Search

Simultaneous multivessel epicardial coronary artery thrombosis is an uncommon finding in acute ST-segment elevation myocardial infarction (STEMI). It generally leads to cardiogenic shock and sudden cardiac death in the hospital. We report a 42-year-old male patient presenting with acute anterior STEMI with triple coronary artery thrombosis. An emergency coronary angiogram showed total occlusion of the left anterior descending artery (LAD) with thrombus formation. At the same time, thrombus formations were also seen in the circumflex artery (CXA), the second obtuse marginal (OM2) branch, and the distal right coronary artery (RCA). We unsuccessfully attempted thrombus aspiration of the LAD. Subsequently, we decided to stent the LAD, and a successful percutaneous coronary intervention (PCI) was performed for the LAD. In a second procedure, RCA thrombosis regressed with 24-hour tirofiban (glycoprotein IIb/IIIa receptor inhibitor) perfusion, although CXA thrombosis and OM thrombosis did not regress. Therefore, we performed stenting of the CXA and OM with a newer provisional technique called the flower petal technique. Thrombolysis in myocardial infarction (TIMI) flow grade III was seen after stenting. The patient was discharged from the hospital 5 days after PCI without any symptoms.

International audience; Background: Flat-panel detectors on mobile C-arm (MC-arm) systems are currently challenging fixed C-arm (FC-arm) systems used in hybrid operating rooms. MC-arm systems offer an alternative to FC-arm systems in the endovascular treatment of peripheral arterial disease (PAD) but their efficiency has not been evaluated comparatively. Methods: Two series of patients undergoing arteriography with intention to treat were included. Each series consisted of 2 nonrandomized groups: an MC-arm group and an FC-arm group. Series 1 evaluated exposure to the patient (MC-arm, n = 113; FC-arm, n = 206) while series 2 evaluated exposure to patients and also health care personnel (MC-arm, n = 24; FC-arm, n = 76). The primary end points for evaluating exposure were air kerma (AK, in mGy) for patients and effective dose for health care personnel (in μSv). Results: After adjustment for the effect of body mass index (analysis of covariance test), AK was found to be lower in the MC-arm group than in the FC-arm group (124.1 ± 142 vs. 173.3 ± 248.7, P = 0.025). There was no difference between the groups with regard to effective dose recorded for senior surgeons or for operating room nurses. However, a higher effective dose was recorded by the MC-arm group external dosimeter for the trainee resident and for nurse anesthetists. Conclusions: In endovascular treatment of lower limb PAD, use of an FC-arm system is associated with more radiation exposure to the patient than an MC-arm system. However, this type of imaging system does not appear to affect exposure to health care personnel. © 2017 Elsevier Inc.

Peroneal pseudoaneurysm is a rarely seen as a complication due to a variety of treatment strategies. Continuous blood flow and decreased vascular wall support associated with pseudoaneurysm can cause rapid enlargement, compression of venous and nerve structures, rupture and mortality. An 84-year-old female patient presented to the emergency department with sudden onset pain and paleness in the right lower extremity. Doppler ultrasound revealed thrombus in the right common femoral artery. The patient underwent emergency embolectomy. Doppler ultrasound due to continuing symptoms on postoperative day one showed 23×30 mm pseudoaneurysm of the distal third of the right peroneal artery. Left femoral artery was catheterised and the peroneal artery aneurysm was coil embolised successfully. Timely diagnosis of complications and rapid treatment are essential in patients with recent vascular interventions. Palpable pulses and intact neurological examination do not rule out most of the complications which would require surgery for correction. © 2017 by The Medical Bulletin of University of Health Sciences Haseki Training and Research Hospital.

The information about the thromboembolic events, the optimal treatment choice, the dose, and duration of antithrombotic therapy in children are limited. More clinical data are required. Recombinant tissue plasminogen activator (r-tPA) is increasingly used in pediatric thrombosis. We retrospectively analyzed the clinical course of 7 children (9.3 ± 2.1 years; 34 days to 16 years) with arterial thrombosis (n = 1) and intracardiac thrombosis (n = 6). The children were treated with r-tPA. The dose ranged between 0.2 and 0.4 mg/kg per h infused for 3 to 4 hours. This dose was repeated between 2 to 7 times till the thrombolysis was achieved. Treatment side effects were closely monitored. Complete clot lysis was achieved in all cases. None of them had severe bleeding except mild recurrent epistaxis occurring in 2 cases. In conclusion, r-tPA is an effective and safe therapy under close hemostatic control in children.

Pulmonary embolism (PE) is a frequently occurring, acute, and potentially fatal condition. Numerous risk factors for PE, both inherited and acquired, have been identified. Adequate diagnosis is mandatory to prevent PE-related morbidity and mortality on the one hand, and unnecessary treatment on the other. Only around 1 in 5 individuals with suspected PE will have the diagnosis confirmed, therefore, the diagnostic work-up for PE should comprise safe, efficient, and noninvasive methods. The first step in the approach to diagnosis of patients with suspected PE is to determine the clinical probability and to perform a D-dimer test. PE can be excluded in patients with a 'low', 'intermediate' or 'unlikely' clinical probability and a normal D-dimer test. Additional imaging is required for those with a 'high' or 'likely' clinical probability or a positive D-dimer test. CT pulmonary angiography or ventilationĝ€"perfusion scintigraphy, followed by additional testing is the next step when test results are nondiagnostic. Although various diagnostic strategies have been introduced and validated, selected patients may require a tailored approach. © 2010 Macmillan Publishers Limited. All rights reserved.

Introduction: Many studies evaluated the association of V617F Jak-2 with the risk of thrombosis in patients with essential thrombocythaemia, but the results of these studies were inconsistent. Few studies evaluated the association of V617F Jak-2 mutation with the risk of thrombosis in patients with idiopathic myelofibrosis. Therefore, we performed a systematic review of the studies that assessed the risk of thrombosis associated with V617F Jak-2 in patients with ET or IM. Materials and Methods: We searched MEDLINE and EMBASE databases and reference lists of retrieved articles. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated for each trial and pooled. Results: We included 21 studies involving patients with essential thrombocythaemia and 6 studies patients with idiopathic myelofibrosis. In essential thrombocythaemia patients, V617F Jak-2 was associated with a significant increased risk of thrombosis (OR 1.92, 95% CI 1.45-2.53), both of venous (OR 2.49, 95% CI 1.71-3.61) and arterial (OR 1.77, 95% CI 1.29-2.43) vessels. In idiopathic myelofibrosis patients, the risk of thrombosis associated with V617F Jak-2 tended to be increased (OR 1.76, 95% CI 0.91-3.41). Conclusions: Our systematic review suggests that V617F Jak-2 increases the risk of thrombosis in essential thrombocythaemia patients by about two fold while its role in idiopathic myelofibrosis patients is uncertain. (C) 2009 Elsevier Ltd. All rights reserved

Purpose: We aim to evaluate the clinical and imaging features of “Top of the basilar” syndrome (TOB-S). Method: We retrospectively evaluated the clinical and imaging features of thirty consecutive TOB-S patients. We analyzed the ischemic parenchymal lesions and vascular disturbances with anatomic correlation by using magnetic resonance imaging (MRI), diffusion-weighted MRI (DWI), computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA). Results: Thirty patients (14 males and 16 females) with a mean age of 61 years (range: 32–78 years) were diagnosed as TOB-S based on the neuroimaging and clinical findings. Large artery atherosclerosis (LAA) was the common etiology (63.3%), including the subgroups of in situ steno/occlusive, artery to artery embolus (AA), arterial branch (AB) occlusion, and AA+AB combination. The other etiologies were cardioembolism (CE) (16.6%), arterial dissection (AD) (10.0%), vasculitis (6.6%), and undetermined (3.3%). The patients represented ‘superficial', ‘deep' and ‘superficial plus deep' infarcts with segmental, territorial or scattered patterns. The most clinical manifestations were motor deficits, alteration of consciousness, visual/oculomotor disturbance, cerebellar dysfunction, behavioral disorder and speech disorder. Conclusion: The accurate evaluation of imaging findings in TOB-S is essential for diagnosis and appropriate management. Familiarity with the vascular anatomy, supplying territories, and infarction patterns of the ischemic lesions is crucial. © 2016, Ege University Press. All Rights Reserved.

Pulmonary artery intimal sarcoma (PAS) is a rare mesenchymal tumor mostly diagnosed in middle-aged women. In a 63-year-old female, the radiological findings showed cavitation in the left upper lobe of the lung and infiltrative tumor mass around the left pulmonary artery. PAS consisted of small, round tumor cells with about 80% of mitotic activity and with myxoid background and specific immunoprofile and diagnosed as undifferentiated sarcoma with round cell features type. The final diagnosis of PAS was established according to the pathohistological, chest computed tomography scan, and surgery finding.

Aim: To present an uncommon, life-threatening case of intestinal ischemia complicated by cerebral stroke, thoraco-abdominal aorta and splenic artery thrombosis, in a woman with thrombophilia presenting common clinical signs. Presentation of Case: A 42-year-old woman was admitted to hospital for lower abdominal pain, vomiting and fever. Emergency abdominal surgery evidenced intestinal ischemia requiring 80 cm ileum resection. The day following surgery, the patient lost consciousness and was admitted to the stroke unit. Thereafter, the patient was transferred to the intensive care unit due to respiratory failure. A brain-thoracic-abdominal CT-angiography showed occlusion of left medium cerebral artery, a thrombotic formation in thoracic and abdominal aorta, and partial occlusion of splenic Case Study Giordano et al.; BJMMR, 10(12): 1-7, 2015; Article no.BJMMR.20540 2 artery. Homocysteine levels were 56.8mmol/l, screening for homozygosis mutation MTHFRC677T positive. Resolution of systemic thrombosis lasted one month. Patient was finally transferred to a rehabilitation center. Discussion: Vascular disease and ischemic stroke have rarely been reported in subjects with thrombophilia and MTHFR polymorphisms. Our patient, affected by thrombophilia and high homocysteine levels, faced multiple vascular and cerebral complications. High concentration of homocysteine, with consequent vessel deposits, was detrimental for endothelium and vessel walls, due to action on blood coagulation factors and lipoproteins, with increased platelet adhesion and aggregation. Conclusion: This case report represents an uncommon, sudden, life-threatening complication in thrombophilic patients, in spite of the common clinical signs presented. This clinical report should alert physicians to the importance of carrying out a careful clinical examination in the presence of thrombophilic patients presenting with apparently common clinical signs, such as abdominal pain, vomiting and fever.

Background: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). We aimed to assess incidence rates of bleeding, recurrence, and mortality in a large prospective cohort of SVT patients after a 2-year follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Information was gathered on baseline characteristics, risk factors and therapeutic strategies. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis, and mortality) during follow-up were collected and reviewed by a Central Adjudication Committee. Major bleeding was defined using the ISTH definition plus the need for hospitalization. The primary analysis was performed up to the first adjudicated major bleeding or thrombotic event. Results: 604 patients from 31 centers were enrolled in this study, 21 (3.5%) were lost to follow-up. Median follow-up duration was 2 years (IQR 1-2). Median age was 54 years (range 16-85); 62.6% were males. Most common risk factors were liver cirrhosis in 27.8% of patients and solid cancer in 22.3%. Portal vein was the most common site of thrombosis. 139 patients were not anticoagulated; 175 received parenteral anticoagulants only (median duration 5.8 months, IQR 3-12) and 290 were started on vitamin K antagonists (median duration 24 months, IQR 7-24). According to the primary analysis, 103 events occurred during follow-up: 35 major bleeding events (3.8/100 patient-years [pt-y]; 95%CI, 2.7-5.2), 2 of which were fatal bleeding, and 68 thrombotic events (7.3/100 pt-y; 95%CI 5.8-9.3), 9 of which were vascular deaths. All-cause mortality occurred in 106 patients (10.3/100 pt-y; 95% CI 8.5-12.5). The incidence of major bleeding events was 4.0/100 pt-y in patients on anticoagulant drugs and 3.4/100 pt-y in patients not receiving anticoagulants. The incidence of vascular events was 5.6/100 pt-y and 9.7/100 pt-y, respectively. Major bleeding and vascular event rates were highest in cirrhotic patients (10.0/100 pt-y and 11.3/100 pt-y, respectively), and lowest in the subgroup of non-malignant non-cirrhotic patients (1.8/100 pt-y and 5.6/100 pt-y, respectively). Conclusions: SVT patients have a non-negligible long-term risk of both bleeding and thrombotic events, but this risk varies according to the pathogenesis of SVT. Anticoagulant treatment is associated with a reduced incidence of thrombotic events without apparently resulting in an increased risk of bleeding.

Introduction: Splanchnic vein thrombosis [SVT] is a challenging disease, because of the concurrent increased risk of bleeding and potentially lifethreatening complications. We aimed to explore the actual management of SVT in a large prospective cohort and to report clinical outcomes during follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis; mortality) were collected. A propensity score [PS], created from baseline characteristics of patients receiving the two main treatments (different dosages of parenteral anticoagulants vs vitamin K antagonists [VKAs]), was used to estimate the effect of therapeutic strategies. We here report the results of the 12-month follow-up. Results: 613 patients were enrolled; mean age 53.1±14.8 years; 62.6% males. Initially, 143 patients were not anticoagulated; 175 received parenteral anticoagulants only (mean duration 6.28±4.21 months) and 295 started VKAs (9.67±3.53 months). Major bleeding occurred in 25 patients, 16 on treatment (4.53/100 patientyears [pt-y]) and 9 off treatment (5.45/100 pt-y); vascular events in 47 patients, 27 and 20 (7.93/100 pt-y vs 11.85/100 pt-y); death in 79 patients, 44 and 35 (12.35/100 pt-y vs 20.30/100 pt-y). Solid cancer, ascites, anemia and thrombocytopenia were inversely associated with the prescription of VKAs in a binary logistic regression. Using PS based on these variables, we matched 102 patients treated with VKAs with 102 patients treated with parenteral anticoagulants. Major bleeding occurred in 5.88% vs 0.98% for VKAs and heparin, respectively; vascular events in 2.94% vs 8.82%; mortality in 5.88% vs 18.63%. Conclusions: In our cohort of SVT patients, the incidence of vascular and bleeding events at 1-year follow-up was relevant. Although the PS matching did not allow for a complete balance of heterogeneity, in designated patients VKA treatment appeared to be sufficiently safe.

Background: After extensive media attention on thromboembolic adverse drug reactions (TE-ADRs) and the use of cyproterone/ethinylestradiol (CE), the Netherlands Pharmacovigilance Centre Lareb received a high number of reports about this association, which prompted for detailed analyses. Objectives: To analyse reports of thromboembolic events associated with the use of cyproterone/ ethinylestradiol submitted to Lareb, focusing on the indication of use, presence of risk factors and time between the initial symptoms and the actual diagnosis of the TE. Methods: Reports submitted to Lareb till 11 February 2014 were analysed. The analysis was focussed on reporter type, seriousness of the reaction, age of the patient, BMI, indication, ADRs classified as arterial thrombosis and venous thrombosis, pulmonary embolism, latency period, outcome of the reaction, treatment of the ADR, delay between the first symptoms and diagnosis of the ADR, presence of risk factors. Results: On 11 February 2014, Lareb had received a total of 786 reports about CE, including 41 cases with a fatal outcome. Of all reports, 438 reports considered TE-ADRs which were analysed in more detail. Reported ADRs consisted of arterial thrombosis (N = 74), venous thrombosis (N = 63), pulmonary embolism (N = 219) and thrombosis with an unspecified location (N = 172). Patient's mean age was 30.5 years (range 14-57 years). The primary indications for use were acne (N = 193), oral contraceptive (N = 181), hirsutism (N = 13), other (N = 18) or the indication was unknown (N = 33). The median time to onset was 4 years, although many patients reported a longer latency period. There was no distinction between the time of onset in respect to the reported ADR. No differences in risk factors seem to exist between labeled and off-label indications. In 382 out of 438 reports (87%), the reporter was a consumer. Some reports mentioned the fact that thrombosis or embolism were not recognized in an early stage. Conclusions: The reported thromboembolic ADRs are a known risk related to the use of CE, but may be misdiagnosed initially. From the reports that Lareb received it is evident that off-label use is frequent.

Pseudoaneurysms rarely occur as a serious complication following incomplete hemostasis of an arterial puncture site. As a result of the increase in diagnostic and therapeutic angiography, the frequency of iatrogenic pseudoaneurysm has increased as well. Iatrogenic pseudoaneurysms associated with angiographic catheterization occur most commonly in the common femoral artery. Here we report a case of iatrogenic superficial external pudendal artery (SEPA) pseudoaneurysm following cardiac catheterization, which was diagnosed with Doppler ultrasound (US) and multidetector computed tomographic angiography (MDCTA) before Doppler US-guided compression therapy. To the best of our knowledge, iatrogenic SEPA pseudoaneurysm, which is an unusual vessel location for pseudoaneurysm occurrence, has not been reported in the literature. In patients in whom anticoagulant-thrombolytic therapy or therapeutic catheterization with larger sized sheath is planned, determination of the precise localization of arterial puncture site is important for the prevention of iatrogenic pseudoaneurysm development. Arterial puncture guided with Doppler US might reduce complications. When suspected, MDCTA is useful in the diagnosis and demonstration of iatrogenic pseudoaneurysms. Treatment of US-guided compression should be the first choice for iatrogenic pseudoaneurysms. Interventional radiologists and cardiologists should have enough experience about the catheterization complications and their treatment in order to decrease the morbidity and mortality related to the intervention.

Introduction: After media attention on thromboembolic adverse drug reactions (ADRs) and the use of cyproterone/ethinylestradiol [1], the Netherlands Pharmacovigilance Centre Lareb received a high number of reports about this association, which called for a more detailed analyses. Aim: To provide an overview of the characteristics of all reports of thromboembolic ADRs associated with the use of cyproterone/ethinylestradiol submitted to Lareb until April 3rd 2013 focusing on character, circumstances, off-label use and degree of recognition of the ADRs. Methods: Reports were selected from the Lareb database based on ATCcode G03HB01 using an MS Access- query. Lareb analysed the reporter type, seriousness of the reaction according to the CIOMS criteria, patient's age at the occurrence of the ADR, patient's BMI (kg/m2), indication, ADRs classified as arterial thrombosis (including MedDRA- Preferred Terms like myocardial infarction, transient ischemic attack), venous thrombosis, pulmonary embolism or unspecified thrombosis, latency period, outcome of the reaction, treatment of the ADR, delay between the first symptoms and diagnosis of the ADR, presence of risk factors including smoking and Factor-V-Leiden deficiency. Results: On April 3, 2013 Lareb had received a total of 621 reports about cyproterone/ethinylestradiol, including 309 reports of thromboembolic ADRs which were further analysed. Reported ADRs consisted of arterial thrombosis (N = 52), venous thrombosis (N = 40), pulmonary embolism (N = 155) and thrombosis with an unspecified location (N = 128). A total of 299 reports of thromboembolic ADRs were classified as serious, including 18 cases with a fatal outcome. Patient's mean age was 30.5 years and mean BMI was 24.3 kg/m2. The primary indications for use were acne (N = 147), oral contraceptive (N = 122), hirsutism (N = 10), other (N = 15) or the indication was unknown (N = 15). Of the 309 patients with a thromboembolic ADR, 261 were known to have been treated with anticoagulant drugs. In 31 cases the thromboembolic ADR was initially not recognized as such by either the patient or their healthcare professional. The median time to onset was 2-3 years, however many patients reported a longer latency period. There was no distinction between the time of onset in respect to the reported ADR. No differences in risk factors seem to exist between labeled and off-label indications. In 291 out of 309 reports, the reporter was a consumer. Conclusions: The reported thromboembolic ADRs are a known risk related to the use of cyproterone/ethinylestradiol, but may be misdiagnosed initially. From the reports that Lareb received it is evident that t offlabel use is frequent.

The recombinant bifunctional urokinase variant, M23 (rscu-PA-40 kDA/Hir), comprising the kringle and protease domain of single-chain urokinase-type plasminogen activator and a C-terminal fragment of hirudin in one single-chain molecule, was evaluated for its thrombin-inhibitory and fibrinolytic properties in vitro and in vivo. M23 inhibited thrombin-activated coagulation of human blood and thrombin-induced aggregation of human platelet rich plasma in a concentration-dependent manner. The ADP-induced aggregation of human platelet rich plasma was not influenced by M23. In contrast, recombinant single-chain urokinase-type plasminogen activator (saruplase) inhibited neither blood coagulation nor platelet I ich plasma aggregation. M23 and saruplase both lysed radiolabelled human thrombi immersed in human plasma (Chandler Loop system) with equal potency. However, there was a significantly lower systemic generation of plasmin (measured as consumption of alpha(2)-antiplasmin) by M23 compared to saruplase. In anaesthetized non-heparinized rabbits, experimental femoral artery thrombosis was treated with intravenous bolus injections of M23 or saruplase (6 mg/kg, each). Thrombolytic restoration of arterial blood perfusion was significantly higher in M23- than in saruplase-treated rabbits. Plasma fibrinogen concentrations were decreased markedly in saruplase-treated animals, but remained at significantly higher levels in M23-treated rabbits. In conclusion, the bifunctional molecule, M23, showed thrombin inhibitory and fibrinolytic properties in human in vitro systems and exerted superior thrombolytic effects to saruplase in rabbit femoral artery thrombosis. In vitro and in vivo data indicate that the fibrinolytic activity of M23 is highly clot-specific.

The recombinant bifunctional urokinase variant, M23 (rscu-PA-40 kDA/Hir), comprising the kringle and protease domain of single-chain urokinase-type plasminogen activator and a C-terminal fragment of hirudin in one single-chain molecule, was evaluated for its thrombin-inhibitory and fibrinolytic properties in vitro and in vivo. M23 inhibited thrombin-activated coagulation of human blood and thrombin-induced aggregation of human platelet rich plasma in a concentration-dependent manner. The ADP-induced aggregation of human platelet rich plasma was not influenced by M23. In contrast, recombinant single-chain urokinase-type plasminogen activator (saruplase) inhibited neither blood coagulation nor platelet rich plasma aggregation. M23 and saruplase both lysed radiolabelled human thrombi immersed in human plasma (Chandler Loop system) with equal potency. However, there was a significantly lower systemic generation of plasmin (measured as consumption of α 2 -antiplasmin by M23 compared to saruplase. In anaesthetized non-heparinized rabbits, experimental femoral artery thrombosis was treated with intravenous bolus injections of M23 or saruplase (6 mg/kg, each). Thrombolytic restoration of arterial blood perfusion was significantly higher in M23- than in saruplase-treated rabbits. Plasma fibrinogen concentrations were decreased markedly in saruplase-treated animals, but remained at significantly higher levels in M23-treated rabbits. In conclusion, the bifunctional molecule, M23, showed thrombin inhibitory and fibrinolytic properties in human in vitro systems and exerted superior thrombolytic effects to saruplase in rabbit femoral artery thrombosis. In vitro and in vivo data indicate that the fibrinolytic activity of M23 is highly clot-specific.

Neurofibromatosis is an autosomal dominant multi-system genetic disorder. Extra-cardiac vascular manifestations of neurofibromatosis have been previously described in many reports. However, coronary arterial involvements have been rarely described. A 17-year-old girl with neurofibromatosis presented to our institute with subacute myocardial infarction. Coronary angiogram revealed an aneurysm with thrombus in the left anterior descending artery.

Objective: Leukotrienes (LT) play a role in inflammation, cardiovascular diseases, and cancer. Although some studies suggest that there are genes that determine variability of some LT-related phenotypes, the genetic influence on these phenotypes has not been evaluated. Methods: The relative contributions of genetic and environmental influences to the 5-lipoxygenase pathway-related phenotypes (5-Lipoxygenase, five lipoxygenase activating protein (FLAP), LTA4-hydrolase and LTC4-synthase expression, and LTB4-plasma concentration and LTB4 production by stimulated whole blood) were assessed in a sample of 934 individuals in 35 extended families. Our design is based on extended families recruited through a probands with idiopathic thrombophilia. This strategy allows us the analysis of the effects of measured covariates (such as sex, age and smoking), genes, and environmental variables shared by members of a household. Results: All of these phenotypes showed significant genetic contributions, with heritabilities ranging from 0.33 to 0.51 for enzyme expression and from 0.25 to 0.50 for LTB4 production of the residual phenotypic variance. Significant phenotypic and genetic correlation among the LT-related traits was found. More importantly, FLAP and LTA4-hydrolase expression exhibit significant genetic correlations with arterial thrombosis, indicating that some of the genes that influence quantitative variation in these phenotypes also influence the risk of thrombosis. Conclusion: This is the first study that quantifies the genetic component of 5-Lipoxygenase pathway phenotypes. The high heritability of these traits and the significant genetic correlations between arterial thrombosis and some of these phenotypes suggest that the exploitation of correlated quantitative phenotypes will aid the search for susceptibility genes. © 2012 Elsevier Ireland Ltd.

Background: Patients with lung cancer (LC) are at increased risk of venous and arterial thrombosis due to cancer itself and its treatment. Although some studies have assessed the incidence of venous thrombosis among LC patients, data on the occurrence of specific venous and arterial thrombotic events is scarce. Objectives: To study the rate of myocardial infarction (MI), ischemic stroke (IS) and pulmonary embolism (PE) before and after LC diagnosis compared with cancer-free controls. Methods: Patients with LC during 2000-2007 were selected from PALGA, the Dutch nationwide registry of histo-and cytopathology, and linked to the PHARMO RLS, including drug use and hospitalizations of approximately three million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. The occurrence of MI, IS and PE were assessed in the 12 months before and after LC diagnosis. Results: This study included 3,717 LC patients, with a mean (±SD) age of 59 (±14) years and 69% males. LC patients were six times as likely as their cancer-free controls to have had a hospitalization for PE in the 12 months before diagnosis, though prevalence was

Background: Patients with lung cancer (LC) are at increased risk of venous and arterial thrombosis due to cancer itself and its treatment. Although some studies have assessed the incidence of venous thrombosis among LC patients, data on the occurrence of specific venous and arterial thrombotic events is scarce. Objectives: To study the rate of myocardial infarction (MI), ischemic stroke (IS) and pulmonary embolism (PE) before and after LC diagnosis compared with cancer-free controls. Methods: Patients with LC during 2000-2007 were selected from PALGA, the Dutch nationwide registry of histo-and cytopathology, and linked to the PHARMO RLS, including drug use and hospitalizations of approximately three million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. The occurrence of MI, IS and PE were assessed in the 12 months before and after LC diagnosis. Results: This study included 3,717 LC patients, with a mean (±SD) age of 59 (±14) years and 69% males. LC patients were six times as likely as their cancer-free controls to have had a hospitalization for PE in the 12 months before diagnosis, though prevalence was

Introduction: Hemophilia A patients have a 50% lower cardiovascular mortality than the general population. Whether this is caused by less atherosclerosis due to hypocoagulability is unclear. We assessed whether hemophilia A patients with obesity, a major atherosclerotic risk factor, have a lower prevalence of 'subclinical' atherosclerosis than obese controls. Methods: Fifty obese (body mass index [BMI] > 30 kg/m2) and 48 normal-weight (BMI 1.3 mm, P = 0.11), irrespective of the severity of hemophilia. (Figure presented) Conclusion: Hemophilia A patients with obesity have the same degree of subclinical atherosclerosis as obese control subjects, which suggests that the lower cardiovascular mortality is likely caused by a decreased risk of arterial thrombosis.

Introduction: Hemophilia A patients have a 50% lower cardiovascular mortality than the general population. Whether this is caused by less atherosclerosis due to hypocoagulability is unclear. We assessed whether hemophilia A patients with obesity, a major atherosclerotic risk factor, have a lower prevalence of 'subclinical' atherosclerosis than obese controls. Methods: Fifty obese (body mass index [BMI] > 30 kg/m2) and 48 normal-weight (BMI 1.3 mm, P = 0.11), irrespective of the severity of hemophilia. (Figure presented) Conclusion: Hemophilia A patients with obesity have the same degree of subclinical atherosclerosis as obese control subjects, which suggests that the lower cardiovascular mortality is likely caused by a decreased risk of arterial thrombosis.

Introduction Animal models of venous and arterial thrombosis are extremely useful to study the efficacy of antithrombotic agents. Variability in efficacy data is often observed in those preclinical studies. The goal of this study was to optimize the methodology for assessing antithrombotic drug efficacy by the use of optical coherence tomography (OCT) and a modified Doppler flow system in rat models of thrombosis. Methods Thrombus formation was assessed in both the rat venous and arterial ferric chloride (FeCl3) models of thrombosis. In the venous model, thrombus volume post-treatment was measured using OCT, and data were correlated against the thrombus weight. In the arterial model, the time to occlusion was measured using a Doppler flow probe connected to a perivascular flow module which allowed the reporting of dynamic blood flow data every 30 s. Heparin (130 or 165 U/kg), argatroban (4.5 mg/kg), bivalirudin (1.3 mg/kg) or saline were administered intravenously. Results In the venous model, for all treatment groups a strong linear correlation (R2 = 0.998) was observed between thrombus volume measured by OCT and thrombus weight. In the arterial model, using a high sampling rate of a dynamic blood flow using a modified Doppler flow system provided data accuracy and precision of the time to occlusion measurement. Discussion This study demonstrates that OCT is a powerful tool for the assessment of antithrombotic drug efficacy. Furthermore, it shows that a high Doppler sampling rates of dynamic blood flow leads to data accuracy and precision.

Introduction: Splanchnic vein thrombosis [SVT] is a challenging disease, because of the concurrent increased risk of bleeding and potentially lifethreatening complications. We aimed to explore the actual management of SVT in a large prospective cohort and to report clinical outcomes during follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis; mortality) were collected. A propensity score [PS], created from baseline characteristics of patients receiving the two main treatments (different dosages of parenteral anticoagulants vs vitamin K antagonists [VKAs]), was used to estimate the effect of therapeutic strategies. We here report the results of the 12-month follow-up. Results: 613 patients were enrolled; mean age 53.1±14.8 years; 62.6% males. Initially, 143 patients were not anticoagulated; 175 received parenteral anticoagulants only (mean duration 6.28±4.21 months) and 295 started VKAs (9.67±3.53 months). Major bleeding occurred in 25 patients, 16 on treatment (4.53/100 patientyears [pt-y]) and 9 off treatment (5.45/100 pt-y); vascular events in 47 patients, 27 and 20 (7.93/100 pt-y vs 11.85/100 pt-y); death in 79 patients, 44 and 35 (12.35/100 pt-y vs 20.30/100 pt-y). Solid cancer, ascites, anemia and thrombocytopenia were inversely associated with the prescription of VKAs in a binary logistic regression. Using PS based on these variables, we matched 102 patients treated with VKAs with 102 patients treated with parenteral anticoagulants. Major bleeding occurred in 5.88% vs 0.98% for VKAs and heparin, respectively; vascular events in 2.94% vs 8.82%; mortality in 5.88% vs 18.63%. Conclusions: In our cohort of SVT patients, the incidence of vascular and bleeding events at 1-year follow-up was relevant. Although the PS matching did not allow for a complete balance of heterogeneity, in designated patients VKA treatment appeared to be sufficiently safe.

Background: After extensive media attention on thromboembolic adverse drug reactions (TE-ADRs) and the use of cyproterone/ethinylestradiol (CE), the Netherlands Pharmacovigilance Centre Lareb received a high number of reports about this association, which prompted for detailed analyses. Objectives: To analyse reports of thromboembolic events associated with the use of cyproterone/ ethinylestradiol submitted to Lareb, focusing on the indication of use, presence of risk factors and time between the initial symptoms and the actual diagnosis of the TE. Methods: Reports submitted to Lareb till 11 February 2014 were analysed. The analysis was focussed on reporter type, seriousness of the reaction, age of the patient, BMI, indication, ADRs classified as arterial thrombosis and venous thrombosis, pulmonary embolism, latency period, outcome of the reaction, treatment of the ADR, delay between the first symptoms and diagnosis of the ADR, presence of risk factors. Results: On 11 February 2014, Lareb had received a total of 786 reports about CE, including 41 cases with a fatal outcome. Of all reports, 438 reports considered TE-ADRs which were analysed in more detail. Reported ADRs consisted of arterial thrombosis (N = 74), venous thrombosis (N = 63), pulmonary embolism (N = 219) and thrombosis with an unspecified location (N = 172). Patient's mean age was 30.5 years (range 14-57 years). The primary indications for use were acne (N = 193), oral contraceptive (N = 181), hirsutism (N = 13), other (N = 18) or the indication was unknown (N = 33). The median time to onset was 4 years, although many patients reported a longer latency period. There was no distinction between the time of onset in respect to the reported ADR. No differences in risk factors seem to exist between labeled and off-label indications. In 382 out of 438 reports (87%), the reporter was a consumer. Some reports mentioned the fact that thrombosis or embolism were not recognized in an early stage. Conclusions: The reported thromboembolic ADRs are a known risk related to the use of CE, but may be misdiagnosed initially. From the reports that Lareb received it is evident that off-label use is frequent.

Objectives: Splanchnic vein thrombosis [SVT] is a challenging disease, because of the concurrent increased risk of bleeding and potentially life-threatening complications. We aimed to explore the actual management of SVT in a large prospective cohort and to report clinical outcomes during follow-up. Methods: Consecutive SVT patients were enrolled in a multicenter international registry, from 2008 to 2012. Clinical outcomes (major bleeding; vascular events, defined as venous or arterial thrombosis; mortality) were collected. A propensity score (PS), created from baseline characteristics of patients receiving the two main treatments (different dosages of parenteral anticoagulants vs. vitamin K antagonists [VKAs]), was used to estimate the effect of therapeutic strategies. We here report the results of the 12-month follow-up. Results: There were 613 patients enrolled: mean age 53.1 ± 14.8 years; 62.6% males. Initially, 143 patients were not anticoagulated; 175 received parenteral anticoagulants only (mean duration 6.28 ± 4.21 months) and 295 started VKAs (9.67 ± 3.53 months). Major bleeding occurred in 25 patients, 16 on treatment (4.53/100 patient-years [pt-y]) and 9 off treatment (5.45/100 pt-y); vascular events in 47 patients, 27 and 20 (7.93/100 pt-y vs. 11.85/100 pt-y); death in 79 patients, 44 and 35 (12.35/100 pt-y vs. 20.30/100 pt-y). Solid cancer, ascites, anemia, and thrombocytopenia were inversely associated with the prescription of VKAs in a binary logistic regression. Using PS based on these variables, we matched 102 patients treated with VKAs with 102 patients treated with parenteral anticoagulants. Major bleeding occurred in 5.88% vs. 0.98% for VKAs and heparin, respectively; vascular events in 2.94% vs. 8.82%; and mortality in 5.88% vs. 18.63%. Conclusion: In our cohort of SVT patients, the incidence of vascular and bleeding events at 1-year follow-up was relevant. Although the PS matching did not allow for a complete balance of heterogeneity, in designated patients VKA treatment appeared to be sufficiently safe.

Pulmonary embolism (PE) is a frequently occurring, acute, and potentially fatal condition. Numerous risk factors for PE, both inherited and acquired, have been identified. Adequate diagnosis is mandatory to prevent PE-related morbidity and mortality on the one hand, and unnecessary treatment on the other. Only around 1 in 5 individuals with suspected PE will have the diagnosis confirmed, therefore, the diagnostic work-up for PE should comprise safe, efficient, and noninvasive methods. The first step in the approach to diagnosis of patients with suspected PE is to determine the clinical probability and to perform a D-dimer test. PE can be excluded in patients with a 'low', 'intermediate' or 'unlikely' clinical probability and a normal D-dimer test. Additional imaging is required for those with a 'high' or 'likely' clinical probability or a positive D-dimer test. CT pulmonary angiography or ventilationĝ€"perfusion scintigraphy, followed by additional testing is the next step when test results are nondiagnostic. Although various diagnostic strategies have been introduced and validated, selected patients may require a tailored approach. © 2010 Macmillan Publishers Limited. All rights reserved.

Each of three distinct, concentric layers of human arterial thrombi, was analysed immunochemically for the plasminogen and fibrin content, and for the ex vivo susceptibility to thrombolysis by various thrombolytic agents in a saline or plasma milieu. The age of the thrombus layer determined: (a) the plasminogen content; (b) the fibrin content, inferred from the recovery of fibrin degradation products after complete lysis and from the binding of a monoclonal anti-fibrin antibody in a perfusion system, and (c) the lysibility of the thrombus. Plotting concentration of the various thrombolytic agents against percentage of lysis at several time points allows for reading of equivalent potencies of the respective units. Undiluted solutions of APSAC and rt-PA, prepared according to the manufacturer's directions, were less effective than diluted solutions, which has consequences for local therapy. All agents were at least as effective in saline as in a plasma milieu. We conclude that the plasminogen content of aged arterial thrombi is sufficient for complete and rapid thrombolysis. Only after several months do fibrin and plasminogen become so far degraded or replaced that the thrombi become resistant to thrombolysis. Chemicals/CAS: alteplase, 105857-23-6; anistreplase, 81669-57-0; plasminogen, 9001-91-6; saruplase, 99149-95-8; streptokinase, 9002-01-1; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; Anistreplase, 81669-57-0; Fibrin Fibrinogen Degradation Products; Fibrin, 9001-31-4; Fibrinolytic Agents; Plasminogen, 9001-91-6; Recombinant Proteins; Sodium Chloride, 7647-14-5; Streptokinase, EC 3.4.-; Tissue Plasminogen Activator, EC 3.4.21.68; Urinary Plasminogen Activator, EC 3.4.21.73

Gangrene presenting at birth is a rare clinical problem; it results from diminished perfusion of a part of the body, usually the extremities. A variety of aetiological factors may account for this situation. Arterial thrombosis, emboli, trauma, congenital heart disease, sepsis, coagulopathy, polycythaemia, congenital bands, and birth trauma are some of the causes which should be considered. In the majority of cases, an aetiological factor is not identified. The management of neonatal gangrene is usually conservative, preventing infection of the affected part and allowing the gangrenous portion to declare itself in order to optimise future reconstruction and rehabilitation. In this paper, two cases of newborn with gangrene of an upper extremity are reported.

Background: β-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of β-blockers, although non-selective β-blockers may have a better effect on arterial thrombosis. The 2002 COMET study showed superiority of carvedilol (non-selective β-blocker) over metoprolol (selective β-blocker) on mortality and cardiovascular events in patients with HF, but this study was criticised for inappropriate formulation of metoprolol. Laboratory findings suggest a reduced prothrombotic response upon sympathetic activation by non-selective β-blockers. Objectives: To compare the incidence of thromboembolic events (acute coronary syndrome (ACS), stroke, or pulmonary embolism) between patients using selective and nonselective β-blockers. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. We identified a cohort of 24,398 patients admitted for HF in the period 1998-2007. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: The median follow up was 2.1 years (interquartile range: 0.8-4.0). In a 3-month time window after discharge, 6,864 patients were prescribed a selective and 2,356 patients a non-selective β-blocker. The incidence of thrombotic events during follow up was 3.3% for non-selective β-blockers and 4.6% for selective β-blockers, resulting in a crude HR of 0.69 (95%CI: 0.59-0.79). After adjustment for confounders, including age, sex, history of ACS, and other drug use, the difference remained significant (HR 0.75, 95%CI: 0.65-0.87). Conclusions: Non-selective β-blockers were associated with a lower risk of thromboembolic events compared to selective β-blockers in patients with HF. The hypothesis that non-selective β-blockers reduce the prothrombotic state in these patients should be explored further.

Background: β-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of β-blockers, although non-selective β-blockers may have a better effect on arterial thrombosis. The 2002 COMET study showed superiority of carvedilol (non-selective β-blocker) over metoprolol (selective β-blocker) on mortality and cardiovascular events in patients with HF, but this study was criticised for inappropriate formulation of metoprolol. Laboratory findings suggest a reduced prothrombotic response upon sympathetic activation by non-selective β-blockers. Objectives: To compare the incidence of thromboembolic events (acute coronary syndrome (ACS), stroke, or pulmonary embolism) between patients using selective and nonselective β-blockers. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. We identified a cohort of 24,398 patients admitted for HF in the period 1998-2007. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: The median follow up was 2.1 years (interquartile range: 0.8-4.0). In a 3-month time window after discharge, 6,864 patients were prescribed a selective and 2,356 patients a non-selective β-blocker. The incidence of thrombotic events during follow up was 3.3% for non-selective β-blockers and 4.6% for selective β-blockers, resulting in a crude HR of 0.69 (95%CI: 0.59-0.79). After adjustment for confounders, including age, sex, history of ACS, and other drug use, the difference remained significant (HR 0.75, 95%CI: 0.65-0.87). Conclusions: Non-selective β-blockers were associated with a lower risk of thromboembolic events compared to selective β-blockers in patients with HF. The hypothesis that non-selective β-blockers reduce the prothrombotic state in these patients should be explored further.

Background: Beta-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of β-blockers, although non-selective β-blockers may have a better effect on arterial thrombosis. The 2002 COMET study showed superiority of carvedilol (a non-selective β-blocker) over metoprolol (selective b-blocker) on mortality and cardiovascular events in patients with HF. However, this study was criticised for inappropriate formulation of metoprolol. Laboratory findings suggest a reduced prothrombotic response upon sympathetic activation by non-selective β-blockers. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in the Netherlands. We identified a cohort of 24 398 patients with documented HF in the period 1998-2007, based on hospital discharge diagnosis. This method has been validated for selecting HF patients. We used Cox regression analysis to assess the difference in the incidence of thromboembolic events (acute coronary syndrome (ACS), stroke, or pulmonary embolism) between patients using selective and non-selective β-blockers. Results: Median follow up was 2.1 years (interquartile range (IQR): 0.8-4.0). In a three-month time period after discharge, 6864 patients were prescribed a selective b-blocker and 2356 patients a non-selective b-blocker. The incidence of thrombotic events during follow up was 4.6% for selective b-blockers and 3.3% for non-selective β-blockers, which resulted in a hazard ratio (HR) of 0.69 (95% confidence interval (CI): 0.59-0.79). After adjustment for potential confounders including age, sex, history of ACS, drug use, the difference remained significant (HR 0.75, 95%CI: 0.65-0.87). Conclusion: Non-selective b-blockers are associated with a lower risk of thromboembolic events compared to selective b-blockers in patients with HF. The hypothesis that non-selective b-blockers reduce the prothrombotic state in these patients should be further explored.

Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence of asymptomatic atherosclerosis. Methods: Eligible articles were identified by searches of MEDLINE and EMBASE to retrieve studies that evaluated the prevalence of arterial thrombosis and asymptomatic atherosclerotic disease (by intima media thickness of the carotid and femoral arteries, or flow mediated dilation of the brachial artery) in patients with hemophilia or VWD. Study selection, data extraction, and quality assessment were independently performed by two reviewers. Weighted standardized mortality ratios (SMR) and weighted mean differences (WMD) were calculated and pooled using a fixed or random effects model. Statistical heterogeneity was assessed by using X2 en I2 statistics. Results: 15 longitudinal and cross-sectional studies with a total of 19.242 patients met the inclusion criteria. The mean age in the various studies ranged between 35 and 54 years. Mortality due to arterial thrombosis was reduced in patients with hemophilia compared to healthy controls (weighted SMR 0.57, 95% confidence interval (CI) 0.46-0.71), and most consistently so in high quality studies (weighted SMR 0.55, 95% CI 0.48-0.63). No results were available for non- fatal arterial events in hemophilia or for patients with VWD. IMT of the carotid and femoral arteries was similar between VWD and hemophilia patients and healthy controls (WMD 0.01 mm (95% CI - 0.02-0.04) and -0.04 mm (95% CI -0.10-0.02)). The prevalence of atherosclerotic plaques was lower in patients with hemophilia and VWD than in controls. Only two studies assessed FMD and the results were inconsistent. Conclusion: Hemophilia is associated with reduced mortality due to arterial thrombosis, while data on non-fatal arterial events and VWD are lacking. This beneficial effect may be associated with a reduced frequency of atherosclerotic plaques.

Background: Beta-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of β-blockers, although non-selective β-blockers may have a better effect on arterial thrombosis. The 2002 COMET study showed superiority of carvedilol (a non-selective β-blocker) over metoprolol (selective b-blocker) on mortality and cardiovascular events in patients with HF. However, this study was criticised for inappropriate formulation of metoprolol. Laboratory findings suggest a reduced prothrombotic response upon sympathetic activation by non-selective β-blockers. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in the Netherlands. We identified a cohort of 24 398 patients with documented HF in the period 1998-2007, based on hospital discharge diagnosis. This method has been validated for selecting HF patients. We used Cox regression analysis to assess the difference in the incidence of thromboembolic events (acute coronary syndrome (ACS), stroke, or pulmonary embolism) between patients using selective and non-selective β-blockers. Results: Median follow up was 2.1 years (interquartile range (IQR): 0.8-4.0). In a three-month time period after discharge, 6864 patients were prescribed a selective b-blocker and 2356 patients a non-selective b-blocker. The incidence of thrombotic events during follow up was 4.6% for selective b-blockers and 3.3% for non-selective β-blockers, which resulted in a hazard ratio (HR) of 0.69 (95% confidence interval (CI): 0.59-0.79). After adjustment for potential confounders including age, sex, history of ACS, drug use, the difference remained significant (HR 0.75, 95%CI: 0.65-0.87). Conclusion: Non-selective b-blockers are associated with a lower risk of thromboembolic events compared to selective b-blockers in patients with HF. The hypothesis that non-selective b-blockers reduce the prothrombotic state in these patients should be further explored.

Neonatal thrombosis is a serious event that can cause mortality or severemorbidity. Although catheters are the most common cause of neonatalthrombosis, spontaneous events can also occur. Arterial thrombosis isvery rare and accounts for approximately half of all thrombotic events inneonates. Genetic prothrombotic risk factors may affect the occurence ofneonatal thrombosis. In this report, a case of left brachial, radial, and ulnararterial thrombosis associated with methylene-tetrahydrofolate reductase(MTHFR) gene C677T and A1298C polymorphism heterozygosity is presented.Plasma homocysteine level and other prothrombotic componentswere normal. Standard heparin, aspirin, vitamin B12, B6 and folic acidwere initiated for treatment. However, the left arm of the patient wasamputated at the shoulder because its capillary stream could not be observed.We suggest that MTHFR gene C677T and A1298C polymorphismheterozygosity might be investigated in neonates with congenital arterialthrombosis in spite of normal serum homocysteine levels., Yenidoğanda tromboz mortaliteye ve/veya ağır morbiditeye neden olabilenciddi bir durumdur. Yenidoğan trombozunun en sık nedeni kateterlerolmakla birlikte, spontan gelişen olgular da görülebilmektedir. Arteriyeltromboz çok nadir görülür ve yenidoğandaki trombotik olayların yaklaşıkyarısını oluşturmaktadır. Genetik protrombotik risk faktörleri yenidoğandatromboz oluşumunu etkilemektedir. Bu yazıda, metilen tetrahidrofolat redüktaz(MTHFR) geni C677T ve A1298C polimorfizmi heterozigotluğu ileilişkilendirilen sol brakiyal, radiyal ve ulnar arter trombozu saptanan bir yenidoğanolgusu sunuldu. Plazma homosistein düzeyi ve diğer protombotikkomponentleri normaldi. Standart heparin, aspirin, vitamin B12, B6 ve folikasit tedavileri başlanan olguda sol kol, kapiller dolaşımı alınamadığı içinomuzdan ampute edildi. Plazma homosistein düzeyleri normal saptansada konjenital arteriyel trombozlu yenidoğanlarda MTHFR geni C677T veA1298C polimorfizmi araştırılmalıdır.

Among 994 patients with essential thrombocythemia (ET) who were genotyped for the MPLW515L/K mutation, 30 patients carrying the mutation were identified (3.0%), 8 of whom also displayed the JAK2V671F mutation. MPLW515L/K patients presented lower hemoglobin levels and higher platelet counts than did wild type (wt) MPL; these differences were highly significant compared with MPLwt/JAK2V617F–positive patients. Reduced hemoglobin and increased platelet levels were preferentially associated with the W515L and W515K alleles, respectively. MPL mutation was a significant risk factor for microvessel disturbances, suggesting platelet hyperreactivity associated with constitutively active MPL; arterial thromboses were increased only in comparison to MPLwt/JAK2wt patients. MPLW515L/K patients presented reduced total and erythroid bone marrow cellularity, whereas the numbers of megakaryocytes, megakaryocytic clusters, and small-sized megakaryocytes were all significantly increased. These data indicate that MPLW515L/K mutations do not define a distinct phenotype in ET, although some differences depended on the JAK2V617F mutational status of the counterpart.

Plasminogen activator inhibitor (PAI-1), is the central component of the fibrinolytic system. A deletion/insertion (4G/5G) polymorphism in the promoter region of the PAI-1 gene has been correlated with levels of plasma PAI-1. The 4G allele is associated with higher levels of PAI-1, and might increase the risk for intravascular thrombosis. However, the contribution of this genetic variant to the risk for thrombosis, both arterial and venous, has not been clearly established. A broad spectrum of findings regarding the effect of the 4G allele on thrombotic risk in different target organs has been reported. Our aim is to summarize the variable influence of this polymorphism on thrombotic events in different tissues or organs and explain the underlying mechanisms accounting for these differences. © 2007 Elsevier Ltd. All rights reserved. 122 6 736 742