Paradoxical intraoperative embolism in a patient with Eisenmenger syndrome undergoing hip arthroplasty. / Embolismo paradójico intraoperatorio en paciente con síndrome de Eisenmenger sometida a hemiartroplastia de cadera.

Hip arthroplasty is associated with a high incidence of embolic events that, although usually not relevant at a clinical level, may be an important cause of morbidity and mortality in certain situations. Extreme caution should be taken in patients with cardiac defects that favor communication between the pulmonary and systemic circulation, due to their greater risk of complications. We present the case of a 72-year-old patient who suffered a paradoxical embolism during the intervention, with devastating consequences.

Multiple Cerebral Infarctions Due to Patent Foramen Ovale in a Patient with Eosinophilic Granulomatosis with Polyangiitis.

A 51-year-old man was diagnosed with eosinophilic granulomatosis with polyangiitis 6 years ago due to asthma, sinusitis, hypereosinophilia, and peripheral neuropathy based on the diagnostic criteria of American College of Rheumatology, and corticosteroid therapy achieved a remission. One year ago, he was hospitalized due to deep venous thrombosis (DVT) and pulmonary embolism, and rivaroxaban was administrated. He was admitted to our hospital for acute onset of diplopia and right hemiparesis. Peripheral blood examinations disclosed leukocytosis with hypereosinophilia. Perinuclear anti-neutrophil cytoplasmic antibodies were positive. Diffusion-weighted imaging showed multiple fresh ischemic lesions. Chronic ischemic lesions were seen in subcortical cerebral region. No stenosis or occlusion was shown in extracranial and intracranial arteries on magnetic resonance angiography. Ultrasonography of leg vein showed DVT. Right-to-left shunt through patent foramen ovale after Valsalva maneuver was seen on transesophageal echocardiography. Treatment with corticosteroid and cyclophosphamide alleviated clinical deterioration. Rivaroxaban was changed to warfarin. Diplopia and muscle strength of right limbs were improved. This is a first case of multiple cerebral infarction caused by paradoxical embolism due to patent foramen ovale with DVT based on hypercoagulable state of hypereosinophilia. Overall this case illustrates that eosinophilic granulomatosis with polyangiitis can be a risk factor for multiple cerebral infarction in the systemic phase and that transesophageal echocardiography and ultrasonography of leg vein should be conducted in stroke patient with eosinophilic granulomatosis with polyangiitis.

D-dimer for prediction of long-term outcome in cryptogenic stroke patients with patent foramen ovale.

Patent foramen ovale (PFO) is a potential cause of cryptogenic stroke, given the possibility of paradoxical embolism from venous to systemic circulation. D-dimer level is used to screen venous thrombosis. We investigated the risk of embolism and mortality according to the presence of PFO and D-dimer levels in cryptogenic stroke patients. A total of 570 first-ever cryptogenic stroke patients who underwent transesophageal echocardiography were included in this study. D-dimer was assessed using latex agglutination assay during admission. The association of long-term outcomes with the presence of PFO and D-dimer levels was investigated. PFO was detected in 241 patients (42.3 %). During a mean 34.0 ± 22.8 months of follow-up, all-cause death occurred in 58 (10.2 %) patients, ischaemic stroke in 33 (5.8 %), and pulmonary thromboembolism in 6 (1.1 %). Multivariate Cox regression analysis showed that a D-dimer level of > 1,000 ng/ml was an independent predictor for recurrent ischaemic stroke in patients with PFO (hazard ratio 5.341, 95 % confidence interval 1.648-17.309, p=0.005), but not in those without PFO. However, in patients without PFO, a D-dimer level of > 1,000 ng/ml was independently related with all-cause mortality. The risk of pulmonary thromboembolism tended to be high in patients with high D-dimer levels, regardless of PFO. Elevated D-dimer levels in cryptogenic stroke were predictive of the long-term outcome, which differed according to the presence of PFO. The coexistence of PFO and a high D-dimer level increased the risk of recurrent ischaemic stroke. The D-dimer test in cryptogenic stroke patients may be useful for predicting outcomes and deciding treatment strategy.

Paradoxical thrombosis, part 2: anticoagulant and antiplatelet therapy.

Arterial thrombosis is the leading causes of morbidity and mortality worldwide, whereas venous thrombosis is the most common preventable cause of hospital death. In either case, venous and arterial thrombosis should be considered autonomous entities, with only minor overlaps in terms of risk factors, predisposing conditions and pathogenesis. Besides the widespread perception of embolization originating from low-pressure venous system and triggering ischemic stroke or peripheral arterial occlusion, "paradoxical" thrombosis might also develop or occur within clinical or biological circumstances where the blood should be less predisposed to clot, and wherein this risk is mostly unpredictable or overlooked. In this article we review epidemiological evidence and potential pathogenetic mechanisms of paradoxical thrombosis developing during antithrombotic therapy with vitamin K antagonists and heparin (i.e. heparin-induced thrombocytopenia), or antiplatelet agents such as aspirin, glycoprotein IIb/IIIa inhibitors or clopidogrel, and mostly attributable to direct effect of the agent.

Paradoxical thrombosis part 1: factor replacement therapy, inherited clotting factor deficiencies and prolonged APTT.

The pathogenesis of venous and arterial thrombosis is complex and multifaceted, entailing a multitude of risk factors, which only marginally overlap between the two vessels districts. Along with conventional and universally recognized risk factors, thrombosis might also develop as a consequence of unusual, atypical, unsuspected and even paradoxical conditions. Although the term "paradoxical embolism" is typically used to identify an embolization process that originates from the low-pressure venous system and may generate ischemic stroke or peripheral arterial occlusion through a cardiac or pulmonary shunt, there are additional clinical circumstances whereby the risk of thrombosis is surprising, unpredicted or even neglected. In this article we thereby analyze the prevalence, as well as the pathogenesis, of thrombosis associated with apparently paradoxical triggers such as during factor replacement therapy in haemophiliacs or in patients with von Willebrand disease; in patients with inherited clotting factor deficiencies especially involving factor XII, factor VII, fibrinogen; or in those with a prolonged activated partial thromboplastin time for the presence of lupus anticoagulant.

New aspects of paradoxical embolism.

Paradoxical emboli have their origin in the low-pressure venous system and can cause ischemic stroke or peripheral arterial embolism through a cardiac or pulmonary shunt. In most cases, a patent foramen ovale (PFO) is found. About 20 % of the population has a patent foramen ovale. This review gives insight into publications concerning the association between the presence of a patent foramen ovale and cryptogenic stroke; the association of PFO, coagulation disorders and stroke; and recurrence rates of stroke in patients with PFO. Diagnostic features are discussed, as are the different therapy modalities, taking existing national and international guidelines into account. Also, our own recommendations are given. In addition some new information on the potential improvement of migraine after PFO closure is discussed. It is widely accepted that the optimal therapy for the prevention of recurrent stroke in patients with PFO and cryptogenic stroke has not yet been found. Randomized, controlled clinical studies are ongoing in the United States and will give even more insight and answer open questions in the future.

Role of elevated alpha2-macroglobulin revisited: results of a case-control study in children with symptomatic thromboembolism.

OBJECTIVE: alpha(2)-Macroglobulin (alpha2MG) is a broad-spectrum protease inhibitor that is known to neutralize alpha-thrombin, plasmin, and activated protein C, which suggests that it has anticoagulant as well as procoagulant properties. The present study was conducted to evaluate the role of alpha2MG in children with venous thromboembolism [VTE: paradoxical embolism causing ischemic stroke (IS) or deep-vein thrombosis (DVT)]. METHODS: alpha2MG levels measured after acute VTE onset in white patients were compared with data obtained from age- and gender-matched healthy controls. In addition, to compare the rate of elevated alpha2MG and prothrombotic risk factors [factor V G1691A, prothrombin G20210A, raised lipoprotein (a)] between patients and controls and to evaluate the interaction between elevated alpha2MG levels and other thrombophilias, odds ratios (ORs) together with 95% confidence intervals (CIs) were estimated using a logistic regression model. The model was adjusted for age and fibrinogen. RESULTS: alpha2MG levels were significantly higher in patients than in controls (320/139-524 vs. 302/109-406; P = 0.005). In the group of patients (IS n = 103; DVT n = 92), the risk of symptomatic thromboembolism was significantly increased with elevated alpha2MG levels, with a gradual increase per mg dL(-1). In addition, when elevated alpha2MG levels > 90th percentile were compared with values below the cut-off, including established prothrombotic risk factors in the multivariate analysis, patients had a significantly increased OR/95% CI for fibrinogen-adjusted alpha2MG levels (IS, 5.9/1.9-18.3; DVT, 7.2/2.1-24.4). CONCLUSIONS: The procoagulant properties of elevated alpha2MG levels independently increase the odds of stroke and DVT in white children.

A case of pregnancy with a history of paradoxical brain embolism.

Brain embolisms in younger persons are rare but are often caused by a paradoxical embolism, the embolic entry of a venous thrombus into the systemic circulation through a right-to-left shunt. A 27-year-old pregnant woman presented with hemiplegia that had been treated with an antiplatelet agent since the occurrence of a paradoxical brain embolism via the pulmonary arteriovenous fistula. A tendency of hypercoagulation is generally observed during pregnancy, so a patient with this condition has a strong risk factor for venous thromboembolism during pregnancy and even more so for arterial thromboembolism under the intense strain of labor, which is much stronger than that of the Valsalva maneuver. This case had been controlled well with an antiplatelet agent and an anticoagulant while the levels of coagulation and fibrinolytic factors were monitored and was followed by a successful pregnancy outcome.