Antithrombin level and circuit thrombosis during hemofiltration after cardiopulmonary bypass.

OBJECTIVE: Hemofilter thrombosis occurs frequently during continuous veno-venous hemofiltration in intensive care units. Among coagulation disorders, antithrombin deficiency has been shown to be linked to hemofilter thrombosis. We investigated whether there was an association between antithrombin level activity and hemofilter thrombosis occurrence during early continuous hemofiltration following cardiopulmonary bypass. DESIGN: Prospective observational study. SETTING: Intensive care unit in University Teaching Hospital. PATIENTS AND PARTICIPANTS: Forty-eight consecutive patients. MEASUREMENTS AND RESULTS: Antithrombin level activity was measured just before the start of hemofiltration, and repeated at 24 h intervals for a total of 3 days. Hemofilter thrombosis episodes were recorded at each 24-h interval following antithrombin level activity measurement. Subjects were classified as HT when one or more episodes of hemofilter thrombosis appeared in this period and NHT if none. Morbidity parameters and mortality were recorded. Mean initial antithrombin level activity was low and not different in HT and NHT groups at day 0 (60.6 +/- 20.9% vs. 63.4 +/- 19.9%, P = 0.68). Antithrombin level activity was lower at day 1 (47.2 +/- 12.0% vs. 58.2 +/- 15.2%, P = 0.03) and day 2 (41.2 +/- 15.3% vs. 53.5 +/- 14.1%, P = 0.04) in HT group. However, antithrombin level activity was not shown to be predictive of HT in multivariate analysis. Morbidity and mortality did not differ significantly between the two groups. CONCLUSION: Only a weak association was found between antithrombin level activity and HT during early veno-venous hemofiltration post-cardiopulmonary bypass. This result was not confirmed in multivariate analysis. DESCRIPTOR: Renal failure: dialysis and hemofiltration.

Familial thrombophilia is an oligogenetic disease: involvement of the prothrombin G20210A, PROC and PROS gene mutations.

Population-based case-control studies and cases previously published suggest that the prothrombin G20210A mutation is a weak risk factor for thrombosis, leading to clinical expression mainly in the presence of other risk factors. We report the results of plasma and genetic analyses performed in a 13-year-old symptomatic boy homozygous for the 20210A allele and in his family, which are in accordance with this suggestion. These analyses demonstrated the presence of several PROC (R-5W, R87H) and PROS (R60C, T103N) gene mutations in this family. These additional mutations have modulating effects on clinical expression of the G20210A mutation. The present family study illustrates the concept of 'mild' mutation and the hypothesis that familial thrombophilia is a multifactorial disease.

Thromboembolic prophylaxis with danaparoïd (Orgaran) in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia (HIT) and Widal's disease.

There is no consensus concerning thromboembolic prophylaxis in high-risk pregnant women with a previous history of heparin-induced thrombocytopenia. An alternative anticoagulant therapy is danaparoïd, whereas unfractioned and low-molecular-weight heparin therapy is contraindicated. We report a case of successful thrombosis prophylaxis using danaparoïd in a high-thrombosis-risk pregnant woman with a history of heparin-induced thrombocytopenia during a previous pregnancy and Widal's disease.

[Thrombopenia caused by pentosan polysulfate]. / Thrombopénies au polysulfate de pentosane.

Two case-reports of thrombopenias induced by pentosane polysulfate (PSP) are reported. PSP may play a direct role in the genesis of the thrombopenia appearing between the 5th and 15th day of treatment, or a sensitizing role where the thrombopenia occurs quite rapidly following heparin treatment. The clinical complications are haematomas, arterial or venous thromboses and haemorrhages. The platelet aggregation test is always positive in the presence of PSP. The immunological origin is probable. Monitoring of the platelet count is recommanded with this treatment.

[Lepirudin during cardiopulmonary bypass in a patient with heparin-induced thrombocytopenia]. / Circulation extracorporelle sous lépirudine (Refludan) dans un contexte de thrombopénie induite par l'héparine.

Lepirudin is an alternative anticoagulant therapy in heparin-induced thrombocytopenia (HIT) during cardiopulmonary bypass (CPB). We report a case of a female patient with HIT referred for aortocoronary bypass graft despite persistence of antibodies to platelet factor 4-heparin complexes. Anticoagulation management is described. Whole blood hirudin concentration attempted during CPB was above 4 microg ml(-1). To obtain this concentration, lepirudin administration was managed as follows: 0.1 mg kg(-1) h(-1) lepirudin during preoperative course, 0.2 mg kg(-1) bolus just before CPB and 0.2 mg kg(-1) in the priming solution, complementary boluses of 5 and 10 mg during procedure (according to whole blood ecarin clotting time). Aprotinin was administered simultaneously according to Royston protocol. Anticoagulation was monitored with whole blood ecarin time performed in the operation room (patient's whole blood was diluted one half and one third with normal whole blood; in vitro calibration curve was constructed using normal whole blood spiked with lepirudin). CPB duration was 73 min. When measured, whole blood hirudin concentration was 3.8-5.8 microg ml(-1). Total lepirudin administration was 44 mg. No haemorrhagic or thrombotic events were observed during surgical procedure and postoperative course. Despite lepirudin administration is not yet clearly precise for CPB procedure, its use seems adapted and safe in subjects without renal insufficiency but requiring precise coordination for anaesthesiological, surgical and biological teams.

[Homonymous lateral hemianopsia revealing cerebral thrombophlebitis. Role of a deficiency of protein S induced by l-asparaginase]. / Hémianopsie latérale homonyme révélant une thrombophlébite cérébrale. Rôle d'un déficit en protéine S induit par la l-asparaginase.

BACKGROUND: Cerebral thrombosis associated with protein S deficiency is very rare and is mainly related to hereditary form of protein S deficiency. CASE REPORT: A 19-year-old girl with acute lymphoblastic leukemia presented hemianopsy within a few days after the first administration of L-asparaginase. Magnetic resonance of the brain showed a cortical infarct. A marked decrease of the level of protein S was documented. Few days later, the patient was free of symptoms and protein S level was restored to the normal suggesting that the cerebral thrombosis was caused by transient protein S deficiency induced by L-asparaginase administration. DISCUSSION: Patients with neurological complication caused by L-asparaginase should be tested for protein S and other anticoagulant deficiencies.

[Chronic idiopathic thrombocytopenia outcome during pregnancy (62 cases)]. / Évolution d'une thrombopénie chronique idiopathique en cours de grossesse (62 grossesses).

PURPOSE: The aim of this study was to assess the platelet count outcome during a pregnancy occurring in a series of 62 women followed for a chronic idiopathic thrombocytopenia. METHODS: We studied the medical files of women who had a previous history of chronic idiopathic thrombocytopenia persistently below 150G/L for at least 1 year, and who became pregnant over a 14-year period. RESULTS: Sixty-two pregnancies (including 41 in women suffering from an immune thrombocytopenic purpura according to updated definition criteria) which occurred in 50 women, were analysed. At the beginning of the pregnancy, platelet count was above 150G/L in 16% of the cases and lower than 50G/L in 8%. Platelets decreased by more than 25% for 55% of the pregnancies, remained stable during pregnancy in 33% and improved in 12%. Platelet count remained above 50G/L in 70% of the pregnancies and higher than 100G/L in 27%. Mean nadir was 84G/L at 31 weeks of gestation. A treatment was started in 40% of pregnancies, among them 64% of the cases during the last month only in order to allow locoregional anaesthesia at delivery. Platelet count was below 150G/L at delivery in 82% of the women (116±56G/L). No bleeding occurred in 83% of the pregnancies. Neonatal mean platelet count was 225±87G/L, thrombocytopenia occurred in 17% of the babies (platelet count below 150G/L), without any serious bleeding. CONCLUSION: Pregnancy worsens chronic idiopathic thrombocytopenia outcome in half of the cases, most of the time without any haemorrhagic complications.

[Three cases of IgM monoclonal gammopathy with haemostasis dysfunction]. / Trois cas de gammapathies monoclonales IgM avec anomalies de l'hémostase.

We relate three cases of IgM gammopathy with haemostatic dysfunction in the perioperative period. The acquired von Willebrand syndrome due to IgM gammopathy is rare and sometimes serious. Its different treatments and their efficiency are discussed: desmopressin, intravenous gammaglobulin, chemotherapy and plasmapheresis.

European registry of babies born to mothers with antiphospholipid syndrome: a result update.

The registry is a prospective, European, multicentric, longitudinal study, which follows a cohort of children born to mothers with antiphospholipid syndrome (APS). It was started in 2003. In this report, we update the results obtained from the study of 110 mothers and 112 children (two twin births). Eighty per cent of the mothers (n = 86) had primary APS. Purely obstetrical, thrombotic and mixed (obstetrical and thrombotic) APS represent 65.5 %, 21.8 % and 12.7 % of the whole cohort respectively. Isolated antiphospholipid antibodies and isolated anticardiolipin antibodies positivity were present in 50 of 109 (46%) and in 34 of 109 (31%) of the pregnant women, respectively. In the babies, in spite of a high rate of prematurity (14.3%) with four (3.6%) of the premature babies born before 33 weeks of gestation and an increased number of newborns small for gestational age (17%), the large majority of the neonates were healthy. Thirty-one infants are now older than 24 months. Among them, three displayed behavioural abnormalities before 3 years of age. After completing data, there will be the possibility to evaluate the newborn status in relation to the mothers' diseases, treatments and antibodies and to follow the neuropsychological development and immunological evolution of the babies during the next 5 years.

Antiphospholipid syndrome in patients with retinal venous occlusion.

INTRODUCTION: We conducted a prospective study to determine the prevalence and the prognosis of antiphospholipid syndrome (APS) in patients with retinal venous occlusion (RVO). PATIENTS: Consecutive patients presenting with retinal vein occlusion were screened for vascular risk factors (diabetes mellitus, hypertension, hyperlipidemia) and for antiphospholipid antibodies (aPL): anticardiolipin (aCL), anti-beta2-glycoprotein I, and lupus anticoagulant. Patients with a serum sample positive for aPL returned at least 6 weeks later for a new screening to determine the prevalence of antiphospholipid syndrome. All patients were followed to determine the outcome. RESULTS: Sixty-eight patients presented with RVO, 16 had vascular risk factors for RVO. After two screenings for aPL, nine cases of antiphospholipid syndrome associated with RVO were diagnosed (13.2%). Eight patients were over age 50 years and none had a previous thrombotic event before RVO. All patients were treated with aspirin (160 mg/day). With a mean follow-up of 26.1+/-8.2 months (range, 16-36 months), there were no recurrences. CONCLUSION: Retinal venous occlusion is multifactorial in origin. In patients aged 50 years and older, without previous thrombotic event, aPL might not be predictive of recurrences and treatment with aspirin might be sufficient. In such patients, the routine screening for aPL does not appear warranted, but a randomized study should be conducted to really ascertain the pathogenic role of aPL and the most appropriate treatment in RVO.

Chlorophacinone intoxication. A biological and toxicological study.

Plasma chlorophacinone determinations were performed in three cases of intoxication. The data collected in this study confirm the particularly prolonged anticoagulant effect of this compound and show that the knowledge of plasma concentrations may be very useful for clinicians since it allows to confirm the diagnosis and to evaluate the duration of the treatment. The determination of half-lives was investigated and the results indicate that the greater the quantity absorbed, the longer the half-life. The effect of phenobarbital on the elimination of cholorophacinone could be studied in one case. An increased elimination was noted when phenobarbital was administered.

Hermansky-Pudlak platelets: further studies on release reaction and protein phosphorylations.

Platelets from a patient with the Hermansky-Pudlak syndrome were studied. These platelets had decreased amounts of serotonin and adenine nucleotides, and a decreased number of mepacrine-labeled dense bodies. beta-Thromboglobulin and acid hydrolases contained in alpha-granules and lysosomes respectively were present in normal amount. Platelets in platelet-rich plasma did not respond to collagen, but arachidonic acid and ionophore A 23187 induced normal aggregation and normal thromboxane (TX) synthesis. Alpha-granule release was found impaired and remained subnormal even with high doses of inducers. In response to thrombin aggregation, release and TX synthesis of isolated metrizamide gradient platelets were found at lower than normal levels. Phosphorylation of P20 and P43 proteins was normal. Only a combination of ADP plus thrombin could restore a normal aggregation, with normal alpha-granule and lysosome release and normal TX synthesis. These results indicated that in the absence of dense bodies: the release of other granules is impaired; the TX synthesis is delayed except when induced by arachidonic acid and A 23187 ionophore; the absence of dense bodies could be compensated for by the addition of ADP which restores the impaired release reaction and TX formation; and P20 and P43 polypeptides were phosphorylated as rapidly as those in normal platelets.

European register of babies born to mothers with antiphospholipid syndrome.

This prospective multicentric register was initiated by the European Forum of Antiphospholipid Antibodies (APL) in 2003 after approval by local ethic committees. This register allows the investigation of infants after written informed parental consent. It collects mothers' clinical pattern of antiphospholipid syndrome (APS), course and outcome of pregnancy, treatment and immunological status. For the babies, clinical and immunological examinations are performed at birth; neurodevelopmental conditions followed up to five years. A re-evaluation of lupus anticoagulant (LA), anticardiolipin (ACL) or other antibodies will be done if they are positive at birth to follow their kinetics. A descriptive and a case control study of babies with versus without APL at birth will be possible after the inclusion of 300 cases.