Home prothrombin time monitoring: a literature analysis

The anticoagulant activity of warfarin sodium is monitored by the prothrombin time (PT) using the international normalized ratio (INR). Standard oral anticoagulant therapy monitoring requires frequent patient visits to physicians' offices and/or laboratories to optimize warfarin dosage. Home PT monitoring by patients can increase testing frequency and may thus decrease complications associated with oral anticoagulant therapy. Clinical studies suggest that home PT monitoring is more effective than uncoordinated management and is as effective as care through specialized anticoagulation clinics for keeping INRs within a therapeutic range. There are accurate and reliable instruments available, but paramount to the success of home PT monitoring is sound patient selection, appropriate patient training, and consistent quality control.     

Complications of warfarin therapy monitored by the international normalized ratio versus the prothrombin time ratio

The objective of our study was to determine the rates of bleeding complications and thromboembolic events in patients receiving oral anticoagulant therapy monitored with the prothrombin time (PT) ratio versus therapy monitored with the International Normalized Ratio (INR) using a retrospective time-series study design. Over 650 patients enrolled in a large anticoagulation clinic were studied during two time periods corresponding to the use of the PT ratio versus the INR to guide anticoagulant therapy, with over 400 patient-years of follow-up for each time period. The rate of bleeding complications using the PT ratio to guide therapy was 6.7% (1.2% major, 5.5% minor) per patient-year, compared with 2.9% (0% major, 2.9% minor) using the INR (p = 0.02). The rate of thromboembolic complications was 1.0% using the PT ratio, compared with 0.2% using the INR (p = NS). Therapy monitored with the INR required 19.8 visits per year, compared with 20.7 visits per year using the PT ratio. We conclude that the INR should be used to monitor oral anticoagulant therapy in an effort to reduce bleeding complications while maintaining an acceptable rate of thromboembolic events.     

Advantages of a cardiologic ambulatory care facility specifically organized for patients undergoing treatment with oral anticoagulant drugs

In patients with artificial heart valve prosthesis oral anticoagulants reduce but not eliminate the thromboembolic complications however, they do increase the risk of bleeding. In the present study, the incidence of thromboembolic and hemorrhagic complications in two homogeneous groups of patients with artificial heart valves on long term oral anticoagulant treatment has been evaluated. Group A (99 patients; total follow-up = 309 years) were resident in the Triveneto regions and received a questionnaire while group B (104 patients; total follow-up = 370 years) were referred to our department's centre for the control of oral anticoagulant treatment. Both groups were kept at a therapeutic range of 20-30% in terms of prothrombin activity. The incidence of thromboembolic and hemorrhagic complications is expressed as the number of episodes per 100 patient/years. Thromboembolic episodes were 2.6 (1.3 fatal) in group A while they were 1.08 (0.27 fatal) in group B; the reduction of fatal thromboembolic events was statistically significant (p less than 0.05). Hemorrhagic episodes were 1.9 (0.63 fatal) in group A while they were 0.81 (0 fatal) in group B. We concluded that an organized control of oral anticoagulant treatment in patients with artificial heart valves is advantageous as it significantly reduces fatal thromboembolism. Moreover, it could reduce the incidence of total thromboembolic and hemorrhagic episodes by more than 50%.     

A complication in anticoagulation using low-molecular weight heparin in a patient with a mechanical valve prosthesis. A case report

All mechanical heart valves are thrombogenic, and are associated with thromboembolic complications becomes ineffective. when anticoagulation Controversy exists with regard to the appropriate and safe anticoagulation regimen of gravid women with mechanical heart valve prostheses. While oral anticoagulants such as warfarin may be associated with fetal complications, the role of low-molecular weight heparin (LMWH) and heparinoids (and their respective appropriate dosage) have still to be determined. In developing countries such as Saudi Arabia, the prevalence of rheumatic fever is high, as is the percentage of female patients with mechanical heart valves and who are of child-bearing age. Thus, the issue of adequate anticoagulation on one hand, and avoidance of warfarin-induced embryopathy on the other hand, is crucial. To date, few reports are available of LMWH as sole anticoagulant in patients with mechanical heart valves. We report a case of massive valve thrombosis with subsequent pulmonary edema after warfarin anticoagulation was changed to LMWH during pregnancy, and administered at too low a dose.     

Improvement of oral anticoagulation therapy by INR self-management

Thromboembolic complications after valve replacement are significantly reduced if the INR is increased from 1.0 to 2.0. Hemorrhagic events increase exponentially with more intensive oral anticoagulation. In INR (patient) self-testing (PST), patients self-check their INR after being appropriately educated and supplied with a coagulometer. Patients contact their home physician if the actual INR tends to run outside an individually defined target INR corridor for correction. For patient self-management (PSM), subjects are trained to self-test their INR and to adjust the anticoagulant dose according to their anticoagulation state. The median difference between self-tested and laboratory-tested INRs was < 5.0%, indicating no significant differences between the two methods. PSM resulted in a significantly more stable oral anticoagulation therapy (OAT), which was the strongest predictor for a low complication rate after valve replacement surgery. Lower rates of thromboembolism (0.9 versus 3.6% per patient-year; pt-yr) and bleeding (4.5 versus 10.9% per pt-yr) (p < 0.001) were seen in PSM subjects than with conventional INR management. A switch from conventional to PSM resulted in a 30% reduction in complication rates in the German Experience with Low Intensity Anticoagulation (GELIA) study. After appropriate education and provision with a handy coagulometer, the vast majority of patients after valve replacement can self-check INRs and adjust the anticoagulant dosage accordingly. PSM results in a significantly more stable oral anticoagulation treatment and consequently in lower incidences of thromboembolic and bleeding events.     

美托洛尔对缺氧-再给氧心肌细胞C-FOS表达和游离钙的影响

目的和方法研究表明,c-fos是细胞核内重要的原癌基因,它的表达产物对细胞具有重要意义,c-fos的表达产物Fos单独不能与DNA结合,Fos和Jun通过亮氨酸拉链形成二聚体,即具有活性的转录因子复合物AP.1,AP.1通过顺式作用激活相关的基因,从而调节基因的表达与蛋白质的合成。在正常情况下,c-fos在细胞中仅有低水平表达,但在心肌缺血再灌注中c-fos表达迅速增加。心肌细胞在缺氧-再给氧（A/R）时会产生大量氧自由基,氧自由基可诱导原癌基因表达,原癌基因表达程度与心肌细胞复氧损伤程度及细胞内游离钙有关。Ca²⁺超载可导致细胞不可逆损伤及细胞信息传递的紊乱,大量氧自由基生成及脂质过氧化物增强是心肌缺血再灌注损伤的主要机制之一。超氧化物岐化酶（SOD）作为重要的抗氧化酶可清除超氧阴离子自由基,保护心肌细胞,减轻心脏功能的损伤程度,其活性高低反映了机体清除氧自由基的能力。本研究通过培养心肌细胞,在细胞水平模拟心肌A/R损伤,用粘附式细胞仪,以荧光探针技术激光共聚焦扫描及免疫组化、灰度分析观察美托洛尔对培养心肌细胞A/R时细胞内钙(Ca²⁺)荧光强度、SOD活性及c-Fos表达的影响。结果心肌细胞A/R后,细胞内Ca²⁺荧光强度升高,对照组为:167.3±32.8,0.3±0.04,A/R组为:562±128.6,97.6±12.8,P<0.01。细胞培养液中SOD活性、平均灰度值降低,P<0.01。美托洛尔组上述改变得到明显改善,细胞内钙(Ca²⁺)荧光强度显著降低为376±39.1,22.8±8.2,细胞培养液中SOD活性、平均灰度值显著增高,P<0.05。^#P<0.01与对照组比较*P<0.05与A/R组比较。结论本实验证实美托洛尔能可明显减少c-fos的表达,提高心肌细胞SOD活性,有效清除超氧阴离子自由基,保护细胞膜结构完整性及阻止Ca²⁺内流,减轻Ca²⁺超载,对A/R心肌具?     

A feasibility study of continuing dose-reduced warfarin for invasive procedures in patients with high thromboembolic risk

BACKGROUND: The management of perioperative anticoagulation therapy for patients having a high risk of thromboembolism who are receiving long-term oral anticoagulant therapy is uncertain. The prevalent approach is to discontinue oral anticoagulation therapy and initiate heparin therapy. Another potential strategy is to continue oral anticoagulation therapy with a temporary adjustment of warfarin intensity to a preoperative international normalized ratio (INR) of 1.5 to 2.0. Such moderate-dose anticoagulation therapy with warfarin has been shown to be hemostatically safe yet effective in the prevention of thromboembolism after hip or knee replacement. METHODS: Over an 11-year period (ie, 1993 to 2003), our hemostatic consultative service prospectively identified 100 consecutive patients for whom we continued warfarin therapy at adjusted doses during the perioperative period, targeting a goal for the INR of 1.5 to 2.0. Patients were assigned a score for venous thromboembolic risk as well as overall surgical risk using published instruments. Score assignment was based on what was deemed to be extremely high risk for thromboembolism in patients who were receiving long-term warfarin therapy. Although the patients were accrued prospectively, the final retrospective analysis was made after all patients were treated. RESULTS: The most common indication (62%) for high-risk assignment was a thromboembolic event within the past 6 months. The second most prevalent reason was prior postoperative venous thromboembolism (VTE) [11%]. Indications for long-term anticoagulation therapy were recent VTE (62%), inherited thrombophilia (7%), antiphospholipid syndrome (13%), mechanical heart valves (18%), and prior cerebrovascular accident (4%). The prevalence of inherited thrombophilia probably has been grossly underestimated, as neither factor V Leiden mutation nor prothrombin 20210 mutation had been described during the bulk of the accrual time. Most surgical procedures (58%) were significantly invasive (Johns Hopkins category 3 to 5). The mean INR values were 2.1 on the day prior to surgery (SD, 0.9594; range, 1.2 to 6.5; n = 65), 1.8 on the day of surgery (SD, 0.4899; range, 1.2 to 4.9; n = 75), and 1.8 on the first postoperative day (SD, 0.4436; range, 1.1 to 3.3; n = 70). Two patients had major bleeding, and four patients had minor bleeding. One patient developed deep venous thrombosis. Several weeks after surgery, one patient with a prosthetic heart valve died from an embolic stroke, which was associated with a failure to increase his anticoagulation to therapeutic levels. CONCLUSIONS: Moderate-intensity anticoagulant therapy with warfarin, targeting a goal INR of 1.5 to 2.0, appears to be a safe and feasible method for preventing thromboembolic complications in high-risk surgical patients who are receiving long-term oral anticoagulant therapy. This may be considered a reasonable method to afford thromboprophylaxis in highly selected patients who are occasionally seen in clinical practice. This observational study does not prove equality, let alone superiority, to other proposed methods of anticoagulation therapy.     

Fulminant thrombosis of mechanical mitral valve prosthesis

In patients with prosthetic heart valves non-cardiac surgery may require temporary discontinuation of oral anticoagulation. Although the risk of valve related thromboembolic complications may generally be only slightly increased during the short perioperative period, in the presence of certain risk factors, replacement of oral anticoagulation with heparin is recommended. In the presented patient, unusually fulminant and finally fatal thrombosis of a mechanical mitral valve prosthesis developed within only 48 hours after non-cardiac surgery despite heparin treatment. The thrombosis was triggered by clinical conditions favouring a hypercoagulable state. This report dramatically shows that despite improvements in prosthetic heart valve design and in the management of anticoagulation, thrombosis remains one of the most dangerous complications after valve replacement with a mechanical prosthesis.


Keywords: complications; mitral valve; mechanical prosthesis; thrombosis     

Antithrombotic therapies in patients with prosthetic heart valves: guidelines translated for the clinician

Patients with prosthetic heart valves require chronic oral anticoagulation. In this clinical scenario, physicians must be mindful of the thromboembolic and bleeding risks related to chronic anticoagulant therapy. Currently, only vitamin K antagonists are approved for this indication. This paper reviews the main heart valve guidelines focusing on the use of oral anticoagulation in these patients.     

Drug insight: an overview of current anticoagulation therapy after heart valve replacement

Vitamin K antagonists, such as warfarin, are the gold standard approach for the long-term anticoagulant therapy of patients with mechanical heart valves. Management decisions are, however, based predominantly on expert consensus and on data from nonrandomized, follow-up studies, which have inherent limitations in their methods. Low-intensity anticoagulation therapy provides protection against thromboembolic complications in patients with most types of modern prosthetic heart valve. The addition of low-dose aspirin is safe if international normalized ratio values below 3.5 are maintained. A combined regimen should be considered in high-risk patients and those with coexistent coronary artery or cerebrovascular disease, and in patients who have suffered a thromboembolic event despite a therapeutic international normalized ratio. Thromboprophylaxis with unfractionated or low-molecular-weight heparins is restricted to specific situations, such as when a patient is intolerant to vitamin K antagonists, when surgical procedures require discontinuation of oral anticoagulation, or when the patient is pregnant. A lack of uniformity across practice guidelines make it difficult to reach treatment decisions. Each patient's preference, expressed after counseling about the risks and benefits of each treatment strategy, and an individual assessment of the patient's risk factors, should guide treatment decisions. At present, new anticoagulant agents such as factor Xa inhibitors do not represent a treatment option for heart valve recipients.     

Thromboembolism in patients with prosthetic heart valves. An adequately controlled intense anticoagulant therapy and its influence on the occurrence of thromboembolism in relation to valve type

This study was designed to evaluate the efficacy of carefully controlled treatment with oral anticoagulants in patients with different mechanical heart valve prostheses. One hundred eighty-one patients with various types of prosthetic valves (mitral 89, aortic 87, combined 5) received oral anticoagulation aiming at Thrombotest (TT) values between 5% and 12%. Median follow-up was 46 months; 80.8% of all TT determinations were below 12%. The thromboembolic rate was 0.25%/year in patients with aortic valve replacement (AVR) and 4.87%/year in patients with mitral valve replacement (MVR). There was a strikingly lower incidence of thromboembolism with newer types of valves (Bj?rk-Shiley convex-concave) in the mitral position under exactly the same intensity and stability of anticoagulant treatment. Clinically overt valve occlusion could be almost completely prevented (0.12%/year) in prostheses at both sites. Severe hemorrhage occurred at a rate of 1.71%/year and fatal bleeding at a rate of 0.37%/year. Our results indicate that carefully controlled anticoagulation is effective in the reduction of thromboembolic complications at a reasonable risk of bleeding.     

Interference of lupus anticoagulants in prothrombin time assays: implications for selection of adequate methods to optimize the management of thrombosis in the antiphospholipid-antibody syndrome

BACKGROUND AND OBJECTIVE: Prolonged anticoagulation aiming at International Normalized Ratio (INR) values > 3.0 has been recommended for patients with thrombosis and the antiphospholipid-antibody syndrome. We evaluated the influence of anticoagulant antibodies in two different prothrombin time (PT) assays carried out on plasma from lupus anticoagulant patients on oral anticoagulation. DESIGN AND METHODS: INR values obtained with a combined (final test plasma dilution 1:20) and a recombinant (final test plasma dilution 1:3) thromboplastin were compared in 17 patients with persistent lupus anticoagulants (LA) receiving oral anticoagulant treatment and monitored for 69.8 patient-years. Doses of anticoagulant drugs were always assigned based on the results obtained with the combined thromboplastin, aiming at a target INR of 2.5 or 3.0 for patients with venous or arterial thromboembolic disease. Paired determinations with both reagents were also obtained throughout the study period in 150 patients on stable oral anticoagulation but free of antiphospholipid antibodies. Total IgG fractions were purified from selected patients to evaluate effect in the two PT assay systems. RESULTS: No patient experienced recurrence of thrombosis or major bleeding complications (95% confidence interval: 0.1-6.5 per 100 patient-years). INR values with the recombinant reagent were significantly higher than with the combined reagent in 8 LA patients (mean DINR ranging from 0.17 to 0.54) of the degree of anticoagulation was overestimated in all but one LA patients with the recombinant reagent when compared to the DINR observed in non-LA patients (-0.64 +/- 0.42). The anti-cardiolipin IgG titer (r(2) = 0.43, p = 0.004) and the anti-b(2)GPI IgG titer (r(2) = 0.30, p = 0.023) were positively associated with the mean deltaINR observed in LA patients. When added to plasmas with different levels of vitamin K-dependent factors, total IgG fractions from 6 LA patients with significant overestimation of the INR with the recombinant reagent (mean DINR ranging from 0.17 to 0.54, group 1) and from 7 LA patients with mean deltaINR < or = 0.0 (ranging from -0.25 to 0.04, group 2) reproduced the effects observed ex vivo in the two assay systems. However, when total IgG fractions were tested at the same final concentration in the two PT assay systems, there was no difference in the clotting times determined with total IgG fractions from group 1 and group 2 LA patients. Addition of negatively charged liposomes (0.4 and 0.8 mg/mL final concentrations) to platelet free plasma from LA-free patients on stable oral anticoagulation caused a 20% to 48% prolongation of the prothrombin time determined with the recombinant reagent. In contrast, no significant prolongation of the prothrombin time determined with the recombinant reagent was observed upon addition of negatively charged liposomes to plasma from group 1 LA patients. INTERPRETATION AND CONCLUSIONS: These results confirm previous suggestions of assay-dependency of INR values in LA patients on oral anticoagulation. For these patients, accurate INR values may be obtained using combined thromboplastin reagents that permit testing at high plasma dilution.     

Analysis and occurrence of adverse events with oral anticoagulant therapy.

The antithrombotic potential of oral anticoagulants is undisputed as the frequency of recurrent thrombosis is high unless anticoagulant therapy is continued after hospital discharge. However, the relationship between potency and/or changes in anticoagulant therapy and frequency of complications remains unclear. Optimizing the clinical management of oral anticoagulation information obtained by databases may be advantageous in addition to meeting safety criteria, as described in the "Saarland Model." The Phoenix-database implicates an association between bleeding complications and the hypertensive elderly. From 1968 to 1993 most reports about cerebral/intraspinal bleedings occurred at prothrombin (PT)-values below 20% in the elder patients (>60 years of age) (12%; 367 reports). In the Saarland Model, 60 patients were followed from our department during a 3-year period. Our findings suggest neither a correlation of the range of PT values and the bleeding events nor an association with age or hypertension. It became obvious that "stable phases" of International Normalized Ratio (INR) [+/-15% change of 4 serial controls using nearly constant weekly oral anticoagulant dosages (+/-15%)] might be considered as a valid criterion of safety. At least the individual risk profile determines the patient's fate.     

Therapeutic target values in oral anticoagulation — Justification of Dutch policy and a warning against the so-called moderate-intensity regimens

Summary Careful scrutiny of relevant thrombosis prevention studies in the light of recent knowledge on the responsiveness to the anticoagulant defect of the various prothrombin time assays used in these studies casts serious doubts on the adequacy of the so-called moderateintensity warfarin regimens, currently recommended by British and North American experts, in the majority of clinical situations. As long as there is strict laboratory monitoring, more intensive anticoagulation provides satisfactory prevention of thromboembolic events. The Federation of Dutch Thrombosis Centers recommends a target of 3.0 International Normalized Ratio (INR) for the primary and secondary prevention of venous thrombosis and thromboembolism, 3.5 INR in case of recurrence under the former regimen and for patients at risk for a cardiogenic embolism from any source (including tissue heart valve replacement) and those with atherothrombotic disease, and 4.0 INR for patients with a mechanical heart valve prosthesis. The risk of hemorrhage at such levels of anticoagulation remains acceptable.     

Hypercoagulability in a patient with hypodysfibrinogenemia: implications for clinical management.

Dysfibrinogenemia accounts for approximately 0.7% of thrombophilia in patients with venous thromboembolic disease. In 20% of these patients, plasma thrombophilic dysfibrinogen is below 1.0 mg/ml, defining hypodysfibrinogenemia. We describe a young female patient, in whom hypodysfibrinogenemia was the cause of several severe thromboembolic events which occurred even under oral anticoagulation monitored by a standard prothrombin time (PT) test. In this patient, the standard PT test according to Quick underestimated the plasma coagulability in vivo, presumably due to the low levels of dysfunctional fibrinogen as the substrate of the thromboplastin reagent. A PT test supplemented with bovine plasma fibrinogen (Thrombotest) revealed lower fibrinogen-independent international normalized ratio (INR) values in the proposita on oral anticoagulation compared to a control group with eufibrinogenemia. Monitoring therapy with the fibrinogen-independent Thrombotest secured safe anticoagulation in this patient. We suggest to consider PT tests with exogenous fibrinogen (e.g. Thrombotest) to monitor oral anticoagulation in the rare thrombophilic patients with hypodysfibrinogenemia.     

Anticoagulation in pregnancy and post partum in heat valve diseases, thrombosis or atrial fibrillation: fetal risk versus maternal thromboembolism

Patients with mechanical valve prostheses are at high risk for thromboembolic events, valve thrombosis and mortality during pregnancy. The most effective anticoagulation for the mother is achieved with oral anticoagulants which may be associated with embryopathy in the baby. The risk of embryopathy and the risk of hemorrhage during the remainder of the pregnancy depend on the intensity of anticoagulation induced in the fetus and the dose of the oral anticoagulant used. Recent studies suggest that a warfarin dose of less than 5 mg and an INR of less than 3 does not induce embryopathy and is associated with a low rate of fetal complications (15%). Heparin has been recommended as the anticoagulant of choice during pregnancy, because it does not cross the placental barrier and does not cause embryopathy. Yet all forms of unfractionated heparin application (low dose, aPTT-ratio-adjusted, during the entire pregnancy or during the first trimester) are associated with a higher rate of maternal complications and death than oral anticoagulants given throughout pregnancy until the 36th week of pregnancy. Also the total fetal outcome (abortion and stillbirth) is not improved by heparin. To avoid fetal and maternal complications, particularly hemorrhage during premature labor, mothers should be admitted to the hospital in the 36th week for conversion from oral anticoagulants to heparin, preferentially given i.v. prior to delivery. Vaginal delivery should be avoided under therapeutic oral anticoagulation and cesarean section preferred after neutralization of anticoagulation. The optimal INR-monitored intensity of anticoagulation by the patient is one promising way to reduce complications and increase efficacy and safety. Randomized studies including low molecular weight heparin and oral anticoagulants in patients with mechanical valve prostheses are needed, with careful monitoring of laboratory parameters and cardiac follow-up. This requires close cooperation between cardiologists, gynecologists and hemostaseologists.     

Anticoagulant management of patients with mechanical prosthetic valves undergoing non-cardiac surgery: indications and unresolved issues

A wide array of recommendations is available for the management of anticoagulation in patients with a prosthetic heart valve scheduled for non-cardiac surgery, ranging from avoidance of replacement anticoagulant therapy in all cases (excluding those with a recent thromboembolic event), to replacement anticoagulant therapy in all, without risk stratification. These guidelines are derived from only a few small- to medium-sized, non-randomized and often methodologically flawed studies conducted during the late 1970s, and applies mainly to caged-ball and caged-disc valves. Furthermore, extrapolation of the thromboembolic risk from data on patients not receiving oral anticoagulants at all is based on assumptions that are not necessarily valid. In this review, the direct and indirect evidence on which these guidelines are based is examined critically. Their applicability to the newer, less thrombogenic valve models is questionable. The need for further prospective, randomized studies is emphasized by the failure of existing studies to adjust properly for the main known or presumed thromboembolic risk factors, and their low statistical power to detect significant differences between protocols in an intention-to-treat manner. The evaluation of obstructive and non-obstructive thrombosis should serve as a secondary outcome measure in the assessment of anticoagulation management before non-cardiac surgery.     

Bioprosthetic aortic valve thrombosis under effective direct oral anticoagulant therapy

With the increase in transcatheter procedures, the use of bioprosthetic valves has become more frequent in clinical practice. However, the optimal antithrombotic management of patients with bioprosthetic valves remains controversial. In this case report, we describe a patient with a bioprosthetic aortic valve who developed a thrombus while receiving effective dose direct oral anticoagulant (DOAC) therapy. A 73-year-old male patient with a bioprosthetic aortic valve replacement 2 years prior presented with a mobile thrombus and early degeneration of the valve, detected during routine follow-up while being treated with apixaban. Although the valve thrombus regressed after switching to a different anticoagulant drug, we observed that the decreased but still high gradient persisted due to the early degeneration. Anticoagulant management of bioprosthetic valve patients demands careful attention. Although evidence supporting the use of DOACs is growing, close patient follow-up and further evaluation in case of doubt remain critical. The development of a thrombus in a bioprosthetic valve patient who is receiving anticoagulation therapy, as in this case, highlights the need for optimal management to prevent thromboembolic complications and valve degeneration.     

Anticoagulant therapy in Japanese patients with mechanical mitral valves.

There are no guidelines for the optimal therapeutic range of anticoagulant therapy in Japanese patients with mechanical heart valves. A total of 214 patients were followed retrospectively after mitral mechanical valve replacement (mean duration of follow-up, 4.8 years; total duration of follow-up, 1,027 patient-years). The target range of the international normalized ratio (INR) for oral anticoagulation was between 1.5 and 2.5. For all patients 10,416 measurements of the INR were obtained during the follow-up period and approximately 76% of the intensity measurements were within the target range. Thromboembolism occurred in 8 patients (0.8 per 100 patient-years) and major bleeding in 5 patients (0.5 per 100 patient-years). There was no correlation between the distribution of the INR and the occurrence of thromboembolic or bleeding complications. In the univariate analysis of the various risk factors, patients who had a tilting valve or did not receive antiplatelet therapy had an increased risk of thromboembolism. However, there were no risk factors with respect to bleeding complications. A target range of 1.5 to 2.5 INR appears to be the optimal range and is safe for thromboembolism or bleeding complications. Thromboembolism may be reduced by additional antiplatelet therapy, and a tilting valve needs more intense anticoagulation.     

Perioperative bleeding and thromboembolic risk during non-cardiac surgery in patients with mechanical prosthetic heart valves: an institutional review.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to determine the risk of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses who underwent non-cardiac surgery under different regimens of perioperative anticoagulation. Data were analyzed on the basis of surgery type and underlying disease. METHODS: A series of 235 patients (mean age 63 +/- 4.5 years) with one or two mechanical heart valves underwent subsequent non-cardiac surgery comprising abdominal, vascular and thoracic, orthopedic, urologic, neurosurgery, ENT, plastic and reconstructive, and gynecologic operations. Mean interval between heart valve replacement and non-cardiac surgery was 3.9 +/- 3.3 years. Perioperative oral anticoagulation was managed by discontinuation of oral anticoagulation and intravenous heparin administration; or by discontinuation and early postoperative re-institution of oral anticoagulation without intravenous heparin; or by no withdrawal of oral anticoagulation. Patients with bioprostheses were excluded. RESULTS: Overall hospital mortality during non-cardiac surgery was 2.9%. Thromboembolic events included cerebral embolism with transient deficit (n = 3), residual defect (n = 1) and irreversible defect (n = 1), as well as peripheral embolism (n = 11). Hemorrhagic complications included wound hematoma (n = 10) and increased postoperative bleeding (n = 8) with re-exploration in five patients. Thromboembolic complications occurred most often in patients with prosthetic mitral valve and atrial fibrillation; the lowest risk was in patients with sinus rhythm after aortic valve replacement. Most complications occurred after discharge and in patients with surgery for malignancy, within 10 days of instituting oral anticoagulation, and despite a therapeutic INR value. CONCLUSIONS: Minor surgical procedures can be performed safely without discontinuing anticoagulation. When major non-cardiac surgery is planned, discontinuing oral anticoagulation and starting perioperative intravenous heparin minimizes bleeding and thromboembolic risks. Thromboembolic complications may occur within one month of surgery, despite adequate oral anticoagulation, though permanent morbidity is low.