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F W G Leebeek

Publications and source records attributed to F W G Leebeek.

At least 19 recordsLinked to original sources
PubMed2006

Hepatocyte-derived fibrinogen-related protein-1 is associated with the fibrin matrix of a plasma clot.

In order to study the multiple functions of fibrinogen and fibrin, we are investigating which proteins bind to the fibrin matrix of a plasma clot by using a proteomic approach. Extracts from washed plasma clots were analysed by 2-D gel electrophoresis. A relatively abundant spot was identified as hepatocyte-derived fibrinogen-related protein-1 (HFREP-1) by MALDI-TOF analysis, molecular mass (34 kDa), iso-electric point (pI 5.5) as well as by Western blot analysis. HFREP-1 in plasma almost completely bound to the fibrin matrix during clot formation. Several purified fibrinogen preparations proved to be contaminated with HFREP-1. It is concluded that HFREP-1 (also named hepassocin), a protein with liver cell growth regulatory properties, occurs in plasma and strongly associates with fibrin and possibly fibrinogen.

Animals↗
PubMed2006

The effect of genetic variants in the thrombin activatable fibrinolysis inhibitor (TAFI) gene on TAFI-antigen levels, clot lysis time and the risk of venous thrombosis.

Thrombin activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis. High TAFI antigen levels are associated with an increased risk of deep venous thrombosis (DVT). Because TAFI levels are partly determined genetically, we assessed the association between three TAFI gene polymorphisms (-438 G/A, 505 A/G and 1040 C/T), TAFI antigen levels and clot lysis times and the risk of DVT. Carriers of the 505G allele, which is associated with lower TAFI antigen levels than the 505A allele, showed an increased risk of DVT. This indicates that the relationship between TAFI and venous thrombosis is more complex than previously suggested.

Adolescent↗
PubMed2006

A simple diagnostic strategy in hospitalized patients with clinically suspected pulmonary embolism.

OBJECTIVES: Diagnostic strategies in patients with suspected pulmonary embolism have been extensively studied in outpatients; their value in hospitalized patients has not been well established. Our aim was to determine the safety and clinical utility of a simple diagnostic strategy in hospitalized patients with suspected pulmonary embolism. DESIGN: Prospective management study. SETTING: Twelve teaching hospitals (five academic, seven general hospitals). SUBJECT: A total of 605 hospitalized patients with clinically suspected pulmonary embolism. All patients completed the study. INTERVENTIONS: First the clinical decision rule (CDR)-score was calculated. An unlikely CDR-score in combination with a normal D-dimer excluded pulmonary embolism. All other patients underwent helical computed tomography (CT). CT either diagnosed or excluded pulmonary embolism, in which case anticoagulants were started or withheld. All patients were instructed to report symptoms of venous thrombosis. Objective tests were performed to confirm venous thromboembolism. The primary outcome was the incidence of symptomatic venous thrombosis during 3-month follow-up. RESULTS: The combination of an unlikely CDR-score and a normal D-dimer excluded pulmonary embolism in 60 patients (10% of all patients); no venous thromboembolic event occurred during follow-up (0%; 95% CI 0-6.7%). CT excluded pulmonary embolism in 380 patients; during follow-up venous thromboembolism occurred in five patients (1.4%; 95% CI 0.4-3.1%). CONCLUSIONS: An unlikely CDR-score in combination with a normal D-dimer appears to exclude pulmonary embolism safely in hospitalized patients. Before clinical implementation it is important this safety is confirmed by others. CT testing was obviated in only 10% of patients. CT can safely exclude pulmonary embolism in hospitalized patients.

Algorithms↗
PubMed2005

High functional levels of thrombin-activatable fibrinolysis inhibitor are associated with an increased risk of first ischemic stroke.

BACKGROUND AND OBJECTIVE: Several studies have suggested that thrombin-activatable fibrinolysis inhibitor (TAFI) levels are associated with the risk of arterial thrombosis, but results have been contradictory. We studied functional TAFI levels and TAFI gene polymorphisms in 124 patients with a recent ischemic stroke and 125 age- and sex-matched controls to establish the role of TAFI in ischemic stroke. METHODS AND RESULTS: Functional TAFI levels, defined as TAFI-related retardation (RT), the difference in clot lysis time (LT) in the absence or presence of a specific activated TAFI inhibitor (potato carboxypeptidase inhibitor [PCI]), were higher in patients than controls (19.5 +/- 4.2 vs. 17.7 +/- 3.7 min, P < 0.005). Clot LTs in the presence of PCI, which were independent of TAFI, were also increased in ischemic stroke patients. This indicates that in these patients fibrinolysis is impaired not only by high TAFI levels, but also by other mechanisms. Individuals with functional TAFI levels in the highest quartile had an increased risk of ischemic stroke compared with the lowest quartile [odds ratio (OR) 4.0, 95% confidence interval (CI): 1.6-9.8]. In an unselected group of 36 of the 125 stroke patients functional TAFI levels were also measured at 3 months, and were persistently high. This indicates that increased functional TAFI levels after stroke are not caused by an acute phase reaction. No difference was found between patients and controls with respect to TAFI genotype distribution. CONCLUSIONS: Increased functional TAFI levels, resulting in decreased fibrinolysis, are associated with an increased risk of ischemic stroke.

Adult↗
PubMed2005

The -148 C/T fibrinogen gene polymorphism and fibrinogen levels in ischaemic stroke: a case-control study.

BACKGROUND: To determine whether -148 C/T fibrinogen gene promoter polymorphism increases stroke risk by modifying the fibrinogen level. DESIGN: A case-control study of patients with first ever ischaemic stroke, confirmed by computed tomography. METHODS: Venous blood samples were collected for fibrinogen and routine coagulation tests one week after the stroke, and after three months in about half the patients. Population controls were age and sex matched. -148 C/T fibrinogen polymorphism was determined by polymerase chain reaction followed by digestion with restriction enzymes HindIII/AluI. RESULTS: There were 124 patients and 125 controls, mean age 56 years (range 18 to 75); 34 patients (27%) and 41 controls (33%) were heterozygous for -148 C/T fibrinogen polymorphism; six patients (5%) and five controls (4%) had the T/T genotype. The odds ratio of ischaemic stroke associated with CC homozygotes v T carriers was 0.8 (95% confidence interval, 0.5 to 1.4). Relative risk for ischaemic stroke associated with fibrinogen levels in the highest quartile was 3.9 (1.9 to 8.4) at one week, decreasing to 1.4 (0.6 to 3.3) at three months. CONCLUSIONS: -148 C/T fibrinogen gene polymorphism was not a strong risk factor for ischaemic stroke. High fibrinogen levels early after acute stroke probably represent an acute phase response.

Adolescent↗
PubMed2004

Effective and safe use of recombinant factor VIIa (NovoSeven) in elderly mild haemophilia A patients with high-titre antibodies against factor VIII.

Three patients with mild haemophilia A who developed high-titre antibodies against factor VIII at high age are reported. These patients had only a limited number of exposure days of FVIII concentrates in the past. The patients had to undergo surgery or presented with recurrent bleeding episodes. Treatment with recombinant FVIIa (rFVIIa) was effective and safe. Despite the high age and the presence of coronary heart disease in one of the patients, no adverse events or thrombotic complications occurred. These cases illustrate that the physician should always be alert on the development of inhibitors, also in elderly patients with mild haemophilia, in whom FVIII inhibitors had never been detectable before and that treatment with rFVIIa was effective and well-tolerated.

Aged↗
PubMed2004

Do antiphospholipid antibodies increase the long-term risk of thrombotic complications in young patients with a recent TIA or ischemic stroke?

BACKGROUND: The purpose of our study was to determine the relative risk of thrombotic events in young patients with a recent TIA or ischemic stroke and positive antiphospholipid antibodies (aPL). METHODS: We included 128 consecutive patients aged 18-45 years with a recent TIA or ischemic stroke. All patients underwent computed tomography scanning and were screened for cardiovascular risk factors, cardiac disorders and large vessel disease. Lupus anticoagulant (LA) was screened for by an APTT-based assay and a diluted PT-assay. Anticardiolipin antibodies (aCL) were tested by enzyme-linked immunosorbent assay, using cardiolipin and anti-human IgG and IgM. Thrombotic events could be TIA, stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism. Product limit estimates of the time free of TIA or stroke and of the time free of any thrombotic event were made. The relative risk was estimated by means of a Cox proportional hazards regression model. RESULTS: Of the 128 patients, 22 (17.2%) had aPL. The mean follow-up was 3 years and 3 months (range 41 days to 6 yrs). The incidence of any thrombotic event per 100 patient years of follow-up was 9.0, and the incidence of recurrent stroke or TIA was 7.9. The relative risk of any thrombotic event in patients with aPL was 0.9 (95% CI: 0.3-2.4) and for recurrent ischemic stroke or TIA 0.7 (95% CI: 0.3-2.2). CONCLUSION: In young patients with a recent TIA or ischemic stroke, aPL do not seem to be a strong risk factor for recurrent stroke or TIA, nor for other thrombotic complications.

Adolescent↗
PubMed2003

In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A.

AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance study, 70 previously treated haemophilia A patients were included (73% severe, 14% moderate and 13% mild haemophilia A). Most of these patients were followed during 4 years for the appearance of adverse events, possible transmissions of blood-borne viruses and the occurrence of antibodies against FVIII. The efficacy of treatment was determined in each patient by the in vivo recovery of FVIII. During this study, only six adverse events, possibly related to the use of AAFACT, were reported. None of these were indicated as serious. Transmissions of HIV, HAV, HBV and HCV in the seronegative patients have not been observed. In none of the patients, inhibitors to FVIII were detected. The in vivo recovery of FVIII during this study was not different from the in vivo recovery observed in eight patients during the preregistration study. There was a correlation of in vivo recovery with age and body weight. From these results, we conclude that the clinical usage of this human plasma-derived FVIII product is efficient and safe.

Adolescent↗
PubMed2002

[From gene to disease; from mutations in the Von Willebrand factor gene to hemorrhagic diathesis and thrombocytopenia].

The broad spectrum of both clinical presentation and severity of bleeding complications observed in Von Willebrand's disease is the result of a high number of mutations. Most are clustered in specific functional domains, leading to quantitative (types 1 and 3) or qualitative (types 2: A, B, M and N or Normandy) defects in the Von Willebrand factor (VWF) protein. Unlike all the other subtypes, type 2B is the result of a 'gain of function' phenotype characterised by an enhanced binding affinity of the VWF protein to the glycoprotein (Gp) Ib complex of platelets, which causes the platelets to disappear from the circulation, resulting in thrombocytopenia. The thrombocytopenia can be triggered by stress or desmopressin, among other causes, and therefore the latter is contraindicated. Type 2B is characterised in vitro by enhanced platelet agglutination with ristocetin. All 2B mutations are located in exon 28, in a small region encoding the Gp-Ib binding site within the A1 domain of VWF. These mutations inactivate a regulatory function of the A1 domain which facilitates Gp-Ib binding.

Hemorrhagic Disorders↗
PubMed2002

[Intermittent thrombocytopenia as a manifestation of Von Willebrand's disease].

A 38-year-old man with Von Willebrand's disease type 2 came to us for treatment advice in relation to a trip abroad, and also a 53-year-old woman with bleeding treated as idiopathic thrombocytopenic purpura (ITP). In the man, a trial dose of desmopressin led to severe thrombopenia, and in the woman, treatments, such as splenectomy and prednisone in the past, had been ineffective. In both patients further investigations led to the diagnosis 'Von Willebrand-disease type 2B'. Despite the fact that Von Willebrand's disease type 2B has distinctive laboratory characteristics, such as thrombocytopenia, a positive Ristocetin Induced Platelet Agglutination (RIPA) test at a low ristocetin concentration, and an abnormal multimer pattern, some cases have incomplete or atypical presentations which can be misleading for the diagnosis. A wrong diagnosis can lead to ineffective and potentially dangerous therapeutic interventions. Molecular genetic analysis of type 2B mutations is simple and can help in making the correct diagnosis in cases of familial thrombocytopenia or for a further characterisation of Von Willebrand type 2.

Adult↗