Incidence Of Thromboembolic Complications Research Articles

Continuous Flow Left Ventricular Assist Device Patients Are Not at Higher Risk of Gastrointestinal Bleeding with More Aggressive Anticoagulation

Purpose Continuous flow left ventricular assist devices (CF-LVADs) have become a cornerstone of heart failure therapy. The risk of gastrointestinal bleeding has been noted to be higher in these CF-LVAD patients than in previous generations of pulsatile flow LVADs. A more aggressive anticoagulation regimen could reduce the incidence of thromboembolic complications. Our aim was to evaluate the risk of gastrointestinal bleeding (GIB) before and after the initiation of an aggressive anticoagulation regimen. Methods and Materials 137 consecutive patients received a CF- LVAD with either a Heartmate II, Heartware or VentrAssist device. We undertook a retrospective review of our database of our single institution experience. We divided patients into two groups, one group was implanted prior to 3/15/2011 under a more conservative anticoagulation protocol and the second group was implanted after 3/15/2011 under a more aggressive anticoagulation protocol. Results The 6 month and 1 year mortality in our patients were 14.3% and 30.9% respectively. Gastrointestinal bleeding occurred in 25 patients with a total of 45 bleeding episodes for an overall rate of 0.53 bleeding episodes per patient year on support. When broken out into conservative and aggressive anticoagulation groups the bleeding rate was 0.51 and 0.63 per patient years on support, which was not statistically different. There were 9 patients (36%) with recurrent GIBs. In patients who suffered a GIB the average INR at the time of the bleeding episode was 2.1, and 57.8% of patients were on a full anticoagulation regimen at the time of their bleeding event. Conclusions CF-LVADs will continue to play a major role in the management of end stage heart failure. We have shown that a more aggressive management strategy for anticoagulation in an effort to reduce thromboembolic complications is safe and does not lead to a significant increase in GIB events in our population.

Non-Responders to Antiplatelet Therapy in Patients with Left Ventricular Assist Devices

Purpose Thromboembolic complications are a deleterious adverse event after left ventricular assist device (LVAD) implantation. Because of individual responsiveness to antiplatelet treatment with the COX-inhibitor aspirin and P2Y12-inhibitors as clopidogrel and prasugrel, personalized treatment based on platelet function testing may significantly reduce thromboembolic complications in LVAD patients. The present study was designed to define the frequency of aspirin and clopidogrel resistence in LVAD patients. Methods and Materials Responsiveness to antiplatelet treatment was prospectively assessed by multiple electrode aggregometry in 39 (mean age 52±11yrs., ischemic cardiomyopathy 56.4%) LVAD outpatients (HVAD® n=30, HeartMate II® n=9). Twenty-five patients received the standard daily dose of 100mg aspirin, four were treated with 200mg aspirin, one patient with 75mg clopidogrel and three with a combination of 100mg aspirin and either 75mg clopidogrel (n=2) or 10mg prasugrel. The daily aspirin dosage was doubled in non-responders and patients were tested again after two weeks. Results Multiple electrode aggregometry revealed non-responsiveness to the initial antiplatelet regimen in three patients (7.7%) and only moderate responsiveness in one patient (2.6%). The remaining 35 patients (89.7%) showed a good in vitro efficacy of the antiplatelet therapy. An adaption of the antiplatelet therapy by doubling the daily aspirin dosage led to adequate platelet inhibition, as revealed by multiple electrode aggregrometry, two weeks after change of treatment. Conclusions As shown by objective measures, non-responsiveness to antiplatelet therapy is a common finding in patients after left ventricular assist device implantation. Therefore, personalized treatment according to the platelet function testing may reduce the incidence of thromboembolic complications.

Abstract TMP25: Rates Of Complications And Aneurysm Occlusion In Patients Undergoing Treatment Of Cerebral Aneurysms Utilizing Flow Diversion With The Pipeline Embolization Device And Algorithm Adjusted Antiplatelet Therapy

Introduction: The need for therapeutic dual antiplatelet therapy in patients with cerebral aneurysms treated with flow-diverting stents increases the risk of thromboembolic and hemorrhagic complications. To balance these risks, we assessed patients for their responsiveness to dual antiplatelet therapy using a modified platelet aggregation study (PIPA). We hypothesized that double doses of clopidogrel or aspirin in patients with antiplatelet non-responsiveness would reduce the incidence of thromboembolic complications without increasing the incidence of hemorrhage or decreasing the rate of aneurysm occlusion. Methods: 79 patients with 98 cerebral aneurysms were treated with the pipeline embolization device. All patients with a suboptimal PIPA received double doses of clopidogrel or aspirin prior to treatment. Aneurysm occlusion was categorized using the Roy-Raymond Occlusion Classification (RROC). Chi-square or Fisher’s exact tests were used for univariate analyses, and logistic regression was used to identify potential predictors of complications and aneurysm occlusion. Results: Seven patients had a major complication and 7 had a minor complication (8.9%). There were 3 cerebral ischemic strokes (3.8%) and 5 cerebral hemorrhages (6.3%). Thirty-eight patients had angiographic follow-up at 6 months. Of these, 18 patients were resistant to clopidogrel or aspirin, and 19 received double dose therapy prior to treatment. Double dose clopidogrel or aspirin was not associated with major, minor, cerebral ischemic or hemorrhagic complications. Twenty-one patients (55.3%) had complete occlusion of their aneurysms (RROC type 1), and 17 patients were categorized as RROC type 2 or 3 at 6 months. Treatment with double dose clopidogrel or aspirin was not associated with reduced occlusion (RROC type 2 or 3) in a univariate and multivariate analysis. Conclusions: In patients treated with flow-diverting stents, the risk of ischemia must be balanced with the risk of hemorrhage. We found that the use of double dose clopidogrel and aspirin in the setting of antiplatelet non-responsiveness is safe. It is not associated with increased hemorrhagic complications. Patients treated with double dose therapy did not exhibit a reduced aneurysm occlusion rate.

Incidence of thromboembolic complications after hip and knee arthroplasty: Interest of systematic post-operative Doppler exploration

Incidence of thromboembolic complications after hip and knee arthroplasty: Interest of systematic post-operative Doppler exploration

Thrombocytosis in asplenia syndrome with congenital heart disease: A previously unrecognized risk factor for thromboembolism

BackgroundThrombocytosis and thromboembolic complications occur after splenectomy. However, there is no previous report investigating the presence of thrombocytosis and its association with thromboembolic events in patients having asplenia syndrome with congenital heart disease. MethodsEnrolled were 161 consecutive patients with functionally single ventricle who underwent cardiac catheterization between 1997 and 2010. They were divided into two groups: patients having asplenia (Group A, n=46) and patients having no asplenia (Group B, n=115). Aspirin therapy was employed in all patients after surgical interventions except for pulmonary artery banding. We retrospectively reviewed the platelet counts at each seven stage of cardiac catheterization (for pre- and postoperative evaluation of the first palliation, Glenn operation, and Fontan operation, and for late evaluation after Fontan operation), incidence of thromboembolic events, and other possible risk factors for thromboembolism. ResultsThe median platelet counts in Group A were consistently higher than those in Group B at any of the seven stages of cardiac catheterizations (p<0.002). The incidence of thromboembolic complications was also higher in Group A than that in Group B (28% vs. 10%, p=0.030). Univariate and multivariate logistic regression analyses showed that a platelet count of more than 550×109/L at the first cardiac catheterization was associated with thromboembolic complications (Odds ratio 3.17; p=0.046). ConclusionsPersistent thrombocytosis is present in patients with asplenia syndrome. It may greatly contribute to the development of thromboembolism during the management of congenital heart disease than expected.

Cardiomyopathie du péripartum : une entité multiple

Peripartum cardiomyopathy (PPCMP) is a dilated and hypokinetic cardiomyopathy occurring during pregnancy or after delivery, with an estimated incidence between 1/1000 and 1/4000 births. It has been defined as a new onset of heart failure in the month preceding or following delivery, without demonstrated aetiology nor previously known heart disease, and with echocardiographic evidences of left ventricular (LV) dysfunction (LV ejection fraction<0.45). It's a multifactorial disease, immunologic, hormonal, and possibly viral mechanisms playing a determinant pathophysiological role. The classical clinical presentation is a rapid and unexpected onset of heart failure in a previously healthy woman, echocardiography being the key examination for positive and differential diagnosis, prognostication, therapeutic decision-making, and follow-up. The potential severity of PPCMP, and its unpredictable evolution in the first days following diagnosis, require that patients be referred to a tertiary care centre with a high skill in intensive cardiology care. Therapeutic management of PPCMP does not offer any specificity when compared to other causes of acute or chronic heart failure (from diuretics to extracorporeal life support), except for ACE-inhibitors, that are contraindicated before delivery. The high incidence of thrombo-embolic complications observed in the disease requires however rapid and curative anticoagulation, and immuno-suppressive treatment has been proposed in fulminant and highly inflammatory presentation, but its efficacy remains controversial. Very recently, promising results have been reported with bromocriptin-a prolactin secretion inhibitor-for reducing 6-month morbidity and mortality, but these findings have to be confirmed in larger scale randomised trials. As for the long-term evolution, approximately half of the patients will heal, while half of the women will keep some degree of LV dysfunction, 25% of them developing moderate to severe chronic heart failure.

Iliofemoral-popliteal deep vein thrombosis at 35th week of pregnancy: treated with cesarean section and vena cava blockage plus thrombectomy

Pregnancy, due to its adaptive physiological changes, is a risk factor for deep vein thrombosis. Incidence of thromboembolic complications during pregnancy ranges from 0.76 to 1.72 per 1000 births. We present in this case report a pregnant woman with iliofemoral-popliteal deep vein thrombosis diagnosed at the 35(th) week of her pregnancy, who was treated with vena cava blockage and thrombectomy followed by cesarean section. Unfortunately, a rethrombosis developed in the patient after three days. We determined that the a-v fistula was blocked and not working. We found additionally that the deep vein thrombosis was closing the iliac vein completely on the left side and the blockage descending down through the inferior vena cava inlet with MRI. The patient underwent insertion of a retrievable vena cava filter, two stent implantation to the venous narrowings and surgical iliofemoral venous thrombectomy with concomitant re-creation of a temporary femoral arterio-venous fistula. Anticoagulation therapy with enoxaparine was started after the operation. The patient was discharged with warfarin under control of the INR value, and also with additional compression therapy (compression stockings) from the clinic. Without jeopardizing the mother and the baby, planning a combined surgical procedure, with a multidisciplinary approach is the best way to eliminate the risks of serious complications such as pulmonary embolism and mortality.

Incidence of thromboembolic complications in patients with atrial fibrillation or mechanical heart valves with a subtherapeutic international normalized ratio: A prospective multicenter cohort study

Subtherapeutic international normalized ratio (INR) is frequently encountered in clinical practice, and patients with high-risk atrial fibrillation (AF) and with mechanical heart valve (MHV) with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events (TE). However, there are no prospective data evaluating this risk. Consecutive patients with a history of stable anticoagulation, but with a subtherapeutic INR, were prospectively included. Data on use and dose of low-molecular weight heparin (LMWH) bridging therapy were collected. The incidence of objectively confirmed TE and of major bleeding events within 90 days after the index INR was assessed. Five hundred and one patients with INR value 0.5-1 INR units below the lower limit of the patient-specific target INR were included in the study (280 with MHV and 221 with AF and CHADS2 score ≥3). LMWH was prescribed for 64 patients (12.8%). During follow-up, seven patients had a TE (1.40%; 95% confidence interval 0.68, 2.86%; 5.58 events for 100 patients year). All the events occurred within 14 days after the index INR. When we consider only patients who did not receive bridging therapy, the incidence of TE was 1.14% (5 of 437 patients; 95% confidence interval 0.49, 2.64%; 4.58 events for 100 patients year). There were no major bleeding events. The risk of TE in this population was not negligible. Given the frequent observation of subtherapeutic INR levels when monitoring vitamin K antagonists, this finding warrants additional investigation to improve the management of these patients.

Embolization of Intracranial Aneurysms with the HydroSoft and HydroFrame Coils: A Single-Center Experience

●Abstract● Objectives: The HydroSoft and HydroFrame coils are a new generation of coils designed to further improve the safety and durability of aneurysm coiling using hydrogel technology. The authors report their experience using the HydroSoft and HydroFrame coils for the treatment of intracranial aneurysms. Methods: Immediate and follow-up angiographic results procedure-related complications and retreatments were retrospectively analyzed for 106 intracranial saccular aneurysms in 103 patients treated with the HydroSoft and HydroFrame coils during a 50-month period. Results: The incidence of thromboembolic complications was 5.7%. Procedure-related morbidity and mortality rates were each 0.9%. None of the patients with unruptured aneurysms developed hydrocephalus. Immediate post-procedure angiograms showed complete aneurysm occlusion in 34.9% of cases neck remnant in 36.8% and incomplete occlusion in 28.3%. Angiographic follow-up was obtained in 51.9% (55 of 106 aneurysms; average 16 months; range 6-45 months). In these 55 aneurysms the rate of immediate complete occlusion was 27.3% after treatment which increased to 50.9% on follow-up and the overall recanalization rate was 14.5%. No recanalization was observed in the 8 aneurysms treated with stent-assisted coiling in combination with HydroSoft and HydroFrame coil placement. Conclusions: The overall safety profile of the HydroSoft and HydroFrame coils appears to be acceptable. Preliminary midterm observation suggests that these new-generation hydrogel coils will improve the durability of angiographic occlusion when compared with immediate post-embolization results and can reduce the rate of aneurysm recanalization.

The Potential Impact of Dietary Vitamin K Status on Anticoagulation Control in Children Receiving Warfarin

There have been significant advances in pediatric medical care and previously fatal conditions, such as congenital cardiac defects, malignancy, and prematurity, are now being successfully managed but at the expense of a rising incidence of thromboembolic complications [1]. The requirement for anticoagulation to treat thrombotic events, as well as for prophylaxis in at risk patients, is therefore increasing. Warfarin remains the anticoagulant of choice for long-term treatment in children. Maintenance of International Normalized Ratio (INR) within the target range is essential in order to prevent the hemorrhagic complications of overdosing and thrombotic events due to underdosing. Poor anticoagulant control is common in children who are anticoagulated with warfarin and other oral vitamin K antagonists, with around 50% of measured INR values being outside of the desired therapeutic range even when home monitoring with a point-of-care testing device is used [2, 3]. There are numerous reasons for poor oral anticoagulant control in children. These include complex underlying health problems, multiple intercurrent viral illnesses and polypharmacy [4]. The variability of age-related dose-response rates is an additional complexity to the appropriate dosing of warfarin in childhood [2]. Warfarin produces an anticoagulant effect by interfering with the cyclic conversion of vitamin K to its reduced form (vitamin K hydroquinone). The latter is an essential cofactor for the γ -carboxylation of the vitamin K–dependent coagulation factors (II, VII, IX, and X), which promotes their calcium binding and activation in the coagulation cascade [4]. The anticoagulant effect of warfarin can be antagonized by vitamin K. The administration of supraphysiological doses of vitamin K orally, intramuscularly, or intravenously is common practice in the reversal of over-anticoagulation with warfarin [5].

Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists

Prothrombin complex concentrates (PCCs) are recommended as the treatment of choice in warfarin-related coagulopathy. However, the risk of thromboembolic complications associated with their use is not well defined. We performed a meta-analysis to estimate the rate of thromboembolic complications in patients receiving vitamin K antagonists (VKAs) treated with PCCs for bleeding or before urgent surgery. Medline and Embase databases were searched. Two reviewers performed study selection and extracted data independently. Studies providing data on incidence of thromboembolic complications in VKA-treated patients were eligible for the study. Weighted mean proportion of the rate of thromboembolic complications and the mortality rate were calculated. Twenty-seven studies (1,032 patients) were included. Seven studies used 3-factor, and 20 4-factor PCCs. Twelve patients had a thromboembolic complication (weighted mean 1.4%; 95% CI 0.8-2.1), of which two were fatal. The incidence of thromboembolic events was 1.8% (95% CI 1.0-3.0) in patients treated with 4-factor PCCs, and 0.7% (95% CI 0.0-2.4) in patients treated with 3-factor PCCs. Total mortality rate was 10.6% (95% CI 5.9-16.6). In conclusion, our results suggest there is a low but quantifiable risk of thromboembolism in VKA-treated patients receiving PCCs for anticoagulation reversal. These findings should be confirmed in randomised, controlled trials.

Effect of Epsilon Aminocaproic Acid on Red-Cell Transfusion Requirements in Major Spinal Surgery

: Randomized, placebo-controlled trial. : To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery. : Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited. : EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours after surgery. Primary end points included total allogeneic RBC transfusions through postoperative day 8 and postoperative allogeneic plus autologus RBC transfusions through postoperative day 8. : Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA vs. 6.9 units placebo; P = 0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units vs. 2.8 units placebo; P = 0.03). There was no significantdifference in mean estimated intraoperative estimated-blood loss (2938 cc EACA vs. 3273 cc placebo; P = 0.32). Mean intensive care unit length of stay was decreased (EACA: 1.8 days vs. 2.8 days placebo; P = 0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs. 6.6% placebo; P = 0.15). : The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a 1-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements.

Incidence of thromboembolic complications in lumbar spinal surgery in 1,111 patients

Deep venous thrombosis (DVT) and pulmonary embolism (PE) cause significant morbidity and mortality in orthopaedic surgical practice, although the incidence following surgery to the lumbosacral spine is less than following lower limb surgery. Our objective was to compare our rate of thromboembolic complications with those published elsewhere and investigate whether the adoption of additional pharmacological measures reduced the incidence of clinically evident DVT and PE. This retrospective study was undertaken to investigate the incidence of DVT/PE during the 10 years from 1 January 1985 to 31 December 1994, and then to assess the effectiveness of an anticoagulant policy introduced during 1995 using low dose aspirin or LMH in high risk cases. All records for spinal operations were reviewed for thrombo-embolic complications by reference to the Scottish Morbidity Record form SMR1. To ensure that all patients were compliant with the policy, data for the whole of 1995 was omitted and the period 1 January 1996 to 31 December 2003 was taken to assess its effectiveness. Surgery was done with the patient in the kneeling, seated prone position which leaves the abdomen free and avoids venous kinking in the legs. Records of a total of 1,111 lumbar spine operations were performed from 1 January 1985 to 31 December 2004 were reviewed. The overall incidence of thrombo-embolic complications was 0.29%. A total of 697 operations were performed from 1 January 1985 to 31 December 1994 with two cases of DVT and no cases of PE giving thromboembolic complication rate of 0.29%. During the period 1 January 1996 to 31 December 2003, 414 operations resulted in one case of DVT and no cases of PE, a rate of 0.24%. The incidence of symptomatic thrombo-embolic complications in lumbar spinal surgery is low in the kneeling, seated prone operating position, whether or not anticoagulation is used.

Incidence of thromboembolic complications in patients with mechanical heart valves with a subtherapeutic international normalized ratio

Subtherapeutic international normalized ratios are frequently encountered in clinical practice, and patients with mechanical heart valves with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events. There are no data on thromboembolic event risk for these patients. We assessed the current practice patterns in the management of patients with mechanical heart valves with subtherapeutic international normalized ratios and assessed the risk of thromboembolic complications in this setting. The charts of patients with mechanical heart valves followed up in two anticoagulation clinics were reviewed. Patients with a history of stable, therapeutic anticoagulation but with a subtherapeutic international normalized ratio were included. Patients who underwent invasive procedures requiring temporary suspension of antithrombotic therapy were excluded. Data on use and dose of low-molecular weight heparin bridging therapy were collected. The incidence of objectively confirmed thromboembolic events within 90 days after obtaining the index international normalized ratio was assessed. Two hundred ninety-four patients with mechanical heart valves were included (mean age 63.3 years, 47.3% male). Low-molecular weight heparin was prescribed in 14 cases (4.8%). At 90 days, 1 patient had a thromboembolic complication (0.3%, 95% confidence interval 0%-1.9%). Patients with previously stable, therapeutic anticoagulation with a subtherapeutic international normalized ratio have a low risk of thromboembolic events. Withholding low-molecular weight heparin bridging therapy is a reasonable therapeutic option in these cases.

Prevention of Pulmonary Embolism in General Surgery Patients

Case Presentation : A 29-year-old woman presented to the emergency department with complaints of pleuritic chest pain, fever, and left ankle swelling and tenderness. Cardiac examination was normal except for tachycardia. A chest computed tomography scan with contrast demonstrated extensive bilateral pulmonary emboli. Thirteen days previously, an intoxicated driver with multiple prior convictions for driving under the influence of alcohol crashed head-on into her car at a high speed. She was 8 months’ pregnant and suffered the loss of the child. She spent 7 days in the hospital and underwent cesarean section, exploratory laparotomy, and splenectomy. No preoperative pharmacological prophylaxis against venous thromboembolism (VTE) was administered. VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and common complication of general surgery. A new era in the postoperative management of surgical patients began in 1975 when the effectiveness of low-dose heparin in preventing postoperative DVT and PE was established by the pivotal International Multicenter Trial.1 The dose was 5000 U subcutaneously every 8 hours, with the first injection administered 2 hours before the skin incision. Compared with control, the incidence of DVT in patients receiving heparin decreased from 24.6% to 7.7%. Similarly, the incidence of autopsy-proven PE was reduced 8-fold. The results of this trial introduced and validated the concept of using low-dose heparin to prevent postoperative VTE. This trial revolutionized surgical practice. By 1994, 90% of North American general surgeons reported the routine use of thromboprophylaxis.2 Most postoperative DVT originates in the deep calf veins, primarily within the valve cusps. Most thrombi remain confined to the calf. Propagation into the proximal veins increases the risk of PE. Symptoms and signs of postoperative VTE such as mild hypoxia or low-grade fever are frequently nonspecific. Moreover, clinical manifestations of postoperative VTE may not occur until …

Tinzaparin prophylaxis against thromboembolic complications in brain tumor patients

1539 Background: Thromboembolic complications are common in brain tumor patients, contribute to the morbidity and mortality and complicate treatment. Twenty to 40% of brain tumor patients develop a deep venous thrombosis and/or pulmonary embolus during their course. Thromboembolic complications are the second leading cause of death in brain tumor patients. One of the low molecular weight heparins, tinzaparin, has increased factor Xa activity as opposed to thrombin inhibition, which may improve the therapeutic:toxicity ratio. Methods: We report a phase II trial of prophylactic tinzaparin for newly diagnosed brain tumor patients. Twenty-seven of the planned 40 patients have been accrued. Patients received daily tinzaparin at a fixed dose of 4500 IU subcutaneously beginning a minimum of 48 hours post-operatively and a maximum of 4 weeks post-operatively. Patients were scheduled to receive tinzaparin for 12 months. During chemotherapy cycles, the blood counts were monitored weekly. If the platelet count was &lt;50,000, the tinzaparin was held until the platelets were &gt;100,000. Results: One of the patients developed a grade 3 CNS hemorrhage, necessitating cessation of the tinzaparin, there have been no grade 4 or 5 CNS hemorrhages or treatment associated mortality. Also, there have been no ≥ grade 2 systemic hemorrhages. One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin secondary to thrombocytopenia. One patient was taken off study for increased liver function tests, possibly secondary to tinzaparin. The patients have taken the tinzaparin for 4–52 weeks, with a median of 18 weeks. Conclusions: Tinzaparin at a fixed prophylactic dose is safe and may decrease the incidence of thromboembolic complications in brain tumor patients. If the completed phase II study yields similar results, a phase III trial is warranted. No significant financial relationships to disclose.

Thromboembolism in Heart Transplantation: Role of Prothrombin G20210A and Factor V Leiden

Thromboembolism has been reported as a frequent complication after cardiac transplantation. Many risk factors for thrombosis may explain this, such as metabolic alterations and the use of cyclosporine. In the general population, two single nucleotide polymorphisms (SNPs), factor V Leiden and prothrombin G20210A (PT G20210A), have been associated with a significant increase in the risk of thrombosis. However, these mutations have not been analyzed in cardiac transplant patients. We describe the protracted history of recurrent thromboembolism in a rare case of homozygosity for the PT G20210A variant. This prompted us to analyze the entire cardiac transplant cohort for the incidence of thromboembolic events and their association with these genetic polymorphisms. We report the study of 84 cardiac transplant recipients. We retrospectively analyzed the frequency of thromboembolic episodes. The genotypes for FVL and PT G20210A were determined and correlated with those episodes. Our results confirm a very high incidence of thromboembolism in this population. We also found a significant increase in the likelihood of thromboembolism in subjects with the PTB G20210A variant (odds ratio 3.08; 95% confidence interval: 1.7-5.5). The incidence of thromboembolic complications after heart transplantation is increased and may be related in part to genetic predisposition.

Cytomegalovirus and Thromboembolism in Renal Transplantation

We welcome this interesting commentary on our article and appreciate the chance it gives us to further clarify some issues. The first point is the incidence of thromboembolic complications (TEC) in the two groups. Indeed, there are a great number of potential reasons for a kidney transplant recipient to develop TEC (1). In our opinion, it would not then be legitimate to perform any statistical analysis without taking into consideration all potential variables (e.g., immunosuppression regimen) that could greatly modify patients’ risk for TEC. We did not perform any statistical analysis in our article because it is not meant to prove a causal relationship. Rather, it describes an observation-based hypothesis that needs further investigation. In the retrospective cohort study by Abbott et al. (2), cytomegalovirus (CMV) infection was not defined. As the data in this study were extracted from a nationwide registry, definition of CMV infection was likely to have greatly varied from one center to another. Moreover, a great number of CMV infections are asymptomatic, and only a systematic CMV monitoring can estimate the true incidence of infection. As a consequence, the incidence of CMV infection is likely to be underestimated in that study, introducing a bias toward the null hypothesis. In our observation, CMV infection was monitored systematically and all the patients presenting with TEC were tested for CMV infection, many of them showing asymptomatic infection. In our observation, all cases of TEC were symptomatic. These patients were hospitalized because of symptoms and signs compatible with a TEC, ranging from a simple calf pain to severe respiratory distress. In our opinion, the atypical presentation and localization of TEC in these patients might effectively show that these complications did not occur in a normal vascular bed but involved an endothelium carrying some degrees of preexisting CMV-induced lesions. Our article was a retrospective case study. Of note, we did not search for TEC in CMV patients but for CMV in patients presenting with TEC. Based on this observation, it seems rather reasonable to search for CMV infection in renal transplant recipients presenting with TEC, especially if any clinical and/or biological sign compatible with this infection accompanies the event. We agree with the author that CMV is not the sole agent associated with a transient increased hypercoagulability state, and that many other infectious/inflammatory conditions could cause the same effect. However, it should be noted that our article discusses clinical cases of venous thrombosis or emboli associated with CMV and not simply a transient mild alteration of biological markers commonly found in association with inflammatory processes. Finally, based on biological evidence (3), we believe that CMV might be implicated in a number of coagulation disorders in a subset of renal transplant recipients. These represent a large spectrum of clinical pathologic situations ranging from bleeding diathesis (4) to TEC. However, as we have emphasized in our article, this observation must only be considered as a preliminary report awaiting controlled prospective trials to prove or refute such a causative relationship. Amir Kazory Didier Ducloux Department of Nephrology and Renal Transplantation Saint-Jacques University Hospital Besançon, France

Is addition of anti-platelet therapy to warfarin beneficial to patients with prosthetic heart valves?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether addition of anti-platelet therapy to warfarin reduced the incidence of thromboembolic complications in patients with prosthetic heart valves. Altogether 253 papers were found using the reported search, of which 11 papers represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that low dose aspirin (80-100 mg daily) in addition to warfarin in patients with prosthetic heart valves reduces all cause long term mortality (NNT=19), with significant reductions in thromboembolism but an increase in bleeding.

EFFICACY AND SAFETY OF RECOMBINANT FACTOR VIIa (rFVIIa) ON TRANSFUSION REDUCTION IN ORTHOTOPIC LIVER TRANSPLANTATION (OLT) – A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL.

O237 Aims: OLT patients are susceptible to massive blood loss during surgery. A correlation between blood transfusion and postoperative morbidity and mortality in patients undergoing OLT has been suggested. We studied the efficacy and safety of rFVIIa, administered immediately prior to and throughout surgery, on transfusion reduction in patients with Child-Pugh score B or C liver disease scheduled for primary OLT. Methods: In a multicentre, randomised, double-blind, placebo-controlled study, eligible patients were randomly assigned on the day of surgery to receive rFVIIa (either 60 μg/kg or 120 μg/kg within 10 minutes prior to first skin cut with repeated dosing every 2 hours until 30 minutes prior to expected start of reperfusion of the transplanted liver, and an additional single dose at completion of surgery), or placebo. During surgery and the 24-hour postoperative period, the volume of blood products administered and blood loss were assessed. Results: 182 patients were analysed for efficacy and 183 for safety; there was no significant effect of rFVIIa on the amount of red blood cells (RBCs) transfused or intraoperative blood loss compared with the placebo group. However, of the 179 patients who completed the study, a significantly higher number of patients in the rFVIIa groups avoided RBC transfusion (placebo: 0/61 (0%); 60 μg/kg rFVIIa: 6/62 (10%); 120 μg/kg rFVIIa: 4/56 (7%); p<0.03). The number of thromboembolic events did not differ significantly between the placebo and rFVIIa groups. Conclusions: Use of rFVIIa during OLT reduced the number of patients requiring RBC transfusion. No increase in the incidence of thromboembolic complications was observed for the rFVIIa groups compared with placebo. These observations need further investigation.