Occurrence Of Thromboembolic Complications Research Articles

Association of preprocedural antiplatelet use with decreased thromboembolic complications for intracranial aneurysms undergoing intrasaccular flow disruption.

This study was conducted to investigate the impact of antiplatelet administration in the periprocedural period on the occurrence of thromboembolic complications (TECs) in patients undergoing treatment using the Woven EndoBridge (WEB) device for intracranial wide-necked bifurcation aneurysms. The primary objective was to assess whether the use of antiplatelets in the pre- and postprocedural phases reduces the likelihood of developing TECs, considering various covariates. A retrospective multicenter observational study was conducted within the WorldWideWEB Consortium and comprised 38 academic centers with endovascular treatment capabilities. Univariable and multivariable logistic regression analyses were performed to determine the association between antiplatelet use and TECs, adjusting for covariates. Missing predictor data were addressed using multiple imputation. The study comprised two cohorts: one addressing general thromboembolic events and consisting of 1412 patients, among whom 103 experienced TECs, and another focusing on symptomatic thromboembolic events and comprising 1395 patients, of whom 50 experienced symptomatic TECs. Preprocedural antiplatelet use was associated with a reduced likelihood of overall TECs (OR 0.32, 95% CI 0.19-0.53, p < 0.001) and symptomatic TECs (OR 0.49, 95% CI 0.25-0.95, p = 0.036), whereas postprocedural antiplatelet use showed no significant association with TECs. The study also revealed additional predictors of TECs, including stent use (overall: OR 4.96, 95% CI 2.38-10.3, p < 0.001; symptomatic: OR 3.24, 95% CI 1.26-8.36, p = 0.015), WEB single-layer sphere (SLS) type (overall: OR 0.18, 95% CI 0.04-0.74, p = 0.017), and posterior circulation aneurysm location (symptomatic: OR 18.43, 95% CI 1.48-230, p = 0.024). The findings of this study suggest that the preprocedural administration of antiplatelets is associated with a reduced likelihood of TECs in patients undergoing treatment with the WEB device for wide-necked bifurcation aneurysms. However, postprocedural antiplatelet use did not show a significant impact on TEC occurrence.

Prasugrel Single Antiplatelet Therapy versus Aspirin and Clopidogrel Dual Antiplatelet Therapy for Flow Diverter Treatment for Cerebral Aneurysms: A Retrospective Multicenter Study.

The optimal antiplatelet regimen after flow diverter treatment of cerebral aneurysms is still a matter of debate. A single antiplatelet therapy might be advantageous in determined clinical scenarios. This study evaluated the efficacy and safety of prasugrel single antiplatelet therapy versus aspirin and clopidogrel dual antiplatelet therapy. We performed a post hoc analysis of 4 retrospective multicenter studies including ruptured and unruptured aneurysms treated with flow diversion using either prasugrel single antiplatelet therapy or dual antiplatelet therapy. Primary end points were the occurrence of any kind of procedure- or device-related thromboembolic complications and complete aneurysm occlusion at the latest radiologic follow-up (mean, 18 months). Dichotomized comparisons of outcomes were performed between single antiplatelet therapy and dual antiplatelet therapy. Additionally, the influence of various patient- and aneurysm-related variables on the occurrence of thromboembolic complications was investigated using multivariable backward logistic regression. A total of 222 patients with 251 aneurysms were included, 90 (40.5%) in the single antiplatelet therapy and 132 (59.5%) in the dual antiplatelet therapy group. The primary outcome-procedure- or device-related thromboembolic complications-occurred in 6 patients (6.6%) of the single antiplatelet therapy and in 12 patients (9.0%) of the dual antiplatelet therapy group (P = .62; OR, 0.712; 95% CI, 0.260-1.930). The primary treatment efficacy end point was reached in 82 patients (80.4%) of the single antiplatelet therapy and in 115 patients (78.2%) of the dual antiplatelet therapy group (P = .752; OR, 1.141; 95% CI, 0.599-2.101). Logistic regression showed that non-surface-modified flow diverters (P = .014) and fusiform aneurysm morphology (P = .004) significantly increased the probability of thromboembolic complications. Prasugrel single antiplatelet therapy after flow diverter treatment may be as safe and effective as dual antiplatelet therapy and could, therefore, be a valid alternative in selected patients. Further prospective comparative studies are required to validate our findings.

D-Dimer: A Primer Biomarker in COVID-19

Aim and Objective: To explore risk factors associated with mortality in COVID-19 patients and assess the use of D-dimer as a first line biomarker for disease severity and clinical outcome.&#x0D; Materials and Methods: We retrospectively analysed the pathological and radiological characteristics of 2087 consecutive cases of COVID-19 in PSH, Vadodara, Gujarat, from March 2021 to July 2022. Graphically, MS-Excel with median values were used. Correlations of D-dimer upon admission with disease severity and in-hospital mortality were analysed accordingly. Data were collected in MS-Excel with median values.&#x0D; Results: 2087 patients having positive RT-PCR and confirm diagnosis of Covid-19 were included upon hospital admission. Whereas, 65.78% (n= 1373) were male and 34.21% (n= 714) were female. Mean age was 52± 4 year. D-dimer level &gt; 250 ng/mL at the time of hospital admission was the only fluctuating value accompanying with increased mortality [(95% CI), P = 0.025]. D-dimer elevation (≥250 ng/mL) was seen in 81.31% patients. Pericardial effusion and Deep vein thrombosis were ruled out in probability of thrombosis based on 2-D echo, X-ray chest and USG. This recommend that hyper-coagulopathy of the fibrin plays a significant role in the occurrence of thromboembolic complications with COVID-19 patients. D-dimer levels was crucially escalated with increasing severity of COVID-19 as determined by clinical improvement (within 5 days of hospital stay) and chest CT staging (CO-RADS score out of 25, P = 0.000). 319 patient were died during above said period and overall in-hospital mortality rate was 15.28%. Additionally, 6.08 % (n=127) patient were on BIPEP and all are died with 100% death ratio. Median D-dimer level in non-survivors (15.29%) was significantly higher than in survivors (84.71%, n = 1768, RR 24.69%). Median elevated D-dimer level was 600.5 ng/ml. Furthermore, the disease activity were higher in the overhead D-dimer level group demonstrated to have anticipating value in differentiating disease severity along with high ESR level and hs-CRP and the fibrinogen level was also upraised indicated seriousness of disease.&#x0D; Conclusion: We concluded that D-dimer level was routinely uplifted in patients with COVID-19 disease. D-dimer levels match up with severity of the disease and are a significant definitive prognostic first line marker for in-hospital mortality for COVID-19 disease. Furthermore, a significant association between the high D-dimer level and severity of COVID-19 disease was noted among comorbid patients. Additionally, raced D-dimer level demonstrated with high ESR level and hs-CRP and the fibrinogen level indicated seriousness of disease in comorbid patients.

Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice.

Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli and is characterized by microangiopathic hemolytic anemia and acute kidney injury. Hitherto, therapy has been limited to organ-supportive strategies. Erythropoietin (EPO) stimulates erythropoiesis and is approved for the treatment of certain forms of anemia, but not for HUS-associated hemolytic anemia. EPO and its non-hematopoietic analog pyroglutamate helix B surface peptide (pHBSP) have been shown to mediate tissue protection via an innate repair receptor (IRR) that is pharmacologically distinct from the erythropoiesis-mediating receptor (EPO-R). Here, we investigated the changes in endogenous EPO levels in patients with HUS and in piglets and mice subjected to preclinical HUS models. We found that endogenous EPO was elevated in plasma of humans, piglets, and mice with HUS, regardless of species and degree of anemia, suggesting that EPO signaling plays a role in HUS pathology. Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS. Administration of EPO or pHBSP improved 7-day survival and attenuated renal oxidative stress but did not significantly reduce renal dysfunction and injury in the employed model. pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation. In conclusion, targeting the EPO-R/IRR axis reduced mortality and renal oxidative stress in murine HUS without occurrence of thromboembolic complications or other adverse side effects. We therefore suggest that repurposing EPO for the treatment of patients with hemolytic anemia in HUS should be systematically investigated in future clinical trials.

Coronavirus disease 2019 (COVID-19): NETosis-associated mechanisms of progression and prospects for therapy regulating the formation of neutrophil extracellular traps (NETs)

Infectious disease COVID-19 caused by the SARS-CoV-2 coronavirus is characterized by high contagiousness, complexity of pathogenesis and unpredictability of the clinical course. In severe cases, which are especially susceptible to men, the elderly and people with underlying medical conditions such as obesity, diabetes, hypertension, cardiovascular and chronic respiratory diseases, the infection leads to respiratory failure and death due to the development of an extensive inflammatory reaction. As a result of many studies, it has been established that one of the leading causes of the severe course and death of patients with COVID-19 is the development of coagulopathy, that is, increased thrombus formation in small vessels due to excessive activity of neutrophils, which form the so-called neutrophil extracellular traps (NETs). Although NETs play a useful role in protecting their host from pathogens, their overgrowth can trigger a cascade of adverse reactions including: the production of antibodies against the host’s DNA (autoimmunization); damage to surrounding tissue; or the occurrence of thromboembolic complications. Therefore, extracellular neutrophil traps and their markers have been identified as targets for new therapeutic strategies aimed at reducing the severity of COVID-19 disease and/or mortality. This article describes the structure of NETs, as well as analyzes the molecular mechanisms that contribute to their overgeneration. In addition, the prospects for COVID-19 therapy aimed at regulating the formation of extracellular traps by creating drugs both limiting the production of NET structures and dissolving their excess amounts in the body of patients are discussed.

Risk of postoperative thromboembolic complication after major digestive surgery in patients receiving antiplatelet therapy: Lessons from more than 3,000 operations in a single tertiary referral hospital

BackgroundAlthough recent studies have suggested that the continuation of preoperative antiplatelet therapy with aspirin does not affect intraoperative or postoperative bleeding in patients undergoing digestive surgery, its preventive effect against thromboembolic complication remains largely unknown. MethodsA total of 3,072 patients who underwent major digestive surgery (esophago-gastrointestinal and hepatobiliary-pancreatic resection for malignancy) between 2005 and 2018 at our institution were enrolled in this study. The patients were divided into 3 groups: patients continuing to receive preoperative antiplatelet therapy with aspirin (continued-antiplatelet therapy group, n = 425), those discontinuing preoperative antiplatelet therapy (discontinued-antiplatelet therapy group, n = 549), and those who were not receiving antiplatelet therapy (non-antiplatelet therapy group, n = 2,117). The CHADS2 and the CHA2DS2-VASc scoring system were used to assess potential thromboembolic risk. Surgical outcomes were compared between the groups and the risk factors for thromboembolic complication, bleeding complication, and operative mortality were determined by multivariate analysis. ResultsThere was no difference between the discontinued-antiplatelet therapy and continued-antiplatelet therapy groups in the rate of high risk patients categorized by CHADS2 and CHA2DS2-VASc scores; however, the occurrence of thromboembolic complication in the discontinued-antiplatelet therapy group was significantly higher compared with the continued-antiplatelet therapy group (2.8% vs 0.5%; P = .006). In a multivariate analysis using the whole cohort, discontinuation of antiplatelet therapy (odds ratio = 4.39; P < .001), poor performance status (odds ratio = 4.14; P = .001), and hypertension (odds ratio = 3.46; P = .005) were the independent risk factors for thromboembolic complication. In the groups of patients receiving antiplatelet therapy, multivariate analysis showed that preoperative aspirin continuation had a significant negative impact (odds ratio = 0.10, P = .029) on the occurrence of thromboembolic complication, but did not affect either postoperative bleeding complication or operative mortality. ConclusionDiscontinuation of antiplatelet therapy during major digestive surgery is the most significant risk factor for thromboembolic complication, and the continuation of preoperative aspirin therapy significantly reduces the occurrence of thromboembolic complication in patients receiving antiplatelet therapy. It is suggested that the preoperative continuation of aspirin monotherapy is one of the preferred options to prevent severe thromboembolic events during major digestive surgery in patients receiving antiplatelet therapy.

Superficial-vein thrombosis of the lower limb: A pathology that is not always benign

Objectives: The value of our observations is to take stock of the interest of the medical and surgical management of superficial vein thrombosis. Case Report: We report three patients with severe superficial vein thrombosis whose symptoms were painful induration along the course of the superficial veins of the lower limb. The diagnosis was confirmed by venous Doppler, follow-up was marked by the occurrence of thromboembolic complications (pulmonary embolism) in one patient. Results: All patients received emergency treatment-anticoagulation for a week with relay by Vitamin K antagonists, surgery as an emergency consisted of ligation of the saphenofemoral junction (SFJ) under local anesthesia in one patient (Case 2). One of the patients had a pulmonary embolism 3 days later, and this patient did not receive surgical ligation. The third patient has progressed well on anticoagulant therapy. Discussion: Superficial vein thrombosis of the lower limbs has long been considered as benign with the natural course often leading to resolution of the thrombus and in rare cases complications which can affect the prognosis of the patient. Anticoagulation should be started urgently especially before extensive thrombosis and surgical ligation of the SFJ considered to prevent thrombus propagation. Conclusion: Superficial vein thrombosis is often considered to have a benign course once diagnosed. Experience from our short series suggests that the management should be more aggressive and robust with anticoagulation and consideration of ligation of the SFJ where thrombosis is extensive and reduce the dreaded complication of a pulmonary embolism. Therapeutic recommendations concerning this disease have a relatively weak level of certitude as no treatment has been proved of benefit. We thought interesting to talk through observational clinical cases and expose our personal attitude to a serious superficial vein thrombosis.

Venous thromboembolic complications with and without intermittent intraoperative and postoperative pneumatic compression in patients with glioblastoma multiforme using intraoperative magnetic resonance imaging. A retrospective study

ObjectiveTo evaluate the effectiveness of intraoperative and postoperative intermittent pneumatic compression (IPC) as a method used to decrease the incidence of deep venous thrombosis (DVT), in comparison to the standard use of graduated compression stockings, low-molecular weight heparin (LMWH) and physiotherapy during the hospital stay. All patients in this study underwent intracranial surgery for glioblastoma multiforme (GBM) using intraoperative magnetic resonance imaging (MRI) guidance. Patients and methodsWe performed a single center retrospective study of a cohort of 153 patients who underwent surgery for GBM aided by intraoperative MRI from October of 2009 to January of 2015 at the International Neuroscience Institute (INI), Hannover, Germany. Out of all patients, 75 in comparison to 78 were operated with and without the additional use of IPC, respectively. Both groups received graduated compression stockings, LMWH and physiotherapy postoperatively as a basic thromboprophylaxis. Postoperatively the patients were screened for DVT by Doppler ultrasonography of the limbs and pulmonary embolism (PE) by CT-scan of the chest. ResultsDVTs were found in 6 patients with IPC and in 3 patients without IPC. The incidence of developing DVTs was therefore not significantly increased with the application of IPC from 3.9% to 8% (P-value: 0.33). No statistically significant differences were found in the probability of occurrence of pulmonary embolism (PE) with a reduction from 2.6% to 1.3% (P-value: 0.59). ConclusionOur results demonstrate, that the surgical intervention and the subsequent patient immobilization, as well as the thromboprophylactic techniques used have a relatively low influence on the occurrence of thromboembolic complications than we expected. Our findings might be attributed to the overall low number of these complications in a glioblastoma multiforme patient population expected to be at a high risk for coagulopathy. In other words, in order to produce statistically significant results, we would need to increase the patient cohort. By doing so we may better detect a positive therapeutic effect. Alternatively, because of the multitude of possible complex risk-factors leading to coagulopathy in a glioblastoma patient population it might be the case that IPC has little or no effect and that there is a different underlying mechanism responsible for the observed coagulopathy.

Anticoagulation for Atrial Fibrillation after Resolution of Dengue Haemorrhagic Fever.

Dear Sir, In a recent publication, Pahadiya et al., presented a young patient with atrial fibrillation (AF) during dengue haemorrhagic fever, suggesting the role of acute viral myocarditis [1]. In this interesting case report, the patient was admitted after five days of dengue symptoms. The cardiac arrhythmia was observed in the 3rd day of hospital admission and persisted until the 8th day, two days after the initiation of steroid therapy with dexamethasone. No specific antiarrhythmic therapy was prescribed. The patient was discharged on 12th day, clinically stable, afebrile and with normal haematological laboratory parameters. Unfortunately, despite of the excellent hospital upshot of this patient, the authors did not present his long-term follow-up neither they contemplated the anticoagulation therapy after hospital discharge, late after resolution of the acute phase. AF is associated with the occurrence of thromboembolic complications, mainly stroke, that are preventable with anticoagulation therapy. The risk of thromboembolism for patients undergoing cardioversion of AF may reach 5% [2]. Pooled data from 32 studies of cardioversion of AF or atrial flutter suggest that 98% of clinical thromboembolic events occur within 10 days after restoration of sinus rhythm [3]. Thus, current guidelines for the management of patients with AF [4] are emphatic in recommending oral anticoagulation for at least 4 weeks after conversion of an episode of 48 hours’ duration or longer, regardless of the CHA2DS2-VASc score for thromboembolism. During the acute phase of haemorragic dengue fever, there is no statement regarding the management of anticoagulation in patients with indication for this therapy, but it seems reasonable the avoidance of any antithrombotic drugs in these days. However, after a good resolution of the acute phase of the infection, those patients must be considered for anticoagulation if their arrhythmia had lasted for more than 48 hours. In our first report of the association of AF with haemorrhagic dengue fever, the patient had the sinus rhythm restored in 24 hours with amiodarone infusion [5]. He did not receive oral anticoagulation due to the short duration of AF. In the case of Pahadiya et al., the episode of atrial fibrillation lasted for 5 days [1]. The decision for anticoagulation in this patient is difficult. However, I do believe that this therapy should have been initiated. Finally, I would like to state that, in our first report of atrial fibrillation due to dengue haemorrhagic fever [5], we had not mentioned some role for steroid therapy, as it was referred in the discussion of Pahadiya et al., [1].

Asymptomatic persistent atrial fibrillation and outcome: Results of the RACE study

Symptoms are a major driver for patients with atrial fibrillation (AF) to seek medical attention and are important to titrate AF therapies. However, a large proportion of patients with AF are asymptomatic. To investigate the clinical profile and prognosis of patients with asymptomatic recurrent persistent AF in the RAte Control versus Electrical cardioversion for persistent atrial fibrillation study. Patients with asymptomatic AF (n = 157 [30%]) were compared with patients with symptomatic AF (n = 365 [70%]). The primary end point was a composite of cardiovascular morbidity and mortality. Patients with asymptomatic AF were younger and more often men than were patients with symptomatic AF. Cardiac diseases were less common. Quality of life (the Medical Outcomes Study Short-form health survey questionnaire) was better in patients with asymptomatic AF and comparable to healthy controls. At baseline and during follow-up, there were no differences in rate control, antiarrhythmic, or anticoagulant drugs; cardioversions; and time in sinus rhythm. After a follow-up of 2.3 ± 0.6 years, the primary end point occurred in 21 (13%) patients with asymptomatic AF and 83 (23%) patients with symptomatic AF. After adjusting for relevant covariates, asymptomatic AF was associated with a lower risk of the primary end point (hazard ratio 0.51; 95% confidence interval 0.29-0.92; P = .024). This difference was driven by significantly less heart failure hospitalizations (0 vs 21 [6%]) and severe effects of antiarrhythmic drugs or digoxin (1 [0.6%] vs 13 [4%]). Importantly, no difference in the occurrence of thromboembolic complications was observed. Patients with asymptomatic AF were more often men and had less cardiac disease. During follow-up, in patients with asymptomatic AF, heart failure hospitalizations and severe adverse effects of antiarrhythmic and rate control drugs occurred significantly less frequently.

Does tranexamic acid stop haemoptysis?: Table 1:

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does tranexamic acid stop haemoptysis'? Altogether 49 papers were found using the reported search strategy, of which 13 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This consisted of one systematic review including a meta-analysis of two double-blind randomized controlled trials (RCTs), the two RCTs, one cohort study, two case-series and seven case reports. Main outcomes included bleeding time, bleeding volume and occurrence of thromboembolic complications after start of treatment. Based on results from the meta-analysis, no difference in remission of bleeding within 1 week was found between tranexamic acid (TA) and placebo groups (odds ratio 1.56, 95% CI: 0.44-5.46). However, overall bleeding time was significantly shorter for the TA group (weighted mean difference -19.47, 95% CI: -26.90, -12.03 h). In one RCT, TA reduced both the duration and the volume of bleeding compared with patients receiving placebo (both P < 0.0005). However, the other RCT failed to find a difference in bleeding time (P = 0.2). In these studies, no patient suffered from thromboembolic complications. Two case reports, however, describe development of pulmonary embolism during TA treatment. Several case reports on the use of TA for treatment of haemoptysis secondary to cystic fibrosis were found. In general, they suggest that TA may be a useful and well-tolerated medication for the treatment of intractable haemoptysis in this patient group. We conclude that limited research on the use of TA for treatment of haemoptysis exists. As aetiology of haemoptysis as well as length of treatment, dosage and form of TA administration varied between the studies, strong recommendations are difficult to give. Current best evidence, however, indicates that TA may reduce both the duration and volume of bleeding, with low risk of short-term thromboembolic complications, in patients with haemoptysis.

Is stopping of anticoagulant therapy really required in a minor dental surgery? - How about in an endodontic microsurgery?

Nowadays, oral anticoagulants are commonly prescribed to numerous patients for preventing cardiovascular accident such as thromboembolism. An important side effect of anticoagulant is anti-hemostasis. In a major surgery, the oral anticoagulant therapy (OAT) regimen must be changed before the surgery for proper post-operative bleeding control. However, in a minor dental surgery and endodontic surgery, the necessity for changing or discontinuing the OAT is open to debate. In this study, risks of the consequences were weighed and analyzed. In patients who stop the OAT, the occurrence of thromboembolic complication is rare but the result is fatal. In patients who continuing the OAT, post-operative bleeding can be controlled well with the local hemostatic measures. In the endodontic surgery, there are almost no studies about this issue. The intra-operative bleeding control is particularly important in the endodontic surgery because of its delicate and sensitive procedures such as inspection of resected root surface using dental microscope and retrograde filling. Further studies are necessary about this issue in the viewpoint of endodontic surgery.

Takotsubo Cardiomyopathy and 5-Fluorouracil: Getting to the Heart of the Matter

Takotsubo cardiomyopathy is a rare but increasingly recognized phenomenon, which can occur as a side-effect of chemotherapeutic agents, in particular, the antimetabolite 5-fluorouracil. We describe a case of delayed Takotsubo cardiomyopathy after 3 weeks of adjuvant 5-fluorouracil for resected rectal adenocarcinoma in a 66-year-old female, supported by angiographic, electrocardiographic, and echocardiographic features. As a complication, she developed an apical mural thrombus with subsequent cerebral thromboembolic events and was successfully anticoagulated to make a full recovery. We present a review of the literature on Takotsubo cardiomyopathy secondary to 5-fluorouracil and the rare occurrence of thromboembolic complications. As this is a significant clinical phenomenon which involves a multispeciality approach to management, oncologists and cardiologists need to recognize it as a potential toxicity of a widely administered chemotherapeutic drug.

Thrombin activatable fibrinolysis inhibitor (TAFI): A molecular link between coagulation and fibrinolysis

Although the maintenance of precise balance between coagulation and fibrinolysis is of utmost importance for normal haemostasis, until recently these two systems were considered as completely separate mechanisms involved in the process of formation and dissolution of blood clot. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently described attenuator of the fibrinolytic rate and is considered to be the molecular link between coagulation and fibrinolysis. TAFI circulates in plasma as an inactive precursor and its conversion in active enzyme (TAFIa) occurs by the action of thrombin or plasmin, but most efficiently by thrombin in the presence of its cofactor thrombomodulin. Once generated, TAFI down-regulates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin; thereby preventing the upregulation of plasminogen binding and activation. Because TAFI is activated by thrombin on one side, and acts as the attenuator of fibrinolysis on another side, it enables fine synchronization between these two systems. The antifibrinolytic function of TAFI mostly depends on TAFI concentration, the rate of its activation and the half-life of TAFIa in plasma. Changes in thrombin generation can have a profound effect on the rate of TAFI activation, and consequently on the rate of fibrinolysis. Therefore, it has been hypothesized that increased thrombin generation seen in thrombophilia patients may enhance TAFI activation, leading to a hypofibrinolytic state, which may further contribute to the thrombotic tendency. However, the results of several studies, in which relation between TAFI level and the occurrence of thromboembolic complications in carriers of hereditary thrombophilia have been investigated, were not consistent.

Antithrombin III in hip surgery

Antithrombin III is an important element of the endogenous thrombosis protection system. Congenital Anti-thrombin III deficiencies are associated with increased incidence of thrombo-embolisms. If Antithrombin III is determined at the time of operation, postoperative deficiencies resulting from an increased turnover rate can be identified. Determination of Antithrombin III is not suitable for prognosticating the occurrence of thrombo-embolic complications in isolated cases. Antithrombin III can be administered in the form of fresh frozen plasma (FFP), though it is also available as Antithrombin III concentrate. So far no investigations have been carried out to establish whether it is possible to improve thrombosis protection with or without heparin prophylaxis by concentrated Antithrombin III substitution.

Incidence and Prognostic Significance of Thrombocytopenia in Patients Treated With Prolonged Heparin Therapy

Despite widespread heparin use in clinical practice, the associated development of thrombocytopenia is an underrecognized and undertreated complication. We analyzed data from consecutive hospitalized patients treated with heparin (unfractionated or low molecular weight) for 4 days or longer to determine the incidence, predictors, prognostic significance, and management of "thrombocytopenia," defined as a platelet count less than 150 x 10(9)/L, reduction in platelet count of 50% or more from the admission level, or both. We enrolled 2420 patients (median age, 65.2 years; 43.8% women) in 48 US hospitals. Thrombocytopenia occurred in 881 patients (36.4%; 95% confidence interval [CI], 34.5%-38.3%). Of those who developed thrombocytopenia, 5.1% died, compared with 1.6% of those without thrombocytopenia (odds ratio [OR], 3.4; 95% CI, 2.1-5.6; P< .001). Thrombocytopenia was also associated with greater risk of myocardial infarction (OR, 2.1; 95% CI, 1.5-2.8; P< .001) and congestive heart failure (OR, 1.3; 95% CI, 1.1-1.6; P= .01). After adjustment for important covariates, thrombocytopenia remained an independent predictor of thrombotic and hemorrhagic events. A relative reduction in platelet count of more than 70% was the strongest independent predictor of death (OR, 13.4; 95% CI, 6.5-27.6; P< .001), followed by a relative reduction in platelet count of 50% to 70%, worse Killip class, occurrence of thromboembolic complications, older age, and longer duration of heparin therapy. Thrombocytopenia occurs frequently after prolonged heparin therapy and is strongly associated with worse short-term clinical outcome. The relative reduction in platelet count is a powerful independent predictor of all-cause mortality in hospitalized patients.

Implication from Randomized Trials of Rate and Rhythm Controls on Management of Patients with Persistent Atrial Fibrillation

Recently, several randomized trials were published on the issue of rate or rhythm control for patients with atrial fibrillation (AF). Patients were typically minor symptomatic, relatively old, with age above 70, presenting with a recurrence of AF and suffering from only mild to moderate underlying heart disease. The main outcome of these trials is that rate control is not inferior to rhythm control for the management of patients with AF concerning morbidity and mortality. Also patients' quality of life did not differ significantly in follow-up in these trials. However, rhythm control is not redundant in the treatment of AF. Focus is now on subgroups of patients who could still have benefit being in sinus rhythm. For severely symptomatic patients, patients presenting with the first episode of AF and probably those with severe congestive heart failure, to restore and maintain sinus rhythm should still be the goal. With the failure of antiarrhythmic therapy, nonpharmacological approaches such as pulmonary vein isolation can be performed. Another finding of the randomized trials is that being in sinus rhythm does not prevent from the occurrence of thromboembolic complications. This means that for patients with AF, with risk factors for thromboembolic events, adequate anticoagulant therapy is indicated irrespective of the current heart rhythm. As with antiarrhythmic therapy, the search for new and safer anticoagulant therapy is underway. This review will focus on the key aspects we have learned from the randomized trials on rate and rhythm controls for patients with AF.

Long-term anticoagulation therapy and thromboembolic complications after the Fontan procedure

Background The necessity for chronic anticoagulation of Fontan patients remains controversial. We determined the prevalence of thromboembolic complications after the Fontan procedure in relation to different long-term anticoagulation strategies. Methods The clinical outcomes, postoperative anticoagulation strategies and occurrence of thromboembolic complications in 102 ethnic Chinese patients who had undergone Fontan procedure between 1980 and 2002 were reviewed. Results The early and late surgical mortalities, all unrelated to thromboembolism, were 10.8% (11/102) and 5.8% (6/104), respectively. Of the 85 survivors, 46 (54%) were maintained on long-term warfarin therapy, 8 (9%) on aspirin prophylaxis while 31 (37%) were not on chronic anticoagulation. Four (4.5%) patients, two with and two without warfarin prophylaxis, developed thromboembolic complications at 0.14 to 7.7 years after the Fontan procedure (0.74%/patient-year). Three had a grossly dilated right atrium after atriopulmonary connection, two of whom had atrial fenestrations. The other had atrial tachycardia. Freedom from development of thromboembolic complications (mean±S.E.) at 1, 5 and 10 years after surgery was 97±19%, 96±2.5% and 92±4.2%, respectively. When compared with those on long-term warfarin therapy, patients without chronic anticoagulation were followed-up longer ( p=0.001), more likely to have undergone atriopulmonary connection ( p<0.001), less likely to have fenestrations ( p=0.02) and cardiac arrhythmias ( p=0.02) but not predisposed to increased risk of thromboembolism ( p=1.00). Conclusion The study supports the contention that chronic anticoagulation may not be required for majority of ethnic Chinese Fontan patients. Nonetheless, it may perhaps be considered in those with grossly dilated right atrium, cardiac arrhythmias and residual right-to-left shunts.

Study of protein C, protein S, and antithrombin III in hypoxic newborns*

The aim of this study was to clarify the effect of hypoxia on the physiologic inhibition system of coagulation including protein S, protein C, and antithrombin III and to study their effect on thromboembolic accidents of hypoxic newborns. Clinical study including ten hypoxic-ischemic neonates and ten normal neonates as a control group. MEDLINE, pediatric textbooks, neonatal intensive care unit, Department of Paediatrics, Faculty of Medicine, Cairo University. The results of this study revealed a marked decrease in the level of the physiologic inhibition system of coagulation including antithrombin III, protein C, and protein S in 100% of the hypoxic-ischemic neonates compared with the control group (p <.001) before the occurrence of thromboembolic complications. Fifty percent of the hypoxic-ischemic neonates developed disseminated intravascular coagulation and died, 40% developed necrotizing enterocolitis and rectal bleeding, 20% developed hematuria, 30% developed hematemesis, 20% developed intracranial hemorrhage, and 100% had convulsions. In this study, we evaluated the effect of asphyxia on the physiologic inhibition system of coagulation in neonates. Care providers should suspect hypoxia resulting from any obstructed labor and perform the necessary laboratory investigations for coagulation, including antithrombin III, protein C, and protein S levels, to help prevent thromboembolic accidents in asphyxiated neonates, including disseminated intravascular coagulation, necrotizing enterocolitis, and intracranial hemorrhage. Based on the development of antithrombin III and protein C concentrates, which are commercially available, require minimal monitoring, and have very few side effects, the time is ripe for evaluation of optimal treatment for thromboembolic accidents after neonatal asphyxia. This could be even more important if successful neuroprotectant strategies are also developed.

413 Occurrence of thromboembolic complications in heart failure

413 Occurrence of thromboembolic complications in heart failure