Anaesthetic management for caesarean section in a patient with hereditary haemorrhagic telangiectasia and severe epistaxis during pregnancy.

A primigravida patient, with a history of hereditary haemorrhagic telangiectasia (HHT) manifesting as nasal angiodysplasia and hepatic arteriovenous malformations (AVM), presented for delivery planning and anaesthetic evaluation at 29 weeks of gestation. She was hospitalised several times during the second and third trimester for serious recurrent epistaxis, leading to severe anaemia. In total, she required the transfusion of 20 units of packed red blood cells during her pregnancy as well as surgical nasal haemostasis under general anaesthesia (GA). The patient was referred to our tertiary centre for delivery. In the context of recurrent severe epistaxis and high cardiac output (due to hepatic AVM) in the third trimester, a multidisciplinary decision was made to plan an elective caesarean section at 35 4/7 weeks combined with nasal packing under GA. This report discusses the implications of HHT, the multidisciplinary planning of the caesarean section, intraoperative anaesthetic management and patient follow-up.

A Unique Case of Acquired Hemophilia A Presenting with Transient Ischemic Attack.

Acquired hemophilia A (AHA) is a rare but serious condition, usually associated with significant spontaneous or traumatic bleeding and a high mortality rate. In this report, we describe the case of an elderly patient presenting a transient ischemic attack concurrently with AHA. A thrombotic event in AHA is occasionally associated with the use of bypassing agents for treatment, but a spontaneous thrombotic event has not ever been described.

Intracranial Hemorrhage and Autoimmune Thrombocytopenia in a Neonate: A Rare "Unpredictable" Event.

Neonatal thrombocytopenia is a rare complication of maternal autoimmune thrombocytopenia, and no maternal predictors of its gravity and potential complications have been identified. Neonatal cerebral hemorrhage, a feared event in the setting of autoimmune thrombocytopenia, is fortunately uncommon, but it can occur in utero or in the perinatal period, with potentially serious consequences. The authors report the case of a boy born to a mother affected by autoimmune thrombocytopenia, who presented with severe thrombocytopenia at birth and developed intracranial hemorrhage despite mild maternal thrombocytopenia at delivery and a prompt preventive treatment of the newborn. Platelet count should be tested at birth in all babies born from mothers with autoimmune thrombocytopenia, irrespective of maternal platelets counts during pregnancy or at delivery, and should be closely monitored during the first days of life. Systematic early and serial cranial ultrasound might be advocated in the setting of neonatal thrombocytopenia.

[Angiology and haemostasis. Highlights on some new data in 2017]. / Angiologie et hémostase. Quelques nouvelles données en 2017.

New data support the fact that prophylactic anticoagulation with direct oral anticoagulants is effective and safe for the long-term prevention of venous thromboembolism. This type of treatment is dedicated for a subgroup of patients only, which is described in this article. With regard to major bleedings occurring with these anticoagulants, new data have been added to those already available for idarucizumab, a specific antagonist of dabigatran. Finally, we summarize the data regarding a breakthrough molecule, emicizumab, which could potentially open a new era in the management of people with haemophilia A.

De nouvelles données viennent conforter le fait qu'une anticoagulation prophylactique avec des anticoagulants oraux directs est efficace et sûre pour la prévention au long cours de la maladie thromboembolique veineuse. Ce type de traitement ne s'adresse cependant qu'à un sous-groupe de patients, décrit dans cet article. Concernant les hémorragies majeures survenant sous anticoagulants oraux directs, de nouvelles données viennent compléter celles que l'on avait déjà sur l'idarucizumab pour contrer l'effet du dabigatran. Finalement, nous effectuons un point de situation concernant un médicament qui pourrait potentiellement révolutionner la prise en charge des personnes avec hémophilie A, l'émicizumab.

[News in Angiology and Hemostasis]. / Angiologie et hémostase.

Several themes were selected from those that marked the year 2016. The analysis of registries with «real life¼ data regarding the use of direct oral anticoagulants is reassuring and overall confirm the data of the pivotal studies. We also present the validation of a prediction rule for risk stratification of thromboembolism recurrence and duration of anticoagulation after an unprovoked event. In addition, new data shed light on the treatment of distal vein thrombosis. We also address the issue of venous thromboembolism risk related to oral contraceptives and the issue of genetic testing prior prescription, and finally present a new factor VIII recently available for the treatment of patients with acquired hemophilia A.

Plusieurs thèmes ont été choisis parmi ceux qui ont marqué l'année 2016. L'analyse des registres de patients de la «vraie vie¼ concernant l'utilisation des anticoagulants oraux directs permet dans l'ensemble de confirmer les données des études pivots. Concernant la maladie thromboembolique veineuse, nous présentons la validation d'une règle de prédiction pour la stratification du risque de récidive et la durée d'anticoagulation après un événement idiopathique. De plus, des données nouvelles apportent un éclairage sur la prise en charge des thromboses veineuses distales. Finalement, nous abordons le risque d'événement thromboembolique veineux en relation avec la contraception orale et l'arrivée sur le marché de tests de dépistage génétique de même que d'un nouveau facteur VIII pour la prise en charge des patients avec une hémophilie A acquise.

Patient-derived anti-ß2GP1 antibodies recognize a peptide motif pattern and not a specific sequence of residues.

Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the ß-2-glycoprotein 1 (ß2GP1), the precise epitope recognized by antiphospholipid antibodies still remains largely unknown. In the study herein, we wanted to identify a sequence in domain I of ß2GP1 able to induce the proliferation of CD4+ T cells isolated from antiphospholipid antibody syndrome patients, but not from healthy donors, and to interact with antiphospholipid antibodies. We have characterized a sequence in domain I of ß2GP1 that triggers CD4+ T-cell proliferation. A comparison of this sequence with the previously reported binding of antiphospholipid antibodies to discontinuous epitope R39-R43 reveals the presence of an indeterminate motif in ß2GP1, in which the polarity determines the characteristics and specificity of antiphospholipid antibodies-interacting motifs. Using point mutations, we characterized the main antiphospholipid antibodies-interacting motif as ϕϕϕζζFxC, but also established ϕϕϕζζFxϕ-related motifs as potential antiphospholipid antibodies epitopes, in which ϕ represents nonpolar residues and ζ polar residues, with charges of the residues not being involved. Of specific importance, these different motifs are present at least once in all antiphospholipid antibodies-related receptors described so far. We have further demonstrated, in vitro, that peptides and domains of ß2GP1 containing these motifs were able to interact with antiphospholipid antibodies and inhibit their monocyte activating activity. These results established that the antiphospholipid antibodies-interacting motifs are determined by the polarity, but not by the sequence or charge, of amino acids. These data could also contribute to the future development of more sensitive and specific diagnostic tools for antiphospholipid antibody syndrome determination and potential peptide- or ß2GP1 domain-based clinical therapies.

Von Willebrand disease in sub-Saharan Africa: a first severe case reported in Cameroon.

In Cameroon, the Yaoundé Hemophilia Treatment Center (HTC) has so far recorded 121 cases of hemophilia and only 10 cases of von Willebrand disease (VWD). We report the case of a 16-year-old girl, living in the north of Cameroon. She presented with severe meno-metrorrhagia, which had increased drastically within the past 3 months, associated more recently by gum bleeding and epistaxis. The coagulation screen showed a prolonged bleeding time. The clinical profile of this young girl and the findings of less than 5% for von Willebrand factor (VWF):Ag and 10% for VWF Ristocetin cofactor suggests a type 3 VWD. Screening for VWF:Ag and other inherited bleeding disorders in Cameroon is still rudimentary, and although VWD is more common than hemophilia, we report this case to highlight some of the challenges faced in resource-limited contexts.

[Hereditary haemorrhagic telangiectasia: importance of a multidisciplinary approach]. / Maladie de Rendu-Osler-Weber: importance d'une prise en charge multidisciplinaire.

The Rendu-Osler-Weber disease, also known as hereditary haemorrhagic telangiectasia, is an autosomal dominant inherited disease. Its main manifestations are nosebleeds and digestive tract bleeding due to angiodysplasia. The presence of arteriovenous malformations in organs such as lung, liver, brain, etc. can cause serious complications (haemorrhage, stroke, brain abscess, hypoxemia, increased cardiac output, pulmonary arterial hypertension). Diagnosis is based on clinical criteria and can be confirmed by genetic analysis. The prevalence of this rare disease is 1/5,000 to 1/10,000 and its expression varies widely, even in the same family. The management must be multidisciplinary and based on prevention and treatment of bleeding complications as well as screening and treatment of arteriovenous malformations.

Preoperative hemostatic assessment: a new and simple bleeding questionnaire.

PURPOSE: Current recommendations for the assessment of the risk of perioperative bleeding limit coagulation testing to patients with a personal and/or family history of bleeding. As no simple preoperative screening questionnaire is currently available, we assessed the performance of a novel screening questionnaire for its ability to detect bleeding disorders. METHODS: A dichotomized, seven-point questionnaire named HEMSTOP (Hematoma, hEmorrhage, Menorrhagia, Surgery, Tooth extraction, Obstetrics, Parents) was applied to three groups of subjects: patients referred to hemostasis specialists for bleeding symptoms for whom any kind of perioperative hemostatic precautions were subsequently recommended (n = 38); patients referred to hemostasis specialists for whom precautions were not required (n = 75); healthy volunteers (n = 70). We calculated the sensitivity and specificity of HEMSTOP scores and compared them with the discriminative performances of standard blood coagulation assays (prothrombin time, activated partial thromboplastin time). RESULTS: Patients requiring perioperative hemostatic precautions had greater median [interquartile range] HEMSTOP scores (2 [2-3]) than patients not requiring precautions (1 [1-2]) and healthy controls (0 [0-0]); P < 0.001. A HEMSTOP score ≥ 2 had a specificity of 98.6% [95% confidence interval (CI), 92.3 to 100] and a sensitivity of 89.5% (95% CI, 75.2 to 97.1). The 26.3% (95% CI, 13.4 to 43.1) sensitivity of the standard coagulation times was much lower. CONCLUSION: The HEMSTOP score discriminates patients at an elevated risk for bleeding with recommended perioperative precautions from those without such recommendations as well as from healthy participants. Further evaluation of the HEMSTOP score is required for a better evaluation of its definitive usefulness to predict the risk of perioperative bleeding.

The first Team Haemophilia Education meeting, 2015, Amsterdam, The Netherlands.

Haemophilia remains a complex disorder to diagnose and manage, requiring close cooperation between multidisciplinary healthcare professionals. There are still many unmet challenges in haemophilia care. The first Team Haemophilia Education (THE) meeting, held on 7-8 May 2015 in Amsterdam, The Netherlands, aimed to promote the optimal care of haemophilia patients through education of the multidisciplinary treatment team. This was achieved by reviewing the latest developments in haemophilia management, considering how these can be implemented in the clinic to improve patient care and providing a platform for networking and debate for all haemophilia treatment team members. Haemophilia treatment centres from several countries were asked to complete a premeeting online questionnaire to establish the biggest challenges that they face when managing patients. The concerns expressed were used to develop the agenda, which comprised a combination of formal presentations, case studies and informal workshops covering such topics as pharmacokinetics, laboratory assays and tailoring of treatment to individual patients. This report is a summary of the key developments in haemophilia care presented by various investigators and healthcare professionals at THE meeting 2015.

Risks of Venous Thromboembolism After Cesarean Sections: A Meta-Analysis.

BACKGROUND: Cesarean sections (CS) are believed to be associated with greater risks of postpartum VTE. Our objective was to systematically review the evidence on this association and on the absolute risk of VTE following CS. METHODS: We searched PubMed, Embase, and conference proceedings from 1980 to November 2015 for reports on the associations of delivery methods with postpartum VTE and on the incidence of VTE following CS. Studies on thrombophilia or recurrent VTE were excluded, and the search was restricted to prospective studies when assessing the incidence of VTE. Pooled relative and absolute risks were estimated with random effects models. RESULTS: The search retrieved 28 mostly retrospective observational studies comparing risks of VTE following CS and following vaginal deliveries (VD) (> 53,000 VTE events) and 32 prospective studies reporting risks of VTE following CS (218 VTE events). Compared with VD, the relative risk of VTE following CS ranged from 1 to 22, with a meta-analytic OR of 3.7 (95% CI, 3.0-4.6). Adjustment for age and BMI had a marginal influence on the estimated pooled OR. Associations were observed for both elective and emergency CS, with stronger estimates of associations for emergency CS. The pooled incidence was 2.6 VTE per 1,000 CS (95% CI, 1.7-3.5) and was greater in studies with a longer and better follow-up in the postpartum period (4.3 per 1,000 CS). CONCLUSIONS: The risk of VTE was fourfold greater following CS than following VD; seemed independent of other VTE risk factors; and was greater following emergency CS than following elective CS. On average, three in 1,000 women will develop a VTE following CS.

Genetic testing to identify women at risk of venous thromboembolism with contraceptive pills: Evidence or hope-based tool ?

Combined oestrogen-progestin oral contraceptives cause venous thromboembolism in women of reproductive age. Healthcare providers typically rely on women's characteristics, medical history and family history to select the most appropriate contraceptives, in an effort to reduce risks of venous thromboembolism. This position paper discusses the use of a new prediction tool (Pill Protect®), available in Switzerland, which adds genetic profiling to clinical characteristics with the aim of predicting individual contraceptive-related thrombotic risks and individualising contraceptive prescription. After reviewing the available data regarding this tool, we believe that its development and validation process may be incomplete and that it is uncertain whether the use of Pill Protect® would lead to better health outcomes. Until we understand the necessarily rigorous scientific validation of this tool, we urge caution to physicians and women who may want to use it.

Direct oral anticoagulants: a guide for daily practice.

In recent years, small oral compounds that specifically block activated coagulation factor X (FXa) or thrombin (FIIa) have become alternatives to the anticoagulants that had been used for several decades. As of today, these direct oral anticoagulants (DOACs) include dabigatran etexilate (thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (inhibitors of FXa). While there is no doubt that DOACs represent a major step forward in the management of patients with venous thromboembolic disease and atrial fibrillation, new challenges have arisen. They need to be addressed with the necessary pragmatism on the basis of evidence. Indeed, a better understanding of the management of these last-generation antithrombotics will favour safer use and increase confidence of the practitioner for the prescription of these drugs. The aim of this article is to present practical suggestions for the prescription and use of these drugs in everyday clinical practice, based on clinical experience and recently updated recommendations of the European Heart Rhythm Association and the American College of Chest Physicians among other scientific organisations. We address issues such as pharmacokinetics, dosing, side effects, limitations of use, drug interactions, switching from and to other anticoagulants, renal function, concomitant administration of antiplatelet agents and perioperative use. We also address the issue of monitoring and reversal, taking advantage of the most recent development in this latter area. Rather than being one additional set of recommendations, our narrative review aims at assisting the practicing physician in his or her daily handling of these novel anticoagulant compounds, based on frequently asked questions to the authors, a group of experienced specialists in the field who have, however, no commitment to issue guidelines.

[News in angiology and hemostasis]. / Angiologie et hémostase.

This update describes contemporary studies of clinical relevance in angiology and hemostasis. We discuss newer developments for the treatment of haemophilia, with a focus on drugs with longer-half lives. Direct anticoagulants (DOAC: rivaroxaban, apixaban, edoxaban and dabigatran) and their approved prescription in Switzerland are summarized, with a description of antidotes that will be available in the near future. We will present new data on the utility of cancer screening at the diagnosis of idiopathic venous thromboembolism (VTE) and on the evaluation of DOAC in patients with cancer-related VTE. Finally, new studies evaluating the clinical risk-benefit of anticoagulation bridging for patients with vitamin K antagonists undergoing procedures do not support the use of such bridging in the majority of patients.

[Direct oral anticoagulants (DOAC) : practical guidance for daily prescription]. / Anticoagulants oraux directs (ACOD) : une aide à la prescription dans la pratique quotidienne.

The widespread introduction of direct oral anticoagulants (DOAC) represents a major step forward in the therapeutic management of patients with venous thromboembolic disease and atrial fibrillation, accompanied by new challenges. A thorough knowledge of the available evidence needs to be associated with pragmatism in order to address patients' individual issues. Access to documents containing practical guidance will certainly contribute to increase the efficacy and safety of prescription of these drugs for patients. The aim of this article is to present suggestions based on scientific data and international recommendations for the prescription and further management of DOACs in everyday clinical practice, based of frequently asked questions to the authors.

L'introduction des anticoagulants oraux directs (ACOD) à large échelle représente une avancée majeure dans la prise en charge des patients présentant une maladie thromboembolique veineuse ou une fibrillation auriculaire, accompagnée de nouveaux défis. Ceux-ci doivent être relevés en se basant sur les données scientifiques associées à des considérations pragmatiques. L'acquisition d'une connaissance croissante de ces médicaments et la possibilité d'avoir recours à des documents d'aide pratique permettent certainement d'augmenter la sécurité de prescription de ces médicaments pour les patients. Le but de cet article est de présenter des suggestions fondées sur les données scientifiques et les recommandations internationales pour la prescription des ACOD dans la pratique clinique, sur la base des questions fréquemment posées aux auteurs.

Restoration of adrenal function after bilateral adrenal damage due to heparin-induced thrombocytopenia (HIT): a case report.

INTRODUCTION: Patients with bilateral adrenal damage due to heparin-induced thrombocytopenia usually need lifelong steroid substitution. So far, no data exists about the natural evolution of such a condition, especially about adrenal function recovery and the real need for lifelong steroids. CASE PRESENTATION: An 81-year-old Caucasian woman with bilateral adrenal damage due to heparin-induced thrombocytopenia presented with fever and severe hypotension. Adrenal failure was confirmed biologically and radiologically. She eventually recovered her adrenal function, allowing for steroid withdrawal. CONCLUSIONS: This case report addresses the different mechanisms of adrenal damage due to heparin-induced thrombocytopenia and its natural evolution with potential recovery. This should encourage clinicians to evaluate the real necessity for lifelong corticosteroid substitution in such a condition.

P-glycoprotein: a clue to vitamin K antagonist stabilization.

BACKGROUND: Acenocoumarol is a vitamin K antagonist used in some European countries. As warfarin, this drug is characterized by a narrow therapeutic index and a large interindividual variability. AIM: The objective of this study was to assess the involvement of ABCB1 polymorphisms on acenocoumarol treatment. MATERIALS & METHODS: An observational cohort study was conducted to assess whether there is an association between the presence of the allelic variants of the ABCB1 gene coding for P-glycoprotein and acenocoumarol stabilization and daily doses during the first 35 days of treatment. RESULTS: One hundred and fifteen patients met the inclusion criteria. The results of the clinical study showed that carriers of ABCB1 c.3435TT were more rapidly stabilized than wild-type patients (HR: 2.97, 95% CI: 1.23-7.18; p = 0.02). The same tendency was observed for the ABCB1 c.2677GT and 2677TT genotypes compared with ABCB1 c.2677GG. The ABCB1 c.2677TT genotype was also associated with a significant increase in doses of acenocoumarol (p = 0.03), the same tendency was observed with the ABCB1 c.3435TT genotype compared with the wild-type patients. CONCLUSION: These data suggest that ABCB1 polymorphisms could be involved in the response to acenocoumarol treatment.

Suspicion of heparin-induced thrombocytopenia in internal medicine: How appropriate is the ordering of anti-PF4/heparin antibody testing?

Thrombocytopenia is frequent in hospitalized patients, and heparin-induced thrombocytopenia (HIT) is often suspected when a decrease in platelet count is concomitant with heparin treatment. ELISA tests used for anti-PF4/heparin antibodies detection usually have high sensitivity but only fair specificity for HIT. Pre-test probability scores (such as 4 Ts or HEP scores) have been validated and a low probability score rules out HIT without anti-PF4/heparin testing. The aims of this study are to evaluate the appropriateness of anti-PF4/heparin testing according to pre-test probabilities of HIT and to compare the abilities of the 4 Ts and HEP scores to avoid inappropriate anti-PF4/heparin testing. This retrospective observational study included 74 consecutive patients hospitalized in a general internal medicine division who had anti-PF4/heparin testing for suspicion of HIT. 4 Ts and HEP scores were computed retrospectively. About 73% of patients who had ordering of an anti-PF4/heparin were at low risk according to the 4 Ts score, and 46% according to the HEP score. Heparin was discontinued in 61% and 62% of low-risk patients according to 4 Ts and HEP scores and switched to alternative anticoagulant in 31% and 32% of them, respectively. No case of HIT was diagnosed in patients with a low-risk score. One major bleeding and no thrombosis were observed. For the 4 Ts score, the sensitivity was 100%, the negative predictive value (NPV) was 100%, the specificity was 77%, and the positive predictive value (PPV) was 20% (95% CI: 7-44). For the HEP score, the sensitivity was 100%, the NPV was 100%, the specificity was 49%, and the PPV was 10%. In conclusion, pre-test probability scores were vastly underused in this internal medicine population despite their ability to rule out HIT without laboratory testing in a large proportion of patients. Appropriate use of those instruments should be actively promoted.

Felty's syndrome and hypofibrinogenemia: an unusual target for anti-cyclic citrullinated peptide antibodies?

BACKGROUND: Rheumatoid arthritis (RA) is a risk factor for the development of Felty's syndrome and large granular lymphocyte (LGL) leukemia. Anti-cyclic citrullinated peptide (CCP) antibodies are considered highly specific for RA and are directed against various citrullinated antigens, including citrullinated fibrinogen. Anti-CCP antibodies may interfere with the detection of citrullinated proteins and their function. In this article, we describe the possible inhibition of fibrinogen by anti-CCP antibodies with clinical consequences which have never been reported in the literature to our best knowledge. CASE REPORT: We present the case of a 79-year-old Caucasian woman with a longstanding history of untreated seropositive RA and who had been investigated for severe neutropenia since several months. The association of splenomegaly led to suspicion of Felty's syndrome. Flux cytometry was compatible with T-cell LGL leukemia. In addition, severe hypofibrinogenemia was detected. The later finding has not been consistently associated with the former clinical entities. Further investigations demonstrated that the anti-CCP antibodies of the patient also recognized the P41 peptide of citrullinated fibrinogen. The patient deceased of intracranial hemorrhage. CONCLUSION: It is likely, yet not definite, that high anti-citrullinated fibrinogen titers may contribute to low fibrinogen levels and could have contributed to the fatal hemorrhagic event.

Outcome measures in haemophilia: a systematic review.

Haemophilia A and B are hereditary X-linked disorders due to deficiency (or absence) of coagulation factor VIII or IX, respectively. Bleeding risk is related to the severity of factor deficiency. Repeated joint bleeding can lead to a severe haemophilic arthropathy resulting in disabilities. Outcome measurements in persons with haemophilia (PWH) have been limited to laboratory evaluation (factor VIII or IX levels) and clinical outcomes (such as bleeding frequency), morbidity (for example linked with arthropathy) and mortality. Due to the new standard of care of PWH, there is a need to consider other outcome measures, such as the early detection and quantification of joint disease, health-related quality of life (QoL) and economic or cost-utility analyses. To investigate this, we performed a 10-yr systematic overview of outcome measures in haemophilia. Only clinical trials including at least 20 patients with haemophilia A or B were included. To facilitate the search strategy, eight issues of outcome measures were selected: physical scores, imaging technique scores, functional scores, QoL measurement, mortality, bleeding frequency, cost and outcome and bone mineral density. The results of these will be discussed. Clearly defined outcomes in haemophilia care are important for many reasons, to evaluate new treatments, to justify treatment strategies, to allow a good follow-up, to perform studies and to allocate resources. The use of such scoring systems is clearly recommended by experts in haemophilia care. However, most centres do not perform such scores outside clinical trials due to reasons such as lack of time and resources.