Immune thrombocytopenia and pregnancy: an exposed/nonexposed cohort study.

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (<30 × 109/L) and/or ITP treatment modification. We also studied the recurrence of ITP worsening and the incidence of NITP and risk factors. The first occurrence of ITP worsening did not differ between pregnant and nonpregnant women with ITP (53.4 per 100 person-years [95% confidence interval {CI}, 40.8-69.9] vs 37.1 [95% CI, 27.5-50.0]; hazard ratio {HR}, 1.35 [95% CI, 0.89-2.03], P = .16). Pregnant women with ITP were more likely to have recurrence of severe thrombocytopenia and treatment modification (HR, 2.71 [95% CI, 1.41-5.23], P = .003; HR, 2.01 [95% CI, 1.14-3.57], P = .017, respectively). However, recurrence of severe bleeding events was not different between groups (P = .4). Nineteen (14%) neonates showed NITP <50 × 109/L. By multivariable analysis, NITP was associated with a previous offspring with NITP and maternal platelet count <50 × 109/L within 3 months before delivery (adjusted odds ratio, 5.55 [95% CI, 1.72-17.89], P = .004 and 4.07 [95% CI, 1.41-11.73], P = .009). To conclude, women with ITP do not increase their risk of severe bleeding during pregnancy. NITP is associated with NITP history and the severity of maternal ITP during pregnancy. These results will be useful for counseling women with ITP.

Hydroxychloroquine levels in pregnancy and materno-fetal outcomes in Systemic Lupus Erythematosus patients.

OBJECTIVES: Data about hydroxychloroquine (HCQ) levels during pregnancy are sparse. We assessed HCQ whole blood levels at first trimester of pregnancy as a potential predictor of maternal and obstetric/fetal outcomes in patients with systemic lupus erythematosus (SLE). METHODS: We included pregnant SLE patients enrolled in the prospective GR2 study receiving HCQ, with at least one available first-trimester whole-blood HCQ assay. We evaluated several cut-offs for HCQ whole blood levels, including ≤200 ng/ml for severe non-adherence. Primary outcomes were maternal flares during the second and third trimesters of pregnancy, and adverse pregnancy outcomes (APOs: fetal/neonatal death, placental insufficiency with preterm delivery, and small-for-gestational-age neonates). RESULTS: We included 174 patients (median age: 32.1 years, IQR 28.8-35.2). Thirty (17.2%) patients had flares, 4 (2.3%) being severe. APOs occurred in 28 patients (16.1%). There were no significant differences in APOs by HCQ level for either those with subtherapeutic HCQ levels (≤500 ng/ml vs >500 ng/ml: 23.5% vs 14.3%, p = 0.19) or those with non-adherent HCQ levels (≤200 ng/ml vs >200 ng/ml: 20.0% vs 15.7%, p = 0.71). Similarly, the overall rate of maternal flares did not differ significantly by HCQ level cut-off, but patients with subtherapeutic (HCQ ≤500 ng/ml: 8.8% vs 0.7%, p = 0.02) and non-adherent HCQ levels (≤200 ng/ml: 13.3% vs 1.3%, p = 0.04) had significantly more severe flares. CONCLUSION: In this large prospective study of pregnant SLE patients, first-trimester subtherapeutic (≤500 ng/ml) and severe non-adherent (≤200 ng/ml) HCQ levels were associated with severe maternal flares, but not with APOs. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02450396.

Combining thrombopoietin receptor agonists with immunosuppressive drugs in adult patients with multirefractory immune thrombocytopenia, an update on the French experience.

Combining drugs could be an effective option for treating multirefractory ITP, that is, patients not responding to rituximab, thrombopoietin receptor agonists (TPO-RA) and splenectomy. We conducted a retrospective, multicenter, observational study including multirefractory ITP patients who received a combination of a TPO-RA and an immunosuppressive drug. We included 39 patients (67% women, median age 59 years [range 21-96]), with a median ITP duration of 57 months [3-393] and a median platelet count at initiation of 10 × 109 /L [1-35]. The combination regimen was given for a median duration of 12 months [1-103] and included eltrombopag (51%) or romiplostim (49%), associated with mycophenolate mofetil (54%), azathioprine (36%), cyclophosphamide (5%), cyclosporin (3%) or everolimus (3%). Overall, 30 patients (77%) achieved at least a response (platelet count ≥30 × 109 /L and at least doubling baseline during at least 3 months), including 24 complete responses (platelet count >100 × 109 /L during at least 3 months) with a median time to response of 30 days [7-270] and a median duration of response of 15 months [4-63]. Severe adverse event related to ITP treatment was observed in 31%. In conclusion, this study confirms that some patients with multirefractory ITP can achieve long lasting response with this combination.

Efficacy and safety of two rituximab biosimilars for treating immune thrombocytopenia: a reference-product matched study.

The emergence of rituximab biosimilars offers the prospect of significant savings to the healthcare system. However, these drugs have never been evaluated for treating immune thrombocytopenia (ITP). This was an observational, matched study. We included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from the historic ITP-ritux registry. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product. Response status was defined according to international criteria. We included 107 patients; 55 receiving Rixathon™ and 52 Truxima™. Three months after the first infusion of rituximab biosimilars, the overall response rate was 47/74 (63.5%) versus 76/142 (53.5%) for the matched controls receiving the reference product (p = .13). The 3-month overall response rate was 76.5% for Rixathon™ versus 51.5% for the matched control group (p = .01) and 21/40 (52.5%) for Truxima™ versus 41/74 (55.4%) for the matched controls (p = .81). For non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product. Rituximab biosimilars seemed safe and effective for ITP treatment.

What is the context? Immune thrombocytopenia (ITP) is an autoimmune disease defined by a low platelet count without any other cause of thrombocytopenia. Patients with ITP may experience severe bleedings.Rituximab, a biotechnological therapy, is a valid second-line treatment option for ITP.Biotechnological therapies are expensive. Because the patent expiratory date of the reference product of Rituximab expired, highly similar drugs called biosimilars have been developed and used in ITP treatment without any direct evaluation in this particular disease.What is new? In this study, we evaluate the efficacy and safety of rituximab biosimilars versus the reference product for treating adult ITPWe included adults who received a rituximab biosimilar for ITP. Each rituximab-naïve biosimilar patient was matched with two controls from a historic registry that included ITP patients treated by the reference product. For non-naïve patients, we compared the response to the biosimilar with that observed with the reference product.For naïve and non-naïve patients, the response pattern was similar to that observed previously with the reference product. Safety was analogous to that observed with the reference product.What is the impact? This study provides further evidence that rituximab biosimilars are safe and effective for immune thrombocytopenia treatment.

Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study.

OBJECTIVES: The specific roles of remission status, lupus low disease activity state (LLDAS), and damage accrual on the prognosis of pregnancies in women with SLE are unknown. We analysed their impact on maternal flares and adverse pregnancy outcomes (APOs). METHODS: We evaluated all women (≥18 years) with SLE enrolled in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity and damage. APOs included: foetal/neonatal death, placental insufficiency with preterm delivery and small-for-gestational-age birth weight. First trimester maternal and disease features were tested as predictors of maternal flares and APOs. RESULTS: The study included 238 women (98.3% on hydroxychloroquine (HCQ)) with 230 live births. Thirty-five (14.7%) patients had at least one flare during the second/third trimester. At least one APOs occurred in 34 (14.3%) women. Hypocomplementemia in the first trimester was the only factor associated with maternal flares later in pregnancy (P=0.02), while several factors were associated with APOs. In the logistic regression models, damage by SLICC-Damage Index [odds ratio (OR) 1.8, 95% CI: 1.1, 2.9 for model 1 and OR 1.7, 95% CI: 1.1, 2.8 for model 2] and lupus anticoagulant (LA, OR 4.2, 95% CI: 1.8, 9.7 for model 1; OR 3.7, 95% CI: 1.6, 8.7 for model 2) were significantly associated with APOs. CONCLUSION: LA and damage at conception were predictors of APOs, and hypocomplementemia in the first trimester was associated with maternal flares later in pregnancy in this cohort of pregnant patients mostly with well-controlled SLE treated with HCQ. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02450396.

Splenectomy for primary immune thrombocytopenia revisited in the era of thrombopoietin receptor agonists: New insights for an old treatment.

Although splenectomy is still considered the most effective curative treatment for immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the approval of thrombopoietin receptor agonists (TPO-RAs). The main objective of the study was to determine whether splenectomy was still as effective nowadays, particularly for patients with failure to respond to TPO-RAs. Our secondary objective was to assess, among patients who relapsed after splenectomy, the pattern of response to treatments used before splenectomy. This multicenter retrospective study involved adults who underwent splenectomy for ITP in France from 2011 to 2020. Response status was defined according to international criteria. We included 185 patients, 100 (54.1%) and 135 (73.0%) patients had received TPO-RAs and/or rituximab before the splenectomy. The median follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) patients had an initial response and 23 (12.4%) experienced relapse during follow-up, for an overall sustained response of 65.4%, similar to that observed in the pre-TPO-RA era. Among patients who received at least one TPO-RA or rituximab before splenectomy, 92/151 (60.9%) had a sustained response. Six of 13 (46%) patients with previous lack of response to both TPO-RAs and rituximab had a sustained response to splenectomy. Among patients with relapse after splenectomy, 13/21 (61.2%) patients responded to one TPO-RAs that failed before splenectomy. In conclusion, splenectomy is still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients with lack of response or with relapse after splenectomy should be re-challenged with TPO-RAs.

Multidisciplinary management of anti-PP1Pk or anti-P alloimmunization during pregnancy: A new case with anti-P and a literature review.

BACKGROUND: Red blood cell alloimmunization is the first cause of fetal and neonatal anemia. Alloimmunizations with anti-PP1Pk or anti-P can cause recurrent miscarriages and hemolytic disease of the fetus and newborn in the 2nd and 3rd trimesters of pregnancy. We report on a pregnant patient immunized with anti-P and a history of recurrent miscarriages. CASE REPORT: This P2k (GLOB:-1; P1PK:-1,3) patient had a first pregnancy marked by a caesarean at 38 weeks of gestation (WG) for non-reassuring fetal heart rate. Then, she had three early spontaneous miscarriages. The fifth pregnancy began with a high titer of anti-P at 128. Early initiation of treatment with Intravenous Immunoglobulins (IVIg) and plasma exchanges (PE) starting at 5 WG permitted us to reduce the titer of anti-P below 32. A healthy infant was delivered by caesarean at 38 WG without anemia at birth and no exchange transfusion was required. DISCUSSION AND REVIEW OF THE LITERATURE: The P and Pk antigens are expressed on placental, trophoblastic, and embryonic cells. This explains why P1k (GLOB:-1; P1PK:1,3), P2k (GLOB:-1; P1PK:-1,3), or Tj(a-)/p (GLOB:-1; P1PK:-1,-3) patients are prone to recurrent abortions in the first trimester of pregnancy. A literature review demonstrated 87% (68/78) of miscarriages in p patients. However, publication biases are possible with the most severe cases being reported. CONCLUSION: Immunizations to P and PP1Pk antigens differ from others in their physiopathology and precocity. The association of PE and IVIg seems to be an effective treatment in the management of anti-PP1Pk or anti-P fetomaternal incompatibilities.

Characteristics, outcome, and response to therapy of multirefractory chronic immune thrombocytopenia.

Refractory immune thrombocytopenia (ITP) was previously defined as lack of a minimum response to splenectomy and the requirement for long-term treatment to reduce the risk of significant bleeding events. In this multicenter study, we included 37 patients with multirefractory ITP, defined as no response to splenectomy, rituximab, romiplostim, and eltrombopag. As compared with a historical cohort of 183 ITP patients, matched on the calendar year of ITP diagnosis with a 5:1 ratio, patients with multirefractory ITP were more likely to have secondary ITP (odds ratio [OR], 4.84; 95% confidence interval [CI], 1.31-17.86; P = .018) and monoclonal gammopathy of undetermined significance (OR, 5.94; 95% CI, 1.08-32.48; P = .04). The median duration of ITP before being recognized as multirefractory was 78 months (range, 6-450). The patients showed failure of a median of 10.5 prior treatment lines for ITP (range, 6-15). At the end of follow-up (median, 84 months; range, 12-455), only 1/14 patients achieved response with immunosuppressant therapy alone. By contrast, 7/10 patients achieved response with a combination of immunosuppressant therapy and thrombopoietin-receptor agonists that lasted for a median of 15 months (range, 6-32). Throughout the course of ITP, 5/37 patients died, 3 with ITP (bleeding, n = 2; sepsis n = 1); 15 (40%) had at least 1 bacterial infection and 9 (24%) at least 1 episode of thrombosis. In conclusion, multirefractory ITP was associated with high morbidity and mortality. Combining an immunosuppressant therapy with thrombopoietin-receptor agonists may be a good strategy for management for these patients with severe disease.

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 × 10(9) /l in 35·6% of pregnancies. During pregnancy the median platelet count nadir was 66 × 10(9) /l (25th-75th percentile: 42-117), with platelet count <30 × 10(9) /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 × 10(9) /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.

Severe Infections in Patients Treated with Tocilizumab for Systemic Diseases Other Than Rheumatoid Arthritis: A Retrospective Multicenter Observational Study.

OBJECTIVE: This study aimed to describe severe infections in patients treated with tocilizumab for systemic diseases other than rheumatoid arthritis. METHODS: Data from patients receiving at least 2 doses of tocilizumab for systemic diseases other than rheumatoid arthritis between January 1, 2012, and July 1, 2020, in the region Poitou-Charentes (France) were retrospectively collected from medical records. Psoriatic arthritis and systemic juvenile idiopathic arthritis were also excluded as usually treated with similar modalities to rheumatoid arthritis. RESULTS: Of 37 patients, mainly suffering from giant cell arteritis, 25 patients (68%) had at least 1 infectious event and 15 severe infections occurred in 6 patients (3.2/100 patient-years), mainly bacterial. Lower respiratory tract and skin were the main sites. Severe bacterial infections were associated with a marked biological inflammatory syndrome, even under a cycle of administration of tocilizumab. Two severe zonas and 1 severe diverticulitis occurred. No tuberculosis or viral hepatitis reactivation was observed. CONCLUSION: The incidence rate of severe infections was 3.2/100 patient-years and seems lower than that reported in rheumatoid arthritis. C-reactive protein dosage could be helpful for the diagnosis of bacterial infectious adverse events in patients on tocilizumab. Further larger studies are needed to confirm these results to assess potential risk factors for severe infections.

Pregnancy outcomes in women with primary Sjögren's syndrome: an analysis of data from the multicentre, prospective, GR2 study.

BACKGROUND: Adverse pregnancy outcomes in women with primary Sjögren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes. METHODS: We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry. Women from the GR2 study were eligible if they had conceived before March, 2021, had primary Sjögren's syndrome according to the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria, and had an ongoing pregnancy at 12 weeks of gestation. In women who entered in the registry with pregnancies before 18 weeks of gestation, we sought to identify factors associated with primary Sjögren's syndrome flare (≥3-point increase in EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] score) or adverse pregnancy outcomes (fetal or neonatal death, placental insufficiency leading to a preterm delivery [<37 weeks of gestation], or small-for-gestational-age birthweight). A matched controlled study compared adverse pregnancy, delivery, and birth outcome rates between pregnant women with primary Sjögren's syndrome from the GR2 registry and matched controls from the general population included in the last French perinatal survey (Enquête Nationale Périnatale 2016). FINDINGS: 1944 pregnancies were identified in the GR2 cohort, of which 106 pregnancies in 96 women with primary Sjögren's syndrome were included in this analysis. The median age at pregnancy onset was 33 years (IQR 31-36). 87 (83%) of 105 pregnancies (with ethnicity data) were in White women, 18 (17%) were in Black women; 92 (90%) of 102 had previous systemic activity (ESSDAI score of ≥1; data missing in four pregnancies), and 48 (45%) of 106 had systemic activity at inclusion. Of 93 pregnancies included at week 18 of gestation or earlier, primary Sjögren's syndrome flares occurred in 12 (13%). No baseline parameters were associated with primary Sjögren's syndrome flare. Four twin pregnancies and one medical termination were excluded from the adverse pregnancy outcome analysis; of the remaining 88, adverse pregnancy outcomes occurred in six (7%). Among pregnancies in women with data for antiphospholipid antibodies (n=55), antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (two [50%] of four pregnancies) compared with those without adverse outcomes (two [4%] of 51 pregnancies; p=0·023). Anti-RNP antibody positivity was also more frequent among pregnancies with adverse outcomes than those without, although this was not statistically significant. In the matched controlled study, adverse pregnancy outcomes occurred in nine (9%) of 105 pregnancies in women with primary Sjögren's syndrome and 28 (7%) of the 420 matched control pregnancies; adverse pregnancy outcomes were not significantly associated with primary Sjögren's syndrome (odds ratio 1·31, 95% CI 0·53-2·98; p=0·52). INTERPRETATION: Pregnancies in women with primary Sjögren's syndrome had very good prognoses for mothers and fetuses, with no overall increase in adverse pregnancy outcome risk compared with the general population. Women with antiphospholipid antibodies or anti-RNP antibodies require close monitoring, because these factors might be associated with a higher risk of adverse pregnancy outcomes. FUNDING: Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

BACKGROUND: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome. METHODS: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396. FINDINGS: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030). INTERPRETATION: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies. FUNDING: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB.

Bone marrow biopsy diagnostic yield in internal medicine.

BACKGROUND: Trephine bone marrow biopsy (BMB) in internal medicine has only been studied in fever of unknown origin and inflammation of unknown origin. The aim was to assess BMB diagnostic yield according to main indications and patient characteristics in internal medicine. Quality of BMB and contribution of bone marrow aspiration (BMA) to BMB were also analyzed. METHODS: BMB performed in the internal medicine department of Poitiers university hospital between January 2000 and December 2015 were retrospectively analyzed. Patient characteristics, BMB indications, quality parameters, and results were collected from medical records. Contributive BMB was BMB allowing accurate final diagnosis. Diagnostic yield was the proportion of contributive BMB among total BMB performed. RESULTS: A total of 468 BMBs conducted for primary diagnostic purpose from 468 patients were analyzed. Cytopenia(s) and the indication 'adenopathy and/or splenomegaly and/or hepatomegaly' represented 70% of the indications. Overall BMB diagnostic yield was 32.7%, lymphoma being the main histologic finding (31%). Among indications, cytopenia(s) had the highest diagnostic yield (49.1%). Isolated fever of unknown origin had low diagnostic yield (5.6%). Factors independently associated with contributive BMB were: anemia, neutropenia, circulating immature granulocytes or blasts, monoclonal gammopathy, period of BMB processing, quality of BMB, and immunohistochemestry (IHC) analysis. Concomitant BMA improved diagnostic yield by 5.5%, mostly for myelodysplastic syndromes. CONCLUSION: Cytopenia(s), blood cythemias and monoclonal gammopathy are indications with the highest diagnostic yield. Concomitant BMA and IHC analysis should be systematically performed to increase BMB diagnostic yield in internal medicine.

Evaluation of the severe preeclampsia classification criterion for antiphospholipid syndrome in a study of 40 patients.

BACKGROUND: The criteria for antiphospholipid syndrome (APS) include severe preeclampsia and/or placental insufficiency leading to preterm delivery before 34 weeks of gestation, but this APS manifestation has been rarely studied. Thus, we report a series of severe preeclampsia occurred in patients with APS. METHODS: We retrospectively analysed data of women with APS (Sydney criteria) who experienced severe preeclampsia with delivery before 34 weeks' gestation between 2000 and 2017 at five French internal medicine departments and one Italian rheumatology unit. RESULTS: The 40 women had a mean age of 30.5 ± 4.6 years at their first episode of preeclampsia; 21 were nulligravid (52.5%), 12 (30%) had already been diagnosed with APS, and 21 (52.5%) had a triple-positive antiphospholipid (aPL) antibody test. Preeclampsia occurred at a median gestational age of 25.5 weeks (IQR 23-29). It was associated with HELLP in 18 cases (45%), eclampsia in 6 (15%), placental abruption in 3 (7.5%), catastrophic APS in 3 (7.5%), and foetal and neonatal death in 11 and 15 cases. Overall, 14 (35%) children survived, born at a median gestational age of 31 weeks. Among other APS criteria, 16 women (40%) experienced at least one thrombosis, 17 (42.5%) an intrauterine foetal death, and 19 (47.5%) at least one episode of HELLP during follow-up (median 5 years, IQR = 2-8). None had three or more consecutive miscarriages. Notably, 12 women (30%) had systemic lupus erythematosus. CONCLUSIONS: Severe preeclampsia led to high mortality in the offspring. Almost half of these women experienced other APS features, but not three consecutive miscarriages.

Large-vessel vasculitis diagnosed between 50 and 60 years: Case-control study based on 183 cases and 183 controls aged over 60 years.

BACKGROUND: Age at onset of large-vessel vasculitis (LVV) is commonly used to distinguish giant cell arteritis (GCA) and Takayasu arteritis (TA). However, LVV between age 50 and 60 years may be difficult to classify. METHODS: We conducted a retrospective study including LVV aged between 50 and 60 years at onset (LVV50-60, cases) and compared them to LVV aged over 60 years (LVV>60, controls). LVV was defined histologically and/or morphologically. Controls fulfilled ACR 1990 criteria for GCA or presented isolated aortitis. RESULTS: We included 183 LVV50-60 and 183 gender-matched LVV>60. LVV50-60 had more frequent peripheral limb manifestations (23 vs. 5%), and less frequent cephalic (73 vs. 90%) and ocular signs (17 vs. 27%) than LVV>60. Compared to LVV>60, CT angiography and PET/CT scan were more frequently abnormal in LVV50-60 (74 vs. 38%, and 90 vs. 72%, respectively), with aorta being more frequently involved (78 vs. 47%). By multivariate analysis, absence of cephalic symptoms, presence of peripheral limb ischemia and aorta involvement, and increased CRP level were significantly associated with LVV50-60 presentation compared to LVV>60. At last follow-up, compared to LVV>60, LVV50-60 received significantly more lines of treatment (2 vs. 1), more frequent biologics (12 vs. 3%), had more surgery (10 vs. 0%), and had higher prednisone dose (8.8 vs. 6.5 mg/d) at last follow-up, CONCLUSION: LVV onset between 50 and 60 years identifies a subset of patients with more frequent aorta and peripheral vascular involvement and more refractory disease compared to patients with LVV onset after 60.

Intrauterine fetal deaths related to antiphospholipid syndrome: a descriptive study of 65 women.

OBJECTIVE: Although one of the three obstetric manifestations of antiphospholipid syndrome (APS) is intrauterine fetal death (IUFD), little is known about it in this context. We report the first large series of patients with APS and IUFD. METHODS: We retrospectively analyzed the history and clinical data of women at four French hospitals. All had (1) APS diagnosis (Sydney criteria) and (2) IUFD at or after 10 weeks of gestation (weeks) between 2000 and 2016. RESULTS: The study included 65 women. Their median age at the index IUFD was 29 years (IQR 26-33); 38 (58%) were primigravidas. The index IUFD was the first APS clinical manifestation in 48 women (74%). Overall, 35% had a triple-positive antibody profile. IUFD occurred at a median gestational age of 24 weeks (IQR 18-27) and was associated with maternal obstetric complications in 16 women (25%), namely, preeclampsia (n = 12), hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) (n = 6), and/or placental abruption (n = 5). Half of the 50 women with available data had a small-for-gestational-age fetus. Overall, including during the follow-up period of 4 years (IQR 2-9), 28 women (43%) had at least one thrombosis, and 29% were diagnosed with systemic lupus erythematosus (SLE). Ultimately, 54 women (83%) had at least one live birth. Only one woman had three consecutive early miscarriages. CONCLUSION: IUFD was most often the inaugural sign of APS. Of the APS classification criteria, IUFD, preeclampsia, and thromboses were common in this cohort, while the "3 consecutive early miscarriages" criterion was met only once. With treatment, most of the women successfully had at least one live birth.