Screening for lupus anticoagulant: improving the performance of the lupus-sensitive PTT-LA

Introduction: The aim of the present work was to verify whether calculating a ratio between clotting times obtained with the sensitive PTT-LA and a less sensitive activated partial thromboplastin time (aPTT)-reagent may represent a valuable aPTT-based screening strategy for lupus anticoagulants (LA). Methods: For the pilot study, plasma samples from normal subjects (n = 15) and from patients with LA (n = 10), therapeutic anticoagulation with vitamin K-antagonists (VKA) (n = 15) or unfractionated heparin (n = 15), coagulation factors deficiency (n = 16), and inhibitory antibodies against factor VIII or IX (n = 11) were studied. For the evaluation study, 1553 consecutive plasma samples from nonanticoagulated patients investigated for LA between January 2005 and December 2007 at our institution were studied. Following screening strategies were employed: Pathromtin-SL (aPTT-SL), PTT-LA (aPTT-LA), ratio aPTT-LA/aPTT-SL (aPTT-ratio), and Russell's viper venom (RVV) based LA-Check. LA positive samples were identified by mixing studies and diluted RVV confirmation test (LA-Check/LA-Sure). Results: Pilot study: All screening strategies had a 100% sensitivity, and the aPTT-ratio reached the highest specificity (82%; 95%CI: 74-90%). Within the evaluation study, following sensitivities for LA screening were observed: aPTT-SL 59.0% (95%CI: 57-61%), aPTT-LA 82.1% (95%CI: 80-84%), aPTT-ratio 92.3% (95%CI: 91-94), and LA-Check 83.3% (95%CI: 82-85%). Conclusion: Calculating a ratio between the LA-sensitive PTT-LA and the less sensitive Pathromtin-SL improves the performance of the PTT-LA itself and represents a simple and sensitive aPTT-based integrated strategy for LA screening.

Relation of psychological distress to the INR in Patients with venous thromboembolism with and without oral anticoagulant therapy

Psychological distress might affect the international normalized ratio (INR), but effects might vary depending on oral anticoagulant (OAC) therapy.

Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis

No data about the use of the pentasaccharide fondaparinux, a highly selective indirect inhibitor of factor Xa, in patients treated with haemodialysis are available. Therefore, we investigated the pharmacokinetics and -dynamics of fondaparinux in 12 patients during haemodialysis. The anti-Xa activity (expressed as fondaparinux equivalent) was monitored, a semiquantitative clotting scale (SQCS) ranging from 0 (no visible traces of coagula) to 3 (complete clotting of the dialysis circuit) was applied, and the digital compression time necessary to achieve haemostasis at the puncture site was determined. After an initial period, when the regular heparin dose was replaced once weekly by fondaparinux, 0.05 mg/kg, the pentasaccharide was administered for nine consecutive haemodialysis sessions. Peak anti-Xa activity increased from 0.61 +/- 0.14 microg/l after the first dose to 0.89 +/- 0.24 microg/l after dose 9 (P < 0.001), whereas predialysis anti-Xa activity steadily rose to 0.32 +/- 0.09 microg/l (P < 0.001). A sufficient but slightly less effective anticoagulation with a mean SQCS of 1.19 +/- 0.71 (n = 121) was obtained by fondaparinux as compared with 0.65 +/- 0.58 (n = 60, P < 0.005) by 4,825 +/- 1,703 U of unfractionated heparin. Mean digital compression time rose slightly during fondaparinux from 23.7 +/- 7.4 minutes to 24.8 +/- 7.5 minutes (P < 0.05) and, more important, six of the 12 patients reported minor bleeding problems during the interdialytic interval. Thus, fondaparinux can be used to prevent circuit clotting during haemodialysis; however, accumulation results in an interdialytic increase of anti-Xa activity. Therefore, fondaparinux should be reserved for patients requiring systemic anticoagulation on the days off dialysis.

Major bleeding of the upper aerodigestive tract due to oral anticoagulant/antibiotic interactions

INTRODUCTION Although a well-known complication in certain medical specialties, major bleeding due to the interaction between oral anticoagulants and antibiotics has been rarely reported concerning the upper aerodigestive tract. We report three cases of life-threatening bleeding of the upper aerodigestive tract in a context of antibiotic therapy in patients treated with oral anticoagulants. CASE SERIES Three male patients under coumadin anticoagulation therapy presented major bleeding in three different contexts (epistaxis, peritonsillar abscess and postoperative course after total laryngectomy). Surgical intervention for hemostasis was required in all cases, with coagulation correction in two. Complications were severe anemia (2/3) and chronic heart failure (1/3). DISCUSSION/CONCLUSIONS Interactions between two drugs commonly used in otolaryngology can result in major bleeding. The goal of this article is to raise practitioners' awareness of a potentially fatal, although rare, complication. We also review the main preventive strategies.

Anticoagulant vs. antiplatelet therapy in patients with cryptogenic stroke and patent foramen ovale: an individual participant data meta-analysis.

AIMS The preferred antithrombotic strategy for secondary prevention in patients with cryptogenic stroke (CS) and patent foramen ovale (PFO) is unknown. We pooled multiple observational studies and used propensity score-based methods to estimate the comparative effectiveness of oral anticoagulation (OAC) compared with antiplatelet therapy (APT). METHODS AND RESULTS Individual participant data from 12 databases of medically treated patients with CS and PFO were analysed with Cox regression models, to estimate database-specific hazard ratios (HRs) comparing OAC with APT, for both the primary composite outcome [recurrent stroke, transient ischaemic attack (TIA), or death] and stroke alone. Propensity scores were applied via inverse probability of treatment weighting to control for confounding. We synthesized database-specific HRs using random-effects meta-analysis models. This analysis included 2385 (OAC = 804 and APT = 1581) patients with 227 composite endpoints (stroke/TIA/death). The difference between OAC and APT was not statistically significant for the primary composite outcome [adjusted HR = 0.76, 95% confidence interval (CI) 0.52-1.12] or for the secondary outcome of stroke alone (adjusted HR = 0.75, 95% CI 0.44-1.27). Results were consistent in analyses applying alternative weighting schemes, with the exception that OAC had a statistically significant beneficial effect on the composite outcome in analyses standardized to the patient population who actually received APT (adjusted HR = 0.64, 95% CI 0.42-0.99). Subgroup analyses did not detect statistically significant heterogeneity of treatment effects across clinically important patient groups. CONCLUSION We did not find a statistically significant difference comparing OAC with APT; our results justify randomized trials comparing different antithrombotic approaches in these patients.

Development of an LC-MS/MS method for the quantitation of 55 compounds prescribed in combined cardiovascular therapy

This paper reports an LC-MS/MS method with positive electrospray ionization for the screening of commonly prescribed cardiovascular drugs in human plasma, including compounds with antihypertensive (57), antidiabetic (12), hypolipemiant (5), anticoagulant (2) and platelet anti-aggregation (2) effects. Sample treatment consisted of a simple protein precipitation with MeOH/0.1 M ZnSO₄ (4:1, v/v) solution after the addition of internal standard, followed by evaporation and reconstitution. Analytes separation was performed on a Polar-RP column (150 m x 2 mm, 4 μm) using a gradient elution of 15 min. The MS system was operated in MRM mode, monitoring one quantitation and one confirmation transition for each analyte. The recovery of the protein precipitation step ranged from 50 to 70% for most of the compounds, while some were considerably affected by matrix effects. Since several analytes fulfilled the linearity, accuracy and precision values required by the ICH guidelines, the method proved to be suitable for their quantitative analysis. The limits of quantitation varied from 0.38 to 9.1 μg/L and the limits of detection from 0.12 to 5.34 μg/L. The method showed to be suitable for the detection of plasma samples of patients under cardiovascular treatment with the studied drugs, and for 55 compounds reliable quantitative results could be obtained.

[Proteins influencing the blood coagulation]

This review describes some natural proteins, which can be employed, either as factor concentrates derived from human plasma or as recombinant drug, to modulate the coagulation system. I will address some biochemical characteristics and the physiological role of von Willebrand factor, the coagulation factors of the extrinsic and intrinsic pathways, and the physiological anticoagulant protein C. In addition, I will detail the pharmacological compounds, which are available for influencing or substituting the coagulation proteins: desmopressin (DDAVP), single coagulation factor concentrates, prothrombin complex concentrates, and protein C concentrate. In particular, I will address some treatment topics of general medical interest, such as the treatment of massive bleeding, the correction of the coagulopathy induced by vitamin K-antagonists in patients with cerebral haemorrhage, and of the coagulopathy of meningococcemia. Finally, I will describe some properties and practical clinical applications of the recombinant anticoagulans lepirudin and bivalirudin, which are derived from hirudin, the natural anticoagulant of the medical leech.

Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study

Clinical scores may help physicians to better assess the individual risk/benefit of oral anticoagulant therapy. We aimed to externally validate and compare the prognostic performance of 7 clinical prediction scores for major bleeding events during oral anticoagulation therapy.

Usefulness of preemptive anticoagulation in patients with suspected pulmonary embolism: a decision analysis

The diagnostic workup of pulmonary embolism (PE) may take several hours. The usefulness of anticoagulant treatment while awaiting the results of diagnostic tests has not been assessed. The objective of this study was to compare the risks and benefits of bid low-molecular-weight heparin vs no treatment in patients with suspected PE.

Treatment of acute ischaemic stroke with thrombolysis or thrombectomy in patients receiving anti-thrombotic treatment

Systemic thrombolysis with alteplase is the only approved medical treatment for patients with acute ischaemic stroke. Thrombectomy is also increasingly used to treat proximal occlusions of the cerebral arteries, but has not shown superiority over systemic thrombolysis with alteplase. Many patients with acute ischaemic stroke are pretreated with antiplatelet or anticoagulant drugs, which can increase the bleeding risk of thrombolysis or thrombectomy. Pretreatment with aspirin monotherapy increases the bleeding risk of alteplase in both observational and randomised trials with no effect on clinical outcome, and the risk of intracerebral haemorrhage is increased with the combination of aspirin and clopidogrel. Antiplatelet drugs should not be given in the first 24 h after alteplase treatment. Data from pooled randomised trials and a large observational study show that thrombolysis can probably be done safely in patients given vitamin-K antagonists if the international normalised ratio is less than 1·7, although bleeding risk is slightly raised. Almost no data are available for the safety of alteplase in patients with atrial fibrillation who have been given novel oral anticoagulants (NOAC) for stroke prevention. Some coagulation parameters could help to identify patients treated with NOAC who might be eligible for thrombolysis. Thrombectomy can be done in patients given antiplatelets and probably in those given anticoagulants; however, conclusions about anticoagulants are based on findings from observational studies with small patient numbers.

A rare cause of fatal right heart failure

Microscopic pulmonary tumor embolism (MPTE) is an uncommon cause of dyspnea in patients with cancer and one of the most difficult to diagnose. MPTE is a syndrome that is pathologically characterized by the occlusion of small pulmonary arteries and arterioles by aggregates of tumor cells. Because the clinical picture resembles that of thromboembolic disease, it is rarely recognized before death. The most common clinical symptom is subacute progressive dyspnea over weeks to months. We recently observed a case of MPTE of exceptional interest as the patient was under aggressive anticoagulant treatment and developed fulminant pulmonary hypertension with fatal right heart failure.

Safety of inferior vena cava filter retrieval in anticoagulated patients

PURPOSES: To evaluate the safety of inferior vena cava (IVC) filter retrieval in therapeutically anticoagulated patients in comparison to prophylactically or not therapeutically anticoagulated patients with respect to retrieval-related hemorrhagic complications. MATERIALS AND METHODS: This was a retrospective study of 115 consecutive attempted IVC filter retrievals in 110 patients. Filter retrievals were stratified as performed in patients who were therapeutically anticoagulated (group 1), prophylactically anticoagulated (group 2), or not therapeutically anticoagulated (group 3). The collected data included anticoagulant and antiplatelet medications (type, form and duration of administration, dosage) at the time of retrieval. Phone interviews and chart review was performed for the international normalized ratio (INR), activated partial thromboplastin time, platelet count, infusion of blood products, and retrieval-related hemorrhagic complications. RESULTS: Group 1 included 65 attempted filter retrievals in 61 therapeutically anticoagulated patients by measured INR or dosing when receiving low-molecular-weight heparin (LMWH). Four retrievals were not successful. In patients receiving oral anticoagulation, the median INR was 2.35 (range, 2 to 8). Group 2 comprised 23 successful filter retrievals in 22 patients receiving a prophylactic dose of LMWH. Group 3 included 27 attempted filter retrievals in 27 patients not receiving therapeutic anticoagulation. Six retrievals were not successful. Five patients were receiving oral anticoagulation with a subtherapeutic INR (median, 1.49; range, 1.16 to 1.69). No anticoagulation medication was administered in 22 patients. In none of the groups were hemorrhagic complications related to the retrieval procedures identified. CONCLUSIONS: These results suggest that retrieval of vena cava filters in anticoagulated patients is safe. Interruption or reversal of anticoagulation for the retrieval of vena cava filters is not indicated.

Venous thromboembolism after retrieval of inferior vena cava filters

PURPOSE: To determine the incidence of venous thromboembolism (VTE) after removal of retrievable inferior vena cava (IVC) filters. MATERIALS AND METHODS: Retrospective study was conducted of 67 patients who underwent 72 consecutive filter retrievals at a single institution. Data collected included VTE status at the time of filter placement, anticoagulant medications at the time of filter retrieval and afterward, new or recurrent VTE after filter removal, and insertion of subsequent filters. Patient questionnaires were completed in 50 cases, chart review in all patients. RESULTS: At the time of filter placement, 30 patients had documented VTE, 19 had a history of treated VTE, and 23 were at risk for but had neither previous nor present VTE. Mean duration of follow-up after filter removal was 20.6 months +/- 10.9. A total of 52 patients (57 filters) received anticoagulation and/or antiplatelet medications after filter removal. There were two documented episodes of recurrent deep vein thrombosis (2.8% of filters removed), both in patients who had VTE at the time of filter placement and underwent therapeutic anticoagulation at the time of filter removal. One of these patients (1.4% of filters removed) also experienced pulmonary embolism. Of the 23 patients without VTE when the filter was placed, none developed VTE after filter removal. Four patients (5.5% of filters removed) required subsequent permanent filters, three for complications of anticoagulation, one for failure of anticoagulation. CONCLUSIONS: VTE was rare after removal of IVC filters, but was most likely to occur in patients who had VTE at the time of filter placement.