Clinical probability assessment and D-dimer determination in patients with suspected deep vein thrombosis, a prospective multicenter management study

Objectives

To investigate the reliability of a combined strategy of clinical assessment score followed by a local D-dimer test to exclude deep vein thrombosis. For comparison D-dimer was analysed post hoc and batchwise at a coagulation laboratory.

Design

Prospective multicenter management study.

Setting

Seven hospitals in southern Sweden.

Subjects

357 patients with a suspected first episode of deep vein thrombosis (DVT) were prospectively recruited and pre-test probability score (Wells score) was estimated by the emergency physician. If categorized as low pre-test probability, D-dimer was analysed and if negative, DVT was considered to be ruled out. The primary outcome was recurrent venous thromboembolism (VTE) during 3 months of follow up.

Results

Prevalence of DVT was 23.5% (84/357). A low pre-test probability and a negative D-dimer result at inclusion was found in 31% (110/357) of the patients of whom one (0.9%, [95% CI 0.02-4.96]) had a VTE at follow up. Sensitivity, specificity, negative predictive value and negative likelihood ratio for our local D-dimer test in the low probability group were 85.7%, 74.5%, 98.2%, and 0,19 respectively compared to 85.6%, 67,6%, 97.9% and 0,23 using batchwise analysis at a coagulation laboratory.

Conclusion

Pre-test probability score and D-dimer safely rule out DVT in about 30% of outpatients with a suspected first episode of DVT. One out of 110 patients was diagnosed with DVT during follow up. No significant difference in diagnostic performance was seen between local D-dimer test and the post hoc batch analysis with the same reagent in the low probability group.     

The incidence of deep vein thrombosis in women undergoing cesarean delivery

Introduction

Venous thromboembolism (VTE) is one of the leading causes of maternal mortality in the United States. Cesarean delivery is a known risk factor. This study was to determine the incidence of deep vein thrombosis (DVT) post cesarean delivery.

Materials and Methods

This was a prospective cohort study where two patients having undergone cesarean delivery each day were randomly selected. A lower extremity compression ultrasound was performed prior to hospital discharge. If no DVT was detected, participants were asked to return for a second ultrasound two weeks postpartum. Participants were also telephone-interviewed at three months for reported VTE.

Results

Of the 194 patients who consented to study participation, only one participant developed DVT after cesarean delivery, giving an overall incidence of 0.5% (95% CI, 0.1 to 2.8%). There were no DVT identified on the second ultrasound nor VTE reported 3 months postpartum.

Conclusions

We found the DVT rate after cesarean delivery to be 0.5%.     

Factor VIII contributes to platelet-fibrin thrombus formation via thrombin generation under low shear conditions

Introduction

Thrombus growth under low blood flow velocity plays an important role in the development of deep venous thrombosis (DVT). Increased plasma levels and activities of coagulation factor VIII (FVIII) comprise risk factors for DVT and pulmonary thromboembolism.

Objective

To localize FVIII in human venous thrombi of DVT and to determine whether FVIII contributes to thrombus formation under low shear conditions.

Methods

The localization of FVIII in venous thrombi obtained from patients with DVT was examined by immunohistochemistry. The role of FVIII in thrombus formation was investigated using a flow chamber system. Venous blood from healthy volunteers were incubated with an anti-FVIII monoclonal antibody (VIII-3776) or non-immunized mouse IgG₁. Blood samples were perfused on immobilized type III collagen at wall shear rates of 70/s and 400/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1+2 (PF1+2) generation was measured before and after perfusion.

Results

Venous thrombi of DVT comprised a mixture of platelets, fibrin and erythrocytes. Factor VIII appeared to be colocalized with glycoprotein IIb/IIIa, fibrin and von Willebrand factor in the thrombi. VIII-3776 specifically recognized the light chain of FVIII and prolonged the activated partial thromboplastin time (aPTT), but not prothrombin time (PT). The antibody significantly reduced platelets and fibrin covering, as well as PF1+2 generation at wall shear rates of 70/s and 400/s.

Conclusions

These results suggest that FVIII contributes to platelet aggregation and fibrin formation via thrombin generation under low shear conditions.     

The G534E-polymorphism of the gene encoding the Factor VII-activating protease is a risk factor for venous thrombosis and recurrent events

Introduction

A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinical role has so far been controversial in part due to small cohort sizes. The aim of the present case-control study was to elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the development of venous thromboembolic disease (VTE) with other known sequence variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963).

Materials and Methods

The study included 891 patients (312 male and 579 female) with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 1283 healthy blood donors with no history of venous thromboembolic disease.

Results

We found that besides to the well-established aforementioned sequence variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95% CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95% CI)). Comparing patients displaying one or more events FSAP-MI was still associated with the development of recurrent thromboembolic events (1.64 (1- 2.69) OR (95% CI)).

Conclusions

We conclude that FSAP Marburg-I genotyping may be used to determine the risk for thromboembolic disorders in patients with suspected thrombophilia and known DVT or PE.     

Depressive symptoms, perceived social support, and prothrombotic measures in patients with venous thromboembolism

Introduction

Psychosocial factors have been associated with both a prothrombotic state and an increased risk of venous thromboembolism (VTE). We examined the relation of depressive symptoms and social support with D-dimer, an integrative measure of enhanced coagulation activity, and several additional prothrombotic measures in patients with VTE.

Methods

We studied 173 patients with a previous deep venous thrombosis and/or pulmonary embolism (mean age ± SD 45 ± 14 years, 55% men). Clinical and lab assessments took place ≥ 3 months after VTE and ≥ 1 month after discontinuation of oral anticoagulants. The patients rated depressive symptoms and social support by validated questionnaires.

Results

After adjusting for sociodemographic and medical covariates, interactions emerged between depressive symptoms and social support for D-dimer (p = 0.012) and aPTT (p = 0.002). As opposed to patients with high levels of social support, those with low levels of social support showed a direct association of depressive symptoms with D-dimer (r = 0.19, p = 0.014) and an inverse relationship with aPTT (r = -0.14, p < 0.09). Depressive symptoms were associated with levels of thrombin-antithrombin complex (r = 0.19, p = 0.016). Greater social support was associated with prolonged aPTT (r = 0.16, p = 0.046). There were no significant associations of depressive symptoms and social support with D-dimer, fibrinogen, FII:C, FV:C, FVII:C, FVIII:C, FX:C, INR, and thrombin time.

Conclusions

Depressive symptoms are associated with enhanced coagulation activity in patients with VTE, particularly so in those who perceive low levels of social support. Conversely, high levels of social support may contribute directly and through buffering the effect of depressive symptoms to attenuated clotting activity in VTE patients.     

Association of blood transfusion and venous thromboembolism after colorectal cancer resection

Introduction

Red blood cell (RBC) transfusion is a common event in the perioperative course of patients undergoing surgery. Transfused blood can disrupt the balance of coagulation factors and modulates the inflammatory cascade. Since inflammation and coagulation are tightly coupled, we postulated that RBC transfusion may be associated with the development of venous thromboembolic phenomena. We queried the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) database to examine the relationship between intraoperative blood transfusion and development of venous thromboembolism (VTE) in patients undergoing colorectal resection for cancer.

Materials and Methods

We analyzed the data from 2005 to 2009 for patients undergoing colorectal resections for cancer based on the primary procedure CPT-4 code and operative ICD-9 diagnosis code. The primary outcome was 30-day deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Intraoperative transfusion of RBC's was categorized as: none, 1-2 units, 3-5 units and 6 units or more. DVT/PE occurrences were analyzed by multivariable forward stepwise regression (p for entry < .05, for exit > .10) to identify independent predictors of DVT.

Results

The database contained 21943 colorectal cancer resections. The DVT rate was 1.4% (306/21943) and the PE rate was 0.8% (180/21943). Patients were diagnosed with both only 40 times and the combined DVT or PE rate (VTE) was 2.0% (446/21943). After adjusting for age, gender, race, ASA (American Society of Anesthesiologists) class, emergency procedure, operative duration and complexity of the procedure (based on Relative Value Units, RVU's), along with six clinical risk factors, intraoperative blood transfusion was a significant risk factor for the development of VTE and the risk increased with increasing number of units transfused. Preoperative hematocrit did not enter the multivariable model as an independent predictor of VTE, nor did open versus laparoscopic resection or wound class.

Conclusion

In this study of 21943 patients undergoing colorectal resection for cancer, blood transfusion is associated with increased risk of VTE. Malignancy and surgery are known prothrombotic stimuli, the subset of patients receiving intraoperative RBC transfusion are even more at risk for VTE, emphasizing the need for sensible use of transfusions and rigorous thromboprophylaxis regimens.     

Thromboprophylaxis following cesarean delivery: one site prospective pilot study to evaluate the application of a risk score model

Background

Venous thromboembolism (VTE) remains an important cause of maternal mortality and morbidity. Cesarean delivery (CD) is a known risk factor for VTE. Data from clinical trials of thomboprophylaxis following CD are lacking and current guidelines are based on experts opinion. Our aim was to assess the efficacy of a risk score model, established at our institution, in preventing CD-related VTE.

Methods

Before undergoing CD women received a risk score assessment based on age, weight, history of thrombosis, thrombophilia, immobility, parity and varicose vein. Women at moderate-high risk received pharmacological prophylaxis; all patients wore antithrombotic stockings. They had a visit before discharge and were advised to come back for visit and ultrasound if required. All received a follow-up phone call after three months.

Results

501 consecutive women were included in the study; 233 (46.5%), at low risk, had no pharmacological prophylaxis; one of them developed a symptomatic leg deep vein thrombosis (DVT); 268 (53.5%), at moderate-high risk, received enoxaparin and none of them developed VTE. Two were lost at follow up. The incidence of DVT was 1/499 (0.2%; 95%CI 0-1.1%). The differences in major and minor bleeding were not significant between women who received or not prophylaxis respectively (1/267 vs 1/232, p = 1 and 3/267 vs 1/232, p = 0.62).

Conclusions

The risk score model applied proved effective in avoiding pharmacological prophylaxis in almost half of women and safe, since the rate of failure resulted very low (0.2%, C.I.95 0-1.1%) and there were not significant differences in bleeding in the two groups.     

Incidence and time course of asymptomatic deep vein thrombosis with fondaparinux in patients undergoing total joint arthroplasty

Introduction

There are many reports concerning fondaparinux prophylaxis of asymptomatic deep vein thrombosis (DVT) after total hip arthroplasty (THA) or total knee arthroplasty (TKA), but little is known about the time course of aymptomatic DVT development during the administration of fondaparinux. The aim of the present study was to define the incidence and time course of aymptomatic DVT development during administration of fondaparinux, and to assess the efficacy of fondaparinux in resolving DVT.

Materials and Methods

We studied consecutive71 patients who underwent THA surgery, and 30 patients who underwent TKA surgery with fondaparinux prophylaxis. Patients received once-daily subcutaneous injections of 2.5 mg of fondaparinux for 14 days after surgery. DVT was diagnosed by ultrasonography, and it was scheduled on the day of surgery on day 1, day 4, and day 14 after surgery.

Results

In patients who received fondaparinux for 14 days after THA surgery, the incidence of DVT was 0% on the day of the surgery, 13.6% at day 1, 27.1% at day 4, and 11.9% at day 14. In patients who received fondaparinux for 14 days after TKA surgery, the incidence of DVT was 4.2% on the day after surgery, 50.0% at day 1, 58.3% at day 4, and 20.8% at day 14. The incidence of DVT after THA or TKA surgery at day 14 was significantly reduced compared to that at day 4.

Conclusion

The incidence of asymptomatic DVT up to day 4 was high, but with 14 days continued treatment of fondaparinux, the incidence of asymptomatic DVT occurring at postoperative day 4 was significantly reduced at day 14.     

Detection of endogenous tissue factor levels in plasma using the calibrated automated thrombogram assay

Background

The calibrated automated thrombogram (CAT) assay measures thrombin generation in plasma.

Objective

Use the CAT assay to detect endogenous tissue factor (TF) in recalcified platelet-rich plasma (PRP) and platelet-free plasma (PFP).

Methods

Blood from healthy volunteers was collected into citrate and incubated at 37 °C with or without lipopolysaccharide (LPS) for 5 hours. PRP and PFP were prepared and clotting was initiated by recalcification. Thrombin generation was measured using the CAT assay.

Results

The lag time (LT) was significantly shortened in PRP prepared from LPS-treated blood compared with untreated blood (10 ± 3 min versus 20 ± 6 min), and this change was reversed by the addition of inactivated human factor VIIa. LPS stimulation did not change the peak thrombin. Similar results were observed in PFP (21 ± 4 min versus 35 ± 5 min). LPS stimulation also significantly reduced the LT of PRP and PFP derived from blood containing citrate and a factor XIIa inhibitor. Finally, a low concentration of exogenous TF shortened the LT of PFP prepared from unstimulated, citrated blood without affecting the peak thrombin.

Conclusion

Changes in LT in the CAT assay can be used to monitor levels of endogenous TF in citrated plasma.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.     

Incidence and characteristics of asymptomatic distal deep vein thrombosis unexpectedly found at admission in an Internal Medicine setting

Introduction

Lower limb deep vein thrombosis (DVT) is the most frequent clinical manifestation of venous thromboembolism (VTE) and can involve proximal or distal veins. Distal DVT (dDVT) is often asymptomatic and data about its incidence and prognosis are scanty, especially in high risk medical inpatients. Therefore, no consensus exists on the value of detecting and treating dDVTs. Aim of study was to evaluate incidence and characteristics of asymptomatic isolated dDVT at admission in an Internal Medicine department.

Materials and methods

Consecutive patients hospitalized for acute medical illnesses, in whom VTE was not the admission diagnosis, underwent Doppler Ultrasonography. For all patients with dDVT standard treatment with therapeutic doses of low molecular weight heparin or fondaparinux was proposed. Follow-up visits were scheduled at 1, 6 and 12 weeks.

Results

One-hundred-fifty-four patients were enrolled. In 4.5% a proximal DVT and in 16.2% an asymptomatic dDVT were found. Female sex, elevated age and renal and electrolyte abnormalities were significantly associated to dDVT (p = 0.014, p = 0.009 and p = 0.046, respectively). Only low degree of mobility (LDM) was independently associated to dDVT [OR 7.97 (95%CI 2.42-26.27), p = 0.001)]. A high mortality rate, not for VTE-related causes, was found, especially in the first week, among dDVT patients.

Conclusions

We found a high incidence of clinically silent dDVTs. LDM evaluation could be useful to select patients at high risk in whom to perform a search for dDVT.     

Venous thromboembolism risk assessment and thromboprophylaxis among hospitalized acute medical patients in China - the RAMP study

Background

In developed countries, hospitalized patients with acute medical conditions are at significant risk for venous thromboembolism (VTE). Little is known about VTE risk and prophylaxis practices in China.

Objective

To determine the VTE risk and the frequency of recommended VTE prophylaxis in hospitalized Chinese patients with acute medical conditions.

Methods

Multi-center, cross-sectional, observational study. Eligibility criteria: ≥ 30 years, admitted to an intensive care unit (ICU)/coronary care unit (CCU) for acute medical illness, had ≥ 1 VTE risk factor/1 disease that predisposes to VTE, and provided informed consent. We used 2004 American College of Chest Physicians (ACCP) evidence-based consensus guidelines to assess VTE risk and the frequency of recommended VTE prophylaxis.

Results

1247 patients from 19 hospitals in 11 cities across 11 provinces of China were enrolled from July 2007 to June 2008. 57.3% patients had > 2 VTE risk factors. Only 20.2% received ACCP-recommended VTE prophylaxis (CCU patients: 22.7%, ICU patients: 16.9%, p = 0.0117).

Limitations

Excluding some patients with VTE risk factors did not allow assessment of the prevalence of VTE risk in the acute hospital-care setting. We could not determine whether the duration of prophylaxis complied with the ACCP recommendations. Our results may not be representative of hospitals in small cities/rural areas in China.

Conclusions

The prevalence of VTE risk factors in Chinese patients was similar to that in developed countries; however, only a small proportion of eligible patients received the recommended VTE prophylaxis. Our findings highlight the need for dissemination and implementation of appropriate VTE prophylaxis guidelines in China.     

Activation of coagulation in amniotic fluid during normal human pregnancy

Introduction

Amniotic fluid (AF) is an important medium for fetal development which exhibits high procoagulant activities; however, the role of these procoagulants during pregnancy has not been elucidated and might be associated with pregnancy complications. The current study aimed to evaluate factor X (FX) activation and its association with tissue factor (TF), tissue factor pathway inhibitor (TFPI) and coagulation activation markers in AF during normal human pregnancy.

Methods

Activation of FX and concentration of TF, free TFPI, D-dimer and prothrombin fragments (F1 + 2) were evaluated in AF samples obtained for chromosome analysis from 91 women with normal pregnancy: 65 samples were taken from patients at 16-20 weeks of gestation, 9 samples were drawn at 21-30 weeks and 17 samples−after 30 weeks of gestation.

Results

Activation of FX in AF significantly increased during normal pregnancy (from 65 ± 41 to 205 ± 80 equivalent RVV ng/mg total protein, P < 0.0001). TF and TFPI levels in AF also rose with gestational age. In contrast, the AF concentration of D-dimer and F1 + 2, markers of coagulation activation significantly decreased when expressed per mg total protein. Levels of free TFPI correlated with TF (r = 0.5, P < 0.001), and were 8-fold higher than those of TF during pregnancy.

Conclusion

High levels of TFPI might be associated with the inhibition of procoagulant activity in amniotic fluid during normal pregnancy, which may account for the rarity of clinical amniotic fluid embolism.     

Plasma factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular events

Introduction

More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events.

Materials and Methods

We studied (1) 100 patients with acute ischemic stroke (n = 50) or transient ischemic attack (TIA) (n = 50) within the first 24 hours from symptom onset, and (2) 100 individuals 1 to 4 years following ischemic stroke (n = 50) or TIA (n = 50). The tissue factor pathway to thrombin generation was simulated with a mathematical model using plasma levels of clotting factors (F)II, V, VII, VIII, IX, X, antithrombin and free tissue factor pathway inhibitor (TFPI).

Results

The plasma levels of free TFPI, FII, FVIII, and FX were higher, while antithrombin was lower, in the acute patients compared to the previous event group (all p ≤ 0.02). Thrombin generation during acute events was enhanced, with an 11% faster maximum rate, a 15% higher maximum level and a 26% larger total production (all p < 0.01). The increased thrombin generation in acute patients was determined by higher FII and lower antithrombin, while increased free TFPI mediated this effect. When the groups are classified by etiology, all stroke sub-types except cardioembolic have increased TFPI and decreased AT and total thrombin produced.

Conclusion

Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors.     

Etiology and VTE risk factor distribution in patients with inferior vena cava thrombosis

Introduction

Inferior vena cava (IVC) thrombosis is a rare event and data detailing the underlying etiology are scarce.

Materials and methods

Therefore, we reviewed all available cases of IVC thrombosis consecutively registered in the MAISTHRO (MAin-ISar-THROmbosis) database and described the prevalence of VTE risk factors and other conditions contributing to IVC thrombosis development.

Results

53 patients (35 F, 18 M) with IVC thrombosis aged 12 to 79 years were identified. 40 patients (75.5%) developed thrombosis under the age of 45. Local problems, such as IVC anomalies or external venous compression, contributed to the development of thrombosis in 12 cases (22.6%). Lupus anticoagulants (10.9 vs. 2.3%, p = 0.013) and malignoma (17.0 vs. 6.4%, p = 0.023) were more prevalent in IVC thrombosis patients compared to 265 age and sex matched controls with isolated lower extremity DVT. No difference was identified with regard to inherited thrombophilia or other known VTE risk factors. Symptomatic pulmonary embolism (PE) occurred in 32.1% of IVC thrombosis patients compared to 15.2% of controls (p = 0.005).

Conclusions

Local problems such as IVC anomalies and external venous compression, malignancy and the presence of lupus anticoagulants contribute to the risk of IVC thrombosis. The risk of symptomatic pulmonary embolism in the acute setting is high.     

Safety profile of tinzaparin versus subcutaneous unfractionated heparin in elderly patients with impaired renal function treated for acute deep vein thrombosis: the Innohep® in Renal Insufficiency Study (IRIS)

Introduction

Trials comparing the use of full dose unfractionated heparin (UFH) or low molecular weight heparins (LMWHs) in very elderly patients with impaired renal function are lacking. IRIS aimed to assess whether LMWH is at least as safe as UFH in this population.

Materials and methods

The study included renally impaired patients ≥ 70 years with acute symptomatic lower limb deep vein thrombosis (DVT). Patients were randomized to initial treatment with either tinzaparin 175 IU/kg once daily (n = 269) or activated partial thromboplastin time-adjusted UFH twice daily (n = 270). After acute management both groups received vitamin K antagonist to day 90.

Results

The trial was stopped prematurely due to a difference in mortality favoring the UFH group (11.5 vs. 6.3%; p = 0.035). Rates of clinically relevant bleedings by day 90 were similar in the tinzaparin (11.9%) and UFH (11.9%) groups, as were rates of confirmed recurrent venous thromboembolism (VTE) (2.6 vs. 1.1%; p = 0.34). As the mortality difference could not be explained by bleedings or recurrent VTE, a post-hoc analysis was performed. This identified six baseline characteristics significantly correlated with mortality, of which five were over-represented in the tinzaparin group.

Conclusion

The IRIS study was a challenging study involving patients (mean age 83 years) usually excluded from clinical studies, but its early termination has left questions unanswered. The mortality difference observed with tinzaparin vs. UFH in elderly, renally-impaired patients with DVT cannot be explained on the basis of bleedings or recurrent VTE, and may reflect an imbalance of mortality risk factors at baseline.     

Thrombomodulin is required for the antithrombotic activity of thrombin mutant W215A/E217A in a mouse model of arterial thrombosis

Introduction

The thrombin mutant W215A/E217A (WE thrombin) has greatly reduced procoagulant activity, but it activates protein C in the presence of thrombomodulin and inhibits binding of platelet glycoprotein Ib to von Willebrand factor and collagen under flow conditions. Both thrombomodulin-dependent protein C activation and inhibition of platelet adhesion could contribute to the antithrombotic activity of WE thrombin.

Materials and methods

To assess the role of thrombomodulin, we administered WE thrombin to thrombomodulin-deficient (TM^Pro/Pro) mice and measured the time to occlusive thrombus formation in the carotid artery after photochemical injury of the endothelium.

Results and conclusions

Doses of WE thrombin ≥ 10 μg/kg prolonged the thrombosis time of wild-type mice (> 1.6-fold), while doses ≥ 100 μg/kg only slightly prolonged the thrombosis time of TM^Pro/Pro mice. We conclude that thrombomodulin plays a predominate role in mediating the antithrombotic effect of WE thrombin in the arterial circulation of mice after endothelial injury. Thrombomodulin-independent effects may occur only when high doses of WE thrombin are administered.     

Thromboembolic complications in membranous nephropathy patients with nephrotic syndrome-a prospective study

Background

Venous thromboembolism (VTE) is one of the most serious complications in membranous nephropathy (MN). We investigate the incidence of VTE in MN patients with nephrotic syndrome (NS).

Methods

A total of 100 MN patients with NS were enrolled into this prospective study. The diagnosis of VTE was based on contrast-enhanced dual source computed tomography angiography.

Results

Venous thromboembolism was demonstrated in 36 patients (36%). 33 patients (33%) had renal vein thrombosis (RVT), 17 patients (17%) had pulmonary embolism (PE).　Flank pain was noted in 5 patients and gross hematuria in 2 patients with RVT. Dyspnea and chest pain were present in 9 patients with PE. The positive predictive value for D-dimer level was 69.4%, negative predictive value for D-dimer level was 96.1% in patients with MN. Of all the risk factors presented, D-dimer level, proteinuria, the ratio of proteinuria to serum albumin were independent risk factors for the development of VTE (P < 0.05), but the plasma level of antithrombin Ш was not correlated with VTE in this study. In follow up, venous thrombosis disappeared after anticoagulant treatment with low-molecular-weight heparins in 28 patients.

Conclusion

Venous thromboembolism was confirmed in 36% of MN patients with NS. Renal vein thrombosis and pulmonary embolism are common and usually asymptomatic. Computed tomography angiography can be used effectively to examine suspected patients. Measurement of D-dimer is helpful in VTE diagnosis. It is important that clinicians are aware that VTE should be considered as a common complication in MN patients with NS.     

Family history as a risk factor for venous thromboembolism

Introduction

There are very few data assessing a family history of venous thromboembolism (VTE) as a risk factor for VTE. This question is nonetheless of interest as inherited risk factors are involved but at least partly unknown.

Methods

The E.D.I.TH. study is a prospective hospital-based case-control study. The family history was assessed by using a standard questionnaire, considering the total number of the first-degree relatives and the number of these relatives who had suffered from VTE. We analysed 698 first VTE cases and their matched controls, 507 pairs without and 191 pairs with a major acquired risk factor (active malignancy, surgery or plaster cast in the past three months, pregnancy or delivery in the past three months).

Results

A family history of VTE was associated with VTE occurrence, irrespective of carrying or not factor V Leiden mutation or G20210A prothrombin gene mutation and irrespective of the presence or absence of major acquired risk factors; adjusted conditional odds ratio: 2.7 (95%CI, 1.8-3.8).

Conclusion

A family history might well be considered when estimating type and duration of prophylaxis for VTE specifically in patients with active cancer or who experienced surgery. Family history of VTE could be added to a prior VTE history to define a concept of clinical thrombophilia which is not necessarily related to carrying a known inherited risk factor.