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Background Computed tomography (CT) pulmonary angiography has simplified the diagnostic approach to patients with clinically suspected acute pulmonary embolism (PE), but alternative imaging tests are still advocated. We aimed to systematically assess the diagnostic accuracy of ventilation/perfusion (V/Q) and Q single-photon emission CT combined with low-dose CT (SPECT/CT) for PE diagnosis. Methods Studies evaluating the diagnostic accuracy of SPECT/CT for the diagnosis of acute PE were systematically searched in MEDLINE and EMBASE databases (up to August 2022). The QUADAS-2 tool was used for risk-of-bias assessment of the primary studies. A bivariate random-effects regression approach was used for summary estimates of both sensitivity and specificity. The PROSPERO registration number is CRD42021276538. Results Eight studies, for a total of 1,086 patients, were included. The risk of bias of all included studies was high. The weighted mean prevalence of PE was 27.1% at the random-effects model. The SPECT/CT bivariate weighted mean sensitivity was 96% (95% confidence interval [CI]: 93–98%), with a bivariate weighted mean specificity of 95% (95% CI: 90–97%). At subgroup analysis, for V/Q SPECT/CT bivariate weighted mean sensitivity and specificity were 96% (95% CI: 89–98%) and 96% (95% CI: 91–99%), while for Q SPECT/CT they were 96% (95% CI: 92–98%) and 84% (95% CI: 66–93%), respectively. Conclusions V/Q SPECT/CT has high sensitivity and specificity for the diagnosis of acute PE, meanwhile Q SPECT/CT has high sensitivity but limited specificity for the diagnosis of PE. Management studies will conclusively ascertain the actual role of SPECT/CT in the diagnostic workup of patients with suspected acute PE.

Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. About a quarter of the anticoagulated patients require temporary cessation of direct oral anticoagulants (DOACs) or vitamin K antagonists for a planned intervention within 2 years from anticoagulation inception. Several clinical issues about DOAC interruption remain unanswered: many questions are tentatively addressed daily by thousands of physicians worldwide through an experience-based balancing of thrombotic and bleeding risks. Among possible valuable answers, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) proposes some experience-based suggestions and expert opinions. In particular, FCSA provides practical guidance on the following issues: (1) multiparametric assessment of thrombotic and bleeding risks based on patients' individual and surgical risk factor, (2) testing of prothrombin time, activated partial thromboplastin time, and DOAC plasma levels before surgery or invasive procedure, (3) use of heparin, (4) restarting of full-dose DOAC after high risk bleeding surgery, (5) practical nonpharmacological suggestions to manage patients perioperatively. Finally, FCSA suggests creating a multidisciplinary “anticoagulation team” with the aim to define the optimal perioperative management of anticoagulation.

SummaryLittle information is available on the incidence of splanchnic vein thrombosis and on mortality rates during the acute phase of the disease. We performed a large epidemiologic study on hospital admissions for portal vein thrombosis (PVT) and the Budd-Chiari syndrome (BCS) between 2002 and 2012 in Northwestern Italy. Primary and secondary discharge diagnoses of PVT and BCS were identified using the 9th edition International Classification of Diseases codes 453.0, 572.1 and 452. Hospitalisations for recurrent events were not included. Information was collected on age and gender, vital status at discharge, duration of hospitalisation, and up to five secondary discharge diagnoses. Comorbidity was evaluated using the Charlson comorbidity index (CCI). A total of 3535 patients with PVT and 287 with BCS were hospitalized. The overall gender-specific incidence rates for PVT were 3.78 per 100,000 inhabitants in males and 1.73 per 100,000 inhabitants in females; for BCS 2.0 and 2.2 per million inhabitants, respectively. In-hospital case fatality was 7.3 % in patients with PVT and 4.9 % in patients with BCS. Age, non-abdominal solid cancer, and CCI were independently associated with in-hospital mortality in both PVT and BCS after stepwise regression analysis, male gender and haematologic cancer were associated with mortality in BCS patients only. In this large study we confirmed the low incidence of BCS and we found an incidence of PVT higher than previously reported. This incidence was stable during the period of observation. In-hospital mortality is not negligible, in particular in PVT patients.

SummaryPulmonary embolism (PE) is a common disorder with high mortality and morbidity rates. However, population-based information on its incidence and prognosis remains limited. We conducted a large epidemiology study collecting data on hospitalisation for PE (from 2002 to 2012) in a population of about 13 million people in Northwestern Italy. Patients were identified using the ICD-9-CM codes: 415.11, 415.19; gender and age specific incidence rate of PE during the study period were estimated using the resident population for each year of the study. Furthermore, time trends in the in-hospital PE-related mortality and case fatality rate were calculated. Results were adjusted for possible confounders. A total of 60,853 patients (mean age 72.8 years, ± 14.1, 59.6 % females) with PE were included; the overall crude incidence rate for the entire study period was 55.4 and 40.6 events per year per 100,000 inhabitants for women and men, respectively (p < 0.001). However, this difference was completely lost after standardisation for age. The incidence of PE significantly increased in both genders during the study period. In-hospital case fatality rate significantly decreased throughout the study period (p < 0.001) in women (from 15.6 % to 10.2 %) and in men (from 17.6 % to 10.1 %). The observed decrease of the in-hospital case-fatality throughout the study period remained significant also after adjustment for possible confounders. In conclusion, time trends over an 11-year period show an increasing incidence of PE, but a significant reduction in mortality during hospitalisation. Reduction in the case fatality rate remained significant after adjustment for these possible confounders.Supplementary Material to this article is available online at www.thrombosis-online.com.

Location of venous thrombosis in patients with FVL or prothrombin G20210A mutations: Systematic review and meta-analysis

SummaryEndocrine disorders affect both the coagulation and fibrinolytic systems, and have been associated with the development of cardiovascular diseases. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a link between coagulation and the fibrinolytic system. The aim of this study was to determine the effect of thyroid hormone excess and deficiency on TAFI levels and function. The effect of hyperthyroxinemia on TAFI was studied in healthy volunteers who were randomised to receive levothyroxine or no medication for 14 days in a crossover design. The effect of hypothyroidism on TAFI was studied in a multicentre observational cohort study. Blood was drawn before treatment of patients with newly diagnosed hypothyroidism and when euthyroidism was achieved. Plasma clot-lysis times, activated TAFI (TAFIa)-dependent prolongation of clot-lysis and TAFI levels were measured. Thyroid hormone excess resulted in a hypofibrinolytic condition and in an enhanced TAFIa-dependent prolongation of clot lysis. A trend towards decreased plasma TAFI levels was observed in healthy volunteers who used levothyroxine. Hypothyroidism resulted in hyperfibrinolysis and a reduced TAFIa-dependent prolongation of clot lysis. In conclusion, alterations of TAFIa-dependent prolongation of clot lysis in patients with thyroid disorders may cause an impaired haemostatic balance. The disturbed haemostatic balance in patients with hyperthyroidism might make them prone to thrombosis, while the risk for bleeding may increase in patients with hypothyroidism.

SummarySeveral coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess;however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo. Data sources included MEDLINE (2006–2012), EMBASE (2006–2012), and reference lists. The sources were combined with our previous search containing studies from 1980–2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.

Presence of residual thromboemboli at least six months after a first episode of symptomatic pulmonary embolism: Do perfusion scintigraphy and angio-computed tomography agree?

SummaryStatins have important pleiotropic effects and have been shown to reduce vascular inflammation. Some evidence suggests that statins may have a role in the primary prevention of atrial fibrillation (AF), whereas little is know on the role of statins in patients with existing AF. We performed a meta-analysis of the literature to assess the effect of statins on the recurrence of AF after electrical cardioversion or ablation. MEDLINE and EMBASE databases were searched up to January 2010. Relative risks (RR) and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of I2 statistics. Sixteen studies were included in our systematic review. Statins did not reduce the risk of AF recurrence after ablation (four studies including 750 patients; RR, 1.04; 95% CI, 0.85–1.28, p=0.71; I2 = 34%). Conversely, the use of statins was associated with a significantly reduced risk of AF recurrence after electrical cardioversion (12 studies including 1790 patients; RR, 0.78; 95% CI, 0.67–0.90, p=0.0003; I2 = 34%). This reduction was not statistically significant when the analysis was restricted to randomised controlled trials (RCTs) only (five studies, 458 patients, RR, 0.76; 95% CI, 0.48–1.20). In conclusion, statins may lower the risk of AF recurrence after electrical cardioversion, but not ablation. However, this finding should be considered with caution, and larger RCTs are warranted to confirm our preliminary results.

SummarySeveral small series have suggested the efficacy of thrombolysis in patients with cerebral vein thrombosis (CVT). However, since no randomised controlled trials have compared the use of thrombolysis with anticoagulant treatment in these patients, the risk to benefit ratio of this approach remains uncertain. The aim of this study is therefore to assess the safety of thrombolysis in CVT estimating mortality and major bleeding complications. MEDLINE and EMBASE databases were searched up to June 2010. Two reviewers performed study selection independently. Studies providing data on mortality and/or on the incidence of major bleeding complications were potentially eligible for the study. Two reviewers independently extracted data on study and population characteristics, type, dose and administration route of thrombolytic treatment; use and dose of concomitant heparin. Weighted mean proportion of the mortality rate and of the rate of major and non-major bleeding complications were calculated. Fifteen studies for a total of 156 patients were included. Twelve patients died after thrombolysis (weighted mean 9.2%; 95% CI 4.3, 15.7%) and 15 patients had a major bleeding complication (weighted mean 9.8%; 95% CI 5.3, 15.6%). Twelve haemorrhages were intracranial (weighted mean 7.6%; 95% CI 3.5, 13.1%), and seven of these patients died (58.3%; 95% CI 32.0, 80.7%). Our results suggest that thrombolysis is associated with a nonnegligible incidence of major bleeding complications, including intracranial bleeding potentially affecting patients outcome. Future studies are necessary to evaluate the safety of thrombolysis in comparison to more conservative strategies.

SummaryOptimal timing for restarting anticoagulant therapy after intracranial bleeding is a critical issue. The purpose of this systematic review is to summarize published studies on the management of oral anticoagulant therapy after intracranial bleeding secondary to the use of vitamin K antagonists in patients with a mechanical heart valve. A computer-assisted search of the MEDLINE and EMBASE electronic databases till January 2008 was performed. Two investigators independently performed study selection and completed a predefined quality assessment and data extraction form. Main inclusion criterion was the enrolment of patients with a mechanical heart valve and intracranial haemorrhage during oral anticoagulant treatment. Any randomised controlled trial, observational cohort study, case series and reports was included. No randomised controlled trials were identified. Six observational cohort studies were included in the final analysis. All studies were of low quality. A total of 120 patients were enrolled. Anticoagulation was restarted within a broad time range (2 days to 3 months). Four ischaemic strokes and two recurrent cerebral haemorrhages occurred after anticoagulation was restarted after a mean follow-up of 7.9 months. Eighteen patients were described in the selected case reports. Anticoagulant therapy was restarted within four days to eight weeks. Two patients had a recurrent haemorrhagic event, and no ischaemic events were reported. In conclusion, restarting oral anticoagulant therapy few days and, indirectly, stopping anticoagulant therapy for a few days (even for 7–14 days) after the occurrence of cerebral haemorrhage are both safe. However, well-designed studies are strongly recommended to provide better evidence.

The 8th American College of Chest Physicians Guidelines – A perspective on venous thromboembolism guidelines

SummaryPost-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Little is known about prognostic factors that might identify patients at high risk for the development of PTS. Body mass index (BMI) has been previously reported to be associated to the development of PTS. The aim of this study was to assess the association between BMI and other anthropometric parameters and PTS in a general population of DVT patients.In a prospective cohort study, 83 consecutive patients with objective diagnosis of DVT underwent physical examination. BMI was recorded at baseline and at 12 months, and waist circumference was recorded at 12 months to assess individual patterns of body fat distribution. The presence of PTS at 12 months was ascertained using a validated clinical scale. Sixty-three patients (75.9%) were overweight or obese at 12 months, 60 (72.3%) had a weight gain over 1 year. Twenty patients developed PTS (24.1%). Mean BMI was significantly higher in patients who developed PTS than in patients who did not (29.6 and 27.2 Kg/m2, respectively, p = 0.022). A BMI of > 28 Kg/m2 predicted early onset of PTS (OR 3.54, 95% CI 1.07-12.08, p = 0.017). Neither patterns of fat distribution nor weight gain in 1 year were correlated with PTS (p = 0.918 and p = 0.775, respectively).BMI is significantly correlated with the development of PTS. Patients with DVT should be encouraged to avoid weight gain. Reducing patient weight might be an important strategy to prevent PTS.

Haemost 2014; 112: 692-699. Historically, hospital-related venous thromboembolism (VTE) has been thought to mainly occur in surgical patients (1). Several phase III randomised controlled trials (RCTs) have investigated benefits and harms of pharmacologic thromboprophylaxis in this setting (1). Subsequently, acutely ill hospitalised medical patients have been recognised to be at increased risk of VTE, with approximately 75% of all VTE-related deaths diagnosed in autopsy studies occurring in non-surgical patients (2). Based on such compelling evidence, a number of RCTs have been carried out which consistently shown the clinical benefit of pharmacologic thromboprophylaxis also in medical inpatients (3, 4). Conversely, 3 phase III RCTs, i.e. EXCLAIM, ADOPT, and MAGELLAN studies, have subsequently failed to support the extended use of thromboprohylaxis beyond the first two weeks of treatment in this setting due to an excess in bleeding rates (5-7). The results of these trials have raised again concerns on the true clinical benefit of anticoagulant prophylaxis in a population that is mainly represented by fragile, elderly patients (8). The widespread existence of these concerns is confirmed by the fact that despite high-quality evidence supporting in-hospital prophylaxis and recommendations from international guidelines, thromboprophylaxis in acutely ill medical inpatients remains substantially underused (9-11). Appropriate patient selection remains a major issue and a number of pitfalls in proposed strategies have been identified. First, the group-specific thromboembolic risk assessment used in the RCTs, that is based on the diagnosis of admission, does not sufficiently take into account the heterogeneity of medical diseases and the role of concomitant patient-specific risk factors; second, immobilisation per se does not represent a sufficient condition for recommending pharmacologic thromboprophylaxis; third, patient bleeding risk has not been adequately addressed and, therefore, used for patient selection (12). The 9th edition of the American College of Chest Physicians (ACCP) guidelines for the first time introduced a new approach to patient selection, based on the application of risk assessment models (RAM) (3). The concept behind RAMs is that VTE risk factors are generally cumulative and the majority of patients hospitalised in medical wards harbour more than one risk factor. The proposed RAM to assess VTE risk for the medical population was the PADUA score, which combines patient specific risk factors (e.g. advanced age, obesity, known thrombophilia, previous VTE) and disease specific risk factors (e.g. cancer, heart failure, respiratory failure, reduced mobility) (13). Although there was no validated RAM to assess the individual risk of bleeding, the guidelines panel proposed to consider the IMPROVE bleeding risk score, yet acknowledging this score is complex and not validated, and therefore suggesting to consider patients to have an excessive risk of bleeding if they had multiple risk factors or one risk factor with the strongest association with bleeding (14). Unfortunately, none of available RAM has been extensively and adequately validated till recently (15). Indeed, the model performance in validation studies is often worse than in development studies (12). In this issue of Thrombosis and Haemostasis, Mahan et al. published the first external validation of any appropriately evidence-derived RAM in acutely ill medical patients (16). They used a large database of 41,486 inpatients from three acute care hospitals to validate the IMPROVE RAM. The seven included VTE risk factors and the assigned points can be summarised by the acronym Im1P3A1C2T2-I1LL2: Immobilisation ≥ 7 days, Previous VTE, Age > 60 years, Cancer, known Thrombophilia, Intensive care / coronary care unit stay, Lower Limb paralysis. In the derivation cohort, a score of 0 to 1 placed patients at low risk of symptomatic VTE (less than 1%), a score of 2 to 3 at moderate VTE risk (1 to 2%), and a score of 4 or more at high VTE risk (> 4.8%) (17). In this study, the incidence of VTE was 0.20% (95% confidence interval [CI] 0.18-0.22), 1.04% (95% CI 0.88-1.25) and 4.15% (95% CI 2.79-8.12) in the low, moderate, and high VTE risk groups, respectively (16). The proportion of patients classified at low, moderate and high VTE risk was 63.3%, 31.1%, and 5.5%, respectively. As the receiver-operating curve was 0.77, we may conclude that another step forward for the correct stratification of VTE risk in medical inpatients has been made. We are only at the beginning of a new era in VTE prevention. As correctly acknowledged by the authors, this external validation study demonstrates a level 2 of evidence for the validation of a RAM, according to McGinn scale (18). An impact analysis remains necessary in order to reach a level 1 of evidence and to use a RAM in a wide variety of settings with confidence that its use can change clinical behaviour and improve patient outcomes. Concomitantly, it is important to perform Invited Editorial Focus

SummaryMany studies showed that the occurrence of cardiovascular and cerebrovascular events exhibits a seasonal and monthly variation. Evidences of a seasonal and monthly variation in the incidence of venous thromboembolism (VTE) are more conflicting. We conducted a systematic review and a meta-analysis of the literature to assess the presence of an infradian rhythm of this disease. MEDLINE and EMBASE databases were searched up to January 2010. Monthly and seasonal variation in the incidence of VTE were analysed. We included studies analysing seasonal or monthly aggregation in the incidence of deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) with an objective diagnosis of VTE. Two authors independently reviewed and extracted data. Seventeen studies for a total of about 35,000 patients were included. Twelve studies analysed the seasonal variation and 10 studies the monthly variation of VTE. Our results showed a significantly increased incidence of VTE in winter (chi-square 146.04, p

SummarySome studies have suggested that high levels of total white blood cell (WBC) count and C-reactive protein (CRP) may be considered as independent prognostic factors in patients with acute coronary syndromes (ACS) and/or after cardiac revascularisation by percutaneous coronary intervention or coronary artery bypass grafting surgery. Evidence on the role of neutrophils in cardiovascular disease is less compelling. Therefore, we conducted a systematic review of the literature with the aim of identifying all the available evidence to clarify the role of neutrophils (absolute or relative count, neutrophil/lymphocyte ratio) as a prognostic risk factor in patients with ACS and/or cardiac revascularisation. All published studies evaluating the role of neutrophils as a risk factor for clinical outcomes were assessed using the MEDLINE and EMBASE databases. Study selection, data extraction and validity assessment was performed independently by two reviewers. Twenty-one studies (17 of which had positive results) for a total of more than 34,000 patients were included. Ten of 13 studies in ACS patients found that neutrophils measured on-admission are related to mortality rate and/or to major adverse clinical events. A predictive value of neutrophils after cardiac revascularisation procedures was reported in seven out of eight studies. Most of the studies showed that neutrophils were independent predictors of cardiovascular outcomes when analysed concomitantly with other markers of inflammation (WBC, CRP). The findings of our systematic review highlight the potential application of this inexpensive and readily available inflammatory marker for risk stratification in patients with ACS and/or cardiac revascularisation.

SummaryProthrombin complex concentrates (PCCs) are recommended as the treatment of choice in warfarin-related coagulopathy. However, the risk of thromboembolic complications associated with their use is not well defined. We performed a meta-analysis to estimate the rate of thromboembolic complications in patients receiving vitamin K antagonists (VKAs) treated with PCCs for bleeding or before urgent surgery. Medline and Embase databases were searched. Two reviewers performed study selection and extracted data independently. Studies providing data on incidence of thromboembolic complications in VKA-treated patients were eligible for the study. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Twenty-seven studies (1,032 patients) were included. Seven studies used 3-factor, and 20 4-factor PCCs. Twelve patients had a thromboembolic complication (weighted mean 1.4%; 95% CI 0.8–2.1), of which two were fatal. The incidence of thromboembolic events was 1.8% (95% CI 1.0–3.0) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0–2.4) in patients treated with 3-factor PCCs. Total mortality rate was 10.6% (95% CI 5.9–16.6). In conclusion, our results suggest there is a low but quantifiable risk of thromboembolism in VKA-treated patients receiving PCCs for anticoagulation reversal. These findings should be confirmed in randomised, controlled trials.

Walter Ageno1; Francesco Dentali1; Alessandro Squizzato1; Trevor Baglin2; James Douketis3; Martin Lansberg4; Maurizio Paciaroni5; Gualtiero Palareti6 1Department of Clinical Medicine, University of Insubria, Varese, Italy; 2Department of Hematology, Cambridge University, Cambridge, UK; 3Department of Medicine, McMaster University, Hamilton, Canada; 4Stanford Stroke Center, Stanford University Medical Center, Palo Alto, USA; 5Department of Vascular Medicine and Stroke Unit, University of Perugia, Perugia, Italy; 6Department of Angiology, University of Bologna, Bologna, Italy

SummaryCurrent strategies for diagnosing pulmonary embolism (PE) include a clinical decision rule (CDR), followed by a D-dimer assay in patients with an unlikely clinical probability. We assessed the implementation of the current guidelines for the diagnosis of PE. A first questionnaire was sent to internists and pulmonologists to assess the proportion of physicians that adequately applied the guidelines. Two versions of a second questionnaire were sent presenting five hypothetical cases of which in two cases with an intermediate clinical probability an abnormal D-dimer test result was added to one version. We assessed the variation of the CDR and compared the proportions of a likely clinical probability between the two versions. A total of 65 physicians responded to the first questionnaire (response rate 75%). Half of the physicians (N=29; 46%) indicated that they use a CDR in all patients and 22 physicians (45%) indicated that they review the D-dimer result after they examined patients. Sixty-two physicians responded on the second questionnaire (response rate 36%). A shift was observed from an unlikely to a likely probability when an abnormal D-dimer test result was added to the clinical information (22% to 41%; p=0.22 and 26% to 50%; p

SummaryResidual venous obstruction (RVO) in patients with previous deep vein thrombosis (DVT) of the lower limbs has been suggested as an independent risk factor for recurrent venous thromboembolism (VTE).RVO could be a marker of a persistent prothrombotic state. We have compared the rate of RVO in patients with DVT and a personal history of at least one previous episode of VTE to the rate of RVO among patients with a first episode of DVT. All patients underwent compression ultrasonography (CUS) of the lower limbs 1 year after index DVT. RVO was arbitrarily defined as a thrombus occupying, at maximal compressibility, more than 20% of the vein area in the absence of compression. 50 consecutive patients with recurrent DVT and 50 age and sex-matched patients with a single episode of DVT were enrolled. The index event was idiopathic in 62% of patients with recurrent DVT and in 60% of patients with a single episode. In 74% of patients with recurrent DVT the index event occurred in either the contralateral leg or in a different segment of the ipsilateral leg. RVO was detected in 50% of patients with a single episode of DVT and in 88% of patients with recurrent DVT (p

SummaryPathophysiological mechanisms of acute vascular thrombosis are not fully understood. It has been suggested that different infectious pathogens are responsible agents of thrombotic disorders. The infection hypothesis is supported by an increasing number of reports on the interaction between acute infection and coagulation. Cytomegalovirus (CMV) is supposed to play an important role in apparently unprovoked thrombosis. We reviewed all human in vitro and in vivo studies on the influence of human CMV infection on the coagulation system, as well as all case reports of acute thrombosis during acute human CMV infection. In the published literature there is mounting evidence that human CMV may play a role in thrombotic disorders. Definitive conclusions, however, cannot be drawn, although the in vitro studies are convincing and offer insight in the pathogenesis.

Post-thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT). Little is known about prognostic factors that might identify patients at high risk for the development of PTS. Body mass index (BMI) has been previously reported to be associated to the development of PTS. The aim of this study was to assess the association between BMI and other anthropometric parameters and PTS in a general population of DVT patients. In a prospective cohort study, 83 consecutive patients with objective diagnosis of DVT underwent physical examination. BMI was recorded at baseline and at 12 months, and waist circumference was recorded at 12 months to assess individual patterns of body fat distribution. The presence of PTS at 12 months was ascertained using a validated clinical scale. Sixty-three patients (75.9%) were overweight or obese at 12 months, 60 (72.3%) had a weight gain over 1 year. Twenty patients developed PTS (24.1%). Mean BMI was significantly higher in patients who developed PTS than in patients who did not (29.6 and 27.2 Kg/m(2), respectively, p = 0.022). A BMI of28 Kg/m(2) predicted early onset of PTS (OR 3.54, 95% CI 1.07-12.08, p = 0.017). Neither patterns of fat distribution nor weight gain in 1 year were correlated with PTS (p = 0.918 and p = 0.775, respectively). BMI is significantly correlated with the development of PTS. Patients with DVT should be encouraged to avoid weight gain. Reducing patient weight might be an important strategy to prevent PTS.

SummaryLow dose oral vitamin K rapidly reverses warfarin-associated coagulopathy. Its effect in patients receiving acenocoumarol is uncertain. We compared the effect of withholding acenocoumarol and administering 1 mg oral vitamin K with simply withholding acenocoumarol in asymptomatic patients presenting with INR values between 4.5 and 10.0. The primary end-point of the study was the INR value on the day following randomisation. We found that patients receiving oral vitamin K had more sub-therapeutic INR levels than controls (36.6% and 13.3%, respectively; RR 1.83, 95% confidence interval 1.16, 2.89) and a lower, but non-significant, proportion of INR values in range (50% and 66.6%, respectively) on the day following randomisation. After 5 ± 1 days, there were more patients with an INR value in range in the vitamin K group than in controls (74.1% and 44.8%, respectively). There were no clinical events during 1 month follow-up. We conclude that the omission of a single dose of acenocoumarol is associated with an effective reduction of the INR in asymptomatic patients presenting with an INR value of 4.5 to 10.0. Furthermore, the use of a 1 mg dose of oral vitamin K results in an excessive risk of overreversal of the INR.

Alessandro Squizzato onderzocht de relatie tussen schildklierziekte, hemostase en klinische manifestaties van trombose en bloedingen. In verschillende studies bewees hij dat een teveel aan schildklierhormoon leidt tot een verhoging van stollingseiwitten en remming van fibrinolyse (het tegenovergestelde van bloedstolling). Oplopende concentraties schildklierhormoon vormen een risicofactor voor het ontstaan van veneuze trombose. Zowel patienten met een te snel werkende schildklier als patienten met een te traag werkende schildklier die recent zijn gestart met medicatie om schildklierhormoon aan te vullen, hebben een verhoogd risico op veneuze trombose. Twee pilotstudies leveren aanwijzingen dat schildklieraandoeningen ook de instelling op antistollingsmedicatie beinvloeden.