Combined life-threatening thromboses and hemorrhages in a patient with afibrinogenemia and antithrombin deficiency.

BACKGROUND: Patients with congenital afibrinogenemia suffer from spontaneous recurrent severe bleeding. While fibrinogen concentrates are known to effectively treat bleeding episodes, thrombotic complications often occur upon replacement therapy, rendering clinical management highly challenging. CASE PRESENTATION: We hereby report a case of combined afibrinogenemia and congenital antithrombin deficiency manifested by recurrent life-threatening bleeding, as well as spontaneous severe arterial occlusion, such as acute coronary syndrome and stroke, and venous thromboses like pulmonary embolism.Secondary fibrinogen prophylaxis is recommended following any initial life-threatening bleeding episode in patients with afibrinogenemia, yet the high associated risk of thrombosis illustrates the complexity of choosing the most effective prophylaxis strategy combining fibrinogen concentrate with antithrombotic agent for optimal protection against the risk of both severe bleeding and thrombosis. For our patient, the thrombin generation assay objectively confirmed her prothrombotic tendency. CONCLUSION: This case may help us better understand the pathophysiology of arterial thrombosis in afibrinogenemia, while highlighting the difficulty of managing such complications.

[Quality standards for ultrasonographic assessment of peripheral vascular malformations and vascular tumors. Report of the french society for vascular medicine. 2018 Update]. / Standards de qualité pour la pratique de l'examen écho-Doppler dans l'étude des malformations et tumeurs vasculaires. Rapport de la Société française de médecine vasculaire (SFMV) : actualisation 2018.

The quality standards of the French Society of Vascular Medicine for the ultrasonographic assessment of vascular malformations are based on the two following requirements: (1) technical know-how: mastering the use of ultrasound devices and the method of examination; (2) medical know-how: ability to adapt the methods and scope of the examination to its clinical indication and purpose, and to rationally analyze and interpret its results. AIMS OF THE QUALITY STANDARDS: To describe an optimal method of examination in relation to the clinical question and hypothesis. To homogenize practice, methods, glossary, and reporting. To provide good practice reference points, and promote a quality process. ITEMS OF THE QUALITY STANDARDS: The 3 levels of examination; their clinical indications and goals. The reference standard examination (level 2), its variants according to clinical needs. The minimal content of the examination report; the letter to the referring physician (synthesis, conclusion and proposal for further investigation and/or therapeutic management). Commented glossary (anatomy, hemodynamics, semiology). Technical bases. Setting and use of ultrasound devices. Here, we discuss ultrasonography methods of using of ultrasonography for the assessment of peripheral vascular malformations and tumors (limbs, face, trunk).

Personalized thromboprophylaxis using a risk score for the management of pregnancies with high risk of thrombosis: a prospective clinical study.

Essentials Pregnancy is a risk factor for thrombosis. Management of thrombosis risk in pregnancy remains a challenge. Prophylaxis needs to be personalized. Our score may be a helpful tool for the management of pregnancies at high risk of thrombosis. SUMMARY: Background Patients with thrombophilia and/or a history of venous thromboembolism (VTE) are at risk of thrombosis during pregnancy. A risk score for pregnancies with an increased risk of VTE was previously described by our group (Lyon VTE score). Objectives The aim of this prospective study was to assess the efficacy and safety of our score-based prophylaxis strategy in 542 pregnancies managed between 2005 and 2015 in Lyon University Hospitals. Patients/Methods Of 445 patients included in the study, 36 had several pregnancies during the study period. Among these 445 patients, 279 had a personal history of VTE (62.7%), 299 patients (67.2%) had a thrombophilia marker, and 131 (29.4%) thrombophilic women had a personal history of VTE. During pregnancy, patients were assigned to one of three prophylaxis strategies according to the risk scoring system. Results In the antepartum period, low molecular weight heparin (LMWH) prophylaxis was prescribed to 64.5% of patients at high risk of VTE. Among them, 34.4% were treated in the third trimester only, and 30.1% were treated throughout pregnancy. During the postpartum period, all patients received LMWH for at least 6 weeks. Two antepartum-related VTEs (0.37%; one with a score of < 3 and the other with a score of > 6) and four postpartum-related VTEs (0.73%; three with scores of 3-5 and one with a score of > 6) occurred. No case of pulmonary embolism was observed during the study period. The rate of bleeding was 0.37%. No serious bleeding requiring transfusions or surgery occurred during the study period. Conclusion The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

Quality of life in systemic lupus erythematosus: description in a cohort of French patients and association with blood hydroxychloroquine levels.

OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.

Determinants of hydroxychloroquine blood concentration variations in systemic lupus erythematosus.

OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.

[An unusual case of duodenal sarcoidosis]. / Sarcoïdose duodénale: à propos d'un cas.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disorder of unknown aetiology. It may rarely affect the gastrointestinal tract. CASE REPORT: We reported a 54-year-old woman with a delayed diagnosis of duodenal sarcoidosis. She presented with gastric and right upper abdominal pain associated with vomiting and marked weight loss. Abdominal computed tomographic scan showed non-compressive retroperitoneal lymph nodes and histological examination revealed non-caseating epithelioid granulomas typical of sarcoidosis. Diagnosis of duodenal sarcoidosis was obtained at the third gastroscopy. The patient's condition improved quickly with corticosteroid therapy. CONCLUSION: Gastrointestinal sarcoidosis should be looked for in patients with digestive symptoms and another sarcoid localisation. Furthermore, it is important to repeat gastroscopy to confirm diagnosis because treatment improved most patients.

[Recurrent aseptic meningitis secondary to nonsteroidal anti-inflammatory drugs in a patient with lupus]. / Méningite aseptique récidivante due aux anti-inflammatoires non stéroïdiens chez une patiente lupique.

We report a 39-year-old woman with systemic lupus who presented with recurrent aseptic meningitis secondary to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). She presented two episodes following ibuprofen administration that were characterized by aseptic meningitis with high protein level in cerebrospinal fluid, and increased serum acute phase reactants. No evidence of an infection or vasculitis was documented. Clinical manifestation resolved rapidly with ibuprofen discontinuation, and corticosteroids therapy was unnecessary. Aseptic meningitis related to NSAIDs reported in lupus patients should be considered because of their specific modality of care and their favourable outcome.

Reversal of the inhibitory effect of fondaparinux on thrombin generation by rFVIIa, aPCC and PCC.

Adverse events associated with the administration of fondaparinux are mainly bleeding complications. Fondaparinux lacks specific antidotes and there is no routine laboratory assay for monitoring the efficacy of fondaparinux. Thrombin generation test measures the kinetic of thrombin formation over time which is a more complete characterisation of the individual coagulation capacity than classical clot based assays. In the present study the reversal effect of three procoagulant molecules was tested on the anticoagulant effect of fondaparinux. A complete correction of thrombin generating capacity was found with low doses of Feiba while rFVIIa was responsible for a partial correction of the coagulation capacity.

Comparison of the capacities of two prothrombin complex concentrates to restore thrombin generation in plasma from orally anticoagulated patients: an in vitro study.

BACKGROUND: Human prothrombin complex concentrates (PCCs) are used for prevention and treatment of bleeding episodes in patients under warfarin therapy. PCCs contain human factor (F) II, FVII, FIX, FX, protein C and protein S. The concentrations of these coagulation factors contained in PCCs are variable and do not reflect entirely the capacity of these drugs to correct hemostasis. Furthermore, commercially available PCCs do not have exactly the same composition, though they are all labelled and prescribed in units per kg of FIX (10-40 IU of FIX/kg). As the final product generated by PCCs is thrombin, a thrombin generation (TG) test could theoretically be used for monitoring the hemostatic correction. METHODS: TG was measured in platelet free plasma in the presence of tissue factor 5 pm and phospholipids 4 microM with a final concentration of PCC of 0-0.1-0.2-0.3-0.4-0.5-0.75-1 IU ml(-1). The activity of vitamin K-dependent coagulation factors (i.e. FII, FVII, FIX, FX, protein C and protein S) were determined for each concentration of two different PCCs available on the French market. RESULTS AND DISCUSSION: Our results showed that the addition of two different PCCs dose-dependently increased the TG capacity in patients with INR of 2-2.5-3-4 and >7 (n = 15 subjects) that reached the normal values. We also found a significant correlation between endogenous thrombin potential (ETP) and INR (Pearson test, P < 0.0001). The two PCCs improved the TG parameters differently with increasing concentrations. The difference in the correction of TG capacity observed between the two drugs could be explained by a variable increase in FX, FVII and protein C with similar doses. These results strongly suggest that TG assay could be used for monitoring the clinical efficacy of PCC and for optimizing the therapeutic regimen towards a more individualized therapy involving the type of the bleeding complications, the level of inhibition of the coagulation system and the molecule content of the PCC.