Chronic Anticoagulation Therapy Research Articles

Clot Lifespan Model Analysis of the Effects of Warfarin on Thrombus Growth and Fibrinolysis: Role of Contact Protein and Tissue Factor Initiation

Warfarin therapy has served as the backbone of chronic anticoagulation therapy for decades to prevent thrombotic morbidity secondary to blood-biomaterial interfaces. Unfortunately, thrombotic and bleeding complications are observed despite maintenance of therapeutic international normalized ratio (INR) values. We proposed to define the effects of warfarin therapy on thrombus growth and disintegration following contact pathway protein or tissue factor (TF) initiation. Normal subject or patient plasma with INR values between 1.8 and 9.6 were exposed to TF or celite and tissue-type plasminogen activator (tPA). Thrombus growth/disintegration kinetics were determined by changes in resistance over time with the clot lifespan model (CSLM), a thrombelastographic-based methodology. Data were collected until clot lysis time was observed. Linear relationships of the difference between the CLSM parameter values obtained from paired celite and TF-activated samples and corresponding INR value were determined and reported as r. The time to clot initiation was progressively prolonged with increasing INR values in all samples, and speed of clot formation, clot strength, and time to onset of fibrinolysis decreased as INR increased. Throughout the range of INR values tested, contact activation resulted in faster growing, stronger, and longer lived thrombi when compared with matched TF-activated plasma samples. Only the time to maximum rate of lysis was correlated with INR (r=0.36, p=0.005). INR values have little correlation with the difference between contact protein and TF-activated coagulation/fibrinolysis.

Robotic-Assisted Radical Prostatectomy in Patients Receiving Chronic Anticoagulation Therapy: Role of Perioperative Bridging

Patients requiring chronic anticoagulation therapy (CAT) with warfarin require special attention perioperatively. We retrospectively reviewed our experience of treating patients requiring CAT who underwent robotic-assisted radical prostatectomy (RARP) to evaluate the role of perioperative bridging therapy. A total of 60 patients receiving cat with warfarin who underwent rarp were identified as having been treated using 1 of 2 protocols: protocol 1, the cessation of CAT 7 days before surgery and its resumption the evening of catheter removal (postoperative day 4-21); or protocol 2, warfarin substituted with perioperative subcutaneous low-molecular-weight heparin, with oral anticoagulation restarted after catheter removal. The decision to use perioperative bridging was made in conjunction with the patient's primary care physician. The peri- and postoperative parameters and complications were compared with a matched control group of 181 contemporary patients who underwent RARP but did not require CAT. The most common indications for CAT were atrial fibrillation (58%) and recurrent deep vein thrombosis (22%). Compared with the control cohort, the patients with CAT had an increased operative time (189 vs 170 minutes, P = .005) and hospital stay (1.4 vs 1.1 days, P = .004). The estimated blood loss (123.9 vs 146.6 mL, P = .07) and 24-hour change in hemoglobin (2.2 vs 2.3 g/dL, P = .44) were similar. When comparing the 2 protocols, a significantly greater transfusion rate (23% vs 2%, P = .042) occurred with protocol 2, but no increase was seen in the complication or readmission rate. One nonfatal thromboembolic event occurred in 1 patient treated using protocol 1. The results of our study have shown that RARP can be performed safely in patients requiring CAT, with and without bridging therapy. Patients in protocol 2 had greater transfusion rates, but this did not translate into increased complications or readmissions.

Outcomes of Partial Nephrectomy in Patients on Chronic Oral Anticoagulant Therapy

We report our experience with patients requiring long-term anticoagulation therapy who underwent open or laparoscopic partial nephrectomy for renal tumors at our institution. We compared outcomes with those in a control group undergoing partial nephrectomy with no anticoagulation requirements. We retrospectively reviewed the records of 1,031 patients who underwent laparoscopic or open partial nephrectomy from 2000 to 2005. Since 2000, 31 open and 16 laparoscopic partial nephrectomies were performed in patients on chronic warfarin, clopidogrel or cilostazol. Anticoagulation was appropriately discontinued perioperatively. The 47 anticoagulated cases were compared with 47 nonanticoagulated controls that were carefully matched for surgical approach, partial nephrectomy defect size, tumor size and location, procedure year and warm ischemia time. Investigators were blinded to all clinical outcomes throughout the matching process. Bleeding and thrombotic outcomes were then analyzed. The 2 groups were well matched for resection bed size, tumor size, tumor location (central vs peripheral), solitary kidney, operative time and warm ischemia time (each p >or=0.3). Controls had significantly higher intraoperative blood loss (300 vs 200, p <0.05) and a greater postoperative decrease in hemoglobin (3.5 vs 2.4 mg/dl, p <0.001). However, transfusion rates were similar in the 2 groups (each 15%). Five patients on anticoagulation had thrombotic events postoperatively vs none in the control group. Patients on anticoagulation are at higher perioperative risk but with careful perioperative management of anticoagulation therapy partial nephrectomy can be performed in a safe and efficacious manner. To our knowledge this is the largest study of outcomes in this complex patient population.

Laparoscopic Renal Oncological Surgery in the Presence of Abdominal Aortic and Vena Caval Pathology: 8-Year Experience

To our knowledge the outcomes of laparoscopic renal oncological surgery in patients with major aortic and/or inferior vena caval pathology are unknown. We present our experience spanning an 8-year period. From March 1998 to October 2006, 1,826 laparoscopic renal procedures were performed for tumor. Of these patients 66 (3.6%) had major abdominal aortic or vena caval pathology concomitantly. Demographics, specific entities of the vascular disease, and intraoperative and postoperative data were reviewed. A total of 66 patients had a history of abdominal aortic disease (54), vena caval disease (9) or both (3). Of the patients 85% had 3 or greater comorbidities, 88% had an American Society of Anesthesiologists score of 3 or greater and 88% were on chronic anticoagulation therapy. A total of 27 patients (41%) had undergone prior surgical treatment for vascular pathology. Laparoscopic renal surgery, which was transperitoneal in 25 cases and retroperitoneal in 41, included radical nephrectomy in 20, partial nephrectomy in 17 and cryoablation in 29. Open conversion was performed in 3 patients (5%). There were 3 intraoperative (5%) and 9 postoperative (14%) complications. One patient died of pulmonary sepsis. There was no statistically significant difference in perioperative outcomes between the aortic and vena caval disease groups. The retroperitoneal approach was associated with less blood loss and shorter operative time (p = 0.0003 and 0.004, respectively). Laparoscopic surgery for renal tumor in the presence of aortic or vena caval disease is safe and feasible. Considerable prior laparoscopic experience is necessary when treating these patients at high risk.

Hemorrhagic and Thromboembolic Complications after Bariatric Surgery in Patients Receiving Chronic Anticoagulation Therapy

Perioperative management of bariatric surgical patients receiving chronic anticoagulation requires an understanding of potential hemorrhagic and thromboembolic risks. The aim of this study is to evaluate hemorrhagic and thromboembolic complications in morbidly obese patients who are on oral anticoagulation treatment and subsequently undergo laparoscopic bariatric surgery. The medical records of all laparoscopic Roux-en-Y gastric bypass (LRYGB) patients from June 2001 to March 2006 were retrospectively reviewed. In addition, data of patients who received chronic anticoagulation therapy with Coumadin and underwent laparoscopic Roux-en-Y gastric bypass was analyzed. Clinical parameters included length of hospitalization, hemorrhagic complications, thromboembolic complications, conversion rate, reoperation, and blood transfusion. During the study period, 1,700 consecutive patients underwent bariatric surgery for the treatment of morbid obesity. Of these, 21 patients were treated with chronic oral anticoagulation; 3 of the 21 (14%) had hemorrhagic complications: one patient had intraluminal hemorrhage and two patients had intraabdominal hemorrhage. Two patients required blood transfusion, and one patient underwent surgical reintervention. None of the 21 laparoscopic operations were converted to open procedures. There were no postoperative mortalities, and there were no thromboembolic events in this series. Laparoscopic bariatric surgery can be performed relatively safely in morbidly obese patients who are treated with chronic oral anticoagulation. Even in the presence of bleeding, patients can be successfully treated without the need for reoperation.

Utilization of dietary vitamin K supplementation to aid in INR stabilization for patients on chronic oral anticoagulant therapy: a series of case reports

Utilization of dietary vitamin K supplementation to aid in INR stabilization for patients on chronic oral anticoagulant therapy: a series of case reports

Sirolimus-associated diffuse alveolar hemorrhage in a renal transplant recipient on long-term anticoagulation

Sirolimus (rapamycin, rapamune) is an effective immunosuppressant that has been widely used in solid organ transplantation. Recently, two disconcerting side effects, namely pulmonary toxicity, usually in the form of interstitial pneumonitis, and the onset of nephrotic range proteinuria, have been recognized. We report the case of a renal transplant recipient who had been on chronic anticoagulation therapy for a mechanical aortic valve, and who developed pulmonary distress necessitating emergent intubation 18 days after starting sirolimus therapy. Open lung biopsy showed diffuse alveolar hemorrhage with fibrin deposits in the alveolar spaces and small bronchi. Urine protein/creatinine ratio at that time was 16.7. Upon discontinuation of sirolimus, alveolar hemorrhage and nephrotic range proteinuria resolved. We suggest that extra vigilance be paid in individuals who are on chronic anticoagulation and who are started on sirolimus.

Left atrial appendage closure for stroke prevention in atrial fibrillation: state of the art and current challenges

Atrial fibrillation (AF) is a major risk factor for disabling ischemic strokes. Anticoagulation is highly effective for stroke prevention in patients with AF, but a substantial number of patients are unable to sustain chronic therapy with warfarin. Most strokes in patients with AF are thought to arise from thrombus formation in the left atrial appendage (LAA); therefore, occlusion of the orifice of the LAA provides a theoretically appealing option for stroke prevention. Surgical exclusion of the LAA is increasingly performed in patients undergoing open-heart surgery, and thoracoscopic epicardial occlusion of the LAA has yielded promising early results. Percutaneous LAA occlusion devices have shown some success initial trials, but additional safety and efficacy data are required before this approach can be routinely considered. Here we discuss the LAA in relation to AF-related embolic stroke, and how LAA occlusion devices could be used in stroke prevention in patients who cannot tolerate chronic anticoagulant therapy.

Direct-to-patient expert system and home INR monitoring improves control of oral anticoagulation

Internet-based disease management programs have the potential to improve patient care. The objective of this study was to determine whether an interactive, internet-based system enabling supervised, patient self-management of oral anticoagulant therapy provided management comparable to an established anticoagulation clinic. Sixty patients receiving chronic oral anticoagulant therapy who had access to the internet and a printer, were enrolled into this prospective, single-group, before-after study from a single clinic and managed between March 2002 and January 2003. Patients learned how to use a home prothrombin time monitor and how to access the system through the internet. Patients used the system for six months, with daily review by the supervising physician. The primary outcome variable was the difference in time in therapeutic range prior to and following introduction of internet-supervised patient self-management. The mean time in therapeutic range increased from 63% in the anticoagulation clinic (control period) to 74.4% during internet-supervised patient self-management (study period). The mean difference score between control and study periods was 11.4% (P = 0.004, 95% confidence interval 5.5-17.3%). There were no hemorrhagic or thromboembolic complications. This novel approach of internet-supervised patient self-management improved time in therapeutic range compared to an anticoagulation clinic. This is the first demonstration of an internet-based expert system enabling remote and effective management of patients on oral anticoagulants. Expert systems may be applicable for management of other chronic diseases.

Day-case laparoscopic cholecystectomy: results of 211 consecutive patients

The purpose of this work was to evaluate the feasibility and outcome of elective laparoscopic cholecystectomy as a day-case procedure in a French university hospital. Since the creation of a surgical day-care centre in 1999, patients without severe chronic disease and anticoagulant therapy were selected for elective laparoscopic cholecystectomy. They were admitted and operated on in the morning hours and discharged after a double check by the surgeon and an anaesthetist 4 to 6 hours later. They were contacted by telephone the day subsequent to surgery and were seen in the outpatient unit 8 to 10 days after. Two hundred eleven laparoscopic cholecystectomies were performed in day-care surgery from January 1999 to December 2005. The proportion of day-case management increased during the six-year period from 32% to 53%. Eighteen percent of patients had an overnight admission. The overall complication rate was 1.8%. None of the patients had an emergency readmission. Incapacity duration went from 1 to 15 days. These results suggest that laparoscopic cholecystectomy can be routinely performed as a day-case procedure.

Chronic oral anticoagulant therapy for extrahepatic visceral thrombosis is safe

Patients with hypercoagulability may thrombose visceral veins with resultant portal hypertension, esophagogastric varices, and hemorrhage. The role of chronic oral anticoagulant therapy in such patients is unclear. On the one hand, such patients are prone to significant hemorrhage and thus anticoagulant therapy may seem contraindicated. On the other hand, because the causal pathophysiology is typically hypercoagulability, it would seem rational to treat these patients with chronic anticoagulant therapy in order to both prevent other visceral and systemic thromboses and perhaps, over time, reduce the degree of portal hypertension. Experience and poor prognosis associated with the more common portal hypertension due to hepatic cirrhosis may bias judgment. We retrospectively reviewed the course of chronic oral anticoagulant therapy regarding both the safety and effectiveness using our long-term follow-up of a cohort of seven patients with visceral thrombosis resulting in extrahepatic non-cirrhotic portal hypertension. Seven consecutive patients encountered over the past 19 years were observed for 78 patient-years, the first 14 patient-years prior to anticoagulant therapy and the latter 64 patient-years on oral anticoagulant therapy. No patients rethrombosed either visceral or systemic vessels while on oral anticoagulant therapy. There were no fatal or serious hemorrhagic events on oral anticoagulant therapy; in fact, upper gastrointestinal bleeding decreased from 1.2 to 0.2 bleeds/year. The endoscopic grade of esophageal varices decreased in four of five patients who underwent serial endoscopy, and platelet counts increased in all seven patients. Chronic oral anticoagulant therapy is safe and not associated with an increase in upper gastrointestinal bleeding in such patients. Additionally, and by inference, perhaps in conjunction with the natural history of portal hypertension, such therapy is possibly effective in reducing portal hypertension in patients with hypercoagulability-induced extrahepatic portal hypertension.

Anticoagulation Management: A New Approach

Anticoagulation therapy has been identified as an area in which new approaches to treatment and monitoring may allow for significant improvements in healthcare quality and costs. We evaluated the potential benefits of a new approach to anticoagulation therapy, utilizing decision support software, point-of-service testing, and workflow redesign. We performed an intervention study in the setting of a university-affiliated primary care clinic, involving 40 patients receiving chronic anticoagulation therapy. Study measurement included anticoagulation control, complications of therapy and related costs, as well as clinic revenue and overhead costs. After implementation of the new approach, the frequency of international normalized ratio (INR) results within therapeutic range increased from 34% to 67%. During a 1-year follow-up period, complications related to anticoagulation therapy were reduced by 91% (p < 0.01). Labor-related overhead costs decreased from approximately 12,600 to 3,100 US dollars. During the same period, the clinic generated approximately 35,000 US dollars in new revenue. For every dollar spent on clinic implementation and maintenance, over 25 US dollars was returned from cost containment and new revenue production. This approach allows a clinic to show improved anticoagulation control and complication rates while simultaneously improving financial performance.

Thromboembolic Events in Patients After a Negative Computed Tomography Pulmonary Angiogram: a Retrospective Study of 165 Patients

To determine the value of computed tomography (CT) angiography of the chest as a diagnostic test to exclude pulmonary embolism and to assess compliance with diagnostic protocols for thromboembolic disease. We retrospectively studied patients who underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. All the patients were followed for 3 months. The percentage of patients diagnosed with a thromboembolic event based on an objective test during the follow-up period was determined. We analyzed the percentage of patients with a negative CT angiogram on whom additional diagnostic tests (ultrasound of the lower limbs and/or ventilation-perfusion lung scintigraphy) were performed. One hundred sixty-five patients underwent CT angiography of the chest because of suspected pulmonary embolism in 2004. Four of the patients were excluded from the study because they were on chronic anticoagulation therapy and a further 2 were excluded because they had a life expectancy of under 3 months. Of the remaining 159 patients, 60 had CT angiograms that were interpreted as high probability for pulmonary embolism (prevalence of 38%). Thirty-nine of the 99 patients with a negative CT angiogram experienced an objectively confirmed thromboembolic event (63% sensitivity; 95% confidence interval, 53%-73%). Other diagnostic tests were not performed in 46% of the cases. In our setting, a negative single-detector helical CT angiogram was not sensitive enough to exclude the diagnosis of pulmonary embolism. Furthermore, compliance with internationally accepted diagnostic protocols was far from optimal.

Comparison of Outcomes Using 2 Delivery Models of Anticoagulation Care

Studies demonstrate the effectiveness of anticoagulation management service (AMS) in providing antithrombotic therapy for eligible patients. We sought to extend this concept by determining whether an interim telephone model (IT) is comparable to our current AMS model at achieving optimal therapeutic outcomes. The 36-month trial (24-month study plus 12-month extension) enrolled 192 eligible patients receiving long-term warfarin therapy at a Veterans Affairs hospital. Consenting participants were randomly assigned to either our current face-to-face clinic model (AMS), or our IT model. The primary outcome was the percentage of time individuals' international normalized ratios (INRs) were maintained within their target INR range (2.0-3.0 or 2.5-3.5). Secondary outcomes included the number of adverse events (eg, thromboembolism or hemorrhage) experienced during the study. We found no statistically significant difference between the 2 groups in the percentage of time maintained within INR target range overall (55.1% for AMS; 57.8% for IT; P = .28) nor over the course of the study. There were no statistically significant differences in the rate of thromboembolic or serious bleeding events between IT and AMS participants. Nevertheless, we did note differences related to intensity of anticoagulation. The IT group receiving treatment at a higher intensity (INR, 2.5-3.5) experienced greater anticoagulation control (P = .04) and fewer complications than the AMS group. The IT participants, however, reported a significantly higher rate of minor bleeding events, experienced mainly by those at an INR range of 2.0 to 3.0. Our IT model is a viable modification of our AMS model for the management of patients undergoing chronic anticoagulant therapy.

Delayed Posttraumatic Acute Subdural Hematoma in Elderly Patients on Anticoagulation

To discuss delayed acute subdural hematoma (DASH), a relatively neglected entity, and to emphasize the potentially elevated risk for DASH among elderly, anticoagulated mild traumatic brain injury (TBI) patients. The authors reviewed clinical and radiological data for four patients who had normal neurological examinations and normal computed tomographic scans after mild TBI, and who subsequently developed DASH and deteriorated rapidly. The patients included two men and two women, aged 65 to 86 years, who presented to the emergency department after mild TBI between January 2002 and June 2004. All were treated with chronic anticoagulation or anti-aggregation therapy. They deteriorated owing to DASH from 9 hours to 3 days after TBI. Three of the four patients underwent craniotomy for evacuation of their hematomas. One patient, who suffered only focal neurological deficit, was treated conservatively, and her hematoma gradually resolved. Two patients died and two reached Glasgow Outcome Scores of 3 and 4 after extended inpatient rehabilitation. A suspicion of DASH should be raised in elderly, anticoagulated, mild TBI patients, including those who present to the emergency department with Glasgow Coma Scores of 15 and normal computed tomographic scans after injury. Based on our experience, we recommend that elderly, anticoagulated mild TBI patients should be admitted for 24 to 48 hours of observation after injury.

Holmium Laser Enucleation of the Prostate in Patients on Anticoagulant Therapy or With Bleeding Disorders

We evaluated the safety and efficacy of HoLEP in patients on anticoagulation with significant obstructive symptoms secondary to BPH refractory to medical therapy. From May 1999 to October 2004, 83 patients with a mean age of 76.6 years who had symptomatic BPH and were on chronic oral anticoagulant therapy or had bleeding disorders underwent HoLEP. Mean preoperative prostate size estimated by transrectal ultrasound was 82.4 cc (range 25 to 222). A total of 14 patients underwent HoLEP without oral anticoagulant withdrawal, 34 underwent surgery with low molecular weight heparin substitution and 33 stopped anticoagulants before surgery, including 8 on antiplatelet therapy. All patients were assessed preoperatively, and 1, 3, 6 and 12 months after surgery. HoLEP was performed successfully in all patients with a mean enucleation time of 86.5 minutes (range 35 to 210). Mean morcellation time was 20.1 minutes (range 3 to 100). Peak urinary flow, post-void residual urine, International Prostate Symptom Score and quality of life score were significantly improved by 1 month after surgery and they continued to improve during subsequent followup. One patient required intraoperative platelet transfusion and 7 required blood transfusion early in the postoperative period due to hematuria coinciding with restarting oral anticoagulant therapy. Mean preoperative and postoperative hemoglobin was 13.5 (range 8.3 to 16.4) and 12.2 gm/dl (range 5.3 to15.4), respectively (p <0.0001). There were no major operative or postoperative complications, or thromboembolic events. HoLEP is a safe and effective therapeutic modality in patients on anticoagulation with symptomatic BPH refractory to medical therapy.

Managing Oral Anticoagulation Requires Expert Experience and Clinical Evidence

The management of patients on chronic oral anticoagulant therapy, namely Vitamin K antagonists such as warfarin, is often associated with difficult and challenging issues for the healthcare practitioner. Many of these issues, such as warfarin failure or resistance, the optimal warfarin initiation dose, the optimal target International Normalized Ratio in antiphospholipid syndrome, the optimal monitoring frequency and use of point-of-care monitoring, the management of oral anticoagulation during invasive procedures, and the management of over-anticoagulation, have not been evaluated in rigorously-designed clinical trials. The latest American College of Chest Physician recommendations concerning these issues are Grade 2C, the weakest recommendations available. It remains up to the experience and expertise of the individual practitioner along with whatever clinical evidence is available in a particular healthcare environment-especially one associated with an anticoagulant management service-to implement management strategies with respect to these issues in patients on oral anticoagulation.

Considerations in Retransplantation of the Failed Renal Allograft Recipient

Routine success in kidney transplantation has significantly improved the quality and length of life for the majority of recipients and made this option the treatment of choice for suitable candidates. Improved patient survival combined with a relative static improvement in long-term graft outcomes has led to an increasing number of transplant recipients with failed allografts who face the eventual option of either returning to dialysis or seeking retransplantation. Although retransplantation is presumed to be a favorable option for many, data to support this belief is limited. Given the wide variance in predicted outcomes for retransplantation, on the basis of the underlying kidney disease and other individual patient comorbidities as well as the expected wait time for a second transplant, each case should be evaluated independently. This review discusses available data and individual considerations that should be taken into account when retransplantation is proposed after failure of a primary allograft.

Anticoagulation with Low Molecular Weight Heparin (LMWH) during Autologous Peripheral Blood Stem Cell Transplantation (PBSCT). Single Institution Experience.

BACKGROUND: Management of a chronic hypercoagulable state during the cytopenic phase of peripheral blood stem cell transplant (PBSCT) poses a significant clinical challenge. Anticoagulation in the presence of significant thrombocytopenia raises the risk of bleeding. However, withholding anticoagulation may increase the risk of thrombotic events. The purpose of this study was to evaluate the safety and efficacy of low dose thromboprophylaxis with low molecular weight heparin (LMWH) during the thrombocytopenic phase of PBSCT.METHODS: We undertook a retrospective analysis of all patients who underwent an autologous PBSCT at our institution from 1998 to 2005 and identified patients that were on therapeutic anticoagulation prior to their admission for transplantation. Institutional review board approval was obtained for this study. Information regarding indication of PBSCT, age, gender, indication for anticoagulation, bleeding or thrombotic event during hospitalization including bleeding or clotting at the site of indwelling central venous catheter, nature of anticoagulation, time to platelet engraftment, and number of platelet transfusions were recorded. Patients at known high risk for thrombosis were maintained on therapeutic dosage of warferin or LMWH until platelet counts decreased to < 50,000/μ liter, at which time LMWH 40 milligram/day subcutaneously was administered. Platelet counts were maintained at > 20,000/μ liter with transfusion support as needed.RESULTS: Eight of seventy evaluable patients were identified during the pre-transplant screening to be maintained on long term anticoagulation. Median age of these patients was 57 years (range: 38–67); Male: Female ratio 1:1; Indications for PBSCT were relapsed non-hodgkins lymphoma (n=2), multiple myeloma (n=5), acute myeloid leukemia (n=1). Indications for long term anticoagulation prior to PBSCT included: Upper extremity DVT (n=1), lower extremity DVT (n=5), pulmonary embolism (n=1), atrial fibrillation (n=1), superior sagital sinus thrombosis (n=1). Prior to transplant, therapeutic anticoagulation was maintained with warfarin (n=4) and LMWH (n=4). Median number of days with platelet counts < 20,000 = 3 (range 1–5); median number of platelet transfusions required = 3 (range 1–4); median number of days requiring LMWH = 8 (range 1–11); median number of days with platelet count < 50,000 = 6 (range 4–9). Median time to platelet transfusion independence was 11 days post stem cell infusion (range 8–15 days). One patient had an indwelling IVC filter at the time of transplantation. No clotting events were noted during and immediately post-transplantation. One patient developed microscopic hematuria and one patient developed macroscopic hematuria during the hospitalization which resolved spontaneously. No additional clinically significant bleeding complications were noted.CONCLUSION: Patients on chronic anticoagulation therapy can be safely transplanted with PBSCs and maintained on prophylactic doses of LMWH during the phase of moderate thrombocytopenia (platelet count < 50,000) without any increased incidence of clotting or bleeding events.

Ximelagatran, the Oral Anticoagulant of the Future An Evidence Based Review

This article presents the available data on Ximelagatran, a novel oral direct thrombin inhibitor and explores its therapeutic potential Recent large clinical trials have evaluated the efficacy and safety of this anticoagulant compared to the standard anticoagulation therapy with warfarin and heparins in several thrombotic disorders. These trials provide strong evidence for the efficacy and safety of ximelagatran in the following clinical indications; the prevention of venous thromboembolism after knee or hip replacement, the treatment of deep venous thrombosis, and prevention of stroke in patients with atrial fibrillation. Further evaluation of this promising oral anticoagulant is warranted in other thrombotic cardiovascular disorders requiring chronic oral anticoagulation therapy such as in patients with prosthetic heart valves, intracardiac thrombi, dilated cardiomyopathy, after myocardial infarction and post percutaneous coronary interventions.