Younger age at presentation of acquired haemophilia A in Asian countries: a single-centre study and systematic review.

Acquired haemophilia A is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). There is a scarcity of acquired haemophilia A studies from Asian countries. The aim of this study was to evaluate clinical characteristics and outcomes of acquired haemophilia A among Asian populations. Data were collected from a retrospective case series and combined with a systematic review. The case series included all patients with acquired haemophilia A from 1999 to 2012 at Chiang Mai University Hospital. The systematic review searched MEDLINE and EMBASE databases for relevant keywords. A total of 111 patients were reviewed in this study (including 26 patients from the present series). There were 56 male (50.5%) and 55 female (49.5%) patients. We compared the demographic data with ECAH2 and UKHCDO studies. The weighted mean (SD) age at diagnosis was 58.10 (16.96) years compared with 75.70 (14.47) years in the European series (absolute difference 17.6 years, 95% confidence interval [CI] 14.20­20.99, P = 0.025). The mean (SD) FVIII activity was 2.97 (3.81) IU dL(−1) and the mean (SD) FVIII inhibitor titre was 26.35 (399.16) BU mL(−1). Fifty-six per cent of the patients underwent immunosuppression with steroids alone. The pool complete remission rate was comparable to the European studies, at 67.2% vs. 66.6% respectively (absolute difference 0.7, 95% CI 0.18 to 1.22, P = 0.99). This study reveals a novel finding of younger age at diagnosis of acquired haemophilia A among Asian patients.

Splenectomy: a strong risk factor for pulmonary hypertension in patients with thalassaemia.

OBJECTIVE: To determine the association between splenectomy and pulmonary hypertension in patients with thalassaemia with anaemia. DESIGN: Prospective cross-sectional study. METHODS: 68 patients with thalassaemia, who had a haemoglobin concentration of less than 100 g/l, were recruited into this study. Echocardiography was performed before clinical data were reviewed. Pulmonary artery pressure was estimated by measuring the systolic transtricuspid pressure gradient from tricuspid regurgitation and adding it to the right atrial pressure, which was estimated by the response of the inferior vena cava to inspiration. Pulmonary hypertension was defined as systolic pulmonary artery pressure > 35 mm Hg. History of splenectomy and other clinical data were compared between patients with and without pulmonary hypertension. RESULTS: 29 patients had pulmonary hypertension and 39 did not. Patients with pulmonary hypertension had significantly more nucleated red blood cells and higher platelet counts, and a higher prevalence of splenectomy (75.8% v 25.6%, odds ratio 9.1, 95% confidence interval 3.0 to 27.7). In multivariate analysis, splenectomy was the only factor significantly related to pulmonary hypertension. CONCLUSION: Splenectomy is a strong risk factor for pulmonary hypertension in patients with thalassaemia.

The surgical treatment of atrial myxomas: clinical experience in 6 patients.

Six patients from 17 to 73 years of age (mean age 37.3 years) underwent excision of atrial myxomas between November 1990 and August 1994 at Maharaj Nakorn Chiang Mai Hospital, Chiang Mai University, Chiang Mai. There were 4 females and 2 males. All the tumors were located in the left atrium, no right atrial or ventricular tumors were identified. Four patients presented with congestive heart failure, one with tachyarrhythmia, and one with cerebral embolism. Symptoms were present from 1 to 80 months before operation. Physical examination revealed murmur of mitral insufficiency in 4 patients, bibasilar rales in 2 patients and peripheral edema in 2 patients. Electro-cardiographic analysis demonstrated that 4 of 6 patients were in sinus rhythm and atrial fibrillation in the remaining patients. All the patients were diagnosed by two-dimensional echocardiography. The myxomas were successfully removed in all patients utilizing extracorporeal cardiopulmonary bypass without hospital mortality. In the early follow-up period (2-27 months), 5 patients are in New York Heart Association class I and one patient is in class II. No recurrent myxomas have been identified clinically in any patient. In this report, good results were obtained by simple excision of the tumor. Long-term clinical and echocardiographic follow-up is recommended since late recurrence, although rare, has been reported.

Improving clinical outcome with centrifugal mechanical assist for postcardiotomy ventricular failure.

Between October 1986 and May 1994, 65 patients undergoing cardiac surgery required centrifugal mechanical assist devices to separate from cardiopulmonary bypass. This experience was arbitrarily divided into early (n = 33) and recent (n = 32) groups for the purpose of comparing trends in morbidity and mortality. The incidence of mechanical assist application decreased from 2.19% in the early group to 0.96% in the recent group (p < 0.0001). Ability to wean patients from centrifugal assist increased from 33% in the early group to 53% in the more recent group, and hospital survival increased from 15 to 28%. The median chest tube drainage during the first 24 h decreased from 3,245 ml to 1,535 ml, and the incidence of renal failure decreased from 39.4% and 18.8% in the more recent group. Clinically relevant improvement in patient outcome following application of centrifugal mechanical assist for postcardiotomy ventricular failure is being observed.

Diagnostic and therapeutic thoracoscopy: lessons from the learning curve.

A variety of video-assisted thoracic operations are being reported with increasing frequency. Problems encountered during the development of this technology have received less attention. During the course of 27 months, 69 consecutive patients underwent minimally invasive procedures at our institution. Conversion to thoracotomy was required in 16 of 49 (33%) patients undergoing diagnostic procedures and 1 of 20 (5%) patients undergoing therapeutic interventions. Fewer complications occurred in those patients with diagnostic procedures (10 of 49, 20%) versus therapeutic interventions (10 of 20, 50%; p = 0.01). Logistic regression analysis showed chronic obstructive pulmonary disease to be an independent risk factor for complications. The mean postoperative stay was 7.9 +/- 6.8 days for diagnostic and 12.8 +/- 9.7 days for therapeutic interventions (p = 0.02). As new technologic improvements were introduced, the mean hospital stay decreased (first 10 months: 14.6 +/- 10.0 days, 10 to 20 months: 9.8 +/- 9.6 days, more than 20 months: 5.2 +/- 3.0 days, p < 0.004). The surgeon's thoracoscopic experience was not as strongly predictive (5 or fewer cases: 8.9 +/- 5.9 days, 6 to 15 cases: 13.1 +/- 12.6 days, more than 15 cases: 5.0 +/- 2.0 days). Although thoracoscopic surgery is promising, the potential for problems requires careful surgical judgment and expertise in dealing with thoracic complications.

Experience with the Sarns centrifugal pump in postcardiotomy ventricular failure.

The reported clinical use of the Sarns centrifugal pump (Sarns, Inc./3M, Ann Arbor, Mich.) as a cardiac assist device for postcardiotomy ventricular failure is limited. During a 25-month period ending November 1988, we used 40 Sarns centrifugal pumps as univentricular or biventricular cardiac assist devices in 27 patients who could not be weaned from cardiopulmonary bypass despite maximal pharmacologic and intraaortic balloon support. Eighteen men and nine women with a mean age of 60.4 years (28 to 83) required assistance. Left ventricular assist alone was used in 12 patients, right ventricular assist in 2, and biventricular assist in 13. The duration of assist ranged from 2 to 434 hours (median 45). Centrifugal assist was successful in weaning 100% of the patients. Ten of 27 patients (37%) improved hemodynamically, allowing removal of the device(s), and 5 of 27 (18.5%) survived hospitalization. Survival of patients requiring left ventricular assist only was 33.3% (4/12). Complications were common and included renal failure, hemorrhage, coagulopathy, ventricular arrhythmias, sepsis, cerebrovascular accident, and wound infection. During 3560 centrifugal pump hours, no pump thrombosis was observed. The Sarns centrifugal pump is an effective assist device when used to salvage patients who otherwise cannot be weaned from cardiopulmonary bypass. Statistical analysis of preoperative patient characteristics, operative risk factors, and postoperative complications failed to predict which patients would be weaned from cardiac assist or which would survive.

Thoracoscopic resection of 85 pulmonary lesions.

Advances in endoscopic surgical equipment and laser technology have expanded the role of thoracoscopy to include thoracoscopic pulmonary resection. Eighty-five thoracoscopic pulmonary resections were performed on 61 consecutive patients with small lesions (less than 3 cm) in the outer third of the lung. Patients with preoperative histologic evidence of bronchogenic carcinoma were excluded unless there was impairment of cardiopulmonary function, advanced age, or concomitant extrathoracic malignancy. These thoracoscopic pulmonary resections were accomplished with the neodymium:yttrium-aluminum garnet laser (31), endoscopic stapler (29), or both (25). The mean diameter of the lesions was 1.3 cm (range, 0.4 to 2.7 cm). There has been one late death (38th postoperative day) unrelated to the operation. Morbidity consisted of postoperative atelectasis (2), pneumonia (2), bleeding requiring transfusion (1), and bronchopleural fistula of greater than 7 days duration (3). There were no wound problems. The mean period of chest tube drainage was 3.3 +/- 3.0 days. Mean postoperative stay was 5.7 +/- 4.9 days. The pathologic diagnosis was benign disease in 28 patients (interstitial fibrosis/pneumonitis, 15; radiation fibrosis, 1; sclerosing hemangioma, 1; rheumatoid nodules, 1; granuloma, 2; nocardia, 1; infarct, 1; hamartoma, 4; scar, 1; cytomegalovirus pneumonia, 1), metastatic malignancy in 20 patients, and bronchogenic carcinoma in 13 patients. Five patients found at thoracoscopic pulmonary resection to have bronchogenic cancer had adequate pulmonary function and therefore underwent formal segmentectomy (3) or lobectomy (2). Thoracoscopic pulmonary resection was the only operation performed on patients with benign disease, patients with metastatic lesions, and selected patients with limited stage bronchogenic carcinoma at increased risk for thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PPACK-thrombin is a noncompetitive inhibitor of alpha-thrombin binding to human platelets.

Recent studies from our laboratory indicate that purified kininogens are noncompetitive inhibitors of human alpha-thrombin but not PPACK-thrombin, binding to human washed platelets. In order to understand the mechanism by which the kininogens inhibit alpha-thrombin binding, investigations were initiated to determine if alpha-thrombin and PPACK-thrombin bound to the same site on human platelets. Initial investigations reveal that alpha-thrombin is a more potent inhibitor of 125I-PPACK-thrombin binding than PPACK-thrombin. Further studies show that PPACK-thrombin is a noncompetitive inhibitor of 125I-alpha-thrombin binding to platelets. These studies suggest that human alpha-thrombin binds on the platelet surface to a different site or binds differently to the same site from PPACK-thrombin. These data indicate that the ability of the kininogens to block alpha-thrombin binding to platelets but not PPACK-thrombin binding results from these thrombins having either two different binding sites or one binding site on the platelet surface which they interact with differently.

Insights on monoclonal antibodies to kininogens' heavy chain which influence kininogens' binding to platelets.

Purified domains of low molecular weight kininogen (LK) can be used directly to determine the epitopes of monoclonal antibodies (mAbs) that have been shown to influence kininogen function. LK, purified from plasma by carboxymethyl-papain-Sepharose 4B affinity chromatography and kaolin adsorption, was digested by trypsin and chymotrypsin. The domains of LK were then separated by gel filtration followed by carboxymethyl-papain-Sepharose 4B affinity chromatography. Using the purified domains of LK's heavy chain, the regions on kininogens' heavy chain which various monoclonal antibodies are directed to were determined by enzyme-linked immunosorbent assay and immunoblotting. MAb 2B5 which neutralized kininogens' ability to inhibit calpain cross-reacted with domains 2 and 3. MAb HKH8 which reacted with kininogens' domain 1 and 2 was found to inhibit 125I-HK binding to platelets. At two-fold molar excess, mAb HKH8 was a better inhibitor of 125I-HK binding to platelets than higher concentrations, where the antibody was shown to cause increased binding to platelets. Alternatively, HKH8 F(ab')2 completely inhibited 125I-HK binding to platelets even at high concentrations of antibody. These studies indicate that purified domains of kininogens' heavy chain can be used to rapidly localize epitopes for antibodies. Further, mAb HKH8 should be a valuable probe to understand the mechanisms of kininogens' binding to platelets.

Time to first pulse after automatic implantable cardioverter defibrillator implantation.

Should automatic implantable cardioverter defibrillator (AICD) power sources be explanted and discontinued if they have not pulsed during the first generator life? We have followed 59 patients an average of 23 months (range, 3 days to 8.4 years) after AICD implantation. The indication for AICD implantation was based on clinical dysrhythmia, history of sudden death, and findings at electrophysiologic study. Thirty-eight of 59 patients (64%) had experienced sudden death and 52/58 (90%) were inducible at electrophysiologic study. Excluding 5 inappropriate pulsing episodes, 31 of 59 patients (53%) had 235 pulses (range, 1 to 36; median, 2 pulses). The time to first pulse after implantation ranged from 1 day to 3.5 years with a median time of 2 months. In 6 patients, the first pulsing occurred later than 1 year after AICD implantation. Fifteen generators demonstrating impending power source failure have been replaced in 11 patients. Power source depletion occurred at an average of 24.1 months (range, 8 to 40 months). In 3 patients, the first pulsing occurred after generator depletion and replacement. By univariate analysis, none of 13 variables (sex, age, cardiac disease process, functional class, previous myocardial infarction, sudden death history, ejection fraction, type of dysrhythmia, inducibility with electrophysiologic testing, number of extra stimuli required for induction, left ventricular aneurysm resection, endocardial resection, or concomitant operation) was found to be a predictor of pulsing (p greater than 0.05). We conclude that the majority of patients with pulses after AICD implantation will have them during the first 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin-induced thrombocytopenia in open heart surgical patients: sequelae of late recognition.

Most patients undergoing open heart operations have had exposure to heparin for diagnostic and/or therapeutic procedures. Heparin antibody formation and heparin-induced thrombocytopenia with repeat heparin administration can cause high morbidity and mortality from thrombotic complications, especially when delay in diagnosis occurs. From 1981 to 1991, heparin-induced thrombocytopenia was diagnosed in 82 of 4,261 open heart surgical patients (1.9%). Platelet counts less than 100 x 10(9)/L (100,000/microL) or new or recurring thrombotic events prompted suspicion of heparin-induced thrombocytopenia. Heparin-dependent antibody was diagnosed preoperatively in 12 patients (group I) and postoperatively in 70 patients (group II). Heparin was not given postoperatively in group I patients, and complications in this group were limited to bleeding in 3 patients. There were no thromboembolic events and all patients survived. Group II patients had late recognition of heparin-dependent antibody postoperatively, and heparin exposure was continued for varying periods postoperatively. Thirty-seven group II patients (53%) had bleeding complications and 31 (44%) had thromboembolic complications. These complications led to death in 23 group II patients (33%). Heparin-dependent antibody may occur in patients having open heart operations and is a major cause of morbidity and mortality if not diagnosed early with cessation of heparin therapy.

Impact of unstable angina on operative mortality with coronary revascularization at varying time intervals after myocardial infarction.

We have performed a retrospective study of patients undergoing coronary artery bypass grafting for postinfarction angina in an effort to determine the influence of recency of myocardial infarction and unstable angina on operative mortality. Time from myocardial infarction to bypass was arbitrarily divided into five intervals. Nine hundred ninety-three patients having isolated coronary bypass for postinfarction angina were analyzed, and a significant trend of increased operative mortality with recency of myocardial infarction was found (p less than 0.001). When patients were operated on during the time interval zero to 24 hours after infarction, the operative mortality rate was 18.6%. In the interval from 1 day to 1 week after infarction, the operative mortality rate was 7.4%; 1 week to 3 weeks, 5.9%; and 3 weeks to 3 months, 2.7%. In patients operated on more than 3 months after infarction, the operative mortality rate was 3.9%. The operative mortality rate in 360 patients with postinfarction stable angina was 0.83% compared with 7.3% in 633 patients with postinfarction unstable angina (p less than 0.001). Of 18 risk factors tested, 12 were found by univariate analysis to be independent predictors of operative mortality, including recency of myocardial infarction and unstable angina. Stepwise logistic regression analysis of independent predictive variables revealed that unstable angina, previous surgical revascularization, preoperative hypotension, nonelective surgery, preoperative cardiac arrest, and female sex were the strongest predictors of mortality; recency of myocardial infarction was not a factor. When acute surgical reperfusion is not the primary treatment strategy for patients with myocardial infarction, operative mortality with coronary bypass is increased with the recency of myocardial infarction. The reason for this increase in operative mortality is a patient selection process in which those with persistent or intermittent myocardial ischemia, as reflected in the clinical syndrome of unstable angina, are selected for operation. Unstable angina is a major determinant of operative mortality after myocardial infarction. In patients with stable angina, operative mortality is not increased by the recency of myocardial infarction.

Centrifugal pump support for repair of thoracic aortic injury.

Spinal cord ischemia and the potential for paraplegia are always of concern during operations for repair of traumatic thoracic pseudoaneurysm. Patients who experience hypotension, loss of intercostal blood supply, or normothermic aortic cross clamp times greater than 30 minutes are more likely to become paraplegic. The preservation of renal perfusion is also a concern.

Thoracoscopic neodymium: yttrium-aluminum garnet laser-assisted pulmonary resection.

The recent explosion of interest in surgical endoscopic techniques has revived the application of an old thoracic surgical procedure--thoracoscopy. We report a case of a transthoracoscopic neodymium: yttrium-aluminum garnet laser resection of a limited-stage peripheral adenocarcinoma of the lung accomplished in an elderly man with serious chronic obstructive pulmonary disease.

The rate of fibrinopeptide B release modulates the rate of clot formation: a study with an acquired inhibitor to fibrinopeptide B release.

An asymptomatic 50-year-old male with a gamma globulin paraprotein was found to have prolonged prothrombin time, activated partial thromboplastin time, and thrombin time but a normal reptilase time. The prolonged clotting times were not the result of a factor deficiency because they were not corrected by the addition of normal plasma. Instead, this patient had an antibody that delayed thrombin-mediated fibrinopeptide B release thereby producing an apparent dysfibrinogenaemia. His isolated IgG prolonged the thrombin clotting time of both normal plasma and fibrinogen. Precincubation of his IgG with fibrinopeptide B, but not with fibrinopeptide A or thrombin, decreased its ability to prolong the thrombin clotting time. The patient's purified IgG but not control IgG delayed thrombin-mediated fibrinopeptide B release from fibrinogen without affecting the release of fibrinopeptide A. These studies define a novel, clinically silent dysfibrinogenaemia due to an antibody that delays thrombin-mediated fibrinopeptide B release from fibrinogen thereby markedly prolonging the clotting times.

Intrathoracic goiter: approaching the posterior mediastinal mass.

The surgical management of posterior mediastinal goiters can pose considerable technical difficulty. We illustrate a method of sterile spoon extraction that can facilitate the cervical or limited cervicomediastinal approach to these lesions.

Neodymium:yttrium-aluminum garnet laser-assisted pulmonary resections.

The neodymium:yttrium-aluminum garnet laser is a new approach to limited pulmonary resection. It avoids distortion of surrounding pulmonary tissue and potential pleural space problems, which can occur with mechanical stapler resections. We have recently used this laser to manage 39 pulmonary lesions in 20 patients. There were no major postoperative complications, and air leak after resection was minimal. Neodymium:yttrium-aluminum garnet laser excision is a useful method that may have an advantage over mechanical stapling techniques for the limited resection of many pulmonary lesions.

The effect of muscle-sparing versus standard posterolateral thoracotomy on pulmonary function, muscle strength, and postoperative pain.

Increased interest in alternative approaches to thoracotomy has developed because of the considerable morbidity associated with the standard posterolateral technique. We conducted a prospective, randomized, blinded study of 50 consecutive patients to compare postoperative pain, pulmonary function, shoulder strength, and range of shoulder motion between the standard posterolateral and the muscle sparing thoracotomy techniques. Pulmonary function (forced expiratory volume in 1 second and forced vital capacity), shoulder strength, and range of motion were measured preoperatively and at 1 week and 1 month postoperatively. Pain was quantitated by postoperative narcotic requirements, the visual analogue scale, and the McGill pain questionnaire. Morbidity, mortality, and hospital stay were compared between the standard posterolateral and muscle-sparing techniques. There were no differences in postoperative pulmonary function, shoulder range of motion, extent of lung resection, surgical approach time, mortality, or hospital stay. There was significantly less postoperative pain in the muscle-sparing group. The narcotic requirement was less in the first 24 hours (p = 0.0169), and visual analogue scale scores were significantly lower (p less than 0.05) throughout the first postoperative week. Shoulder girdle strength was decreased at 1 week in the standard incision group whereas the strength was preserved with the muscle-sparing approach. Muscle strength had returned to preoperative levels by 1 month in both groups. Morbidity was identical in the two groups with the exception of postoperative seromas. The prevalence of seroma was 23% in the muscle-sparing group and 0% in the standard incision group (p = 0.0125). We have demonstrated that the muscle-sparing incision may be a reasonable alternative to the standard posterolateral approach.

Direct CO2 laser "revascularization" of the myocardium.

Evidence of regional myocardial perfusion and contractile function after direct CO2 laser myocardial revascularization (DLR) is lacking. We examined myocardial segment shortening, adenine nucleotide concentrations, and regional blood flow after DLR of the left anterior descending coronary artery (LAD) distribution before and after its proximal ligation in seven anesthetized conditioned dogs. Sonomicrometry assessed myocardial fiber shortening and radioactive microspheres were used to estimate baseline regional blood flows. Cardiopulmonary bypass was followed by cardioplegia arrest. Laser channels (1 mm diameter) were made every 3 to 5 mm in the LAD region with an 80 watt Laser-sonics CO2 unit. Bypass was terminated, the LAD occluded, and parameters reassessed. Core samples of myocardium from the lased LAD and control circumflex area were taken to assess adenine nucleotides. After occlusion, LAD distribution blood flow and myocardial shortening were reduced to pre-lasting ischemic controls. Adenine nucleotides were reduced in the LAD region relative to the control CMX area. DLR cannot be relied upon to acutely revascularize the ischemic myocardium.

Internal mammary artery graft to pulmonary vasculature fistula: a cause of recurrent angina.

Recurrent angina pectoris developed in a 59-year-old man 3 years after coronary artery bypass grafting using the left internal mammary artery. Cardiac catheterization showed a fistula between the left internal mammary artery and the pulmonary vasculature. This is an unusual documented case of postoperative internal mammary artery graft to pulmonary vasculature fistula after coronary artery bypass grafting. Division of this fistulous communication resulted in resolution of the patient's angina.