Pregnancy outcome in women with antiphospholipid antibodies

Summary The association of antiphospholipid antibodies (APA) or lupus anticoagulant (LA) and recurrent fetal loss (RFL) is well established; however, the spectrum of pregnancy outcome in relation to various therapeutic approaches versus placebo is unknown. We studied 49 women with RFL, 14 with immune thrombocytopenia (ITP) 13 of whom without a history of RFL, and 32 controls (all in the first trimester of pregnancy) for the presence of APA. Tests for APA were positive in 15/49 women with RFL (30%), 6/14 ITP (43%) and 2/32 controls (6%). Treatment in the APA positive patients consisted of: no treatment for the 8 patients who had no history of RFL (Group A; all 34 previous pregnancies successful), aspirin alone (Group B, 5 patients; all 30 previous pregnancies unsuccessful), aspirin with prednisolone (Group C, 9 patients; 69/80 previous pregnancies unsuccessful), or aspirin, prednisolone and immunoglobulin G for resistant cases (Group D, 4 patients, previously in Group C). 10/11 (90.9%), 3/7 (43%), 7/13 (53.8%) and 4/7 (57.1%) pregnancies were successful in Group A, B, C and D, respectively. There was a total of 19/45 (42%) failures including 3 pregnancies in one patient who failed to respond to all forms of therapy.This open study with small subgroups of patients draws attention to a wide range of pregnancy outcome in women with APA and to the fact that APA may serve only as a marker for a wide range of pathological conditions with variable degrees of disease severity. More studies are, however, needed to explore the real mechanism of RFL in women with APA and RFL, especially those who are resistant to therapy.     

Primary antiphospholipid syndrome: functional outcome after 10 years

OBJECTIVE: To analyze the 10 year functional outcome of primary antiphospholipid syndrome (APS). METHODS: We identified 39 patients with primary APS (35 female, 4 male) who developed a first thrombotic or pregnancy event before 1990. Patients meeting American College of Rheumatology criteria for systemic lupus erythematosus or other connective tissue disorders (secondary APS) were excluded. Medical records were reviewed for detailed histories and functional outcomes. RESULTS: At 10 years' followup, 15 patients (38.4%) had organ damage in the form of hemiparesis (n = 8), dementia (n = 3), quadriplegia (n = 1), dilated cardiomyopathy-myocardial infarction (n = 1), vascular insufficiency-massive pulmonary infarction (n = 1), and endstage renal disease (n = 1). Eight patients (20.5%) with organ damage were unable to perform everyday activities important to their quality of life (functionally impaired). Causes of functional impairment were cognitive dysfunction (n = 3), cardiovascular disease (New York Heart Association Functional Classification Class IV) (n = 2), aphasia (n = 1), expressive aphasia (n = 1), and locked-in syndrome (n = 1). CONCLUSION: Functional prognosis is poor in an important minority of primary APS patients with > 10 years of disease. One-third of primary APS patients had organ damage and one-fifth were functionally impaired.     

Prospective observational study of antiphospholipid antibodies in acute lung injury and acute respiratory distress syndrome: comparison with catastrophic antiphospholipid syndrome

Detection of antiphospholipid (aPL) antibodies in bronchoalveolar lavage fluid (BALF) of patient with acute respiratory distress syndrome (ARDS) suggests involvement of autoimmune mechanisms in the pathogenesis of ARDS. We investigated whether aPL antibodies could be detected in the serum as well as BALF of patients with acute lung injury (ALI) and ARDS. IgG anticardiolipin, IgG anti-beta2-glycoprotein I, IgG antiphosphatidic acid and IgG antiphosphatidylserine antibodies were detected by ELISA in low titers within the normal range in the BALF and serum of nine patients with ALI and 17 patients with ARDS. However, one out of 27 patients investigated had high levels of aPL antibodies in both BALF and serum. This patient suffered from severe ARDS due to sepsis. The high aPL antibody levels in serum possibly triggered by sepsis were associated with high aPL antibody levels in BALF, which can be explained by high capillary-alveolar permeability. Computed tomography scan revealed widespread infarctions in brain, spleen and kidneys, and pulmonary thromboembolism, suggesting the diagnosis of catastrophic antiphospholipid syndrome.     

Possible episodes that trigger thrombotic events in patients with antiphospholipid syndrome

The presence of antiphospholipid antibodies and/or lupus anticoagulant (LA) increase the risk of thrombosis, while the onset of thrombosis is usually sudden. The objective of this study was to determine whether or not some episodes triggered thrombotic events in patients possessing antiphospholipid antibodies. Fifteen patients who presented with thrombosis (primary antiphospholipid syndrome (APS), six cases; secondary APS, nine cases) were retrospectively examined to discover whether or not any specific episodes occurred prior to a total of 21 thrombotic events. In five events occurring in five female patients, specific episodes were identified, including the wearing of tight underwear, dehydration due to fever and standing in hot and humid weather, fever following the extraction of a carious tooth, steroid pulse therapy, toxemia during pregnancy, and intrauterine fetal death. To prevent the occurrence of thrombosis in patients possessing antiphospholipid antibodies, it appears to be important to avoid such triggering episodes and also to reduce the risk factors for thrombosis. Received: May 18, 1999 / Accepted: October 14, 1999     

Limitations of transoesophageal echocardiography in patients with focal cerebral ischaemic events.

OBJECTIVE--To investigate the detection rate of cardiac sources of embolism by transoesophageal echocardiography in patients with focal cerebral ischaemic events and to relate the echocardiographic findings to other clinical findings. DESIGN--Prospective study with blinded analysis of the echocardiographic data and subsequent comparison with the other clinical findings. SETTING--Regional cardiothoracic unit based in a teaching hospital. PATIENTS--131 consecutive patients with focal ischaemic cerebral events (49 with a transient ischaemic attack, 77 with a cerebrovascular accident, and five with a retinal arterial embolus) referred for echocardiography. INTERVENTIONS--Full M mode, cross sectional, Doppler, and contrast echocardiography by both the precordial and transoesophageal techniques. RESULTS--Precordial echocardiography detected a cardiac abnormality in 72 patients. Transoesophageal echocardiography confirmed all the precordial findings (except left ventricular hypertrophy, which at present cannot be defined with this technique) and detected other abnormalities in a further 20 patients (18 with potential right-to-left shunts and two with valve vegetations). It also showed spontaneous contrast echoes in 27 of 28 patients with a large left atrium and showed atrial thrombus in three. Cardiac abnormalities were clinically detected in 53 patients, all of which were confirmed or documented by echocardiography. In the 78 patients with no clinically detectable cardiac abnormality six had mitral valve prolapse and one had a regional wall motion defect (identified by precordial echocardiography) and 17 had potential right-to-left shunts (11 of which were identified only by transoesophageal echocardiography). CONCLUSIONS--Transoesophageal echocardiography is more sensitive than precordial echocardiography in detecting potential sources of embolism in these patients. However, except for the detection of a potential right-to-left shunt, the yield in patients with no cardiac abnormality is low. Moreover, the abnormalities detected in those with previously detected cardiac disease merely confirm the clinical diagnosis. Patients with left atrial spontaneous contrast echoes may benefit from anticoagulation but this requires further study. Until more data are available on this feature and on the role of potential right-to-left shunts in this population, the contribution of echocardiography, precordial or transoesophageal, remains limited.     

Limitations of transoesophageal echocardiography in patients with focal cerebral ischaemic events.

OBJECTIVE--To investigate the detection rate of cardiac sources of embolism by transoesophageal echocardiography in patients with focal cerebral ischaemic events and to relate the echocardiographic findings to other clinical findings. DESIGN--Prospective study with blinded analysis of the echocardiographic data and subsequent comparison with the other clinical findings. SETTING--Regional cardiothoracic unit based in a teaching hospital. PATIENTS--131 consecutive patients with focal ischaemic cerebral events (49 with a transient ischaemic attack, 77 with a cerebrovascular accident, and five with a retinal arterial embolus) referred for echocardiography. INTERVENTIONS--Full M mode, cross sectional, Doppler, and contrast echocardiography by both the precordial and transoesophageal techniques. RESULTS--Precordial echocardiography detected a cardiac abnormality in 72 patients. Transoesophageal echocardiography confirmed all the precordial findings (except left ventricular hypertrophy, which at present cannot be defined with this technique) and detected other abnormalities in a further 20 patients (18 with potential right-to-left shunts and two with valve vegetations). It also showed spontaneous contrast echoes in 27 of 28 patients with a large left atrium and showed atrial thrombus in three. Cardiac abnormalities were clinically detected in 53 patients, all of which were confirmed or documented by echocardiography. In the 78 patients with no clinically detectable cardiac abnormality six had mitral valve prolapse and one had a regional wall motion defect (identified by precordial echocardiography) and 17 had potential right-to-left shunts (11 of which were identified only by transoesophageal echocardiography). CONCLUSIONS--Transoesophageal echocardiography is more sensitive than precordial echocardiography in detecting potential sources of embolism in these patients. However, except for the detection of a potential right-to-left shunt, the yield in patients with no cardiac abnormality is low. Moreover, the abnormalities detected in those with previously detected cardiac disease merely confirm the clinical diagnosis. Patients with left atrial spontaneous contrast echoes may benefit from anticoagulation but this requires further study. Until more data are available on this feature and on the role of potential right-to-left shunts in this population, the contribution of echocardiography, precordial or transoesophageal, remains limited.     

Hypertension negatively affects the pregnancy outcome in patients with antiphospholipid syndrome

The impact of hypertension in the pregnancies from autoimmune patients is not unequivocally defined. We have prospectively followed 168 pregnancies from 135 patients from four Italian centres to verify the potential impact of hypertension in the antiphospholipid syndrome (APS). The rate of preeclampsia, mean neonatal weight and gestational age at delivery were significantly lower in patients with both APS and hypertension than in patients with hypertension or APS alone. This information may be relevant for counselling and care of these patients.     

Prognosis of patients with ascites after PleurX insertion: an observational study

Objective: To evaluate the safety of PleurX in cirrhotic patients with refractory ascites.

Methods: We prospectively registered patients who received a PleurX catheter cirrhosis-associated refractory ascites at our department from July 2015 to November 2016. Our control group consisted of matched cirrhotic patients with refractory ascites treated with large volume paracentesis (LVP) and patients with malignant ascites treated with PleurX during the same period.

Results: We included 25 patients with cirrhosis-related ascites (7 in PleurX group) and 17 with malignant ascites (14 in PleurX group). Of these, six patients had hepatocellular carcinoma and cirrhosis (5 in PleurX group). None were eligible for insertion of a TIPS or liver transplantation. The maximum duration of follow-up was (480 days) in the PleurX group and 366 days in the LVP group (median 84 and 173 days, respectively). There was no difference in mortality when comparing PleurX with LVP treatment (hazard ratios: 3.0 and 1.0, p?=?.23 and .96, respectively). Mortality was higher in patients with malignant ascites (p=?.01). We found no significant differences in adverse events (incl. spontaneous bacterial peritonitis) or in P-albumin, P-creatinine and P-sodium between the groups.

Conclusion: PleurX insertion for the treatment of refractory ascites in cirrhotic patients appears to be safe. Prospective randomized trials are necessary in order to confirm these findings.     

Transoesophageal echocardiography in the investigation of stroke: experience in 135 patients with cerebral ischaemic events

Background : The importance of cardiogenic embolism as a cause of cerebral ischaemic events may be underestimated if potential cardiac sources of embolism remain undetected. Transoesophageal echocardiography (TOE) is more sensitive in detecting such abnormalities than earlier methods and may result in more frequent recognition of cardiogenic embolism.
Aims: To establish in an unselected stroke population the prevalence of potential cardiac sources of embolism detectable on TOE and their relationship to atrial fibrillation and carotid stenosis.
Methods : One hundred and thirty-five consecutive patients with cerebral ischaemic events were studied using transthoracic and monoplane transoesophageal contrast echocardiography and carotid Duplex imaging or cerebral angiography.
Results : Thirty patients (22%) had atrial fibrillation. In 43 patients (32%), no cardiac source of embolism was identified; in eight echocardiography was normal. At least one potential cardiac source of embolism was identified in 92 patients (68%) with multiple findings in 41; these patients were older (70 ± 9 years vs 61 ± 14 years; P = 0.0001), more frequently in atrial fibrillation (28/92 vs 2/43; p = 0.0017) and more frequently had cortical or large subcortical stroke (71/92 vs 23/43; p = 0.005). Carotid stenoses were detected in 55% of patients, not significantly different in those with and without cardiac abnormalities.
Conclusions : When bias in selection of patients is avoided, TOE detects a potential cardiac source of embolism in most patients with cerebral ischaemia, particularly those older and in atrial fibrillation. Multiple cardiac abnormalities and coexistent carotid disease are common. The implication of these findings for prevention of stroke awaits age-matched controlled studies. (Aust NZ J Med 1993; 23: 477–483.)     

Thrombotic events in patients with antiphospholipid syndrome treated with rivaroxaban: a series of eight cases

Clinical Rheumatology - The current treatment for antiphospholipid syndrome (APS) with thrombotic manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are usually the agents of...     

Long-term outcome of mycophenolate mofetil treatment for patients with microscopic polyangiitis: an observational study in Chinese patients

This study aimed to retrospectively analyze the long-term outcome of mycophenolate mofetil (MMF) therapy for microscopic polyangiitis (MPA) with mild to moderate renal involvement in Chinese patients. Thirty-four MPA patients (24 females, 10 males, aged 44.7 ± 17 years, BVAS score 13.8 ± 3.2, SCr 2.2 ± 1.1 mg/dl) with SCr < 5 mg/dl and who received glucocorticoids plus MMF therapy for inducing and maintaining remission were included in this study. The remission and relapse rates, patient and renal survival rates and adverse events were retrospectively analyzed. We found that 31 (91.2 %) of 34 patients achieved remission and were continuously treated with glucocorticoids plus MMF for maintaining remission. The median duration of MMF treatment was 24 months (IQR 15–53 months) and follow-up time was 86 months (IQR 29–124 months). During the follow-up, 7 (22.6 %) patients relapsed, one patient died, and one patient progressed into end-stage renal disease. The 5-year patient and renal survival rates were 92.8 and 95.2 %, respectively. 11 (32.4 %) patients suffered 16 adverse events, 13 of which were pulmonary infection. In conclusion, glucocorticoids plus MMF regimen as induction and maintenance therapy could achieve high remission rate and good long-term renal survival in MPA patients with mild to moderate renal involvement. Prospective controlled trials with a large sample size are needed to confirm the efficacy of MMF in this population.