warfarin and Mucocutaneous-Lymph-Node-Syndrome

To compare the safety and efficacy of warfarin plus aspirin versus aspirin alone for the treatment of children with giant coronary artery aneurysm (CAA) secondary to Kawasaki disease (KD).. We searched the PubMed, EMBASE, Cochrane Library, CNKI, WANFAN and VIP databases. We selected case-controlled trials of warfarin plus aspirin versus aspirin alone for the treatment of children with giant CAA secondary to KD.. Six retrospective studies met our inclusion criteria. There was no significant difference between the warfarin plus aspirin and aspirin alone groups in the rate of CAA regression (OR 1.38, 95% CI 0.52-3.68, p = 0.52) or the incidence of persistent CAA (OR 2.34, 95% CI 0.16-33.50, p = 0.53), coronary artery stenosis (OR 0.55, 95% CI 0.18-1.72, p = 0.30) or thrombus formation (OR 0.50, 95% CI 0.15-1.69, p = 0.26). There was evidence that warfarin plus aspirin reduced the incidence of coronary artery occlusion (OR 0.08, 95% CI 0.02-0.29, p < 0.0001), cardiac infarction (OR 0.27, 95% CI 0.11-0.63, p = 0.003) and death (OR 0.18, 95% CI 0.04-0.88, p = 0.03).. Warfarin plus aspirin therapy reduced the incidence of occlusion, cardiac infarction and death in children with giant CAA secondary to KD.

Topics: Anticoagulants; Aspirin; Child; Coronary Aneurysm; Drug Therapy, Combination; Humans; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Warfarin

Patients with coronary artery aneurysms caused by Kawasaki disease are at increased risk of coronary thrombosis and ischemia. To prevent coronary thrombosis, long-term anti-thrombosis using anti-platelet drugs, such as aspirin, dipyridamole, ticlopidine, clopidogrel, and abciximab, with or without warfarin is recommended by official guidelines. In fact, aspirin or aspirin with warfarin are the most frequently administered regimen in these patients with coronary aneurysms. However, there has been paucity of data and no randomized controlled study to determine the efficacy of these drugs. This short article attempts to summarize the efficacy and safety of these drugs based on currently available literatures and our multi-institutional experience.

Topics: Aspirin; Child, Preschool; Coronary Aneurysm; Coronary Thrombosis; Humans; Infant; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Warfarin

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Aspirin; Child; Child, Preschool; Female; Heart Diseases; Humans; Infant; Infant, Newborn; Japan; Lymphatic Diseases; Male; Middle Aged; Mucocutaneous Lymph Node Syndrome; Prednisone; United States; Warfarin

The substantial risk of thrombosis in large coronary artery aneurysms (CAAs) (maximum z-score ≥ 10) after Kawasaki disease (KD) mandates effective thromboprophylaxis. We sought to determine the effectiveness of anticoagulation (low-molecular-weight heparin [LMWH] or warfarin) for thromboprophylaxis in large CAAs.. Data from 383 patients enrolled in the International KD Registry (IKDR) were used. Time-to-event analysis was used to account for differences in treatment duration and follow-up.. From diagnosis onward (96% received acetylsalicylic acid concomitantly), 114 patients received LMWH (median duration 6.2 months, interquartile range [IQR] 2.5-12.7), 80 warfarin (median duration 2.2 years, IQR 0.9-7.1), and 189 no anticoagulation. Cumulative incidence of coronary artery thrombosis with LMWH was 5.7 ± 3.0%, with warfarin 6.7 ± 3.7%, and with no anticoagulation 20.6 ± 3.0% (P < 0.001) at 2.5 years after the start of thromboprophylaxis (LMWH vs warfarin HR 1.5, 95% confidence interval [CI] 0.4-5.1; P = 0.56). A total of 51/63 patients with coronary artery thrombosis received secondary thromboprophylaxis (ie, thromboprophylaxis after a previous thrombus): 27 LMWH, 24 warfarin. There were no differences in incidence of further coronary artery thrombosis between strategies (HR 2.9, 95% CI 0.6-13.5; P = 0.19). Severe bleeding complications were generally rare (1.6 events per 100 patient-years) and were noted equally for patients on LMWH and warfarin (HR 2.3, 95% CI 0.6-8.9; P = 0.25).. LMWH and warfarin appear to have equivalent effectiveness for preventing thrombosis in large CAAs after KD, although event rates for secondary thromboprophylaxis and safety outcomes were low. Based on our findings, all patients with CAA z-score ≥ 10 should receive anticoagulation, but the choice of agent might be informed by secondary risk factors and patient preferences.

Topics: Anticoagulants; Canada; Chemoprevention; Child, Preschool; Coronary Aneurysm; Female; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Male; Mucocutaneous Lymph Node Syndrome; Registries; Risk Adjustment; Thrombosis; United States; Warfarin

The inflammatory mediators play an important role in the progression of coronary vasculitis in Kawasaki disease (KD), but effects of KD serum including inflammatory mediators on endothelial cells remain unknown. We hypothesized that serum activity to stimulate in vitro human umbilical vein endothelial cells (HUVEC) tube formation might be impaired in KD.. Serum from patients with coronary aneurysms was less active in stimulating HUVEC tube formation than serum from patients without coronary aneurysms or febrile controls. In patients with coronary aneurysms, the reduction in the serum angiogenic activity was documented already before KD treatment (p=0.03 vs healthy controls, p=0.08 vs febrile controls) and enhanced after intravenous immune globulin plus aspirin (p<0.001 vs healthy controls, p=0.002 vs febrile controls); both drugs did not affect the assay studied. This reduction was greater in patients who later developed giant aneurysms >8 mm compared with those who developed small to moderate aneurysms (p=0.01). The reduced serum angiogenic activity was partly caused by the reduction in the serum activity of stimulating HUVEC proliferation.. Serum activity to stimulate HUVEC tube formation was impaired in KD patients who later developed larger coronary aneurysms, which may be associated with the severity of vascular injury.

Topics: Angiogenesis Inhibitors; Anticoagulants; Aspirin; Cell Proliferation; Cells, Cultured; Child; Child, Preschool; Coronary Aneurysm; Dexamethasone; Endothelium, Vascular; Glucocorticoids; Heparin; Humans; Immunoglobulins, Intravenous; Infant; Mucocutaneous Lymph Node Syndrome; Neovascularization, Physiologic; Prednisolone; Serum; Severity of Illness Index; Umbilical Veins; Warfarin

The long-term prognosis of patients with Kawasaki disease (KD) complicated by coronary artery aneurysms (CAA) is still unclear. The present, multicenter registry study aimed to study the factors associated with coronary events (CE) and determine an appropriate management method for patients with KD complicated with CAA. Patients with KD with onset after 2015 and with a medium-sized or large CAA having an actual diameter ≥ 4 mm or a Z-score ≥ 5.0 at 30 days and later after KD onset were included in the annual survey. The primary endpoint was the time-dependent incidence of CE. Associated factors were also examined. In total, 179 patients from 53 centers were enrolled and followed up for a median of 501 days. The median age at KD onset was 2.2 years, 137 patients were male (77%), 47 had incomplete KD (26%), and 36 had large CAA (20%). CE occurred in 13 patients (7%; 95% confidence interval: 4-12%); eight (62%) experienced CE within 1 year, and all the patients experienced a CE within 2 years. All but one patient received antiplatelet drugs and warfarin. Patients with a large CAA had significantly more CAA (2.8 vs. 1.7, p < 0.001), more cases of warfarin use (86% vs. 43%, p < 0.001), and were more likely to have CE (28% vs. 2%, p < 0.001) than those with a medium-sized CAA. On univariate Cox regression analysis, the factors significantly associated with CE were large CAA (hazard ratio (HR): 17.0), three or more CAA (HR: 23.3), and beaded CAA (HR: 15.9). Multivariable Cox regression analysis revealed that the only associated factor was a large CAA.. Patients with a large CAA were more likely to have a CE within 2 years. Antithrombotic therapy with warfarin did not eliminate the CE risk, and better therapies are desirable.. • Coronary artery aneurysms are a serious complication of Kawasaki disease, and coronary events are sometimes fatal. • In previous, retrospective studies in Japan, large aneurysms, male sex, and refractoriness to initial immunoglobulin therapy were considered risk factors for coronary events.. • Of 179 patients with a medium sized or large aneurysm, 13 (7%) experienced coronary events, all of which occurred within 2 years of onset. Factors significantly associated with coronary events were large aneurysms, three or more aneurysms, and beaded aneurysms.

Topics: Child, Preschool; Coronary Aneurysm; Coronary Vessels; Female; Humans; Immunoglobulins, Intravenous; Infant; Male; Mucocutaneous Lymph Node Syndrome; Retrospective Studies; Warfarin

BACKGROUND Kawasaki disease (KD), a systemic vasculitis, affects children aged <5 years and is the leading acquired cardiovascular disease in developed countries. Although intravenous immunoglobulin is an effective treatment for KD and decreases the rate of cardiovascular complications, some patients still develop coronary sequelae, including coronary aneurysms and myocardial infarction. CASE REPORT A 9-year-old boy was diagnosed with KD at the age of 6 years. For coronary sequelae of a giant coronary artery aneurysm (CAA) 8.8 mm in diameter, he was prescribed aspirin and warfarin. At 9 years old, he visited the Emergency Department because of acute chest pain. Electrocardiography revealed an incomplete right bundle branch block and ST-T change over right and inferior leads. Also, troponin I was elevated. Coronary angiography found acute thrombotic occlusion of the right CAA. We performed aspiration thrombectomy with intravenous tirofiban. Coronary angiography and optical coherence tomography (OCT) images later found white thrombi, calcification, destruction of media layer, irregular intimal thickening, and uneven intima edge. We prescribed antiplatelet therapy and warfarin, and he was doing well at a 3-year follow-up. CONCLUSIONS OCT is a promising modality that can impact the clinical care in patients with coronary artery disease. This report presents treatment management and OCT images of KD complicated with a giant CAA and acute myocardial infarction. We used aspiration thrombectomy in combination with medical treatments as the initial intervention strategy. Afterward, the OCT images showed vascular wall abnormalities, which were helpful for defining the future risk and decision making of further coronary interventions and medical treatments.

Topics: Child; Coronary Aneurysm; Coronary Angiography; Coronary Vessels; Humans; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Tomography, Optical Coherence; Warfarin

The most severe complication associated with giant coronary aneurysm in children with Kawasaki disease is ischemic cardiomyopathy (ICM) caused by thrombosis. Addition of tissue plasminogen activator, Alteplase, in the treatment regimen can be an efficient thrombolytic therapy, and therefore can have a significantly positive impact on patients' quality of life in long term.. Total four male KD patients with central thromboses in coronary aneurysm were treated in Pediatric Cardiology Department of Shengjing Hospital, China Medical University, from January 2020 to August 2021. These patients received thrombolytic treatments including Alteplase once + Heparin for 1 week followed by continuous oral Warfarin + Aspirin + Clopidogrel.. 4 young male KD patients had coronary aneurysm (CAA) complicated with total 7 occurrences of central thrombosis. These patients were given alteplase and heparin/oral Warfarin + Aspirin + Clopidogrel treatment. 9 days to 2 months later, thromboses were significantly dissolved. The treatment successfully diminished the thrombosis complication.. 1. Pediatric KD patients complicated with coronary aneurysm thrombosis are prone to recurrence of thrombosis. 2.  In KD patients complicated with coronary aneurysm thrombosis, treatments described in Method can be used for treating either small thromboses formed less than 1 month with strong echo and convex lumen or large thromboses with mixed strong and weak echo. With these treatments, coronary artery blood flow can be improved or completely recovered. 3. Clinical experiences at our center in treating these KD patients suggest that Alteplase can be considered in thrombolytic treatment beyond the limitation of less than 12 h of thrombosis occurrence.

Topics: Aspirin; Child; Clopidogrel; Coronary Aneurysm; Coronary Thrombosis; Fibrinolytic Agents; Heparin; Humans; Male; Mucocutaneous Lymph Node Syndrome; Quality of Life; Tissue Plasminogen Activator; Warfarin

In the 2017 American Heart Association (AHA) Kawasaki disease (KD) guidelines, risk levels (RLs) for long-term management are defined by both maximal and current coronary artery (CA) dimensions normalized as z-scores. We sought to determine the degree to which current recommended practice differs from past actual practice, highlighting areas for knowledge translation efforts. The International KD Registry (IKDR) included 1651 patients with CA aneurysms (z-score > 2.5) from 1999 to 2016. Patients were classified by AHA RL using maximum CA z-score (RL 3 = small, RL 4 = medium, RL 5 = large/giant) and subcategorized based on decreases over time. Medical management provided was compared to recommendations. Low-dose acetylsalicylic acid (ASA) use ranged from 86 (RL 3.1) to 95% (RL 5.1) for RLs where use was "indicated." Dual antiplatelet therapy (ASA + clopidogrel) use ranged from 16% for RL 5.2 to 9% for RL 5.4. Recommended anticoagulation (warfarin or low molecular weight heparin) use was 65% for RL 5.1, while 12% were on triple therapy (anticoagulation + dual antiplatelet). Optional statin use ranged from 2 to 8% depending on RL. Optional beta-blocker use was 2-25% for RL 5, and 0-5% for RLs 3 and 4 where it is not recommended. Generally, past practice was consistent with the latest AHA guidelines, taking into account the flexible wording of recommendations based on the limited evidence, as well as unmeasured patient-specific factors. In addition to strengthening the overall evidence base, knowledge translation efforts may be needed to address variation in thromboprophylaxis management.

Topics: Adolescent; Anticoagulants; Aspirin; Child; Coronary Aneurysm; Female; Guideline Adherence; Humans; Male; Mucocutaneous Lymph Node Syndrome; Registries; Retrospective Studies; Venous Thromboembolism; Warfarin

Topics: Anticoagulants; Aspirin; Computed Tomography Angiography; Coronary Aneurysm; Coronary Angiography; Coronary Thrombosis; Echocardiography; Female; Humans; Imaging, Three-Dimensional; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Tomography, X-Ray Computed; Vascular Calcification; Warfarin; Young Adult

Topics: Adult; Anticoagulants; Cardiologists; Child; Coronary Aneurysm; Coronary Vessels; Heparin; Humans; Mucocutaneous Lymph Node Syndrome; Registries; Venous Thromboembolism; Warfarin

Long-term oral warfarin is recommended in pediatric Kawasaki disease patients with large coronary artery aneurysms; however, heterogeneity is considerable. This study aimed to determine variables affecting warfarin dosage in Kawasaki disease. The enrolled individuals (194 children) were divided into four groups: (1) Cases with severe coronary artery lesions (CAL) of IV to V degrees or thrombogenesis treated with oral warfarin were assigned to Group A; (2) Group B, CAL of I degrees; (3) Group C, CAL of II and III degrees cases with small or medium-sized CAL not treated with warfarin; (4) Group D, normal children without Kawasaki disease. The relevant genotypes of CYP2C9, VKORC1 (1173, - 1639, and 3730), and CYP4F2 were assessed. There were no statistically significant differences in CYP2C9, VKORC1, and CYP4F2 mutation frequencies among the 4 groups. In the 44 Group A patients, demographic features, clinical characteristics, and genotypes were recorded, and their associations with warfarin dose variability were assessed. Multivariate linear regression analysis revealed that height, VKORC1 1173, and CYP2C9 accounted for 61.2%, 7.9%, and 4.3% of dosing variability, respectively. Conclusions: Patient height is the main factor determining warfarin dosage, while genotype effects on warfarin dosage vary among studies. New formula should be defined using data obtained from children in cases with demonstrated efficacy.

Topics: Adolescent; Anticoagulants; Body Height; Case-Control Studies; Child; Child, Preschool; China; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Humans; Infant; Linear Models; Male; Mucocutaneous Lymph Node Syndrome; Multivariate Analysis; Mutation; Retrospective Studies; Vitamin K Epoxide Reductases; Warfarin

Giant coronary artery aneurysms are a complication of Kawasaki disease and can be fatal if associated with thrombosis. We describe the clinical outcome of a boy with Kawasaki disease who exhibited "supergiant" coronary artery aneurysms at the age of 14 months and, despite treatment with anticoagulant and antiplatelet medication, developed a left coronary artery thrombosis and presented following a myocardial infarction at 2 years old. Although his symptoms were minimal, the myocardial infarction was identified by abnormal Q-waves and giant negative T-waves in precordial leads of routine electrocardiography. Intensive anticoagulant therapy combining heparin injections and high-dose warfarin was successful. The abnormal Q-waves and negative T-waves had completely disappeared 2 weeks later, likely in association with confirmed reperfusion. On the basis of prompt identification of abnormal Q-waves by electrocardiography, the patient could avoid thrombolytic therapy and catheter or surgical intervention.

Topics: Anticoagulants; Asymptomatic Diseases; Coronary Angiography; Echocardiography; Electrocardiography; Follow-Up Studies; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Thrombolytic Therapy; Warfarin

Kawasaki disease (KD) is the leading cause of acquired heart disease due to its complicated coronary artery lesions. Up to now, few studies were focused on the status of persistent coronary artery aneurysms (CAA) in KD patients. The present study was designed to identify the coronary artery outcomes and seek the risk factors associated with the regression of CAA in KD patients. One hundred and twenty KD patients with CAA hospitalized in Children's Hospital of Soochow University from Jan 2008 to Dec 2013 were prospectively studied by a 3-year follow-up. Data regarding demographic, clinical, laboratory, and echocardiographic characteristics were documented and further analyzed. It was estimated that 39.2% of the patients had complete regression of CAA within 4 weeks, 59.2% within 8 weeks, and 70.0% within 16 weeks. No fatal cardiac events occurred. We found patients who aged ≤ 1 year, received initial intravenous immunoglobulin (IVIG) treatment after the 10th day of illness, and IVIG non-responders were associated with the regression of persistent CAA. The relative risks were 1.55, 1.87, and 1.88, respectively. Age, initial IVIG treatment, and IVIG response were risk factors of persistent CAA, and more attention should be paid on these patients.

Topics: Adolescent; Anticoagulants; Antipyretics; Aspirin; Child; Child, Preschool; China; Coronary Aneurysm; Female; Fever; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Infant; Male; Mucocutaneous Lymph Node Syndrome; Prospective Studies; Remission Induction; Risk Factors; Time Factors; Warfarin

Warfarin therapy is recommended in children with giant coronary artery aneurysms (GCAAs) after Kawasaki disease (KD). Large individual variability makes it difficult to predict the warfarin dose. Polymorphisms in the vitamin K expoxide reductase 1 (VKORC1) and cytochrome P4502C9 (CYP2C9) genes have been reported to influence the warfarin dose. We investigated the effects of the VKORC1 and CYP2C9 genotypes on the warfarin dose in pediatric patients with giant CAAs after KD. We attempted to create a dosing algorithm.. The clinical and genetic data of patients were documented. VKORC1 (rs 9923231) and CYP2C9 *3 (rs 1057910) were genotyped using TaqMan real-time polymerase chain reaction. A linear regression analysis was performed to evaluate the contribution of clinical and genetic factors to the warfarin maintenance dose.. Forty-seven patients were enrolled. Patients with the CT or CC genotype of VKORC1 had a relatively higher warfarin dose than did those with the TT genotype (p < 0.05). Three patients with CYP2C9*1/*3 had a lower warfarin dose than did those with the wild CYP2C9*1/*1 genotype, but the difference did not reach significance (p > 0.05). Weight and the VKORC1 genotype predominantly contributed to the warfarin dose, with 33.0% and 11.2% of variability, respectively. The observed warfarin dose was correlated with the predicted dose based on the algorithm used in our study (r = 0.45, p < 0.01).. Weight and the VKORC1 genotype primarily determined the warfarin dose in Chinese pediatric patients with KD. Further studies are warranted to verify the findings of our study.

Topics: Body Weight; Cytochrome P-450 CYP2C9; Dose-Response Relationship, Drug; Female; Genotype; Humans; Male; Middle Aged; Mucocutaneous Lymph Node Syndrome; Vitamin K Epoxide Reductases; Warfarin

To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications.. We reviewed the time in therapeutic range; percentage of international normalization ratios (INRs) in range (%); bleeding events, clotting events; INRs ≥6; INRs ≥5 and <6; and INRs <1.5.. In 9 patients (5 male), median age 14.4 years (range 7.1-22.8 years), INR testing was prescribed weekly to monthly and was done by home monitor (n = 5) or laboratory (n = 3) or combined (1). Median length of warfarin therapy was 7.2 years (2.3-13.3 years). Goal INR was 2.0-3.0 (n = 6) or 2.5-3.5 (n = 3), based on CAA size and history of CAA thrombosis. All patients were treated with aspirin; 1 was on dual antiplatelet therapy and warfarin. The median time in therapeutic range was 59% (37%-85%), and median percentage of INRs in range was 68% (52%-87%). INR >6 occurred in 3 patients (4 events); INRs ≥5 <6 in 7 patients (12 events); and INR <1.5 in 5 patients (28 events). The incidence of major bleeding events and clinically relevant nonmajor bleeding events were each 4.3 per 100 patient-years (95% CI 0.9-12.6). New asymptomatic coronary thrombosis was detected by imaging in 2 patients.. Bleeding and clotting complications are common in patients with Kawasaki disease on warfarin and aspirin, with INRs in range only two-thirds of the time. Future studies should evaluate the use of direct oral anticoagulants in children as an alternative to warfarin.

Topics: Adolescent; Anticoagulants; Child; Female; Hemorrhage; Humans; Incidence; International Normalized Ratio; Male; Mucocutaneous Lymph Node Syndrome; Retrospective Studies; Thrombosis; Warfarin; Young Adult

Topics: Anticoagulants; Blood Coagulation; Child; Humans; Mucocutaneous Lymph Node Syndrome; Thrombolytic Therapy; Warfarin

To explore effective and convenient rescue therapy options for coronary artery aneurysms (CAA) with thrombosis in Kawasaki disease (KD). A total of 210 patients with KD between the years 2003 and 2013 were retrospectively reviewed in our institute. 144 of these 210 KD developed CAA, and 10 patients with CAA had associated thrombosis. Thrombosis was confirmed by two-dimensional echocardiograms (2-DE). Laboratory values for CAA were analyzed with and without the thrombus group. The characteristics of CAA were monitored by ultrasound. All patients with thrombus received intravenous (IV) antithrombotic therapy, including urokinase, heparin, and oral warfarin. The effectiveness of antithrombotic treatment was evaluated by measuring the ability to dissolve the thrombus. All thrombi in these patients were preceded by a giant CAA and a history of KD. There are no differences in the blood analyses of both CAA with and without thrombus. Moreover, typical KD symptoms and acute myocardial infarction were not found in CAA with thrombosis. The progression of coronary thrombosis in these patients was arrested by antithrombotic and anti-platelet treatment including low-dose urokinase and heparin. Neither clinical features nor laboratory data could reliably predict CAA associated thrombosis. Therapy with IV anti-thrombus and anti-platelet treatment with low-dose warfarin can effectively dissolve thrombi in KD patients.

Topics: Child; Child, Preschool; Coronary Thrombosis; Dose-Response Relationship, Drug; Echocardiography; Female; Fibrinolytic Agents; Heparin; Humans; Male; Mucocutaneous Lymph Node Syndrome; Treatment Outcome; Urokinase-Type Plasminogen Activator; Warfarin

Topics: Anticoagulants; Aspirin; Coronary Aneurysm; Humans; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Warfarin

Topics: Anticoagulants; Aspirin; Coronary Aneurysm; Humans; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Warfarin

To evaluate the efficacy and safety of evaluation,treatment and follow-up of Kawasaki coronary artery disease based on the clinical severity classification.. This study evaluated 52 patients admitted to the Children's Hospital of Fudan University between July 2005 and December 2013 who were diagnosed with Kawasaki Disease with coronary artery disease.Inclusion criteria were a disease course of more than two months, initial echocardiography showing severity of grade IV and above, and confirmation of disease severity by angiography. Of those studies, 44 were male and eight were female, aged 6 to 142 (average 41) months. Treatment was planned according to protocols in "Suggestions for Management of Kawasaki Coronary Artery Disease" with follow-up. Those patients with grade IV and above confirmed by angiogram were given oral low-dose asprin and warfarin, and those with grade Vb were given coronary artery bypass grafting (CABG) after comprehensive evaluation. Analysis was carried out for diagnosis, treatment, complications, and results of follow-up.. (1) Satisfied images were shown by the angiography of all 52 cases. Forty five patients (86%) had giant aneurysm or multiple aneurysms, with thrombosis found in 10 of 45 patients (22%). Coronary artery lesions occurred in 138 coronary branches, and more common in left anterior descending branch (47 branches, with incidence 34%) and right coronary artery (48 branches, with incidence 35%). There were no complications during or after angiography. (2) After angiography, 49 patients remained at grade IV or above, and three improved to grade III. Ultimately, clinical severities of coronary artery disease included three patients at grade III, 31 patients at grade IV, nine patients at grade Va, and nine patients at grade Vb. (3) Thirty-eight patients were properly using aspirin and warfarin, and two patients with severely elevated international normalized ratio (INR) levels presented with knee joint and gastric hemorrhage, both of which were treated successfully.Patients with INR levels between 1.5 and 2.5 did not show signs of hemorrhage. (4) In follow-up visits between 6 months and 8 years, one patient had representation of thrombosis on angiography, but did not lead to coronary stenosis; four patients were improved from grade IV to either grade III or II. The remaining showed no new thrombotic formation or stenosis. (5) Of the nine grade Vb patients, five underwent coronary artery bypass grafting. The youngest of these patients, a 22 months old girl, died intraoperatively. The remaining four recovered postoperatively and were followed up for 8 to 90 months. One patient had a preoperative left ventricular ejection fraction (LVEF) of only 32.8%, with LVEF remaining abnormal post-CABG, between 35% and 44%. The remaining three patients had normal heart size, cardiac function, and electrocardiogram.Of the other four grade Vb patients, two were contraindicated for surgery due to severe heart failure and loss of myocardial activity. Two other cases are being followed up closely due to their young age of 9 months.. Coronary angiography is safe and efficacious in children, and even in infants.It is the current gold standard tool for grading Kawasaki coronary artery disease. Proper anticoagulation therapy can markedly decrease the incidence of coronary artery occlusion in patients with Kawasaki coronary artery disease. Safe ranges of corrected INR should be between 1.5 and 2.5 after taking warfarin. CABG is an effective treatment for severe coronary artery disease with myocardial ischemia.

Topics: Aspirin; Child; Child, Preschool; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Disease Management; Echocardiography; Electrocardiography; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Treatment Outcome; Ventricular Function, Left; Warfarin

Topics: Anticoagulants; Aspirin; Coronary Aneurysm; Humans; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Warfarin

Patients with coronary artery aneurysms caused by Kawasaki disease are at increased risk of coronary thrombosis and ischemia. To prevent coronary thrombosis, long term thromboprophylaxis using anti-platelet drugs, such as aspirin, dipyridamole, ticlopidine, clopidogrel, and abciximab, with or without warfarin is recommended by official guidelines. In fact, aspirin or aspirin with warfarin are the most frequently administered regimen in these patients with coronary aneurysms. However, still there has been paucity of data and no randomized controlled study to determine the efficacy of these drugs. This short article describes the currently accepted practice of thromboprophylaxis in patients with coronary aneurysms caused by Kawasaki disease.

Topics: Aspirin; Coronary Aneurysm; Coronary Thrombosis; Humans; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Warfarin

Kawasaki disease is an acute multisystemic vasculitis occurring predominantly in infants and young children and rarely in adolescents and adults. At elderly age, Kawasaki disease may remain unrecognized with a subsequent delay in appropriate therapy and an increased risk of coronary artery aneurysms. We report a case of intravenous immunoglobulin- and aspirin-resistant Kawasaki disease and severe cardiovascular damage in an adolescent boy. The article discusses major issues associated with the management of refractory Kawasaki disease.

Topics: Adolescent; Anticoagulants; Aspirin; Coronary Aneurysm; Drug Resistance; Humans; Immunoglobulins, Intravenous; Male; Mucocutaneous Lymph Node Syndrome; Rare Diseases; Treatment Outcome; Warfarin

Patients with severe coronary artery involvement after Kawasaki disease (KD) require long-term systemic anticoagulation. We sought to compare our experience with thrombotic coronary artery occlusions, safety profile, and degree of coronary artery aneurysm regression in KD patients treated with low molecular weight heparin (LMWH) versus warfarin. Medical records of all KD patients diagnosed between January 1990 and April 2007 were reviewed. Of 1374 KD patients, 38 (3%) received systemic anticoagulation, 25 patients received LMWH from diagnosis onward, 12 of whom were subsequently switched to warfarin, and 13 received warfarin from onset. The frequency of thrombotic coronary artery occlusions was similar between drugs. Severe bleeding was more frequent in patients on warfarin, but minor bleeding was more frequent for patients on LMWH. Patients on warfarin were at greater risk of underanticoagulation or overanticoagulation (defined as achieving an anti-activated factor X level or an international normalized ratio below or above target level) than patients on LMWH (P < 0.05). Maximum coronary artery aneurysm z-scores diminished with time for patients on LMWH (P = 0.03) but not for those on warfarin (P = 0.55). This study suggests that LMWH is a potentially viable alternative for patients, especially young ones, with severe coronary artery involvement after KD.

Topics: Anticoagulants; Child, Preschool; Coronary Disease; Dose-Response Relationship, Drug; Echocardiography; Female; Follow-Up Studies; Heparin, Low-Molecular-Weight; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome; Warfarin

This report describes the rapid buildup of an intraluminal thrombus and secondary myocardial ischemia after a brief therapeutic withdrawal of warfarin in a case of Kawasaki-related chronic giant coronary aneurysm. The importance of tight antithrombotic control in such cases is underscored.

Topics: Anticoagulants; Coronary Aneurysm; Coronary Thrombosis; Humans; Mucocutaneous Lymph Node Syndrome; Myocardial Ischemia; Warfarin

To determine the prognosis of patients with giant coronary aneurysms (GA) caused by Kawasaki disease (KD) treated with combined oral warfarin and aspirin.. A multicenter follow-up study of 83 patients (65 males, 18 females) with GA who had been treated for > or =3 months with warfarin. Most patients were placed on the combination therapy as soon as the GA was detected and remained on it for 6.0 +/-5.3 years, giving a total of 482 patient-years. Target international normalized ratio of prothrombin time ranged from 1.5 to > or =2.5. During this observational period, 5 patients suffered from 8 episodes of acute myocardial infarction and 1 died. Coronary thrombus formation enforced 6 courses of intracoronary thrombolysis in 3 patients (1-4 times). Consequently, freedom of cardiac events was 92.5% at 1 year and 91% at 10 years and the linearized cardiac event rate was 2.9% patient-year. Hemorrhagic complications occurred on 8 occasions (1 subdural hematoma) in 5 patients, giving 1.7% patient-year.. The combination of warfarin and aspirin has an acceptably high cardiac-event-free survival in patients with GA caused by KD, though it has a certain risk of hemorrhagic complications.

Topics: Administration, Oral; Adolescent; Anticoagulants; Aspirin; Child; Child, Preschool; Coronary Aneurysm; Coronary Thrombosis; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Prognosis; Retrospective Studies; Risk Factors; Treatment Outcome; Warfarin

Topics: Anti-Inflammatory Agents; Aspirin; Child; Facial Nerve Diseases; Facial Paralysis; Humans; Immunoglobulins, Intravenous; Male; Mucocutaneous Lymph Node Syndrome; Platelet Aggregation Inhibitors; Prednisolone; Ultrasonography; Warfarin

Kawasaki disease is a systemic vasculitis occurring in children of all ages. Coronary arterial aneurysms are one of the main fatal complications of the disease, and are usually observed with the onset of coronary arterial disease in adults. We report a young male presenting with myocardial infarction due to coronary arterial aneurysms, but in the absence of previous symptoms of Kawasaki disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Aspirin; Biomarkers; Captopril; Child; Coronary Angiography; Diagnosis, Differential; Drug Therapy, Combination; Echocardiography; Electrocardiography; Humans; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Platelet Aggregation Inhibitors; Warfarin

We retrospectively investigated the effect of warfarin therapy in improving the clinical outcome of Kawasaki disease (KD) patients with giant coronary aneurysms (GAs). We followed 2350 KD patients from 1973 to 2004. The GAs (> or =8 mm in diameter) were diagnosed by coronary angiography. Sixty-eight patients (54 males and 14 females) were retrospectively studied. Patients were divided into two groups. One group consisted of 19 patients with 33 branches treated with a combination of low-dose aspirin and warfarin (target international normalized ratio: 1.5 - 2.5 IU). The second group consisted of 49 patients with 102 branches treated with low-dose aspirin without warfarin. The incidence of myocardial infarction was significantly less in the combination therapy group than in patients treated with aspirin without warfarin (1 patient vs. 16 patients, p < 0.05). Sudden death occurred in seven patients taking aspirin without warfarin, but none of the patients receiving warfarin died. No major bleeding events occurred in either group. Combination therapy of warfarin with aspirin is associated with a decreased risk of myocardial infarction in KD patients with GAs.

Topics: Adolescent; Anticoagulants; Child; Child, Preschool; Coronary Aneurysm; Coronary Angiography; Electrocardiography; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Retrospective Studies; Treatment Outcome; Warfarin

There are few studies of the therapeutic regimens for the prevention of stenotic transformation of aneurysms in Kawasaki disease (KD). The aim of this study was to assess the prophylactic effect of combined therapy in the acute stage and convalescent- to chronic-stage against the formation of stenotic lesions.. In 85 patients, 103 giant aneurysms (ANl), 46 medium-sized aneurysms (ANm), and 13 small aneurysms (ANs) were analyzed. With respect to therapy in the acute stage, no localized stenosis of ANl in the left coronary artery was noted in patients who received high-dose gamma globulin therapy (G). For ANm, the group (G) showed a significantly higher regression rate than the aspirin group and steroids group. Furthermore, no coronary artery occlusion/recanalization of ANl occurred with the prophylactic regimen of aspirin and warfarin {aw}. Prophylaxis {aw} and the prophylactic regimen of aspirin alone {a} significantly lowered the incidence compared with either the prophylactic regimen of warfarin {w} or no prophylaxis {n}. However, no significant differences were noted between prophylaxis {w} and {n}.. High-dose gamma globulin therapy in the acute stage of KD is the first choice for the prevention of stenotic transformation. Prophylaxis {aw} is recommended for ANl.

Topics: Acute Disease; Aspirin; Coronary Aneurysm; Coronary Stenosis; gamma-Globulins; Humans; Longitudinal Studies; Mucocutaneous Lymph Node Syndrome; Prednisolone; Retrospective Studies; Warfarin

Kawasaki disease (KD) has potentially serious cardiac complications including coronary artery aneurysms. Children who develop giant aneurysms (GA) are at increased risk of thrombosis and ischemia, and although longterm oral anticoagulation with warfarin is recommended, its efficacy has not been studied. We examined the longterm outcome of patients with GA secondary to KD, to determine if anticoagulation with warfarin aids in the prevention of myocardial ischemia.. We studied patients with KD followed between May 1990 and April 2000.. Thirty-nine GA occurred in 2.2% of patients with KD (22/997 patients), and 33 non-GA were also identified in these patients. Patients were divided into 2 groups, those taking warfarin and no warfarin. Most patients in both groups were also taking antiplatelet agents. The demographics of the 2 groups were statistically similar, except the median duration of followup was significantly longer for patients in the no-warfarin group (6.9 vs 13.3 yrs; p = 0.008). Four early ischemic events (< 1 year after KD diagnosis) occurred (3 myocardial infarctions and one stroke). Screening for late ischemic events by stress nuclear medicine myocardial perfusion imaging revealed only one patient, in the no-warfarin group, with reversible perfusion defects. No patient had clinical signs or symptoms of late myocardial ischemia. Echocardiographic regression of aneurysms was observed in both groups. In the warfarin vs no-warfarin group, the diameters of the GA regressed a median 22% vs 32% (p = 0.27), and non-GA regressed a median of 30% vs 25% (p = 0.61). Compliance with anticoagulation was good, and no major bleeding complication of anticoagulation occurred.. Regression of GA occurred in most of our patients, and minimal late ischemia was observed. Further studies are required to evaluate the use of oral anticoagulation in patients with GA secondary to KD.

Topics: Adolescent; Aneurysm; Anticoagulants; Child; Child, Preschool; Coronary Thrombosis; Coronary Vessels; Female; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Ischemia; Retrospective Studies; Treatment Outcome; Warfarin

Topics: Angiography; Aspirin; Coronary Aneurysm; Electrocardiography; Fever; Heart Murmurs; Humans; Immunoglobulins, Intravenous; Infant; Male; Mucocutaneous Lymph Node Syndrome; Pericardial Effusion; Tachycardia, Sinus; Warfarin

A 37-yr-old white female was admitted to hospital with an evolving anterior myocardial infarction. Coronary arteriography revealed multiple aneurysms in the left anterior descending (and right) coronary arteries. In the left anterior descending artery, there was evidence of extensive thrombus formation. The patient was successfully treated with intracoronary urokinase, intravenous heparin, and oral warfarin. There was partial thrombolysis in 16 hr and complete thrombolysis noted 6 wk later. This case of multiple coronary aneurysms, secondary to presumed Kawasaki disease, is the first documentation of antemortem intra-aneurysmal coronary thrombosis treated successfully by thrombolytic and anticoagulant therapy.

Topics: Administration, Oral; Adult; Cardiac Catheterization; Coronary Aneurysm; Coronary Angiography; Coronary Thrombosis; Drug Therapy, Combination; Female; Heparin; Humans; Infusions, Intravenous; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Thrombolytic Therapy; Urokinase-Type Plasminogen Activator; Warfarin

We report an unselected series of eight patients younger than 6 months of age with Kawasaki disease evaluated between January 1982 and May 1984. The incidence of coronary artery aneurysms (six patients) and the mortality (two patients) were unusually high in this small series. Because of the confusing clinical presentation in three patients, diagnosis was delayed until pathologic or echocardiographic evidence of coronary vasculitis or aneurysm was discovered. The currently accepted clinical criteria for Kawasaki disease may not always identify patients with the pathologic findings of the syndrome who are younger than 6 months of age. The diagnosis of Kawasaki disease and echocardiographic evaluation of the coronary arteries should be considered in young infants with prolonged fever of unknown origin.

Topics: Aspirin; Coronary Aneurysm; Dipyridamole; Drug Therapy, Combination; Echocardiography; Electrocardiography; Female; Fever; Humans; Infant; Male; Mucocutaneous Lymph Node Syndrome; Myocardium; Risk; Warfarin

Ninety-two patients with Kawasaki disease were treated with five different types of drug therapy: a steroid preparation (prednisolone), aspirin, an antibiotic, a combination of steroid plus aspirin, and a combination of steroid plus warfarin. One or two months after the onset of the disease, coronary angiography demonstrated coronary aneurysms in 20% of cases treated with an antibiotic alone, 64.7% of cases in the steroid-treated group, and 11% of those in the aspirin-treated group. These findings suggest that the steroid might act adversely to cause a progression of coronary lesions of the disease. The aspirin-treated group did not have a significantly lower incidence of coronary lesions compared with the group treated with an antibiotic alone. But in view of the fact that the direct cause of sudden death of the disease is thrombotic occlusion of a coronary artery, aspirin might act as the effective means for prevention of sudden death due to Kawasaki disease.

Topics: Aspirin; Cephalexin; Child, Preschool; Coronary Angiography; Coronary Circulation; Coronary Disease; Drug Therapy, Combination; Heart Aneurysm; Humans; Infant; Lymphatic Diseases; Mucocutaneous Lymph Node Syndrome; Prednisolone; Warfarin