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Background Left atrial appendage (LAA) closure (LAAC) could prevent stroke in patients with atrial fibrillation. However, LAAC may impair the compliance of the left atrium and result in poor prognosis. This study aimed to comparatively evaluate the prognosis of LAAC among patients with different sizes of LAA orifice. Methods and Results Three hundred two consecutive patients who underwent successful LAAC were included and divided into 4 groups based on LAA orifice size that was measured using transesophageal echocardiography. Clinical outcomes including thromboembolic events, major cardiocerebrovascular adverse events, and acute heart failure (AHF) were compared among 4 quartile groups and between propensity-score matched groups of large and small LAAs. Through follow-up of 39.6±8.4 months, survival of thromboembolic events was similar. Survival of major cardiocerebrovascular adverse events was significantly lower in the group with the largest LAA orifice (log-rank P <0.001), including a higher incidence of AHF with New York Heart Association class III to IV (21.4%, log-rank P =0.009). A large LAA orifice (by cutoff) could predict major cardiocerebrovascular adverse events (hazard ratio, 3.749 [95% CI, 2.074-6.779]) in most patients, except for subgroups of those aged <65 years, with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Further compared with a propensity-score matched small-LAA group, the large-LAA orifice group still presented worse survival of AHF with New York Heart Association class III to IV (log-rank P =0.010). Conclusions Patients with a larger LAA orifice presented a worse prognosis after LAAC, including a higher incidence of AHF. A large LAA orifice could predict a post-LAAC AHF event in most patients, except for young patients, patients with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Registration URL: clinicaltrials.gov; Unique identifier: NCT04185142.

Background Liver cirrhotic patients with nonvalvular atrial fibrillation have been excluded from randomized clinical studies regarding oral anticoagulants for stroke prevention. Whether non-vitamin K antagonist oral anticoagulants ( NOAC s) are superior to warfarin for these patients remains unclear. Methods and Results This nationwide retrospective cohort study, with data collected from the Taiwan National Health Insurance Research Database, enrolled 2428 liver cirrhotic patients with nonvalvular atrial fibrillation taking apixaban (n=171), dabigatran (n=535), rivaroxaban (n=732), or warfarin (n=990) from June 1, 2012, to December 31, 2016. We used propensity score-based stabilized weights to balance covariates across study groups. Patients were followed until the occurrence of an event or the end date of study. The NOAC group (n=1438) showed risk of ischemic stroke/systemic embolism and intracranial hemorrhage comparable to that of the warfarin group (n=990) after adjustment. The NOAC group showed significantly lower risk of gastrointestinal bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.79]; P=0.0030) and all major bleeding (hazard ratio: 0.51 [95% CI, 0.32-0.74]; P=0.0003) compared with warfarin group. Overall, 90% (n=1290) of patients were taking a low-dose NOAC (apixaban 2.5 mg twice daily, rivaroxaban 10-15 mg daily, or dabigatran 110 mg twice daily). The subgroup analysis indicated that both dabigatran and rivaroxaban showed lower risk of all major bleeding than warfarin. The advantage of lower gastrointestinal and all major bleeding with NOACs over warfarin is contributed by those subgroups with either nonalcoholic or nonadvanced liver cirrhosis. Conclusions NOACs have a risk of thromboembolism comparable to that of warfarin and a lower risk of major bleeding among liver cirrhotic Asian patients with nonvalvular atrial fibrillation. Consequently, thromboprophylaxis with low-dose NOAC s may be considered for such patients.

Background: Female sex is a risk factor for thromboembolism (TE) in atrial fibrillation (AF); however, the underlying mechanisms are unclear. We postulated that left ventricular (LV) diastolic dysfunction (LVDD) could be associated with increased thromboembolic risk in women., Methods: From a retrospective cohort, 158 patients (female : male = 79:79) with nonvalvular AF were propensity score-matched for age, presence of diabetes, hypertension, coronary artery disease, congestive heart failure, embolic history, AF type, and AF duration. Cardiac size and function and central aortic stiffness parameters were evaluated. Diastolic function was classified as normal, indeterminate, and LVDD according to recent guidelines. Surrogate markers for thromboembolism (dense spontaneous echo contrast and thrombus) were evaluated using transesophageal echocardiography., Results: Surrogate markers for TE showed a trend to be more frequent in women than in men (21.5% vs 11.4%, P = .086). LVDD was more prevalent in women than in men (22.8% vs 2.5%, P < .001); however, the prevalence of indeterminate diastolic function was not different between sexes (26.6% vs 20.3%, P = .453). Surrogate markers for TE were detected mostly in women with LVDD. LV diastolic parameters showed a restrictive pattern, and aortic stiffness parameters were worse in women than in men. Women with LVDD had increased aortic stiffness compared to women with indeterminate and normal function, whereas aortic stiffness did not differ among men in all groups. Significant relations between LV diastolic function and aortic stiffness parameters were observed only in women., Conclusion: LVDD due to increased aortic stiffness could be related to a higher thromboembolic risk in women with AF., (© 2018 Wiley Periodicals, Inc.)

Background: Dyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation., Methods and Results: Using data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14 884 atrial fibrillation patients. Median length of follow-up was 1.9 years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70 g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81; P <0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome ( P =0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both P values ≥0.2448)., Conclusions: In patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984., (© 2018 The Authors and Bristol‐Myers Squibb. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: In contrast to systemic hypertension, the significance of arterial waves in pulmonary hypertension (PH) is not well understood. We hypothesized that arterial wave energy and wave reflection are augmented in PH and that wave behavior differs between patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH)., Methods and Results: Right heart catheterization was performed using a pressure and Doppler flow sensor-tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery. Wave intensity analysis was subsequently applied to the acquired data. Ten control participants, 11 patients with PAH, and 10 patients with CTEPH were studied. Wave speed and wave power were significantly greater in PH patients compared with controls, indicating increased arterial stiffness and right ventricular work, respectively. The ratio of wave power to mean right ventricular power was lower in PAH patients than CTEPH patients and controls. Wave reflection index in PH patients (PAH: ≈25%; CTEPH: ≈30%) was significantly greater compared with controls (≈4%), indicating downstream vascular impedance mismatch. Although wave speed was significantly correlated to disease severity, wave reflection indexes of patients with mildly and severely elevated pulmonary pressures were similar., Conclusions: Wave reflection in the pulmonary artery increased in PH and was unrelated to severity, suggesting that vascular impedance mismatch occurs early in the development of pulmonary vascular disease. The lower wave power fraction in PAH compared with CTEPH indicates differences in the intrinsic and/or extrinsic ventricular load between the 2 diseases., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Increasing age predisposes to both thromboembolic and bleeding events in patients with atrial fibrillation; therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. We investigated 1-year outcome with different antithrombotic approaches in very elderly atrial fibrillation patients (age ≥85 years) compared with younger patients., Methods and Results: We accessed individual patients' data from the prospective PREFER in AF (PREvention oF thromboembolic events-European Registry in Atrial Fibrillation), compared outcomes with and without oral anticoagulation (OAC), and estimated weighed net clinical benefit in different age groups. A total of 6412 patients, 505 of whom were aged ≥85 years, were analyzed. In patients aged <85 years, the incidence of thromboembolic events was 2.8%/year without OAC versus 2.3%/year with OAC (0.5% absolute reduction); in patients aged ≥85 years, it was 6.3%/year versus 4.3%/year (2% absolute reduction). In very elderly patients, the risk of major bleeding was higher than in younger patients, but similar in patients on OAC and in those on antiplatelet therapy or without antithrombotic treatment (4.0%/year versus 4.2%/year; P =0.77). OAC was overall associated with weighted net clinical benefit, assigning weights to nonfatal events according to their prognostic implication for subsequent death (-2.19%; CI, -4.23%, -0.15%; P =0.036). We found a significant gradient of this benefit as a function of age, with the oldest patients deriving the highest benefit., Conclusions: Because the risk of stroke increases with age more than the risk of bleeding, the absolute benefit of OAC is highest in very elderly patients, where it, by far, outweighs the risk of bleeding, with the greatest net clinical benefit in such patients., (© 2017 The Authors and Daiichi Sankyo Europe GmbH. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Despite higher thromboembolism risk, women with atrial fibrillation have lower oral anticoagulation (OAC) use compared to men. The influence of the CHA 2 DS 2 -VASc score or the introduction of non-vitamin K OACs on this relationship is not known., Methods and Results: Using the PINNACLE National Cardiovascular Data Registry from 2008 to 2014, we compared the association of sex with OAC use (warfarin or non-vitamin K OACs) overall and by CHA 2 DS 2 -VASc score and examined temporal trends in OAC use by sex. Multivariable regression models assessed the association between sex and OAC use in those with CHA 2 DS 2 -VASc scores ≥2. Temporal analyses assessed changes in OAC use by sex over time. Of the 691 906 atrial fibrillation patients, 48.5% were women. Women were significantly less likely than men to use any OAC overall (56.7% versus 61.3%; P <0.001) and at all levels of CHA 2 DS 2 -VASc score (adjusted risk ratio 9% to 33% lower, all P <0.001). Compared to other thromboembolic risk factors, female sex was associated with lower use of OAC (risk ratio 0.90, 95%CI 0.90-0.91). Over time, non-vitamin K OAC use increased at a slightly higher rate in women (56.2% increase per year, 95%CI 54.6% to 57.9%) compared to men (53.6% increase per year, 95%CI 52.0% to 55.2%), yet women remained less likely to receive any OAC at all time points ( P <0.001)., Conclusions: Among patients with atrial fibrillation, women were significantly less likely to receive OAC at all levels of the CHA 2 DS 2 -VASc score. Despite increasing non-vitamin K OAC use, women had persistently lower rates of OAC use compared to men over time., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: The contemporary role of prophylactic anticoagulation following extensive anterior wall ST-segment myocardial infarction (STEMI) is unclear., Methods and Results: We evaluated anterior STEMI patients with left ventricle dysfunction (left ventricular ejection fraction ≤40%) ("high risk"), categorized by prophylactic warfarin use, within a regional STEMI. Patients with pre-existing atrial fibrillation were excluded. The primary outcome was an adjusted (for Global Registry of Acute Coronary Events risk score) 1-year composite of recurrent ischemia, stroke/transient ischemic attack/systemic embolism, or all-cause death. Of the 2032 STEMI admissions, 436 (21.5%) were high risk. After excluding 19 (4.4%) patients with definite left ventricle thrombus and 21 (4.8%) in-hospital deaths (2 had left ventricle thrombus), prophylactic warfarin was utilized in 236/398 (59.3%) high-risk survivors. Prescriptions were comparable across sex, but recipients were on average younger (58.5 years versus 64.0 years, P <0.001) and lower risk (Global Registry of Acute Coronary Events risk: 163 versus 181, P <0.001). No association on the adjusted ischemic composite (23.3% versus 25.3%, odds ratio 0.96, 95% CI 0.60-1.55) or thromboembolic events (2.1% versus 1.2%, odds ratio 1.99, 95% CI 0.38-10.51) was observed, but reduced 1-year all-cause mortality was noted (2.5% versus 8.6%, odds ratio 0.30, 95% CI 0.11-0.81); numerically higher major bleeding was observed at 1 year (2.5% versus 1.2%, odds ratio 2.17, 95% CI 0.43-10.96)., Conclusions: A high utilization of prophylactic warfarin occurs in anterior STEMI patients with left ventricle dysfunction, yet appears to provide no additional benefit on the ischemic composite. The association with lower all-cause mortality, but higher bleeding, calls for an improved understanding of its role in high-risk STEMI., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Lymphoma patients are at increased risk of thromboembolic events but thromboprophylaxis in these patients is largely underused. We sought to develop and validate a simple model, based on individual clinical and laboratory patient characteristics that would designate lymphoma patients at risk for thromboembolic event. The study population included 1,820 lymphoma patients who were treated in the Lymphoma Departments at the Clinics of Hematology, Clinical Center of Serbia and Clinical Center Kragujevac. The model was developed using data from a derivation cohort (n = 1,236), and further assessed in the validation cohort (n = 584). Sixty-five patients (5.3%) in the derivation cohort and 34 (5.8%) patients in the validation cohort developed thromboembolic events. The variables independently associated with risk for thromboembolism were: previous venous and/or arterial events, mediastinal involvement, BMI>30 kg/m(2) , reduced mobility, extranodal localization, development of neutropenia and hemoglobin level < 100g/L. Based on the risk model score, the population was divided into the following risk categories: low (score 0-1), intermediate (score 2-3), and high (score >3). For patients classified at risk (intermediate and high-risk scores), the model produced negative predictive value of 98.5%, positive predictive value of 25.1%, sensitivity of 75.4%, and specificity of 87.5%. A high-risk score had positive predictive value of 65.2%. The diagnostic performance measures retained similar values in the validation cohort. Developed prognostic Thrombosis Lymphoma - ThroLy score is more specific for lymphoma patients than any other available score targeting thrombosis in cancer patients. Am. J. Hematol. 91:1014-1019, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

In the era of novel biological agents, multiple myeloma (MM) is often approached as a chronic condition. While survival continues to improve, population-level data indicate that early mortality remains a substantial barrier to advances in MM outcomes. Here we provide "do's and don'ts" management recommendations that may minimize the risk of early mortality and ensure that patients have the opportunity to benefit from the long term impact of new effective MM agents. Such recommendations encompass the early introduction of novel agents even in the presence of comorbidities and advanced age and aggressive management of MM-related complications., (© 2015 Wiley Periodicals, Inc.)

Background: Patients with mechanical heart valves (MHV) require warfarin to prevent thromboembolism. Although dabigatran was as effective as warfarin for stroke prevention in atrial fibrillation when compared with warfarin in patients with MHV, the study was stopped early because of more strokes and bleeding with dabigatran. To determine why dabigatran was less effective than warfarin, we compared their effects on thrombin generation induced by MHV., Methods and Results: Thrombin generation in the absence or presence of valve leaflets or sewing ring segments (SRS) was quantified. Studies were done in control plasma, plasma depleted of factors (F) XII, XI, or VII, plasma containing varying concentrations of dabigatran, or plasma from patients on dabigatran or warfarin with varying dabigatran concentrations or international normalized ratio (INR) values. Mean endogenous thrombin potential (ETP) increased 1.2-, 1.5-, and 1.8-fold in the presence of leaflets, Teflon SRS, and Dacron SRS, respectively. Whereas ETP in FVII-depleted and control plasma was similar, ETP was reduced to background levels in FXII-depleted plasma and abrogated in FXI-depleted plasma. Dabigatran had little effect on ETP at concentrations below 400 ng/mL, whereas in plasma from warfarin-treated patients, ETP was suppressed with INR values over 1.5., Conclusions: MHV induce thrombin generation via the intrinsic pathway and generate sufficient thrombin to overwhelm clinically relevant dabigatran concentrations. In contrast, warfarin is more effective than dabigatran at suppressing MHV-induced thrombin generation. These data explain why dabigatran failed in MHV patients and suggest that strategies targeting FXII or FXI may suppress the root cause of thrombosis in such patients., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

We report a very rare case of a 43-year-old patient with fatal left ventricular subepicardial aneurysm rupture complicating embolic myocardial infarction due to mitral valve infective endocarditis., (© 2014, Wiley Periodicals, Inc.)

The antiphospholipid syndrome (APS) is diagnosed in patients with recurrent thromboembolic events and/or pregnancy loss in the presence of persistent laboratory evidence for antiphospholipid antibodies. Diagnostic tests for the detection of antiphospholipid antibodies include laboratory assays that detect anticardiolipin antibodies, lupus anticoagulants, and anti-β(2)-glycoprotein I antibodies. These assays have their origins beginning >60 years ago, with the identification of the biologic false positive test for syphilis, the observation of "circulating anticoagulants" in certain patients with systemic lupus erythematosus, the identification of cardiolipin as a key component in the serologic test for syphilis, and the recognition and characterization of a "cofactor" for antibody binding to phospholipids. Although these assays have been used clinically for many years, there are still problems with the accurate diagnosis of patients with this syndrome. For example, lupus anticoagulant testing can be difficult to interpret in patients receiving anticoagulant therapy, but most patients with a thromboembolic event will already be anticoagulated before the decision to perform the tests has been made. In addition to understanding limitations of the assays, clinicians also need to be aware of which patients should be tested and not obtain testing on patients unlikely to have APS. New tests and diagnostic strategies are in various stages of development and should help improve our ability to accurately diagnose this important clinical disorder., (Copyright © 2012 Wiley Periodicals, Inc.)

A 75-year-old woman underwent emergency coronary artery bypass surgery after acute anterior wall myocardial infarction. Because of the presence of a local peritonitis, an emergency laparotomy was performed in which necrotizing Meckel's diverticulum was found and resected. Microscopically, sections through the diverticulum revealed a fresh thrombus occluded the arterial lumen of diverticulum. The patient had an uneventful postoperative course. We believe that the cause of Meckel's diverticulum ischemia was the development of atrial fibrillation with left atrium thrombus formation followed by embolic obliteration of Meckel's diverticulum feeding artery.

D-dimer (DD) is a fibrin degradation product present in negligible amounts in healthy individuals, but in thrombotic/fibrinolytic conditions substantially increases in plasma. Over the last two decades numerous studies have explored whether DD measurements would help stroke clinicians. An easy, reliable, and inexpensive test for stroke diagnosis, determination of stroke subtype, severity, prognosis, and recurrence risk is being sought. We searched the database, of studies indexed in English on MEDLINE, using the keywords 'cerebral venous thrombosis, D-dimer, deep vein thrombosis, intracerebral hemorrhage, ischemic stroke, outcome, prognosis, and subarachnoid hemorrhage' for relevant studies. Here, we systematically review current evidence on plasma DD levels in patients with ischemic and hemorrhagic strokes, transient ischemic attacks, and cerebral venous thrombosis. Numerous studies showed that patients with various strokes and stroke-related diseases had acutely increased plasma DD levels. Plasma DD levels, however, are neither sensitive nor specific enough to be utilized in stroke diagnostics and cannot replace either clinical or radiological evaluation. Regarding prediction of patient outcome, good clinical evaluation is clearly superior to DD testing.

Background: Atrial fibrillation (AF) occurs due to various etiologies that carry different risks for thromboembolism. However, the effect of different etiologies on left atrial appendage (LAA) function has not been investigated. This study aimed to examine the LAA function in AF that occurred under various etiologies and to compare the findings with a novel tissue Doppler imaging (TDI) technique by using transesophageal echocardiography (TEE)., Methods: LAA function was assessed in 84 patients with permanent AF according to various etiologies [mitral stenosis in 20 (24%), hypertension in 44 (52%), and hyperthyroidism in 20 (24%) patients] and in 23 controls with sinus rhythm. LAA area change, PW-Doppler and tissue velocities of LAA were measured. The presence of SEC or thrombus and their relation to LAA function was evaluated., Results: LAA velocities were lowest in mitral stenosis and highest in hyperthyroidism. Moderate-severe LAA SEC was detected in 61 and thrombi in 23 patients. Factors associated with the severity of SEC were the percentage of the LAA area change, PW-Doppler peak emptying velocity, and TDI septal wall downward velocity. The percent of the LAA area change and PW-Doppler peak emptying velocity were the significantly related factors for the presence of thrombi (OR = 0.84, 95% CI = 0.74-0.95, P = 0.005 and OR = 0.85, 95% CI = 0.74-0.98, P = 0.02, respectively)., Conclusion: LAA function deteriorated most severely in mitral stenosis and least in hyperthyroidism. The LAA area change and PW-Doppler emptying velocity were important predictors for SEC or thrombi. Although TDI was not superior to classical methods, it provided complementary data to PW-Doppler velocities for predicting SEC and thrombi.

We report the case of an 82-year-old woman with a diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) for more than 10 years, who developed an ischemic stroke during infusion of immunoglobulin (IVIG). She had received IVIG intermittently for several years, and the previous 86 doses were well tolerated. Thromboembolism was suspected based on magnetic resonance angiogram and on further extension of the deficit after 4 days of evolution. Strokes were associated with the use of IVIG in different clinical circumstances. Pre-existing thrombogenic risk factors should be carefully considered for patients undergoing treatment with IVIG. Clinical evaluation, with attention to history, a focused vascular work-up, and looking for markers of dehydration, can identify the high-risk patient for whom a careful analysis of the risk/benefit ratio is warranted.

Thromboembolic complications following splenectomy for hematologic diseases occur in up to 10% of patients and may range from portal vein thrombosis (PVT) to pulmonary embolism (PE) and deep vein thrombosis (DVT). Up to now there exist no recommendations for the duration and intensity of prophylactic anticoagulation, which usually follows local institutional protocols. We report on three consecutive patients with severe portal vein thrombosis and/or pulmonary embolism--one with fatal outcome--7 to 35 days after splenectomy for autoimmune hemolytic anemia, immunothrombocytopenia, and indolent lymphoma, respectively. Incidence and pathophysiology of thromboembolic events (TE) in this patient group as well as prophylactic anticoagulation will be discussed, including a review of the current literature on this topic., (Copyright 2004 Wiley-Liss, Inc.)

The association between malignancy and clinical thrombosis has been recognized for nearly 140 years. The purpose of this review is to examine our current understanding of thrombosis as a complication of cancer and cancer therapy. The review includes a discussion of the epidemiology, pathophysiology, diagnosis and treatment., (Copyright 2002 Wiley-Liss, Inc.)

Each year millions of patients experience a venous thromboembolic event. Due to the significant morbidity and mortality associated with venous thromboembolism (VTE), prevention is critical. Several groups, such as those undergoing orthopedic or general surgery, and patients experiencing acute myocardial infarction, are known to be at high risk for VTE. General medical patients-the medically ill-are also at risk, but they receive insufficient prophylaxis, which may be due to underestimation or lack of assessment of their risk. The American College of Chest Physicians recommends either unfractionated heparin or low-molecular-weight heparin to prevent VTE in these patients. The different pharmacologic profiles and dosing methods of these two groups of agents suggest that efficacy and safety may not be equivalent. Due to heterogeneity of medically ill patients and variability in clinical trials, a detailed review of the literature was performed to assist clinicians in assessing risk and choice of a regimen to prevent VTE.

The objective of the study was to determine the changes in the plasma activities of protein C and protein S that occur during normal pregnancy In this prospective cross-sectional study, plasma activities of protein C and protein S were measured in 32 normal pregnant women in the first, second and third trimester and 6 weeks after delivery There was a significant fall in protein C and protein S activities during normal pregnancy compared with the post-puerperal period. The activities of protein C and protein S also gradually decreased throughout pregnancy (p < 0.01). Increasing plasma volume during normal pregnancy and its dilutional effect might play some role in the low activities of protein S observed. The normal falls in protein S and protein C activities make it difficult to diagnose protein S and C deficiency during pregnancy. Based on our findings, if a woman has a thromboembolic event during pregnancy, testing for a definitive diagnosis of protein C or protein S deficiency or functional failure should be delayed until at least 6 weeks postpartum.

Aims: The study was conducted to determine whether the method for selecting cases of venous thromboembolism (VTE) from general practice databases significantly affected the findings of an epidemiological study., Methods: Cases of VTE were identified from the UK General Practice Research Database (GPRD) by searching for codes for deep vein thrombosis (DVT) and pulmonary embolism (PE). These had to be supported by evidence of anticoagulation and be exposed to a combined oral contraceptive (COC) at the time of the event. Additional information about the event was sought from general practitioners who were requested to complete a questionnaire and to supply anonymised copies of hospital letters and discharge summaries., Results: Of the 285 cases identified from the GPRD, additional information was available for 177 VTE events. This information showed that 84% of those events were supported by hospital investigations or a death certificate. Using only verified cases, rather than all GPRD identified events, did not alter the results of the epidemiological study., Conclusions: The GPRD provides information of sufficiently high quality to allow valid epidemiological research of VTE events. Excluding cases without a database record of hospital admission would lead to valid events being overlooked, and an under-estimate of the disease incidence.

Patients with a history of heparin-induced thrombocytopenia (HIT) and antibodies to hirudin were re-exposed to recombinant (r)-hirudin for prophylaxis of thromboembolism. Four patients were re-exposed to 2 x 25 mg of subcutaneous r-hirudin for 8-27 d. Two patients were re-exposed once, one patient twice and one four times. Re-exposure was well tolerated in all patients and no thromboembolism occurred. Antihirudin IgG (4/4 patients), IgA and IgM (1/4 patients) antibody levels increased. Baseline ecarin clotting times showed high variability. Patients with antibodies to hirudin may be re-exposed but anticoagulant monitoring is mandatory.

Thromboembolic complications are frequent in patients with multiple trauma. The efficacy of unfractionated heparin for venous thrombosis prophylaxis has not been established. Based on limited prospective data, low-molecular-weight heparin appears to be more effective than unfractionated heparin and at least as effective as compression devices for preventing thromboembolic complications in these patients. Vena cava filters should be considered in high-risk patients who cannot receive anticoagulant therapy, but long-term filter use without concomitant anticoagulant therapy is associated with a substantial risk of recurrent thromboembolism.

An 11-y-old girl who presented with cellulitis and clinical signs of deep vein thrombosis (DVT) is reported here. She developed staphylococcal sepsis, recurrent septic emboli and a large vegetation on the tricuspid valve. The patient was found to be heterozygous for the Arg506Gln mutation in factor Va and had low levels of protein C and protein S during the sepsis. The coexistence of the two thrombophilic states may explain the severe thromboembolic manifestations.

The effect of platelet contamination and freeze-thawing on the activated protein C sensitivity ratio (APCsr) was determined. With increasing platelet count there was a progressive reduction in the ratio. Filtration of samples through a 0.2 microm filter before or after freeze-thawing abolished the development of resistance to the addition of activated protein C indicating that the phenomenon is due to the presence of a particulate factor. Contamination of normal plasma with platelets from a patient with homozygous factor V (FV) deficiency was also associated with the same development of resistance to activated protein C, indicating that the phenomenon was not due to exposure of platelet-derived factor V that might be inaccessible to APC. 82% (96/117) of FVQ506 and 32% (138/430) of FVR506 individuals had APC resistance on analysis of unfiltered plasma. However, 85% (42/50) of FVQ506 individuals had APC resistance on analysis of filtered plasma, whilst only 1/50 FV R506 individuals had APC resistance after filtration. For the purpose of identifying individuals at increased risk of venous thromboembolism due to the presence of the FVQ506 and associated APC resistance a PCR-based genotypic analysis is recommended.