Bleeding complications and antithrombotic treatment in 264 pregnancies in antiphospholipid syndrome.

Purpose The purpose of this study was to evaluate the safety of antithrombotic treatments prescribed during pregnancy in patients with antiphospholipid syndrome (APS). Methods This international, multicenter study included two cohorts of patients: a retrospective French cohort and a prospective US cohort (PROMISSE study). Inclusion criteria were (1) APS (Sydney criteria), (2) live pregnancy at 12 weeks of gestation (WG) with (3) follow-up data until six weeks post-partum. According to APS standard of care, patients were treated with aspirin and/or low-molecular weight heparin (LMWH) at prophylactic (pure obstetric APS) or therapeutic doses (history of thrombosis). Major bleeding was defined as abnormal blood loss during the pregnancy and/or post-partum period requiring intervention for hemostasis or transfusion, or during the peripartum period greater than 500 mL and/or requiring surgery or transfusion. Other bleeding events were classified as minor. Results Two hundred and sixty-four pregnancies (87 prospectively collected) in 204 patients were included (46% with history of thrombosis, 23% with associated systemic lupus). During pregnancy, treatment included LMWH ( n = 253; 96%) or low-dose aspirin ( n = 223; 84%), and 215 (81%) patients received both therapies. The live birth rate was 89% and 82% in the retrospective and prospective cohorts, respectively. Adverse pregnancy outcomes occurred in 28% of the retrospective cohort and in 40% of the prospective cohort. No maternal death was observed in either cohort. A combined total of 45 hemorrhagic events (25%) occurred in the retrospective cohort, but major bleeding was reported in only six pregnancies (3%). Neither heparin nor aspirin alone nor combined therapy increased the risk of hemorrhage. We also did not observe an increased rate of bleeding in the case of a short interval between last LMWH (less than 24 hours) or aspirin (less than five days) doses and delivery. Only emergency Caesarean section was significantly associated with an increased risk of bleeding (odds ratio (OR) 5.03 (1.41-17.96); p=.016). In the prospective cohort, only one minor bleeding event was reported (vaginal bleeding). Conclusion Our findings support the safety of antithrombotic therapy with aspirin and/or LMWH during pregnancy in high-risk women with APS, and highlight the need for better treatments to improve pregnancy outcomes in APS. PROMISSE Study ClinicalTrials.gov identifier: NCT00198068.

Thrombotic events during long-term follow-up of obstetric antiphospholipid syndrome patients.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/or venous thromboses and/or pregnancy-associated morbidity. Some patients develop only obstetric complications (obstetric APS), but data on the frequency of thrombotic events during the follow-up of these patients are scarce. This study was undertaken to evaluate the rate of thrombotic events after obstetric APS diagnosis according to the 2006 revised criteria. In total, 32 obstetric APS patients were retrospectively studied, with mean follow-up of 50 ± 37 months. After delivery, aspirin was prescribed to all patients as primary thrombosis prevention. The thrombosis rate was 3.3/100 patient-years and was 4.6, 4.5 and 10/100 patient-years when we considered at least two antiphospholipid antibody positivities (among lupus anticoagulant, anticardiolipin and anti-ß2-glycoprotein-I), antinuclear antibody positivity or systemic lupus erythematosus-associated APS patients, respectively. The thrombosis rate was high after obstetric APS diagnosis, even for patients taking aspirin. Larger, prospective studies are needed to confirm this high frequency and determine the associated risk factors.

Long-term (15-25 years) outcome of childhood hemolytic-uremic syndrome.

The short-term prognosis of the "typical", "post-enteropathic" form of infantile HUS is usually good, with a complete recovery of renal function. However, the extent of the renal damage observed on some biopsies may raise concern for the long-term prognosis. Therefore, we studied the outcome of 29 patients affected with classical HUS in infancy or early childhood and followed-up for 15-28 years (m = 18 yrs). Initial renal symptoms ranged from a moderate renal failure with normal diuresis to a 12-day anuria: 21 children had to be treated by peritoneal dialysis. Twenty-five patients underwent a renal biopsy shortly after recovery: lesions of glomerular thrombotic microangiopathy (TMA) were found in 14 patients, and patchy cortical necrosis was diagnosed in the other 11. At latest examination 10 patients had no renal abnormality, 12 had residual renal symptoms (hypertension in 7, proteinuria in 4 and midly reduced GFR in 1), 3 were in chronic renal failure (CRF), and 4 had reached end-stage renal failure (ESRF) 16-24 years after onset; 2 of these latter 4 had a normal GFR at 10-year examination. The long-term evolution was not correlated with the initial clinical severity but appeared well correlated with the extent of the histological damage: 10 of the 11 patients with cortical necrosis have either ESRF (4), CRF (3) or renal sequelae (3), and 4 of the 5 patients with TMA involving more than 50% of glomeruli present with moderate sequelae, whereas the 9 patients with TMA involving less than 50% of glomeruli are symptom-free or have mild sequelae. Thus, the risk of renal failure 20 years after a seemingly cured childhood HUS is not negligible, and renal histology is the best indicator of long-term prognosis.

[Renal botryomycosis. Clinicopathologic study of a case]. / Botryomycose rénale. Etude anatomo-clinique d'un cas.

Botryomycosis is a chronic bacterial infection characterized histologically by granules containing bacteria in microabscesses. Although Staphylococcus aureus is the most common causative agent, other bacteria have been reported to cause botryomycosis. Several factors have been hypothesized to be important in the pathogenesis of botryomycosis including foreign bodies, quantity and virulence of bacterial microorganisms and host immunity. We report a case of renal botryomycosis in a 60 year-old woman. The diagnosis was based on clinical findings of Escherichia coli urinary infection, histological findings of granules and immunohistologic findings of anti-Escherichia coli granules staining. This is the seventh reported case of renal botryomycosis.

Infantile chronic tubulo-interstitial nephritis with cortical microcysts: variant of nephronophthisis or new disease entity?

Over a 15-year period we observed seven children (four girls, three boys) who presented within the first months of life with severe renal failure and acidosis, associated with hypertension in five patients and polyuria in four. In addition, one patient had a severe cholestatic liver disease. In two families, a similarly affected sibling had died previously. Four patients were referred with the clinical diagnosis of polycystic kidney disease because of moderate enlargement of kidneys, but renal imaging (intravenous pyelography and ultrasonography) did not confirm this diagnosis. A renal biopsy, performed in all patients, showed similar features characterized by a diffuse chronic tubulo-interstitial nephritis (TIN) and particularly by the presence of microcystic dilatation of proximal tubules and Bowman's space. Liver pathology was normal in two patients, including one with hepatomegaly. However, in the patient with cholestasis there was inflammatory portal fibrosis with mild duct proliferation. Progression of the renal disease was extremely rapid and all patients reached end-stage renal failure (ESRF) before the age of 2 years (11-22 months). Two children had successful renal transplants. Although this chronic TIN shares some features with nephronophthisis, we suggest that it represents a distinct entity both on clinical and morphological grounds. The specific clinical features of this disease are its early onset and rapid progression to ESRF. Pathologically, it differs from nephronophthisis by the absence of medullary cysts and thickened tubular basement membranes and by the presence of cortical microcysts.

[Intrafamilial renal transplantation in children after donor blood transfusions]. / Transplantation rénale intrafamiliale chez l'enfant après transfusions du sang du donneur.

This article represents an update of our experience with deliberate donor specific blood transfusions (D.S.T.) prior to living-related renal transplantation in children. Eighteen recipients with a negative cross- match to donor T and B cells entered the D.S.T. protocol without regard to the results of the mixed lymphocyte cultures and third party transfusion. The D.S.T. procedure involves the administration of fresh packed cells on 2 or 3 separate occasions at 4 weeks intervals. The potential recipient's sensitization is closely monitored against donor's isolated T and B lymphocytes and against a random panel. This immunological monitoring is done 10 to 20 days after each D.S.T. and just prior to grafting. A negative T and B cross-match at 37 degrees C is a pre-requisite for transplantation. Sixteen patients have been transplanted. All kidneys are functioning with follow-ups ranging from 6 to 48 months; 10 patients have normal renal function, 2 of them experienced reversible acute rejection and 6 have chronic rejection. The benefits derived from pretransplant D.S.T. in parental renal transplantation appear to be substantial, although the nature of the various immunological mechanisms remains unclear.

[Captopril treatment of arterial hypertension in children after renal transplantation]. / Traitement par le captopril de l'hypertension artérielle chez l'enfant après transplantation rénale.

52 children with renal allograft received captopril during 56 periods of treatment. High blood pressure (BP) was due to renal artery stenosis in 22 patients, to diffuse vascular lesions (mainly due to chronic rejection) in 13, to high-dose corticosteroid treatment in the early phase in 11, and to various or unknown causes in 10 patients. In the last 3 groups (including 34 cases) captopril use did not induce any marked drawback. In the absence of overload, a good control of BP was obtained with a mean dosage of 2.2 mg/kg (0.7----5 mg/kg). A mild, transient renal failure (RF) was observed in 6 patients, who were given diuretics without any need. The 22 patients with renal artery stenosis received captopril during 26 periods of treatment. The mean dosage was 1.6 mg/kg (0.3-4.4). The result was excellent in 12 cases (normal BP without any RF), less good in 8 cases (moderate RF +/- borderline BP) and poor (acute RF) in 6. Sodium depletion, due to diuretics in 9, was present in all 14 cases with RF and in 10 of them captopril could be continued or reintroduced without any reappearance of RF after the correction of salt depletion. We conclude that sodium depletion is the main cause of renal failure in transplanted patients receiving captopril and that avoidance of diuretics largely diminishes the risk of RF.

[Captopril in severe arterial hypertension of childhood (authors transl)]. / Captopril et hypertension artérielle sévère de l'enfant.

Twenty patients with severe arterial hypertension were treated with Captopril (an inhibitor of angiotensin 1 converting enzyme). Decrease in blood pressure occurred early and was sometimes important. Significant changes in plasma renin activity, plasma aldosterone and converting enzyme activity were observed. There was a significant inverse correlation between the action of Captopril on blood pressure and the level of extra-cellular volumes. Eighteen patients received long-term treatment (m = 10.05 +/- 1.32 mo.). Side-effects consisted of positive antinuclear antibodies and a possible kidney failure in cases with stenosis of the renal artery.

[Nephrotic syndrome, antithrombin III deficiency and recurrent thrombosis. The value of vitamin K antagonists]. / Syndrome néphrotique, déficit en antithrombine III et thromboses à répétition. Intérêt des antagonistes de la vitamine K.

In a 7 year-old girl presenting with nephrotic syndrome and repeated episodes of thrombosis, a decrease in antithrombin III and in vitro inactivity of heparin were observed. Treatment by vitamin K antagonists prevented further thromboembolic episodes.

[Malignant lymphopathy in a patient suffering from acute disseminated lupus erythematosus (author's transl)]. / Lymphopathie maligne chez un malade ayant un lupus érythémateux aigu disséminé.

The authors report a case of acute disseminated lupus erythematosus in a 55 years old patient, receiving small doses of corticosteroids, progressing over three years. During an acute exacerbation of the disease, the development of a cervical adenopathy led to a biopsy. Histological examination revealed a lymphocytic type malignant proliferation (centro-follicular lymphoma). This case is compared with findings reported in the literature and leads to a discussion of the relationship between ADLE and malignant disorders due to a disturbance of immune control mechanisms and the possible role of immune-depressant therapy in their onset.

[Thyroid dysgenesis in mother and daughter]. / Dysgenesie thyroidienne chez une mere et sa fille.

A case of congenital hypothyroidism with lingual thyroid in a woman and her daughter is presented. The scarcity of familial cases of thyroid malformations leads to discuss the genetic factors involved.