Intelligent classification of platelet aggregates by agonist type.

Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.

Platelets are small cells in the blood that primarily help stop bleeding after an injury by sticking together with other blood cells to form a clot that seals the broken blood vessel. Blood clots, however, can sometimes cause harm. For example, if a clot blocks the blood flow to the heart or the brain, it can result in a heart attack or stroke, respectively. Blood clots have also been linked to harmful inflammation and the spread of cancer, and there are now preliminary reports of remarkably high rates of clotting in COVID-19 patients in intensive care units. A variety of chemicals can cause platelets to stick together. It has long been assumed that it would be impossible to tell apart the clots formed by different chemicals (which are also known as agonists). This is largely because these aggregates all look very similar under a microscope, making it incredibly time consuming for someone to look at enough microscopy images to reliably identify the subtle differences between them. However, finding a way to distinguish the different types of platelet aggregates could lead to better ways to diagnose or treat blood vessel-clogging diseases. To make this possible, Zhou, Yasumoto et al. have developed a method called the "intelligent platelet aggregate classifier" or iPAC for short. First, numerous clot-causing chemicals were added to separate samples of platelets taken from healthy human blood. The method then involved using high-throughput techniques to take thousands of images of these samples. Then, a sophisticated computer algorithm called a deep learning model analyzed the resulting image dataset and "learned" to distinguish the chemical causes of the platelet aggregates based on subtle differences in their shapes. Finally, Zhou, Yasumoto et al. verified iPAC method's accuracy using a new set of human platelet samples. The iPAC method may help scientists studying the steps that lead to clot formation. It may also help clinicians distinguish which clot-causing chemical led to a patient's heart attack or stroke. This could help them choose whether aspirin or another anti-platelet drug would be the best treatment. But first more studies are needed to confirm whether this method is a useful tool for drug selection or diagnosis.

Longitudinal Toxicity over Time (ToxT) analysis to evaluate tolerability: a case study of lenalidomide in the CALGB 50401 (Alliance) trial.

Evaluation of tolerability is increasingly relevant for patients with haematological malignancies treated with chronically administered therapies. Adverse events from these agents might affect the ability of patients to tolerate treatment over time. Conventional toxicity tables that include the incidence of high-grade adverse events, defined by the Common Terminology Criteria for Adverse Events, do not provide information on the time profile of these adverse events or reflect the continuous, lower grade symptomatic toxicities that are particularly relevant to treatment tolerability for patients living with indolent disease. Modern approaches to the evaluation and reporting of toxicity that capture the tolerability of treatment to the patient are imperative. In this Viewpoint, we present a focused, pilot, and longitudinal Toxicity over Time analysis of adverse events from lenalidomide and lenalidomide with rituximab in patients with follicular lymphoma treated in the CALGB 50401 (Alliance; NCT00238238) trial to define the trajectory of adverse events and quantify the burden of continuous, low-grade events. Toxicity over Time analyses provided clinically relevant descriptions of neutropenia and fatigue trajectories caused by lenalidomide that were not identified by standard analysis of the maximum grade events defined by the Common Terminology Criteria for Adverse Events. Systematic, rigorous incorporation of patient-reported outcomes in clinical trials will be crucial to our understanding of the tolerability of chronically administered therapies in patients with haematological malignancies.

Robotic Radical Nephrectomy and Thrombectomy for Left Renal Cell Carcinoma with Renal Vein Tumor Thrombus: Superior Mesenteric Artery as an Important Strategic Dividing Landmark.

Objective: The aim of this study was to explore a new treatment strategy for left renal vein tumor thrombus directed at the thrombus level and the therapeutic effect of robotic surgery. Materials and Methods: Fifteen patients with left renal cell carcinoma with renal vein tumor thrombus (Mayo level 0) who underwent robotic radical nephrectomy and thrombectomy from July 2013 to July 2017 were included in this series. If the left renal vein thrombus transcended the superior mesenteric artery (SMA), the thrombus was classified as level 0b, the patient was positioned right side up for thrombectomy and repositioned left side up for nephrectomy, and angioembolization of left renal artery was necessary; otherwise, the thrombus was classified as level 0a and the patient was positioned left side up for both nephrectomy and thrombectomy. Baseline, perioperative, and follow-up data were analyzed. Results: Of all 15 patients, 10 had a level 0a tumor thrombus and 5 had a level 0b tumor thrombus. For level 0a patients, median operating time was 130 minutes, median estimated blood loss was 125 mL, with no patient receiving transfusion, and median hospital stay was 3.5 days. For level 0b patients, median operating time was 180 minutes, median estimated blood loss was 250 mL, with one patient receiving transfusion, and median hospital stay was 5 days. No perioperative complications or positive surgical margins occurred. For level 0a patients, one patient with preexisting lumbar vertebral metastasis died during a median follow-up of 39 months. For level 0b patients, all patients were alive at a median follow-up of 16.5 months. Conclusions: Our initial experience shows that the new treatment strategy for left renal vein tumor thrombus with the SMA as a dividing landmark directed at the thrombus level is safe and feasible. A larger cohort of level 0b patients and longer-term follow-up are needed to further assess the strategic advantages.

Incidence, Risk Factors, Progression, and Treatment of Endovenous Heat-Induced Thrombosis Class 2 or Greater After Endovenous Radiofrequency Ablation.

BACKGROUND: Endovenous heat-induced thrombosis (EHIT) is a thrombus that extends from an ablated saphenous vein into the common femoral vein after endovenous radiofrequency ablation (RFA). OBJECTIVE: To investigate the incidence, progression, treatment, and risk factors associated with EHIT-2 or greater after RFA. MATERIALS AND METHODS: This retrospective study included patients diagnosed with symptomatic superficial venous incompetence that were treated by RFA of the great saphenous vein or anterior accessory saphenous vein during the July 2012 to December 2016 study period. Duplex ultrasound scanning was performed at 1 week, 1 month, 3 months, and every year after RFA to detect EHIT. RESULTS: A total of 317 legs from 274 patients were included. The incidence of EHIT-2 or greater was 7.0%, including 5.4% EHIT-2, 1.3% EHIT-3, and 0.3% EHIT-4. No symptomatic pulmonary embolism was found. The independent risk factors for EHIT-2 or greater were vein diameter (p = .027) and concomitant sclerotherapy (p = .037). CONCLUSION: The risk factors found to be independently associated with EHIT-2 or greater were large vein size and concomitant sclerotherapy. Screening for EHIT should be performed in patients with one or both of these risk factors within 1 week after RFA and in patients with postoperative symptoms suggestive of venous thromboembolism.

Analysis of Patient Characteristics and Risk Factors for Thrombosis After Surgery for Congenital Heart Disease.

OBJECTIVES: Thrombosis is a cause of morbidity in 4-15% of children who undergo pediatric cardiac surgery. Data on how to prevent this complication are sorely needed. We aimed to identify risk factors for thrombosis following pediatric cardiac surgery and determine if use of low molecular weight heparin prophylaxis is associated with a reduction in thrombosis risk. DESIGN: Retrospective cohort study. SETTING: Tertiary pediatric cardiovascular ICU. PATIENTS: Patients who underwent cardiac surgery between June 2014 and December 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from patients with venous or arterial thrombosis confirmed by radiologic studies were matched two-to-one to controls based on age, Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery mortality category, and gender. Thrombosis was detected in 33 patients (6.2%): 25 patients (76%) had venous thromboses, five patients (15%) had arterial thromboses, and three patients (9%) had both. Median time to thrombosis detection was 13 days (25-75%; 7-31 d). On multivariate analysis, which included adjustment for postoperative disease severity, fresh frozen plasma exposure was independently associated with thrombosis (odds ratio, 3.7; 95% CI, 1.4-9.4). Twenty-eight patients (85%) had central venous catheter-related thromboses. Low molecular weight heparin prophylaxis use in this subset of patients was not statistically different from controls (50% vs 45%, respectively; p = 0.47). On multivariable analysis, fresh frozen plasma exposure was also independently associated with central venous catheter-related thrombosis (odds ratio, 3.6; 95% CI, 1.2-10.6). CONCLUSIONS: The occurrence of thrombosis after pediatric cardiac surgery at our institution was 6.2%, similar to what has been reported in other studies, despite frequent use of low molecular weight heparin. Further study is needed to determine the role of low molecular weight heparin for thromboprophylaxis and the relationship between fresh frozen plasma and thrombosis risk in children who undergo cardiac surgery.

Assessment of aortic wall thrombus predicts outcomes of endovascular repair of complex aortic aneurysms using fenestrated and branched endografts.

OBJECTIVE: The goal of this study was to investigate the correlation between atherothrombotic aortic wall thrombus (AWT) and clinical outcomes in patients treated by fenestrated-branched endovascular aortic repair (F-BEVAR) and present a new classification system for assessment of AWT burden. METHODS: The clinical data of 301 patients treated for pararenal and thoracoabdominal aortic aneurysms (TAAAs) by F-BEVAR was reviewed. The study excluded 89 patients with extent I to III TAAA because of extensive laminated thrombus within the aneurysm sac. Computed tomography angiograms were analyzed in all patients to determine the location, extent, and severity of atherothrombotic AWT. The aorta was divided into three segments: ascending and arch (A), thoracic (B) and renal-mesenteric (C). Volumetric measurements (cm3) of AWT were performed using TeraRecon software (TeraRecon Inc, Foster City, Calif). These volumes were used to create an AWT index by dividing the AWT volume from the total aortic volume. A classification system was proposed using objective assessment of the number of affected segments, thrombus type, thickness, area, and circumference. Clinical outcomes included 30-day mortality, neurologic and gastrointestinal complications, renal events (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease [RIFLE]), and solid organ infarction. RESULTS: The study included 212 patients, 169 men (80%) and 43 women (20%), with a mean age of 76 ± 7 years. A total of 700 renal-mesenteric arteries were incorporated (3.1 ± 1 vessels/patient). AWT was classified as mild in 98 patients (46%) and was considered moderate or severe in 114 (54%). There was one death (0.5%) at 30 days. Solid organ infarction was present in 50 patients (24%), and acute kidney injury occurred in 45 patients (21%) by RIFLE criteria. An association with higher AWT indices was found for time to resume enteral diet (P = .0004) and decline in renal function (P = .0003). Patients with acute kidney injury 2 by RIFLE criterion had significantly higher (P = .002) AWT index scores in segment B. Spinal cord injury occurred in three patients (1.4%) and stroke in four (1.9%), but were not associated with the AWT index. Severity of AWT using the new proposed classification system correlated with the AWT index in all three segments (P < .001). Any of the end points occurred in 35% of the patients with mild and in 53% of those with moderate or severe AWT (P = .016). CONCLUSIONS: AWT predicts solid organ infarction, renal function deterioration, and longer time to resume enteral diet after F-BEVAR of pararenal and type IV TAAAs. Evaluation of AWT should be part of preoperative planning and decision making for selection of the ideal method of treatment in these patients.

Management and Outcomes of Patients with Occlusive Thrombosis after Pediatric Cardiac Surgery.

OBJECTIVES: To evaluate management and outcomes of thrombosis after pediatric cardiac surgery and stratify thrombi according to risk of short- and long-term complications to better guide therapeutic choices. STUDY DESIGN: Retrospective review was performed of 513 thrombi (400 occlusive) diagnosed after 213 pediatric cardiac operations. Long-term outcomes over time were assessed with the use of parametric hazard regression models. RESULTS: Serious complications and/or high-intensity treatment occurred with 17%-24% of thrombi depending on location, most commonly in thrombi affecting the cardiac and cerebral circulation. Bleeding complications affected 13% of patients; associated factors included thrombolytics (OR 8.7, P < .001), greater daily dose of unfractionated heparin (OR 1.25 per 5 U/kg/day, P = .03), and extracorporeal support (OR 4.5, P = .007). Radiologic thrombus persistence was identified in 30% ± 3% at 12 months; associated factors included extracorporeal support (hazard ratio [HR] 1.9, P = .003), venous (HR 1.7, P = .003), and occlusive thrombi at presentation (HR 1.8, P = .001); greater oxygen saturation before surgery (HR 1.13/10%, P = .05) and thrombi in femoral veins (HR 1.9, P = .001) were associated with increased hazard of resolution. Freedom from postthrombotic syndrome was 83% ± 4% at 6 years, greater number of persistent vessel segment occlusions (HR 1.8/vessel, P = .001) and greater fibrinogen at diagnosis (HR 1.1 per g/L, P = .02) were associated with increased hazard. CONCLUSIONS: Thrombosis outcomes after pediatric cardiac surgery remain suboptimal. Given that more intensive treatment would likely increase the risk of bleeding, the focus should be on both thrombosis-prevention strategies, as well as in tailoring therapy according to a thrombosis outcome risk stratification approach.

Rational classification of portal vein thrombosis and its clinical significance.

Portal vein thrombosis (PVT) is commonly classified into acute (symptom duration <60 days and absence of portal carvernoma and portal hypertension) and chronic types. However, the rationality of this classification has received little attention. In this study, 60 patients (40 men and 20 women) with PVT were examined using contrast-enhanced computed tomography (CT). The percentage of vein occlusion, including portal vein (PV) and superior mesenteric vein (SMV), was measured on CT image. Of 60 patients, 17 (28.3%) met the criterion of acute PVT. Symptoms occurred more frequently in patients with superior mesenteric vein thrombosis (SMVT) compared to those without SMVT (p<0.001). However, there was no significant difference in PV occlusion between patients with and without symptoms. The frequency of cavernous transformation was significantly higher in patients with complete PVT than those with partial PVT (p<0.001). Complications of portal hypertension were significantly associated with cirrhosis (p<0.001) rather than with the severity of PVT and presence of cavernoma. These results suggest that the severity of PVT is only associated with the formation of portal cavernoma but unrelated to the onset of symptoms and the development of portal hypertension. We classified PVT into complete and partial types, and each was subclassified into with and without portal cavernoma. In conclusion, neither symptom duration nor cavernous transformation can clearly distinguish between acute and chronic PVT. The new classification system can determine the pathological alterations of PVT, patency of portal vein and outcome of treatment in a longitudinal study.

How to manage thrombosis in myeloproliferative neoplasms.

PURPOSE OF REVIEW: In this article, an updated overview of risk factors and management of vascular complications in myeloproliferative neoplasms (MPN) is presented. RECENT FINDINGS: The rate of thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis is elevated and a risk-oriented therapeutic approach is recommended to avoid inappropriate exposure to cytotoxic drugs on one side or suboptimal treatment on the other. Established thrombosis risk factors are age and previous vascular events but novel disease-related determinants such as leukocytosis and JAK2V617F mutational status and/or mutational burden are now under active investigation. The theory that elevated platelet count increases thrombosis risk in these diseases is now challenged. SUMMARY: Recent recommendations by the European Leukemia Net suggest that MPN patients should be stratified and treated according to conventional risk factors (age and previous events) and that baseline leukocytosis and JAK2V617F mutation should be considered once more information is available and when they have been eventually validated in prospective studies.

In Germany diabetic patients with coronary artery disease are treated more intensively than diabetic patients with other manifestations of atherothrombosis--results from the REACH registry.

INTRODUCTION: Atherothrombosis can present as coronary artery disease (CAD) cerebrovascular disease (CVD) and peripheral arterial disease (PAD). It is unknown whether diabetics with CAD differ from those with other manifestations of atherothrombosis such as CVD or PAD regarding clinical characteristics, biochemical parameters, or medications. MATERIAL AND METHODS: The REACH (REduction of Atherothrombosis for Continued Health) registry evaluated 67 888 patients with established atherothrombosis or risk factors. Of 5 646 recruited German patients, 2 381 (42%) are diabetic. Of these 1 438 (60%) have CAD (either only CAD or in combination with CVD and/or PAD - CAD group) and 520 (22%) have other manifestations of atherothrombosis (either CVD or PAD or both - other manifestation group) and 18% have only risk factors. Differences between diabetics with CAD and diabetics with other manifestations of atherothrombosis were evaluated with multivariate models (79% male, 69+/-9 years, BMI 29+/-5 kg/m (2)) (SAS9.1). RESULTS: After correcting for age, sex and BMI, CAD patients receive (OR; 95% CI) more aspirin (1.5; 1.2-1.9; p=0.0002), statins (3.1; 2.6-3.7), beta-blockers (4.0; 3.8-4.8), diuretics (1.4; 1.2-1.6), ACE-inhibitors/ARBs (1.4; 1.2-1.7) and nitrates (8.8; 6.7-11.7) and significantly less often metformin (0.75; 0.61-0.93; p=0.01) with no differences concerning other antidiabetics. This resulted in significantly (p<0.05) lower blood-pressure (CAD 142/81 mmHg, other manifestations 145/82 mmHg) and LDL-cholesterol levels (CAD 108+/-37 mg/dl, other manifestations 123+/-37 mg/dl). Therefore more CAD patients reach LDL and blood-pressure-goals (CAD 47%/33%; other manifestations 30%/24%, respectively). Only few patients (CAD 7.1%, other manifestations 4.1%) reach all treatment goals. Furthermore, less CAD patients than patients with other manifestations of atherothrombosis are current smokers (11% vs. 22%). DISCUSSION: These data indicate considerable treatment differences between diabetics with CAD and those with other manifestations of atherothrombosis such as CVD or PAD. CAD patients are treated more intensively and therefore reach lower lipid and blood-pressure values.

Flegmasia cerulea dolens: reporte de un caso y revisión de la literatura / Flegmasia cerulea dolens: case report and literature review

Phlegmasia Caerulea Dolens is a rare complication of deep vein thrombosis. It presents with a sudden onset of pain, swelling, discoloration and arterial compromise of the affected limb. There’s usually history of prothrombotic events such as malignancy, femoral vein catheterism, antiphospholipid syndrome, recent surgery, pregnancy, etc. Left without treatment, it can evolvein to gangrene, septic shock and death. Diagnosis usually only requires clinical appreciation.Confirmation can be done with ultrasonographic studies with doppler. Treatment can be both medical and surgically based. Medical therapy can be done with heparin and elevation of the affected limb or the use of thrombolytic, whilst surgical therapy can be either venous thrombectomy or amputation. We present the case of a 57-year old smoker, diabetic, and with systemic lupus erythematosus history female patient, that goes to the emergency room with sudden left leg pain, with cyanosis and absence of distal pulses. Besides she presented with lower respiratory symptoms. Diagnosis was confirmed with ultrasound and CT pulmonary angiography was performed showing pulmonary embolism. Medical treatment was initiated with good response.

Thrombocytosis and thrombosis.

The aim of this review is to discuss current diagnostic approaches to, and classification of, patients presenting with thrombocytosis, in light of novel information derived from the discovery of specific molecular abnormalities in chronic myeloproliferative disorders (CMPD), which represent the most common cause of primary thrombocytosis. The JAK2V617F and the MPLW515L/K mutations have been found in patients with essential thrombocythemia, polycythemia vera, and primary myelofibrosis, and less frequently in other myeloproliferative disorders complicated by thrombocytosis. However, neither mutation is disease specific nor is it universally present in patients with elevated platelet counts due to a CMPD; therefore, distinguishing between reactive and primary forms of thrombocytosis, as well as among the different clinical entities that constitute the CMPD, still requires a multifaceted diagnostic approach that includes as a key step the accurate evaluation of bone marrow histology. The role of elevated platelet counts in thrombosis, which represent the predominant complication of CMPD,significantly affecting prognosis and quality of life as well as, paradoxically, in the pathogenesis of the hemorrhagic manifestations, will be discussed. Established and novel potential risk factors for thrombosis, including the clinical relevance of the JAK2V617F mutation, and current management strategies for thrombocytosis are also briefly discussed.

Segurança dos stents farmacológicos no infarto agudo do miocárdio em lesões com trombos visíveis à angiografia / Safety of drug eluting stents in acute myocardial infarction in lesions with angiographically detectable thrombi

Objetivo: Demonstrar a segurança dos stents farmacológicos (SF) no IAM em lesões com elevado risco de trombose quando comparados aos stents convencionais. Métodos: Estudo prospectivo não-randomizado em queforam analisados, de forma consecutiva, 86 pacientes submetidos à angioplastia primária, no período de 01/01/2005 a 31/10/2006, que apresentavam lesões tipo B2 ou C e evidência de trombos à angiografia na lesão culpada, definidos como falha de enchimento visualizadaem mais de uma incidência. Foi comparada a ocorrência de trombose subaguda (TSA) e trombose aguda (TA) em um grupo de pacientes que usou SF (Grupo I) com um grupo que usou SC (Grupo II). As características dos dois grupos são: Grupo I: idade média 64,3±12,69 anos; 57,1% hipertensos; 37,1% diabéticos; 25,7% tabagistas; 51,4% dislipidêmicos; 74,2% do sexo masculino; 88,5% fizeram uso de antagonistas do receptor de IIb/IIIa ; nenhum caso de TA e apenas 1 caso de TSA. Grupo II: idade média 66,54±10,81; 57,1% hipertensos (p=0,19); 15,6% diabéticos (p=0,02); 35,2% tabagistas (p=0,35); 62,7% dislipidêmicos (p=0,29); 84,3% fizeram uso de antagonistas do receptorde IIb/IIIa (p=0,36); nenhum caso de TA e TSA. Resultados: Os grupos analisados foram homogêneos,não apresentando significância estatística para os elementos analisados à exceção do maior número de pacientes diabéticos no Grupo I. A diferença entre os grupos de trombose aguda ou subaguda não atingiu relevância estatística. Conclusão: O uso de SF no IAM em lesões com trombos visualizados à angiografia é seguro e não está associado a um aumento da incidência de trombose quandocomparado ao stent convencional.

Objective: To demonstrate the safety of drug eluting stents (DES) in AMI in lesions with high risk of thrombosis when compared to conventionalstents. Methods: Non-randomized prospective study of 86 consecutive patients submitted to primary angioplasty from January 1st 2005 to October 31st 2006 who presented type B2 or C lesions and evidence of thrombus in angioplasty in the affectedlesion, defined as a filling gap visualized in more than one incidence. The occurrence of subacute thrombosis (SAT) and acute thrombosis (AT) werecompared between a group of patients that used DES (Group I) and a group that used CS (Group II). The characteristics of both groups are: Group I: mean age 64.3±12.69 years; 57.1% hypertensive; 37.1% diabetic; 25.7% tobacco users; 51.4%dyslipidemic; 74.2% males; 88.5% used IIb/IIIa receptor antagonists; no cases of AT and only one case of SAT. Group II: mean age of 66.54±10.81years; 57.1% hypertensive (p=0.19); 15.6% diabetic (p=0.02); 35.2% tobacco users (p=0.35); 62.7%dyslipidemic (p=0.29); 84.3% used IIb/IIIa receptor antagonists (p=0.36); no cases of AT or SAT. Conclusion: The use of DES in AMI in lesions withthrombi visualized in angiography is safe and is not associated with an increase in the incidence of thrombosis when compared to conventional stent.

Stearic, oleic, and linoleic acids have comparable effects on markers of thrombotic tendency in healthy human subjects.

Because human studies concerning the effects of stearic acid on thrombotic tendency are inconsistent, we compared the effects of stearic acid with those of its unsaturated derivatives, oleic acid and linoleic acid. In this randomized, crossover study, 45 subjects (27 women and 18 men) consumed, in random order, 3 experimental diets, each for 5 wk. Diets contained approximately 38% of energy as fat. Dietary compositions were the same except for 7% of energy from stearic, oleic, or linoleic acids. At the end of each period, ex vivo and in vitro platelet aggregation, and variables of coagulation, fibrinolysis, and hematology were evaluated. In men, ex vivo platelet aggregation time as measured by filtragometry (P = 0.036 for diet effects) was favorably prolonged during consumption of the linoleic acid diet compared with the stearic acid diet (P = 0.040), but there was no difference with consumption of the oleic acid diet (P = 0.198). In vitro platelet aggregation induced by collagen and ADP, and variables of coagulation (factor VII amidolytic activity and concentrations of fibrinogen and prothrombin fragment 1 and 2) and fibrinolysis [plasminogen activator inhibitor (PAI) activity and concentrations of tissue plasminogen activator (tPA)/PAI-1 complexes] did not differ among the 3 diets. The mean platelet volume of the subjects decreased during consumption of the stearic acid diet by 0.32 fL compared with the oleic acid diet (P < 0.001) and by 0.35 fL compared with the linoleic acid diet (P < 0.001). In conclusion, our results do not suggest that stearic acid is highly thrombogenic compared with oleic and linoleic acids.

The contribution of factor V Leiden and prothrombin G20210A mutation to the risk of central venous catheter-related thrombosis.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the incidence of central venous catheter (CVC)-related thrombosis and the contribution of two common inherited coagulation disorders (factor V Leiden, prothrombin G20210A mutation) to this complication in a large hospital population. DESIGN AND METHODS: In a prospective setting, patients were assessed daily for signs and symptoms suggestive of thrombosis. Routine Doppler-ultrasound was performed weekly in all patients until CVC removal. Doppler-ultrasound examinations were stored on videotape and assessed by two blinded observers. In the case of clinically suspected thrombosis the physicians followed routine diagnostic and therapeutic procedures. The presence of factor V Leiden and prothrombin G20210A mutation and other potential risk factors were assessed in all patients. RESULTS: In 252 consecutive patients the cumulative incidence of-CVC related thrombosis was 30% (clinically manifested thrombosis: 7%). The relative risk of factor V Leiden or prothrombin G20210A mutation for thrombosis was 2.7 (CI95% 1.9 to 3.8). In addition, a personal history of venous thrombosis was associated with CVC-related thrombosis, whereas the severity of thrombosis was affected by the absence of anticoagulants and the presence of cancer. INTERPRETATION AND CONCLUSIONS: Thrombosis is frequently observed after central venous catheterization. Common inherited abnormalities in blood coagulation contribute substantially to CVC-related thrombosis. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in vulnerable patients, a priori determination of common inherited and acquired risk factors may form a basis to guide these treatment decisions.

Analysis of pediatric thrombotic patients in Turkey.

This study analyzes the data of thrombotic children who were followed up in different pediatric referral centers of Turkey, to obtain more general data on the diagnosis, risk factors, management, and outcome of thrombosis in Turkish children. A simple two-page questionnaire was distributed among contact people from each center to standardize data collection. Thirteen pediatric referral centers responded to the invitation and the total number of cases was 271. All children were diagnosed with thromboembolic disease between January 1995 and October 2001. Median age at time of first thrombotic event was 7.0 years. Of the children 4% of the cases were neonates, 12% were infants less than 1 year old, and 17% were adolescents. Thromboembolic event was mostly located in the cerebral vascular system (32%), deep venous system of the limbs, femoral and iliac veins (24%), portal veins (10%), and intracardiac region (9%). Acquired risk factors were present in 86% of the children. Infection was the most common underlying risk factor. Inherited risk factors were present in 30% of the children. FVL was the most common inherited risk factor. Acquired and inherited risk factors were present simultaneously in 19% of the patients. Eleven children had a history of familial thrombosis. Due to the local treatment preferences, the treatment of the children varied greatly. Outcome of the 142 patients (52%) was reported: 88 (62%) patients had complete resolution, 47 (33%) had complications, 12 (9%) had recurrent thrombosis, and 34 (24%) died. Three children (2.1%) died as a direct consequence of their thromboembolic disease. The significant morbidity and mortality found in this study supports the need for multicentric prospective clinical trials to obtain more generalizable data on management and outcome of thrombosis in Turkish children.

[Refinement of cytopathology of CT-guided fine needle aspiration biopsies with additional histologic examination of formalin-fixed blood-clots]. / Verfeinerung der zytologischen Diagnostik von CT-gesteuerten Feinnadelaspirationsbiopsien durch histologische Zusatzuntersuchung Formalin-fixierter Blutkoagel.

PURPOSE: To evaluate formalin-fixed blood-clot for diagnostic efficacy and safety in percutaneous CT-guided fine needle aspiration biopsy (FNAB) in addition to cytopathology. MATERIALS AND METHODS: 61 CT-guided FNABs were entered into a prospective trial. FNAB was performed in 22 female and 39 male patients (32 - 83 years, m = 62.8 +/- 10.9 y) using 20- (n = 7) and 22-gauge (n = 54) needles. After correct placement within the tumor, material for cytopathological work-up was harvested. Additional material was sampled by needling (stirring and aspirating) within the lesion. These blood-clots were fixed in buffered formalin and delivered for histopathological work-up along with the smears. All results were correlated with the clinical course of the patient; cases of negative biopsies underwent surgery or were followed clinically for a minimum of 13 months (m = 14.8 +/- 1.4 months). Finally, all puncture-related side-effects and complications were analyzed and compared with data from 108 transthoracic FNABs performed over a two-year period before using this technique. RESULTS: Tissue samples adequate for pathological diagnosis were obtained in 93.4 % (57 of 61 patients). Malignant cells were found in 50 samples, and 7 biopsy results were negative. The relevant pathological changes were depicted on both smear and blood-clot in 47 cases (82.4 %). In the remaining patients, the diagnoses were exclusively established by cytopathology (n = 6) and histopathology (n = 4). Altogether, additional information was obtained in 20 of the 57 FNABs (35.1 %). In the 47 cases with relevant findings obtained with both methods, the routine stain already led to the correct diagnosis in 9 cases by showing cohesive layers of malignant cells, and immunocytochemistry allowed subclassification of the biopsy material in additional 7 cases. Pneumothorax occurred in 12 of 38 transpleural punctures (31.6 %), hemoptysis in one patient (2.6 %). Four pneumothoraces required further treatment (3 thoracocenteses, 1 chest tube placement). Hemorrhagic complications requiring further treatment were not seen, but two minor hematomas were observed in the 19 abdominal punctures. The overall rate for pneumothorax was 38.9 % (42 of 108 interventions) for the FNAB performed in standard technique. CONCLUSION: Histological work-up of sampled blood-clots yielded a higher accuracy of CT-guided FNABs. Additional immunocytochemical studies allowed subclassification of tumor material. The complication rate of this technique was not higher than for FNAB alone.

Heparin-induced thrombocytopenia and thrombosis.

Heparin remains the most commonly used parenteral medication in hospitalized patients. Heparin induced thrombocytopenia (HIT) and heparin induced thrombocytopenia with thrombosis syndrome or the white clot syndrome are important complications of heparin use. This article provides an in-depth review of the etiopathogenesis, clinical manifestations, diagnosis, and management options in patients with HIT. Clinical problems associated with HIT such as antiphospholipid antibody syndrome and venous gangrene are described. The management options of HIT patients during cardiac interventional procedures and coronary surgery as well as recent advances in therapeutic options are summarized.

Erythromelalgia--a thrombotic complication in chronic myeloproliferative disorders.

Erythromelalgia is a very specific, thrombotic syndrome related with thrombocythemia that may occur during the course of chronic myeloproliferative disorders (MPD), especially polycythemia vera (PV) and essential thrombocythemia (ET). This poorly understood clinical syndrome is characterized by red, congested distal extremities and painful burning sensations, usually confined to the ball of the foot and one or more toes or fingers. If left untreated, it may progress towards acrocyanosis and even peripheral gangrene. Sometimes, it may precede the diagnosis of MPD by months or years. The pathophysiological aspects of erythromelalgia as well as its differentiation with erythermalgia have been reviewed in this study.