-
Felix J M van der Meer
[show abstract]
[hide abstract]
ABSTRACT: Recent meta-analysis has demonstrated that self-management in oral anticoagulant therapy results in fewer thromboembolic complications and a decrease in mortality in comparison to conventional treatment, while the number of bleeding complications remains unchanged. We discuss the importance of these findings for the situation in the Netherlands with its specialized anticoagulation clinics and the possible consequences for the introduction of new anticoagulants like dabigatran and rivaroxaban.
Nederlands tijdschrift voor geneeskunde 01/2011; 155(30-31):A3691.
-
[show abstract]
[hide abstract]
ABSTRACT: Venous thrombosis of the upper extremity is a rare disease. Therefore, not as much is known about risk factors, treatment and the risk of recurrence as for venous thrombosis of the leg. Only central venous catheters and strenuous exercise are commonly known risk factors for an upper extremity venous thrombosis. In this review an overview of the different risk factors, possible treatments and the complications for patients with a venous thrombosis of the upper extremity is given.
Journal of Thrombosis and Haemostasis 06/2008; 6(8):1262-6. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: One of the causes of unstable anticoagulant control in patients using vitamin K antagonists is a fluctuating intake of vitamin K. Research suggests that patients with a low dietary intake of vitamin K have a less stable anticoagulant control than patients with a higher intake.
To study whether supplementation with a low daily dose of vitamin K improves anticoagulant control.
We performed a double-blind, randomized, placebo-controlled trial. 200 patients of the Leiden anticoagulation clinic, who used the vitamin K antagonist phenprocoumon, were randomized to receive either adjusted-dose phenprocoumon and 100 mug vitamin K once daily or adjusted-dose phenprocoumon and a placebo. Treatment duration was 24 weeks. The primary outcome was the percentage of time the International Normalized Ratio was within the therapeutic range.
The time in the therapeutic range was 85.5% in the placebo group and 89.5% in the vitamin K group (adjusted difference 3.6%; 95% CI -0.8% to 8.0%). The time below the therapeutic range was 3.1% in the placebo group and 2.1% in the vitamin K group (adjusted difference -0.7%; 95% CI -2.5% to 1.1%) and the time above the therapeutic range was 11.4% in the placebo group and 8.5% in the vitamin K group (adjusted difference -2.9%; 95% CI -6.9% to 1.1%). The relative risk (RR) of a maximal stability in the vitamin K group compared to the placebo group was 1.8 (95%, CI 1.1-2.7).
Supplementation of vitamin K antagonists with 100 mug vitamin K improves stability of anticoagulant therapy. Because the risk of side effects is inversely related to anticoagulant stability, such an improvement is likely to reduce the number of bleeding and thrombotic events.
Journal of Thrombosis and Haemostasis 11/2007; 5(10):2043-8. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Efforts to improve dosing quality in oral anticoagulant control include the use of computer algorithms. As current algorithms are simplistic and give dosage proposals in a small fraction of patients, we developed an algorithm based on principles of system and control engineering that gives proposals in nearly all patients.Objective: To evaluate the new algorithm in clinical practice.
We conducted a double-blind randomized controlled trial among 712 patients with an indication for long-term anticoagulant treatment at the Leiden Anticoagulation Clinic. We compared oral anticoagulant dosing supported by the new algorithm (ICAD) with the standard algorithm (TRODIS).
The percentage of time spent in the therapeutic range was similar for the new and standard algorithm groups, 79.8% vs. 80.2% (difference 0.4%, 95% CI: -1.7-2.6%). The new algorithm produced a dosage proposal in 97.5% of visits, and the standard algorithm in 60.8% (difference 36.7%, 95% CI: 35.4-38.0%). Of proposals of the new algorithm, 79.3% were accepted by the physician vs. 90.9% for the standard algorithm (difference 11.6%, 95% CI: 10.2-13.0%). This implies that the new algorithm gave an acceptable proposal in 77.4% of all patient visits vs. 55.3% for the standard algorithm (difference 22.1%, 95% CI 20.4-23.8%).
Substantially more dosage proposals were generated and accepted with the new than with the standard algorithm, and the new algorithm will therefore improve the efficiency of anticoagulant monitoring without loss of quality.
Journal of Thrombosis and Haemostasis 09/2007; 5(8):1644-9. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The International Normalized Ratio (INR) target range is a relatively narrow range in which the efficacy of oral anticoagulant treatment, i.e. prevention of extension and recurrence of thrombosis, is balanced with the risk of hemorrhagic complications. Over the years, different INR target ranges have been implemented for individual indications, depending on their thrombotic potential. In most of the studies defining these INR targets, the treatment of the patients was aimed at a certain INR range, but in the analysis no account was taken of the time that the patients spent within this range in reality.
The Leiden Thrombophilia Study (LETS) is a population-based case-control study on risk factors for venous thrombosis, in which many genetic and acquired factors have been investigated. Our aim was to investigate the effect of the quality of the oral anticoagulant therapy for the initial venous thrombosis and its relationship with recurrence of thrombosis. Quality of anticoagulation was defined as the time spent at various INR levels during treatment, and we focused on the effect of sustained intensities above a certain INR in preventing recurrences later on.
Two hundred and sixty-six patients with a total follow-up of 2495 patient-years were studied. The mean duration of the initial anticoagulant therapy was 194.5 days (range 48-4671). During follow-up, 58 recurrences were diagnosed (cumulative recurrence rate of 21.8% over 9 years). The mean INR during initial therapy was 2.90, with 90.3% [95% confidence interval (CI) 88.4-92.3%] of the time being spent above an INR of 2.0, and 39.1% (95% CI 35.5-42.7%) above an INR of 3.0. Patients who spent more time below the target range, or who had a shorter duration of anticoagulation, did not experience a higher risk of recurrence after the initial period of anticoagulation had passed.
Provided that oral anticoagulant treatment is adequately managed, according to international guidelines, recurrent thrombosis cannot be ascribed to variation in the primary treatment. Further attempts to reduce the risk of recurrence should therefore be aimed at identifying other explanatory factors, and subsequently fine-tuning the target ranges.
Journal of Thrombosis and Haemostasis 06/2007; 5(5):931-6. · 5.73 Impact Factor
-
Journal of Thrombosis and Haemostasis 04/2006; 4(3):691-2. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The incidence of venous thrombosis (VT) for cancer patients is increased compared with patients without cancer, but estimations of the incidence for different types of cancer have rarely been made because of the low incidence of various types of cancer. Large registries offer an opportunity to study the risk of VT in large cohorts of cancer patients, which is essential in decisions on prophylactic anti-coagulant treatment.
This cohort study estimates the incidence of VT in cancer patients by using record linkage of a Cancer Registry and an Anticoagulation Clinic database in the Netherlands. Cumulative incidences in patients with different types of malignancies were estimated. We calculated relative risks (RRs) in relation to the presence of distant metastases and treatment.
Tumors of the bone, ovary, brain, and pancreas are associated with the highest incidence of VT (37.7, 32.6, 32.1, and 22.7/1000/0.5 year). Patients with distant metastases had a 1.9-fold increased risk [RRadj: 1.9; 95% confidence interval (CI): 1.6-2.3]. Chemotherapy leads to a 2.2-fold increased risk (RR(adj): 2.2; 95% CI: 1.8-2.7) and hormonal therapy leads to a 1.6-fold increased risk (RRadj: 1.6; 95% CI: 1.3-2.1) compared with patients not using these treatment modalities. Patients with radiotherapy or surgery did not have an increased risk.
We compared the overall incidences of VT in the first half year in our study to the risk of major bleeding as described in the literature. For patients with distant metastases, for several types of cancer, prophylactic anti-thrombotic treatment could be beneficial.
Journal of Thrombosis and Haemostasis 04/2006; 4(3):529-35. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been shown that computerized algorithms for the prescription of coumarin derivates can improve the quality of long-term anticoagulation treatment. These algorithms are usually based on an empiric relationship between dosage and International Normalized Ratio and do not quantify the delaying effect of the drug's pharmacokinetics or the effect of alternating doses that are used to approximate a certain average dosage. Our objective was to develop a mathematical model that takes into account these effects and to develop a new algorithm based on this model that can be used to further optimize the quality of long-term anticoagulation treatment. We simplified a general model structure that was proposed by Holford in 1986 so that the parameters can be estimated using data that are available during long-term anticoagulation treatment. The constant parameters in the model were estimated separately for phenprocoumon and acenocoumarol using data from 1279 treatment courses from three different anticoagulation clinics in the Netherlands. The only variable parameter in the model is the sensitivity of the patient, which is estimated during the course of each treatment. A total of 194 dosage and appointment intervals that were proposed by the new algorithm were scored as 'good', 'acceptable', or 'bad' by two dosing experts. One hundred and seventy-eight (91.8%) proposals were considered good by at least one expert and bad by none. In 39 cases the experts disagreed. We believe that this algorithm will allow further improvement of anticoagulation treatments.
Journal of Thrombosis and Haemostasis 06/2005; 3(5):915-21. · 5.73 Impact Factor
-
C Y Vossen,
J Conard,
J Fontcuberta,
M Makris, F J M VAN DER Meer,
I Pabinger,
G Palareti,
F E Preston,
I Scharrer,
J C Souto,
P Svensson,
I D Walker,
F R Rosendaal
[show abstract]
[hide abstract]
ABSTRACT: Reliable risk estimates for venous thrombosis in families with inherited thrombophilia are scarce but necessary for determining optimal screening and treatment policies.
In the present analysis, we determined the risk of a first venous thrombotic event in carriers of a thrombophilic defect (i.e. antithrombin-, protein C- or protein S deficiency, or factor V Leiden).
The asymptomatic carriers had been tested prior to this study in nine European thrombosis centers because of a symptomatic carrier in the family, and were followed prospectively for 5.7 years on average between March 1994 and January 2001. Annually, data were recorded on the occurrence of risk situations for venous thrombosis and events (e.g. venous thrombosis, death).
Twenty-six of the 575 asymptomatic carriers (4.5%) and seven of the 1118 controls (0.6%) experienced a first deep venous thrombosis or pulmonary embolism during follow-up. Of these events, 58% occurred spontaneously in the carriers compared with 43% in the controls. The incidence of first events was 0.8% per year (95% CI 0.5-1.2) in the carriers compared with 0.1% per year (95% CI 0.0-0.2) in the controls. The highest incidence was associated with antithrombin deficiency or combined defects, and the lowest incidence with factor V Leiden.
The incidence of venous events in asymptomatic individuals from thrombophilic families does not exceed the risk of bleeding associated with long-term anticoagulant treatment in the literature (1-3%).
Journal of Thrombosis and Haemostasis 04/2005; 3(3):459-64. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation.
Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women.
Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4).
If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.
Thrombosis Research 02/2005; 115(5):387-92. · 2.44 Impact Factor
-
C Y Vossen,
J Conard,
J Fontcuberta,
M Makris, F J M Van Der Meer,
I Pabinger,
G Palareti,
F E Preston,
I Scharrer,
J C Souto,
P Svensson,
I D Walker,
F R Rosendaal
[show abstract]
[hide abstract]
ABSTRACT: We started a large multicenter prospective follow-up study to provide reliable risk estimates of venous thrombosis in families with various thrombophilic defects.
This paper describes data collected at study entry on venous events experienced before study inclusion, i.e. the baseline data.
All individuals (probands, relatives) registered in nine European thrombosis centers with the factor (F)V Leiden mutation, a deficiency of antithrombin, protein C or protein S, or a combination of these defects, were enrolled between March 1994 and September 1997. As control individuals, partners, friends or acquaintances of the thrombophilic participants were included. Incidence and relative risk of objectively confirmed venous thrombotic events (VTEs) prior to entry were calculated for the relatives with thrombophilia and the controls.
Of the 846 relatives with thrombophilia (excluding probands), 139 (16%) had experienced a VTE with an incidence of 4.4 per 1000 person years. Of the controls, 15 of the 1212 (1%) controls had experienced a VTE with an incidence of 0.3 per 1000 person years. The risk of venous thrombosis associated with familial thrombophilia was 15.7 (95% CI 9.2-26.8) and remained similar after adjustment for regional and sex-effects (16.4; 95% CI 9.6-28.0). The highest incidence per 1000 person years was found in relatives with combined defects (8.4; 95% CI 5.6-12.2), and the lowest incidence was found in those with the FV Leiden mutation (1.5; 95% CI 0.8-2.6).
Considerable differences in the lifetime risk of VTE were observed among individuals with different thrombophilia defects.
Journal of Thrombosis and Haemostasis 10/2004; 2(9):1526-32. · 5.73 Impact Factor
-
C Y Vossen,
F E Preston,
J Conard,
J Fontcuberta,
M Makris, F J M van der Meer,
I Pabinger,
G Palareti,
I Scharrer,
J C Souto,
P Svensson,
I D Walker,
F R Rosendaal
[show abstract]
[hide abstract]
ABSTRACT: As the placental vessels are dependent on the normal balance of procoagulant and anticoagulant mechanisms, inherited thrombophilia may be associated with fetal loss.
We performed a prospective study to investigate the relation between inherited thrombophilia and fetal loss, and the influence of thromboprophylaxis on pregnancy outcome.
Women were enrolled in the European Prospective Cohort on Thrombophilia (EPCOT). These included women with factor (F)V Leiden or a deficiency of antithrombin, protein C or protein S. Controls were partners or acquaintances of thrombophilic individuals. A total of 191 women (131 with thrombophilia, 60 controls) had a pregnancy outcome during prospective follow-up. Risk of fetal loss and effect of thromboprophylaxis were estimated by frequency calculation and Cox regression modelling.
The risk of fetal loss appeared slightly increased in women with thrombophilia without a previous history of fetal loss who did not use any anticoagulants during pregnancy (7/39 vs. 7/51; relative risk 1.4; 95% confidence interval 0.4, 4.7). Per type of defect the relative risk varied only minimally from 1.4 for FV Leiden to 1.6 for antithrombin deficiency compared with control women. Prophylactic anticoagulant treatment during pregnancy in 83 women with thrombophilia differed greatly in type, dose and duration, precluding solid conclusions on the effect of thromboprophylaxis on fetal loss. No clear benefit of anticoagulant prophylaxis was apparent.
Women with thrombophilia appear to have an increased risk of fetal loss, although the likelihood of a positive outcome is high in both women with thrombophilia and in controls.
Journal of Thrombosis and Haemostasis 05/2004; 2(4):592-6. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Oral anticoagulant therapy (OAT) implies frequent blood checks and dose changes to prevent thromboembolic or hemorrhagic complications. This may interfere with patients' social and working circumstances in addition to the possible stress caused by the condition necessitating this treatment. We studied whether patient self-management could be a way to improve quality of life in these patients.
Within a multicenter randomized study performed by two Dutch anticoagulation clinics, designed to study the effect on treatment quality (time within target range) of different modalities of patient self-management, we looked at the effect of increased patient education (n = 28), self-monitoring of the International Normalized Ratio (INR) (n = 47) and full patient self-management (INR monitoring and dosing of the OAT) (n = 41) on the quality of life of the patients. This was done with the aid of a written questionnaire (32 questions, minimum score = 1, maximum score = 6) at baseline (n = 163), and after 26 weeks (n = 118). We compared the results after 26 weeks with those at baseline, as well as between groups.
General treatment satisfaction was already high under routine care (5.11 on a scale of 1-6) and increased further through self-monitoring of the INR (+0.19) and full self-management (+0.32). Distress (-0.44), perceived daily hassles (-0.31) and strain on the social network (-0.21) were reduced through full self-management. Improved patient education was associated with increased distress (+0.33) and perceived daily hassles (+0.23). Comparison at 26 weeks between groups showed similar improvements on these outcomes for self-monitoring and self-management vs. routine care after education.
Journal of Thrombosis and Haemostasis 05/2004; 2(4):584-91. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Several studies have demonstrated that patient self-management of oral anticoagulant therapy (OAT) can improve treatment quality. However, most of these studies were not conducted within a specialized anticoagulation care system. The objective of the present study was to determine whether patient self-management of OAT improves the quality of care delivered by anticoagulation clinics.
In this randomized study by 2 Dutch anticoagulation clinics 341 patients aged between 18 and 75 years and receiving long-term OAT were divided into 4 groups: an existing routine care group of patients untrained in self-management; a routine care group of trained patients; a group managed weekly at an anticoagulation clinic where international normalized ratios were measured by trained patients; and weekly patient self-management. A 2-step randomization procedure was followed: first, a Zelen-design randomization was performed to distribute patients (without informing them) to the existing care group or to receive training in self-management; second, trained patients were randomized to the 3 other study groups.
Only 25.6% of invited patients agreed to participate in the training program. Patients who remained in the existing care group were within the international normalized ratio target range 63.5% of the time. The type of coumarin taken was a major predicting factor of OAT quality. In all study groups phenprocoumon outperformed acenocoumarol by 11.6% (95% confidence interval [CI], 6.6%-16.5%). Weekly management with phenprocoumon led to a 6.5% improvement (95% CI, 0.0%-13.1%) in time in the international normalized ratio target range when patients were managed at an anticoagulation clinic and to an 8.7% improvement (95% CI, 1.6%-15.9%) when patients were self-managed. Weekly management with acenocoumarol did not improve the quality of OAT.
With selected patients, the quality of OAT obtained through patient self-management is at least as high as that delivered by specialized physicians at anticoagulation clinics. Weekly management of OAT with long-acting phenprocoumon has to be preferred at anticoagulation clinics or, where possible, through patient self-management.
Archives of Internal Medicine 12/2003; 163(21):2639-46. · 11.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the clinical features associated with histologically proven rheumatoid vasculitis (HRV) and the additional diagnostic value of serological markers in an inception cohort of 81 patients with rheumatoid arthritis (RA) suspected of RV.
The presence and number of recently developed extra-articular manifestations (EAMs) and a weighted EAM score, as well as the levels of serological markers, were compared between 31 patients with RA with histologically proven vasculitis and 50 patients with RA in whom vasculitis could not be documented histologically. The following markers were evaluated: circulating immune complexes, complement components C3 and C4, class-specific rheumatoid factors (IgM RF, IgG RF, IgA RF), antineutrophil cytoplasmic antibodies, antinuclear antibodies, antiendothelial antibodies, circulating intercellular adhesion molecule-1 and -3, circulating vascular cell adhesion molecule and E-selectin, cellular fibronectin, von Willebrand factor antigen, and C reactive protein. The diagnostic value of these markers, in addition to the clinical features, was evaluated with logistic regression analysis.
Peripheral neuropathy or purpura/petechiae, or both, were the most important clinical features to discriminate patients with RA with and without histologically proven RV. The presence of a high number of EAMs and a higher weighted EAM score in patients with RA suspected of vasculitis were also associated with an increased probability of histologically proven RV. After adjustment for EAMs, only the combination of an increased serum IgA RF level and a decreased serum C3 level appeared to make an additional contribution to the diagnosis histologically proven RV. Evidence of systemic vasculitis was found in a muscle biopsy of the rectus femoris in 9/14 (64%) patients with vasculitis with neuropathy and in 3/11 (27%) patients with purpura/petechiae and vasculitis of the skin.
In the diagnostic process of RV the presence of peripheral neuropathy and/or purpura/petechiae or a high weighted EAM score will increase the probability of histologically proven RV. Of the circulating factors previously suggested to be markers for RV only IgA RF and C3 further increase the probability of histologically proven RV and may be useful to guide diagnostic decisions.
Annals of the Rheumatic Diseases 06/2003; 62(5):407-13. · 8.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Paracetamol (acetaminophen) is routinely advised when non-steroidal anti-inflammatory drugs (NSAID) are necessary during oral anticoagulant treatment (OAT) because it has no relevant effect on the primary hemostasis. However, in a recent case-control study a dose-related effect was observed of paracetamol intake on the International Normalized Ratio (INR) values making its use controversial during OAT. Our objectives were to determine the effect of paracetamol on the INR values during OAT independent of underlying illness. A double-blind randomized controlled trial in which 31 out-patients on coumarin oral anticoagulant therapy with phenprocoumon, aged 18-70 years, with a planned treatment duration of more than 12 weeks, and an INR target range of 2.5-3.5, were included. Patients were randomized for placebo (10 patients), paracetamol 1500 mg daily (11 patients) or paracetamol 3000 mg daily (10 patients) for 14 days during the stable phase of coumarin OAT and INR values at day 1, 8, 15, 22 and 29 were measured. At day 8 a mean rise of 0.46 INR was seen in both paracetamol groups compared to placebo. At day 15 there was no difference between placebo and paracetamol 1500 mg daily, and a small mean rise of 0.22 INR in the paracetamol 3000 mg daily group. The sustained use of paracetamol (acetaminophen) during oral anticoagulant therapy in itself does not provoke clinically relevant INR changes. Any important INR rise will predominantly be the result of the illness necessitating the intake of this medication. A difference has to be made between those patients taking paracetamol (acetaminophen) for pain relief or as an antipyretic during infectious diseases.
Journal of Thrombosis and Haemostasis 05/2003; 1(4):714-7. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: ObjectiveRecently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation.MethodsPlasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women.ResultsMean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0–8.7) or without hypertension (OR 2.0, CI 0.7–6.4).ConclusionIf the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.
Thrombosis Research.
-
Journal of Thrombosis and Haemostasis, 4(3), 529 - 535 (2006).
-
C Y Vossen,
I D Walker,
P Svensson,
J C Souto,
I Scharrer,
F E Preston,
G Palareti,
I Pabinger, F J M van der Meer,
M Makris,
J Fontcuberta,
J Conard,
F R Rosendaal
Arteriosclerosis Thrombosis and Vascular Biology, 25(9), 1992 - 1997 (2005).
