Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies.

Introduction: Idiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication. Method: This is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aß2GP1). Results: Among the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aß2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37-1.71], p = 1 and RR: 0.7 [95% CI: 0.33-1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.

Influence of surgical bleeding on the relationship between admission coagulopathy and risk of massive transfusion: lesson from 704 severe trauma patients.

BACKGROUND: This study hypothesized that the relationship between early coagulopathy and massive transfusion (MT) in trauma was highly dependent on the presence of surgical bleeding. METHODS: Consecutive severe trauma patients admitted to our institution over a 4-year period were included in this retrospective study. Surgical bleeding was defined as an injury requiring an invasive endovascular or surgical haemostatic procedure. The ability of prothrombin time ratio (PTr) and activated partial thromboplastin time ratio (aPTTr) to predict MT (≥10 units of packed red blood cells during the first 24 h) was determined by ROC curves. The strength of association and interaction between PTr, surgical bleeding and MT was assessed using a logistic regression analysis. RESULTS: Among the 704 patients included (ISS 21·0 ± 16·2), MT rate was higher in patients with surgical bleeding than in those with no surgical bleeding (47% vs. 5%; P < 0·001). The global performance of PTr and aPTTr to predict MT was only fair in our study population (AUCs 0·83 and 0·81). MT rate was widely higher in the surgical bleeding group whatever the severity of coagulopathy (P < 0·001). PTr was found to be significantly associated with TM [PTr ≥ 1·5, OR 23·6 (95% CI 13·4-41·7); PTr 1·2-1·5, OR 3·0 (95% CI 1·7-5·3)]. Corresponding ORs were reduced after adjusting for the surgical bleeding: 12·1 (95% CI 6·5-22·5) and 2·1 (95% CI 1·2-4·0), respectively. However, no significant interaction was found regression models. CONCLUSION: The strength of association between MT and coagulation status on admission was found strongly influenced by surgical bleeding. The admission coagulopathy monitoring in trauma patients without considering the surgical bleeding does not allow a reliable determination of MT probability.

[Argatroban, a new antithrombotic treatment for heparin-induced thrombocytopenia application in cardiac surgery and in intensive care]. / L'argatroban, nouvel antithrombotique pour la thrombopénie induite par l'héparine en chirurgie cardiaque de l'adulte: utilisation en chirurgie cardiaque et en réanimation.

OBJECTIVES: Although heparin-induced thrombocytopemia (HIT) is uncommon, its thromboembolic complications are potentially life-threatening. The low-molecular weight heparins are less responsible of HIT than unfractionated heparin (UFH) but this latter is still indicated in some circumstances such as cardiac surgery. Argatroban, a selective thrombin inhibitor, recently available, has been indicated in HIT treatment. This review presents the main pharmacological characteristics, its indications and uses in the context of cardiac surgery and in intensive care medicine. METHODS: Review of the literature in Medline database over the past 15 years using the following keywords: argatroban, cardiac surgery, circulatory assistance, cardiopulmonary bypass. RESULTS: Despite its short-acting pharmacokinetic, argatroban cannot be recommended during cardiopulmonary bypass. On the contrary, argatroban is indicated in many circumstances in postoperative period of various cardiac surgeries (on-pump, off-pump, circulatory assistance). Nevertheless, after cardiac surgery, doses have to be adapted according to coagulation laboratory testing (ACT), particularly in patients presenting acute organ failure (kidney injury, heart failure, liver failure). This compound has no antagonist and is excluded during severe hepatic failure. The continuous intravenous administration is a drawback. CONCLUSION: Argatroban is a new direct competitive thrombin inhibitor well evaluated as treatment of HIT after cardiac surgery. In HIT management, argatroban is an interesting alternative to lepirudin that is not anymore available and danaparoid because of supply disturbances.

[Chordoma]. / Les chordomes.

PURPOSES: To review in the literature, all the epidemiological, clinical, radiological, histological and therapeutic data regarding chordomas as well as various notochordal entities: ecchordosis physaliphora, intradural and intraparenchymatous chordomas, benign notochordal cell tumors, parachordomas and extra-axial chordomas. To identify different types of chordomas, including familial forms, associations with tuberous sclerosis, Ollier's disease and Maffucci's syndrome, forms with metastasis and seeding. To assess the recent data regarding molecular biology and progress in targeted therapy. To compare the different types of radiotherapy, especially protontherapy and their therapeutic effects. To review the largest series of chordomas in their different localizations (skull base, sacrum and mobile spine) from the literature. MATERIALS: The series of 136 chordomas treated and followed up over 20 years (1972-2012) in the department of neurosurgery at Lariboisière hospital is reviewed. It includes: 58 chordomas of the skull base, 47 of the craniocervical junction, 23 of the cervical spine and 8 from the lombosacral region. Similarly, 31 chordomas in children (less than 18 years of age), observed in the departments of neurosurgery of les Enfants-Malades and Lariboisière hospitals, are presented. They were observed between 1976 and 2010 and were located intracranially (n=22 including 13 with cervical extension), 4 at the craniocervical junction level and 5 in the cervical spine. METHODS: In the entire Lariboisière series and in the different groups of localization, different parameters were analyzed: the delay of diagnosis, of follow-up, of occurrence of metastasis, recurrence and death, the number of primary patients and patients referred to us after progression or recurrence and the number of deaths, recurrences and metastases. The influence of the quality of resection (total, subtotal and partial) on the prognosis is also presented. Kaplan-Meier actuarial curves of overall survival and disease free survival were performed in the entire series, including the different groups of localization based on the following 4 parameters: age, primary and secondary patients, quality of resection and protontherapy. In the pediatric series, a similar analysis was carried-out but was limited by the small number of patients in the subgroups. RESULTS: In the Lariboisière series, the mean delay of diagnosis is 10 months and the mean follow-up is 80 months in each group. The delay before recurrence, metastasis and death is always better for the skull base chordomas and worse for those of the craniocervical junction, which have similar results to those of the cervical spine. Similar figures were observed as regards the number of deaths, metastases and recurrences. Quality of resection is the major factor of prognosis with 20.5 % of deaths and 28 % of recurrences after total resection as compared to 52.5 % and 47.5 % after subtotal resection. This is still more obvious in the group of skull base chordomas. Adding protontherapy to a total resection can still improve the results but there is no change after subtotal resection. The actuarial curve of overall survival shows a clear cut in the slope with some chordomas having a fast evolution towards recurrence and death in less than 4 years and others having a long survival of sometimes more than 20 years. Also, age has no influence on the prognosis. In primary patients, disease free survival is better than in secondary patients but not in overall survival. Protontherapy only improves the overall survival in the entire series and in the skull base group. Total resection improves both the overall and disease free survival in each group. Finally, the adjunct of protontherapy after total resection is clearly demonstrated. In the pediatric series, the median follow-up is 5.7 years. Overall survival and disease free survival are respectively 63 % and 54.3 %. Factors of prognosis are the histological type (atypical forms), localization (worse for the cervical spine and better for the clivus) and again it will depend on the quality of resection. CONCLUSIONS: Many different pathologies derived from the notochord can be observed: some are remnants, some may be precursors of chordomas and some have similar features but are probably not genuine chordomas. To-day, immuno-histological studies should permit to differentiate them from real chordomas. Improving knowledge of molecular biology raises hopes for complementary treatments but to date the quality of surgical resection is still the main factor of prognosis. Complementary protontherapy seems useful, especially in skull base chordomas, which have better overall results than those of the craniocervical junction and of the cervical spine. However, we are still lacking an intrinsic marker of evolution to differentiate the slow growing chordomas with an indolent evolution from aggressive types leading rapidly to recurrence and death on which more aggressive treatments should be applied.

[Acquired von Willebrand syndrome: a case series of nine patients and literature review]. / Syndrome de Willebrand acquis: étude d'une série de neuf patients et revue de la littérature.

PURPOSE: Whereas von Willebrand disease is the most common constitutional bleeding disorder, acquired von Willebrand syndrome is rare. METHODS: Retrospective, monocentric descriptive study of consecutive cases of acquired von Willebrand syndrome diagnosed between 2000 and 2012. Diagnostic criteria included: absence of a past history of mucocutaneous bleeding, with low plasma levels of factor VIII (FVIII) and von Willebrand factor (VWF), ristocetine cofactor activity (RCo) and antigen (Ag). RESULTS: Nine men were diagnosed with von Willebrand syndrome. Six of them presented with recent mucocutaneous bleeding. In eight cases, the biological phenotype was a type 2 von Willebrand disease, with decreased VWF:RCo/VWF:Ag ratio. A lymphoproliferative disease with circulating paraprotein was identified in all patients, including one chronic lymphoid leukemia, three Waldenström and one marginal zone lymphomas, four monoclonal gammapathies of unknown significance. Screening for an anti-VWF inhibitor was negative. Symptomatic treatment using infusion of VWF concentrates was administrated in the presence of severe mucocutaneaous bleeding. Five patients received intravenous immunoglobulins with a good response only in patients with G isotype paraprotein. A chemotherapy was initiated if indicated for the underlying disorder. Three of the four patients who achieved remission of the associated lymphoma had a subsequent improvement of plasma VWF levels, while all other patients remained deficient. CONCLUSION: Acquired von Willebrand syndrome is a rare but potentially serious disease. The diagnostic should be suspected in adults with unusual mucocutaneous bleeding, with or without prolonged partial thromboplastin time (PTT), and confirmed with a decreased plasma level of VWF (Ag and RCo). An associated haematological, neoplastic or cardiac valvular disease must be searched.

[Thyrotoxic periodic paralysis: a case series of four patients and literature review]. / Paralysie périodique thyréotoxique hypokaliémique : quatre observations et revue de la littérature.

PURPOSE: Periodic thyrotoxic hypokalemic paralysis (TPP) is a neuromuscular complication of hyperthyroidism. It is more common in young Asian males than in Caucasian and African patients. We report four new cases and review the literature. CASE REPORTS: Four consecutive patients were diagnosed with TPP. They were all men with a median age of 34.5 years at presentation. Two patients originated from the Philippines, one was African and one was Caucasian ethnic background. They all presented with a paresis or flaccid paralysis, without respiratory failure. Previous similar episodes in their past medical history, the presence of profound hypokalemia (mean serum potassium level of 2 mmol/L) and the presence of clinical and biological signs of hyperthyroidism led to the diagnosis of TPP. All four patients were diagnosed with Graves' disease. Outcome was favourable in all four patients with the symptomatic treatment of TPP and treatment of Graves' disease. CONCLUSION: TPP is a severe condition, due to a dysfunction of the Na(+)-K(+) ATPase pump. Initial management relies on ß-blocker treatment and careful potassium supplementation. Then, medical or surgical etiological treatment of the thyrotoxicosis is essential to prevent a recurrence. The disease is probably underdiagnosed: it must be suspected when a profound hypokaliema resolves very quickly (<12hours); hyperthyroidism should always be included in the differential diagnosis of a paresis associated with hypokalemia.

Povidone iodine: features of critical systemic absorption.

Povidone iodine (PI), a skin antiseptic, is sometimes used internally but this procedure exposes to potentially lethal iodine absorption. Indeed, a 41-year-old woman, with no relevant medical history, developed a transient hypotension, anuric renal failure, hemolysis, coagulopathy and uterine infarction after intra-uterine injection of PI as a dye to check the fallopian tube patency (hydrotubation). Iodemia peaked at 6929 µg/dL (normal range 3.4-8.0 µg/dL), and decreased over the 9 days of renal replacement therapy. Extreme caution should be exercised when PI is in contact with a mucosa, the early recognition of iodine toxicity being of utmost importance to rapidly prompt renal replacement therapy. The main purpose of this report is to highlight the clinical features of PI absorption, whatever the route of administration.

Alafosfalin as a selective agent for isolation of salmonella from clinical samples.

The selectivity of a range of culture media for the detection of Salmonella was assessed using 435 strains of gram-negative bacteria. These media showed limited ability to inhibit non-Salmonella strains found in stool samples. We report the evaluation of alafosfalin as a selective agent for isolation of Salmonella from stool samples. Susceptibility studies with this agent showed that non-typhi Salmonella strains were relatively resistant (mean MIC, 10.2 mg/liter) compared to many coliforms including Escherichia coli (mean MIC, 0.7 mg/liter). A chromogenic medium, ABC medium, was modified to incorporate alafosfalin and was compared with standard ABC medium and Hektoen enteric agar for the isolation of Salmonella from 1,000 stool samples. On direct culture, modified ABC medium showed higher recovery of Salmonella (53.6%) compared with either ABC medium (35.7%) or Hektoen enteric agar (48.2%). We conclude that alafosfalin is a useful selective agent for the isolation of Salmonella from stool samples.