Objective. To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression.Methods. The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database.Results. The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean ؎ SD age of 42 ؎ 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a

ObjectivesTo assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later.MethodsIn 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years.Results53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%.ConclusionsPatients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.

Objectives:To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance.Methods:The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed.Results:200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected.Conclusion:Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).

Summary. A multicentre modified World Health Organization (WHO)-type international sensitivity index (ISI) calibration has been performed at 10 European Concerted Action on Anticoagulation (ECAA) national laboratories using non-citrated whole-blood on two point-of-care test (POCT) prothrombin time (PT) monitor systems, CoaguChek Mini and TAS PT-NC, using single lots of test cards/strips. The relevant species (human and rabbit) WHO international reference preparations (IRPs) were tested with the manual PT technique on citrated plasma from the same blood donations. The ISI was calculated from the slope of the orthogonal regression line relating log PT (POCT) to log PT (IRP). The mean ISI of the CoaguChek Mini system was 1AE75 and 1AE13 with the prothrombin time non-citrated Thrombolytic Assessment System (TAS PT-NC). With the CoaguChek Mini system, seven out of 10 calibrations exceeded the current 3% WHO recommended limit for the coefficient of variation (CV) of the slope with conventional PT testing, whereas with the TAS PT-NC system, it was eight out of 10. All the POCT calibrations had a CV of the slope < 5%. It is suggested that this level of precision be adopted as the limit of acceptability of calibration of these monitor systems. In these circumstances, the modified WHO-type ISI calibration appeared to be satisfactory for the POCT whole-blood monitors.

The study did not find differences between the two treatment groups, for the evaluated parameters. This finding is clearly important in the light of the recent epidemiological reports on third-generation COCs. However, differences were found among the various periods of administration of both COCs.

Renal function studies were performed in 41 patients with sickle cell-β thalassaemia (S/b thai) and compared to 14 normal controls and 8 sickle cell (SS) patients. Polyuria, hyposthenuria and mild proteinuria were common in both S/b thai and SS patients. A renal concentrating defect was manifest in all patients studied, and in 4 of the 7 S/b thai patients tested, an abnormal acidification test was found. A statistically significant negative correlation (n=19, r = -0.48, p < 0.05) was noted between creatinine clearance (CCr) and age for the patients over 30 years. There was no correlation between hemoglobin and CCr; on the contrary, a statistically significant negative correlation was found between CCr and hemoglobin F (n = 29, r=-0.428, p < 0.05) Our S/b thai and SS patients showed a decreased daily excretion of sodium, calcium, phosphate and magnesium and lower serum magnesium levels than the controls. One third of the S/b thai patients showed hyperuricosuria, and a statistically significant negative correlation was noted between serum uric acid and its fractional excretion in all S/b thai patients (n = 41, r = -0.450, p < 0.01). Serum phosphate levels were independent of age. A statistically significant positive correlation was found between the tubular reabsorptive capacity for phosphate and the number of painful crises per year (n = 33, r = 0.836, p < 0.001). We conclude that renal involvement in the double heterozygous state is as severe as in homozygous sickle cell disease.

We present two patients who acquired factor VIII antibodies in the immediate postoperative period. One patient was receiving warfarin that was temporarily discontinued but reintroduced after the procedure. Preoperatively, none gave a history of bleeding, even with past surgeries, and both had normal coagulation tests. Within days of surgery, hemorrhage with prolonged activated partial thromboplastin time, low factor VIII levels, and demonstrable factor VIII antibodies were observed. For the patient who was receiving warfarin the severe bleeding was attributed, at the beginning, only to the high international normalized ratio (INR), which resulted in a fatal delay in diagnosis and appropriate treatment. We would like to raise awareness of surgery as a precipitating cause of acquired hemophilia, which is something to be considered with unusual postoperative bleeding. This syndrome is remarkable for its abrupt onset within days of surgery, severe bleeding but potential successful outcome with combined hemostatic control with recombinant activated FVII (rFVIIa) and elimination of the antibody by immunosuppression.

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