Morbidity and mortality in the antiphospholipid syndrome during a 5-year period: a multicentre prospective study of 1000 patients.

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).

European Concerted Action on Anticoagulation (ECAA): multicentre international sensitivity index calibration of two types of point-of-care prothrombin time monitor systems.

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 1.75 and 1.13 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 investigation of the significance of a positive direct antiglobulin test in blood donors.

Sixty-two samples from 62 donors were investigated to determine the significance of warm IgG autoantibodies that were detected using a gel system during compatibility testing. The presence of autoantibodies on the red cells was confirmed by elution studies. Twelve of 23 strongly positive samples, 7 of 19 moderately positive samples, and 6 of 11 weakly positive samples were studied. The remaining nine samples were found positive during crossmatching, then negative when it was repeated. These nine samples were not included in this study. With a tube test, most of the antibodies had titers from 4 to 8. IgG subclass studies showed that 14 of 25 samples with reactive eluates contained IgG1, one contained IgG1+IgG2, one contained IgG1+IgG4, and two contained IgG1+IgG3 weak. The frequency of donors with a positive direct antiglobulin test (DAT) was approximately 1 in 3000 and males were twice as likely to be DAT positive (8 females vs. 17 males in this study). None of the donors had hemolysis. Two donors showed low-titer anticardiolipin antibodies. We conclude that DAT-positive donors can be a problem during compatibility testing when sensitive methods are used.

Surgery-associated acquired hemophilia A.

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.

Cardiac tamponade due to post-cardiac injury syndrome in a patient with severe haemophilia A and HIV-1 infection.

An 18-year-old man with severe haemophilia A (FVIII:C < 1%) and human immunodeficiency virus 1 (HIV-1) infection was admitted to the hospital with fever and chest pain for 7 days. Eight weeks prior to his admission he had an accident for which he underwent, at another hospital, clinical and laboratory examination that revealed bone fractures of the nose cavity, and he was given factor VIII concentrates for seven days due to nasal bleeding. On admission, chest roentgenogram showed a large cardiac silhouette and echocardiography confirmed the presence of a large quantity of pericardial fluid. A presumptive diagnosis of the post-cardiac injury syndrome was made and he was given anti-inflammatory drugs plus infusion of recombinant factor VIII concentrate (35 units kg-1 b.i.d.). On the seventh day he exhibited cardiac tamponade for which he underwent subxiphoid pericardiotomy with drainage of approximately 1500 mL of bloody exudate. He had an uncomplicated recovery and 10 days later he left hospital. He was given a continuous prophylactic treatment of 15 units kg-1 of recombinant FVIII every 2 days for 6 months, and 30 months after this episode the patient is free of any symptom.

Effects of two combined monophasic and triphasic ethinylestradiol/gestodene oral contraceptives on natural inhibitors and other hemostatic variables.

OBJECTIVE: To evaluate the effects of two preparations of combined oral contraceptives (COCs), the monophasic COC containing 30 micrograms ethinylestradiol and 75 micrograms gestodene and the triphasic COC containing 30/40/30 ethinylestradiol and 50/70/100 micrograms gestodene on seven natural inhibitors and hemostatic variables. METHOD: Forty-four healthy young women, randomly allocated into two groups (A and B) received the two preparations of COCs, respectively. The following variables were tested in a basic examination and at 1-, 3- and 6-month intervals to evaluate the role of the above preparations on the hemostatic balance of prothrombin time, fibrinogen, antithrombin III activity, protein C activity, total protein S antigen, plasminogen activity and lupus anticoagulant. RESULTS: Group A women presented shorter prothrombin time at 6 months, an increased fibrinogen level at 3 months, no influence on the anticoagulant factors, antithrombin III, protein C and total protein S and an increased plasminogen activity at the 1st and 3rd months of treatment. On the other hand, group B women presented shorter prothrombin time at 3 months, no increase in fibrinogen, a decrease in antithrombin III activity and total protein S activity at the 6th month, whereas protein C and plasminogen activities were found to be increased at the 3rd and 1st, 3rd and 6th month, respectively. CONCLUSIONS: 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 involvement in sickle cell-beta thalassemia.

Renal function studies were performed in 41 patients with sickle cell-beta thalassaemia (S/b thal) and compared to 14 normal controls and 8 sickle cell (SS) patients. Polyuria, hyposthenuria and mild proteinuria were common in both S/b thal and SS patients. A renal concentrating defect was manifest in all patients studied, and in 4 of the 7 S/b that patients tested, an abnormal acidification test was found. A statistically significant negative correlation (n = 19, r = -0.48, p less than 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 less than 0.05) Our S/b thal 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 thal patients showed hyperuricosuria, and a statistically significant negative correlation was noted between serum uric acid and its fractional excretion in all S/b thal patients (n = 41, r = -0.450, p less than 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 less than 0.001). We conclude that renal involvement in the double heterozygous state is as severe as in homozygous sickle cell disease.

Normal platelet aggregating properties of Ehlers-Danlos syndrome "collagen".

Normal platelet aggregating activity of collagen taken from a patient with Ehlers-Danlos syndrome is reported.