O. Pourrat

European registry of babies born to mothers with antiphospholipid syndrome

Objectives This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the childs immunological profile with their mothers. Methods A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years. Results 134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β2 glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mothers antibodies before 6 months of age (p<0.05). Conclusion Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.

Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators

Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity.

Grossesse et syndrome des antiphospholipides

Antiphospholipid syndrome (APS) is associated with a risk of obstetrical complications, affecting both the mother and the fetus. Obstetrical APS is defined by a history of three consecutive spontaneous miscarriages before 10 weeks of gestation (WG), an intra-uterine fetal death after 10 WG, or a premature birth before 34 WG because of severe pre-eclampsia, eclampsia or placental adverse outcomes (intrauterine growth retardation, oligohydramnios). Pregnancy in women with a diagnosis of obstetric APS is at increased risk for placental abruption, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelet count) syndrome and thrombosis that may be part of a catastrophic antiphospholipid syndrome (CAPS). A previous thrombosis and the presence of a lupus anticoagulant are risk factors for pregnancy failure. A multidisciplinary approach, associating the internist, the anesthesiologist and the obstetrician, is recommended for these high-risk pregnancies. Preconception counseling is proposed to identify pregnancy contraindications, and to define and adapt the treatment prior and during the upcoming pregnancy. Heparin and low-dose aspirin are the main treatments. The choice between therapeutic or prophylactic doses of heparin will depend on the patients medical history. The anticoagulant therapeutic window for delivery should be as narrow as possible and adapted to maternal thrombotic risk. There is a persistent maternal risk in the postpartum period (thrombosis, HELLP syndrome, CAPS) justifying an antithrombotic coverage during this period. We suggest a monthly clinical and biological monitoring which can be more frequent towards the end of pregnancy. The persistence of notches at the Doppler-ultrasound evaluation seems to be the best predictor for a higher risk of placental vascular complications. Treatment optimization and multidisciplinary antenatal care improve the prognosis of pregnancies in women with obstetric APS, leading to a favorable outcome most of the time.

Effect of pregnancy on the course of immune thrombocytopenia: a retrospective study of 118 pregnancies in 82 women

In women with pre‐existing immune thrombocytopenic purpura (ITP), the effect of pregnancy on the course of the disease is poorly known. We performed a dual‐centre retrospective cohort study of 118 pregnancies in 82 women with primary ITP. In early pregnancy, the platelet count was <100 × 109/l in 35·6% of pregnancies. During pregnancy the median platelet count nadir was 66 × 109/l (25th–75th percentile: 42–117), with platelet count <30 × 109/l for 26 pregnancies (22%). In 49% of pregnancies, a significant decrease of the platelet count required treatment at least transiently in preparation for delivery. At the time of delivery, the median platelet count was 110 × 109/l (77–155). Compared to before pregnancy, at 3 months post‐partum, only 11% of pregnancies [95% confidence interval (95% CI): 6·8–20·2] showed disease worsening. Previous splenectomy was the only factor significantly associated with ITP worsening after pregnancy (53·9% vs. 10·3%, P < 0·001). For 8·3% of the pregnancies (95% CI: 3·8–15·1), neonatal thrombocytopenia required treatment, especially in case of previous maternal splenectomy (adjusted odds ratio 16·7, 95% CI: 2·61–106). The overall risk of exacerbation of ITP and severe thrombocytopenia during pregnancy is acceptable.

ADAMTS13 deficiency in severe postpartum HELLP syndrome.

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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.

Article originalÉvolution d’une thrombopénie chronique idiopathique en cours de grossesse (62 grossesses)Chronic idiopathic thrombocytopenia outcome during pregnancy (62 cases)

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.

Bell's palsy in pregnancy: underlying HELLP syndrome or pre-eclampsia?

Bells palsy is not uncommon during pregnancy. An association with pre-eclampsia (PE) has been reported previously. Furthermore, it has even been suggested that Bells palsy could be a predictor of PE. We report three cases illustrating various possible aspects of this association, one of them including the features of HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome.

Atelier FMC sur l’hypertension artérielle au cours de la grossesse, 63e Congrès de la Société nationale française de médecine interne, Poitiers, 10 juin 2011

(Philippe Sosner, hôpital Jean Bernard, Poitiers). Les objectifs de et exposé étaient d’apprécier le caractère normal ou pathologique es chiffres de pression artérielle mesurés chez la femme enceinte ar différentes techniques. Chez la femme enceinte, comme en dehors de la grossesse, les rois techniques de mesure de la pression artérielle sont la méthode uscultatoire clinique classique et les mesures ambulatoires, qu’il ’agisse de la mesure automatique de la pression artérielle (MAPA) es 24 heures ou bien des automesures pratiquées par le patient domicile. Si la mesure classique reste la méthode de référence our dépister l’hypertension artérielle au cours de la grossesse HTAG), la plus grande fiabilité des mesures ambulatoires a été oulignée, d’autant que l’effet « blouse blanche » est encore plus fréuent au cours de la grossesse qu’en dehors, puisqu’il est de l’ordre e 29 %. Lorsqu’on découvre une hypertension artérielle (HTA) chez a femme enceinte par la méthode clinique auscultatoire, il est donc ndispensable de réaliser une MAPA sur 24 heures. Les résultats des mesures tensionnelles chez la femme enceinte mènent à constater que les chiffres sont plus bas en cours de rossesse, dans la population générale mais également chez une atiente donnée, par rapport aux valeurs mesurées en dehors de a grossesse. En fait, il n’existe pas de niveau tensionnel établi perettant de définir l’HTAG que ce soit par MAPA ou par automesures domicile et il n’existe pas de valeurs de référence au cours de a grossesse. On est donc conduit à retenir comme valeurs norales celle de la population générale : inférieure à 140/90 mmHg n mesure auscultatoire clinique, inférieure à 135/85 mmHg en oyenne des automesures à domicile, inférieure à 130/80 mmHg n moyenne des 24 heures à la MAPA. Quelques aspects techniques de la mesure doivent être soulinés : il est essentiel pour la mesure clinique et l’automesure à omicile que la patiente soit assise, avec un brassard positionné u niveau du cœur. En automesure, on réalise habituellement trois esures cliniques consécutives matin et soir pendant trois jours

Que faire en pratique à la découverte d’une thrombopénie en cours de grossesse ?

PURPOSE The practical management of a pregnant woman with a platelet count below 150 x 10(9) per liter is very simple. KEY POINTS A spurious thrombocytopenia must be discarded and isolated thrombocytopenia (begnin idiopathic gestational thrombocytopenia and idiopathic thrombocytopenic purpura) must be first differenciated from associated forms. It must be determined if thrombocytopenia appeared recently and therefore is directly specific of pregnancy. Severity is indicated by a very low platelet count and a high speed in lowering. Platelet count of the newborn must always be checked on ombilical cord blood at the time of the birth. Steroid therapy may be needed in some cases of idiopathic thrombocytopenic purpura, lupus or HELLP syndrome. Platelet counts must be checked, in every case, three months after delivery and in case of subsequent pregnancy. CONCLUSION Low platelet count is a demonstrative example of the help the internist can afford to the obstetrician in the management of pregnancy-associated conditions.