normal thrombin generating capacity.

Early fibrinogen degradation coagulopathy is predictive of parenchymal hematomas in cerebral rt-PA thrombolysis: a study of 157 cases.

BACKGROUND: Little is known about the coagulation factors as predictors of cerebral bleeding in rt-PA thrombolysis. The aim of this study was to determine what early coagulation parameters could predict early hemorrhagic lesions. METHODS: Consecutive patients were included in the Lyon rt-PA protocol. Early hematomas (within 24 hours), diagnosed on an anatomoradiological basis (symptomatic and not symptomatic) were considered for the study. Fibrinogen and fibrin(ogen) degradation products (FDP) were assessed at entry and at 2 and 24 hours after the beginning of thrombolysis. RESULTS: Of 157 patients, 11 had early parenchymal hematomas (7%), 31 had early hemorrhagic infarcts (19.7%), and 115 had no bleeding (73.2%). In logistic regression, FDP at 2 hours was the single predictor of parenchymal hematomas (OR: 2.5; CI: 1.09 to 5.8), whereas an increase of FDP >200 mg/L multiplied the odds of parenchymal hematoma by 4.95 (IC: 1.09 to 22.4). Early parenchymal hematomas were indicative of a poor prognosis at 3 months (P=0.001). CONCLUSIONS: Early parenchymal hematomas appear as both "malignant" and exclusively related to an explosive increase of FDP at 2 hours, ie, an early fibrinogen degradation coagulopathy (EFDC). All patients scheduled to rt-PA thrombolysis should have an assay of FDP 2 hours after the beginning of thrombolysis: patients with an established EFDC (FDP >200 mg/L) should be monitored specifically, with no antithrombotic drug during the first 72 hours. Patients with FDP >100 mg should share the same monitoring.

A splicing donor site point mutation in intron 6 of the plasmin inhibitor (alpha2 antiplasmin) gene with heterozygous deficiency and a bleeding tendency.

A new case of familial plasmin inhibitor (alpha2 antiplasmin) deficiency is reported. The bleeding symptoms are moderate, happening after surgery or trauma or consisting of abnormal uterine bleeding induced by hormone replacement therapy. It is easily corrected with tranexamic acid. Gene sequencing makes it possible to find a splicing donor site mutation of intron 6, leading to exon 6 skipping. Neither a shortened variant nor an abnormal plasmin interaction was found in plasma by immunoblotting, and fibrin binding is unaffected. The mutation is heterozygous, associated with an intermediate decrease of both antiplasmin activity and antigen levels, and was found in four other family members out of five tested. It is different from the five mutations previously reported. At the time of diagnosis, the patient was living in Artas, France, allowing the defect to be named plasmin inhibitor (alpha2 antiplasmin) Artas.

In vitro tests for assessing heparin-induced thrombocytopenia in patients after elective hip replacement. A medico-economical evaluation.

OBJECTIVES: Considering the previously published incidences of heparin-induced thrombocytopenia (HIT) in patients receiving a thromboprophylactic therapy, the role of the hemostasis laboratory is essential in making a clinical decision. The purpose of this project was to compare the strategies of diagnosis and associated care of patients with suspected HIT after elective hip replacement using platelet aggregation assay, carbon 14-serotonin release, and "doing nothing." METHODS: The authors used an incremental cost-effectiveness analysis based on data extracted from the literature. The effectiveness of the strategies was represented by the number of deep venous thromboses prevented. Cost data were collected from the observation of biological and medical practice at Edouard Herriot University Hospital, Lyon, France, in 1999. RESULTS: In comparison with the strategies of doing nothing using no biological test for diagnosis, and clinical care of HIT-suspected patients, the strategy using platelet aggregation test was more expensive and less effective. With respect to the strategy using carbon 14-serotonin release assay, the incremental cost-effectiveness ratio, expressed as U.S. dollars per deep venous thrombosis prevented, reached $200,000, with a marginal effectiveness of eight deep venous thromboses prevented for 10,000 HIT-suspected patients. CONCLUSION: This study suggests that clinical hemostasis laboratories might consider replacing the platelet aggregation test with the carbon 14-serotonin release assay or should use another functional assay such as the flow cytometric assay for the diagnosis and care of patients with suspected HIT.