Frequency and circumstances of falls in people with inclusion body myositis: a questionnaire survey to explore falls management and physiotherapy provision.

OBJECTIVES: To survey the incidence and circumstances of falls for people with inclusion body myositis (IBM) in the UK, and to investigate the provision of physiotherapy and falls management. DESIGN: Postal questionnaire survey. SETTING: Participants completed questionnaires at home. PARTICIPANTS: Ninety-four people diagnosed with IBM were screened against the inclusion criteria. Seventy-two potential participants were sent a questionnaire, and 62 were completed and returned. Invited participants were sent an adapted Falls Event Questionnaire pertaining to falls, perceived causes of falls and the provision of physiotherapy. Questionnaires were returned anonymously. MAIN OUTCOME MEASURES: The proportions of respondents who reported a fall or a near fall, along with the frequencies of falls and near falls were calculated. Descriptive data of falls were collected pertaining to location and cause. Data analysis was performed to investigate provision of physiotherapy services. RESULTS: The response rate was 86% [62/72, mean (standard deviation) age 68 (8) years]. Falls were reported by 98% (61/62) of respondents, with 60% (37/62) falling frequently. In this study, age was not found to be an indicator of falls risk or frequency. Twenty-one percent (13/62) of respondents had not seen a physiotherapist in relation to their IBM symptoms, and of those that had, 31% (15/49) had not seen a physiotherapist until more than 12 months after IBM was diagnosed. Only 18% (11/61) of fallers reported that they had received falls management input. CONCLUSIONS: Falls are a common occurrence for people with IBM, independent of age and years since symptoms first presented, and are poorly addressed by appropriate physiotherapy management. National falls guidelines are not being followed, and referral rates to physiotherapy need to improve.

Longitudinal observational study of sporadic inclusion body myositis: implications for clinical trials.

Sporadic inclusion body myositis (IBM) is the most common acquired myopathy occurring in adults aged over 50 years. The aim of the study was to assess prospectively the clinical features and functional impact of sporadic inclusion body myositis (IBM). Clinical data, manual muscle testing (MMT), quantitative muscle testing (QMT) of quadriceps muscle and IBM functional rating scale (IBM-FRS) were collected according to a standardised protocol at baseline (n=51) and one-year follow-up (n=23). MMT, quadriceps QMT and IBM-FRS significantly declined after one year (by 5.2%, 27.9%, and 13.8%, respectively). QMT of the quadriceps muscle and IBM-FRS were the most sensitive measures of disease progression. After a median time of seven years of disease duration, 63% of patients had lost independent walking. Disease onset after 55 years of age, but not sex or treatment, is predictive of a shorter time to requirement of a walking stick. We detected no differences in disease presentation and progression between clinically and pathologically defined IBM patients. The study provides evidence that quadriceps QMT and IBM-FRS could prove helpful as outcome measures in future therapeutic trials in IBM.

A systematic evaluation of laboratory testing for drug-induced immune thrombocytopenia.

BACKGROUND: Drug-induced immune thrombocytopenia (DITP) can be confirmed by the demonstration of drug-dependent platelet antibodies in vitro; however, laboratory testing is not readily accessible and test methods are not standardized. OBJECTIVE: To identify drugs with the strongest evidence for causing DITP based on clinical and laboratory criteria. PATIENTS/METHODS: We developed a grading system to evaluate the quality of DITP laboratory testing. The 'DITP criteria' were: (i) Drug (or metabolite) was required for the reaction in vitro; (ii) Immunoglobulin binding was demonstrated; (iii) Two or more laboratories obtained positive results; and (iv) Platelets were the target of immunoglobulin binding. Laboratory diagnosis of DITP was considered definite when all criteria were met and probable when positive results were reported by only one laboratory. Two authors applied the DITP criteria to published reports of each drug identified by systematic review. Discrepancies were independently adjudicated. RESULTS: Of 153 drugs that were clinically implicated in thrombocytopenic reactions, 72 (47%) were associated with positive laboratory testing. Of those, 16 drugs met criteria for a definite laboratory diagnosis of DITP and thus had the highest probability of causing DITP. Definite drugs were: quinine, quinidine, trimethoprim/sulfamethoxazole, vancomycin, penicillin, rifampin, carbamazepine, ceftriaxone, ibuprofen, mirtazapine, oxaliplatin and suramin; the glycoprotein IIbIIIa inhibitors abciximab, tirofiban and eptifibatide; and heparin. CONCLUSIONS: We identified drugs with the strongest evidence for an association with immune thrombocytopenia. This list may be helpful for ranking potential causes of thrombocytopenia in a given patient.

Hypercoagulability after trauma: hemostatic changes and relationship to venous thromboembolism.

BACKGROUND: Major trauma induces a hypercoagulable state, which is frequently complicated by pathological thrombosis. However the sequential changes in coagulation markers and their relationship to clinical thrombosis have been poorly characterized. METHODS: We measured several markers of in vivo coagulation and fibrinolysis and their regulation serially for 2 weeks after multi-system trauma in a prospective cohort of patients who received no anticoagulant prophylaxis. Asymptomatic deep vein thrombosis (DVT) was assessed by routine bilateral venography between day 12 and 14. Clinically suspected DVT and pulmonary embolism (PE) were investigated in a standardized manner. RESULTS: Among the 135 cohort patients the overall venous thromboembolism (VTE) rate was 59%. Markers of thrombin generation were markedly increased within 24 hours of injury, remained persistently elevated for about 5 days and then decreased by day 14. No early compensatory increase in Tissue Factor Pathway Inhibitor (TFPI) or the complex of Factor Xa and TFPI (FXa-TFPI) was seen; FXa-TFPI remained depressed throughout the study. There was no inverse relationship demonstrated between markers of thrombin generation and thrombin regulation. Acquired APC resistance and hypofibrinolysis did not appear to be important contributors to hypercoagulability after trauma. None of the coagulation markers were independently predictive of VTE. Increasing age was the only significant, independent predictor of VTE. CONCLUSION: Major trauma leads to significantly increased and persistent thrombin generation with disruption of its regulation. Coagulation markers do not appear to add independent predictive value in detecting VTE. Increasing age is the most important clinical predictor of VTE after trauma.

Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C).

Activation of platelets and coagulation in vivo was studied in nine patients with hemophilia A and inhibitors to human Factor VIII, prior to and following treatment with porcine Factor VIII (PFVIII; HYATE:C). In addition, six hemophiliac patients were similarly studied after treatment with recombinant Factor VIII (rFVIII). Platelet activation was also examined in vitro using porcine von Willebrand factor (PvWF)-enriched and PvWF-depleted fractions obtained by fractionation of PFVIII. Coagulation was assessed by measuring the concentrations of plasma prothrombin fragment 1+2 concentrations (prothrombinase generation) and Factor Xa-ATIII. Patients treated with PFVIII had significantly increased numbers of circulating platelets expressing CD62 and CD63 (markers of platelet activation) and annexin V (marker of platelet procoagulant activity) compared to patients treated with rFVIII; the former patients also demonstrated an increase in plasma coagulability after therapy. In in vitro experiments it was observed that the platelet-activating and procoagulant capacity of PFVIII resided in the PvWF-enriched fraction, and the same was true for the plasma hypercoagulability following exposure of platelets to PFVIII. These results support the hypothesis that PFVIII-induced platelet activation provides a mechanism for enhancing hemostasis, separate from, and additional to, that due to increased circulating Factor VIII, and it is due to residual PvWF in the PFVIII preparation.

Urgent heart surgery for an atrial mass: metastatic hepatocellular carcinoma.

Extension of metastatic hepatocellular carcinoma into the right atrium is exceedingly rare and has a very poor prognosis. We report a case of successful surgical excision of hepatic tumor extension into the right atrium that was causing hemodynamic compromise.

Empyema thoracis: lack of awareness results in a prolonged clinical course.

OBJECTIVE: To assess the hypothesis that empyema thoracis (ET) is a problem often not optimally treated. Long delays in diagnosis are common, long hospital stays are typical and recovery with surgery is relatively rapid. DESIGN: A chart review. SETTING: The Regina Health District associated hospitals, a tertiary referral centre. PATIENTS: The charts of 34 consecutive patients having primary respiratory tract disease and seen during the 6-year period Apr. 1, 1991, to Mar. 31, 1997, were identified. OUTCOME MEASURES: Patient presentation, time until diagnosis of ET, number of radiologic investigations, microbiologic features, treatment methods, postoperative course and mortality. RESULTS: The mean delay in diagnosis, defined as the time of admission to the time of correct diagnosis, was 44.2 days (range from 0 to 573 days) and the mean delay until thoracic surgery referral was 47.4 days (range from 0 to 578 days). On average each patient underwent CT 10.1 times, had 2.6 percutaneous drainage procedures and 2.0 chest tube insertions. The mean time from the first percutaneous chest drainage to the date of diagnosis was 29.8 days (range from 0 to 564 days). Of the 26 patients who underwent CT, the mean time from the first CT of the chest to the date of diagnosis was 9.5 days (range from 0 to 75 days). Cultures of pleural fluid grew no organisms in 17 patients; in the remaining 17 patients cultures grew 23 different microorganisms. Of 26 patients who were referred for surgical opinion, 18 underwent decortication; 8 were not considered to be surgical candidates. Pathological examination showed 17 cases of inflammatory empyema and 1 case of mesothelioma (unrecognized clinically). The mean length of hospital stay postoperatively was 15.2 days. CONCLUSIONS: Early suspicion of ET facilitates its treatment, resulting in fewer investigations and shorter hospital stays. When percutaneous drainage does not eliminate pleural effusions, empyema must be considered. Recovery from surgical decortication is rapid in comparison with the typical protracted preoperative hospital course.

A trypsin-like platelet protease propagates protease-activated receptor-1 cleavage and platelet activation.

Protease-activated receptor-1 (PAR-1) is a G-protein-linked receptor on platelets and perivascular cells activated by alpha-thrombin and the PAR-1-activating peptide, SFLLRN. alpha-Thrombin activates PAR-1 by cleaving it at R41-S42 to release the 41-residue peptide TR(1-41). Unexpectedly, platelet activation with SFLLRN was also associated with PAR-1 cleavage and the release of TR(1-41). Both PAR-1 cleavage and platelet activation resulting from SFLLRN addition to platelets were markedly inhibited by the serine protease inhibitor 4, 2-(aminoethyl)-benzene sulphonylfluoride.HCl (pefabloc SC) and soybean trypsin inhibitor, but not by inhibitors of calpain, cysteine proteases or metalloproteases. Thus, a trypsin-like platelet protease propagates SFLLRN-dependent PAR-1 cleavage and platelet activation.

Probable regulation of factor VIIa-tissue factor and prothrombinase by factor Xa-TFPI and TFPI in vivo.

Given that factor VIIa-tissue factor (TF) probably initiates coagulation in vivo, this study investigated the relationship between plasma concentrations of factor VIIa and prothrombin fragment 1 + 2 in plasma (the latter as an index of prothrombinase activity in vivo). The relationships between these two parameters and the concentrations of tissue factor pathway inhibitor (TFPI) and factor Xa-TFPI in plasma were also investigated. TFPI inactivates factor Xa in a reaction accelerated by heparin, whereas factor Xa-TFPI inactivates factor VIIa-TF and prothrombinase. Established enzyme-linked immunosorbent assays (ELISAs) were used to quantify TFPI and prothrombin fragment 1 + 2, whereas we developed an ELISA to quantify factor Xa-TFPI using affinity purified rabbit (anti-human TFPI)-IgG and chicken anti-(human factor Xa-TFPI)-IgY as the capture and detector antibodies, respectively. Plasma factor VIIa was quantified using truncated tissue factor. The concentrations of factor VIIa and prothrombin fragment 1 + 2 increased in parallel in the plasmas of up to 145 healthy adults assayed (P = 0.007), as did the concentrations of factor VIIa and TFPI (P = 0.0039), and prothrombin fragment 1 + 2 and TFPI (P = 0.013). In contrast, there was an inverse relationship between the concentrations of free factor Xa-TFPI and factor VIIa (P < 0.0001) and free factor Xa-TFPI and prothrombin fragment 1 + 2 (P = 0.0095). These results are consistent with factor Xa-TFPI regulating factor VIIa-tissue factor and prothrombinase in vivo.

Age-related changes in factor VII proteolysis in vivo.

Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

Plasmin accelerates platelet-dependent prothrombinase formation without activating the platelets.

Patients with acute myocardial infarction who undergo thrombolytic therapy may shortly thereafter present evidence for increased platelet activation and thrombin activity, and recurrent thrombosis. This study investigated whether plasmin activates platelets and prothrombin in recalcified platelet-rich plasma (RPRP) to cause (at least in part) these side-effects of thrombolytic therapy. Plasmin (0.1 and 1.0 CU/ml) addition to RPRP with microM r-tick anticoagulant peptide (the latter a factor Xa inhibitor which abrogates prothrombin activation by prothrombinase at the concentration used) resulted in no change in the concentration of prothrombin fragment 1 + 2, or in the expression of GMP-140, the resting and activated GP IIb-IIIa conformers, and GPIb on platelets. Thus, plasmin neither activates platelets nor prothrombin in RPRP. However, plasmin accelerated platelet activation and secretion, and prothrombin fragment 1 + 2 production in RPRP. When combined with 1 microM r-tick anticoagulant peptide and 1 or 10 mM alpha-thrombin to RPRP, plasmin also increased the number of GMP-140 molecules expressed/platelet without enhancing alpha-thrombin binding to the platelets. Additionally, plasmin accelerated prothrombin activation when it was added to washed platelets resuspended in factor V depleted plasma simultaneously with 10 mM CaCl2, 10 nM alpha-thrombin for 10 s (to activate platelets and platelet factor V), followed by 4 microM hirudin and 1 nM factor Xa. Thus, plasmin potentiates the platelet release reaction in response to alpha-thrombin (probably by increasing the availability of factor V on the platelets) to enhance prothrombin activation in RPRP. These actions of plasmin may contribute to the increased platelet activation and thrombotic side-effects that can occur after thrombolytic therapy.

Unilateral versus bilateral internal mammary revascularization. Survival and event-free performance.

BACKGROUND: The influence of unilateral (UL) and bilateral (BL) mammary artery revascularization, within age groups < or = 60 years and > 60 years, on patient survival, ischemic-related events, and interventional management was studied in 1142 patients who had coronary artery bypass graft surgery between 1984 and 1992. METHODS AND RESULTS: UL revascularization was performed in 765 (67%) and BL in 377 (33%) patients with supplemental vein grafts. The overall early and hospital mortality rate was 2.7%. For UL in the age group < or = 60 years, it was 1.1%; for BL < or = 60 years, 1.3% (P = NS); for UL > 60 years, 4.3%; and for BL > 60 years, 2.8% (P = NS). Twenty-five preoperative patient characteristics representing demographics, extent of disease, concomitant disease, ventricular dysfunction, previous surgery, and status did not differentiate the patient groups (P = NS). Patient survival at 5 years was not different: 94% for UL < or = 60 years, 95% for BL < or = 60 years, 91% for UL > 60 years, and 86% for BL > 60 years (P = NS). The freedom from ischemic-related events was not different at 5 years (P = NS). The freedom from recurrent angina was 78% for UL < or = 60 years, 88% for BL < or = 60 years, 82% for UL > 60 years, and 83% for BL > 60 years (P = NS). The myocardial infarction freedom was 98% for UL < or = 60 years, 96% for BL < or = 60 years, 99% for UL > 60 years, and 97% for BL > 60 years (P = NS). The freedom from sudden unexpected death and cardiac death did not differentiate the groups (P = NS). The freedom from angioplasty and reoperation did not differentiate the groups (P = NS). The freedom from all ischemic-related and interventional events was 76% for UL < or = 60 years, 84% for BL < or = 60 years, 81% for UL > 60 years, and 79% for BL > 60 years (P = NS). A trend exists for less angina pectoris in the bilateral population < or = 60 years, which reflects in the trend in the freedom from overall events. CONCLUSIONS: UL and BL mammary artery revascularizations have the same early mortality regardless of age but do not reveal any advantage for BL revascularization at 5 to 7 years.

Measurement of factor Xa-antithrombin III in plasma: relationship to prothrombin activation in vivo.

The M(r) of the complexes formed when factor Xa reacts with antithrombin III (ATIII) in plasma were estimated by gel filtration and SDS-polyacrylamide electrophoresis. The predominant species of factor Xa-ATIII detected after plasma and plasma to which factor Xa had been added were gel filtered on Sephadex G-200 and Sepharose 4B had apparent M(r) > 200,000, in which factor Xa-ATIII was associated with vitronectin. Addition of factor Xa-ATIII to ATIII-depleted plasma also resulted in the formation of factor Xa-ATIII-vitronectin complexes with M(r) > 200,000. Using polyclonal antibodies to human factor Xa-ATIII and ATIII as the capture and detector antibodies, respectively, a sensitive and specific enzyme-linked immunosorbent assay was developed to quantify factor Xa-ATIII in plasma. The relationship between factor Xa-ATIII production and prothrombinase activity in vivo was investigated by quantifying factor Xa-ATIII and prothrombin fragment 1 + 2 endogenous to the plasmas of blood donors and patients with Hodgkin's and non-Hodgkin's lymphoma. Whereas the concentrations of prothrombin fragment 1 + 2 in the 84 normal plasmas increased with age, those of factor Xa-ATIII (mean +/- SD of 34.7 +/- 13.8 pM) did not, and no correlation existed between the concentrations of the two parameters in normal plasmas. In contrast, a highly significant correlation between the concentrations of these two parameters was found in the plasmas of the cancer patients which coincidentally also had higher concentrations of both factor Xa-ATIII and prothrombin fragment 1 + 2 than the normal plasmas. Thus, ATIII may differentially influence prothrombinase formation and activity in normal individuals and cancer patients.

Inhibition of thrombin by antithrombin III and heparin cofactor II in vivo.

The critical role of thrombin in the pathogenesis of venous and arterial thrombosis, and the effectiveness of glycosaminoglycans as antithrombotic drugs are well known. Antithrombin III is a major inhibitor of thrombin and augmentation of its inhibitory actions by heparin is the basis for the clinical uses of heparin. Recent clinical and experimental studies have demonstrated that another glycosaminoglycan, dermatan sulfate, is an effective antithrombotic drug. Dermatan sulfate catalyses the inhibition of thrombin by heparin cofactor II. The concentrations of heparin cofactor II are higher in the plasmas of individuals with congenital antithrombin III deficiency and pregnant women than controls. The role of heparin cofactor II as a physiologic thrombin inhibitor is unknown. Enzyme-linked immunosorbent assays were used to quantify thrombin-heparin cofactor II and thrombin-antithrombin III endogenous to the plasmas of adult antithrombin III-Hamilton deficient subjects, their siblings with normal antithrombin III levels, pregnant women at term and 3 to 5 days after delivery. Both thrombin-antithrombin III and thrombin-heparin cofactor II complexed with vitronectin were detected in all the plasmas. Significantly, the concentrations of thrombin-heparin cofactor II-vitronectin were higher in the plasmas of congenital antithrombin III deficient subjects and in pre- and post-delivery plasmas than those of normal subjects. In addition, the concentrations of thrombin-heparin cofactor II decreased 3 to 5 days after delivery, reflecting the disappearance of the catalytically active dermatan sulfate elaborated by the placenta. Thus, heparin cofactor II normally inactivates thrombin in vivo, with its role increasing in conditions associated with high levels of heparin cofactor II and/or dermatan sulfate.

Heparin and low molecular weight heparins inhibit prothrombinase formation but not its activity in plasma.

Factor V activation is a critical step preceding prothrombinase formation. This study determined the contributions of factor Xa and thrombin, which activate purified factor V with similar catalytic efficiency, to plasma factor V activation during coagulation. Prothrombin activation began without a lag phase after a suspension of coagulant phospholipids, CaCl2, and factor Xa was added to factor X-depleted plasma. Hirudin, a potent thrombin inhibitor, abrogated prothrombin activation initiated with 0.5 and 1.0 nM factor Xa, but not with 5 nM factor Xa. In contrast, hirudin did not abrogate prothrombin activation in plasmas pre-incubated with 0.5, 1.0 or 5 nM alpha-thrombin for 10 s followed by the coagulant suspension containing 0.5 nM factor Xa. Thus, thrombin activates plasma factor V more efficiently than factor Xa. At concentrations which doubled the clotting time of contact-activated normal plasma, heparin and three low Mr heparins also abrogated prothrombin activation initiated with 0.5 nM factor Xa, but not with 5 nM factor Xa. If factor V in the factor X-depleted plasma was activated (by pre-incubation with 10 nM alpha-thrombin for 60 s) before adding 0.5, 1.0, or 5 nM factor Xa, neither hirudin nor the heparins altered the rates of prothrombin activation. Thus, none of the five anticoagulants inactivates prothrombinase. When 5 or 10 pM relipidated r-human tissue factor and CaCl2 were added to normal plasma, heparin and the three low Mr heparins delayed the onset of prothrombin activation until the concentration of factor Xa generated exceeded 1 nM, and they subsequently inhibited prothrombin activation to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)

The hypercoagulable state in cancer patients: evidence for impaired thrombin inhibitions.

Activation of prothrombin and the subsequent reactions of thrombin with its substrates and its major inhibitors, antithrombin III (AT III) and heparin cofactor II (HC II), likely reflect both intravascular and extravascular coagulation. Several studies have reported increased in vivo coagulation in cancer. Whether the increased thrombin production in malignancy is accompanied by a corresponding increase in thrombin inhibition is unknown. This study quantified prothrombin fragment 1 + 2 (F1 + 2), thrombin-AT III (TAT), thrombin-AT III-vitronectin (TAT.V), and thrombin-HC II-vitronectin (THCII.V) in the plasmas of healthy volunteers (n = 37); patients with localized solid tumours before treatment was initiated (n = 39); and five patients with non-Hodgkin's lymphoma, both before and during weekly chemotherapy. Two of the five non-Hodgkin's lymphoma patients developed deep venous thrombosis (DVT) during chemotherapy. In normal plasma, where the concentrations of the four parameters likely reflect haemostasis, the sum of TAT, TAT.V and THCII.V was 61% that of F1 + 2, compared with 30% in cancer plasmas. In addition, the mean +/- SEM of F1 + 2 in the plasmas of cancer patients (1.56 +/- 0.09 nM) was significantly elevated (P < 0.001) when compared with healthy volunteers (0.89 +/- 0.06 nM). Eight weeks of chemotherapy increased the F1 + 2 and the binary TAT in plasmas of the non-Hodgkin's lymphoma patients by approximately 1.5- and 2.9-fold, respectively. Thus, increased prothrombin activation in cancer patients, without corresponding increases in concentrations of thrombin-inhibitor complexes, raise the possibility that a significant portion of the thrombin generated in vivo escapes inhibition in cancer and contributes to the high risk of DVT in malignancy.

Prophylactically equivalent doses of Enoxaparin and unfractionated heparin inhibit in vivo coagulation to the same extent.

This study compared how Enoxaparin and unfractionated (UF) heparin influenced in vivo coagulation in patients randomized to receive, by twice daily subcutaneous injections, either 30 mg of Enoxaparin or 7500 I.U. of UF heparin after elective hip surgery. These two regimens were equally effective in reducing the incidence of post-operative deep vein thrombosis DVT. We compared the concentrations of endogenous thrombin-antithrombin III in pre- and post-surgical plasmas to determine how each prophylactic regimen influenced prothrombinase activity in vivo, and found the same concentrations of endogenous thrombin-antithrombin III in post-heparin and post-Enoxaparin plasmas. However, significantly higher concentrations of endogenous thrombin-antithrombin III were found in pre- and post-surgical plasmas of patients who developed post-operative DVT than the levels found in comparable plasmas of patients who remained DVT-negative, regardless of the drug received for prophylaxis. Human factor Xa was added to an equal volume of each patient's plasmas and the amount of added enzyme inactivated by antithrombin III measured using an enzyme-linked immunosorbent assay for factor Xa-antithrombin III. Post-heparin and post-Enoxaparin plasmas inactivated approximately 4 times more factor Xa than the pre-surgical plasmas, regardless of the clinical outcome. Thus, before and after surgery, a higher than normal in vivo prothrombinase activity may be a significant risk factor for developing post-operative DVT.

Factors affecting cervical anastomotic leak and stricture formation following esophagogastrectomy and gastric tube interposition.

Following esophagectomy, restoration of swallowing by gastric tube interposition with cervical esophagogastric anastomosis reduces morbidity and mortality associated with intrathoracic anastomoses at the expense of an increased incidence of both anastomotic leak and stricture formation. A retrospective study of 165 patients with either squamous cell carcinoma or adenocarcinoma of the distal esophagus or gastric cardia undergoing esophagogastrectomy with gastric tube interposition and cervical anastomosis at Vancouver, British Columbia, or London, Ontario, was undertaken. Forced-entry multiple logistic regression analysis of factors believed to influence anastomotic outcome was performed. Anastomotic leak occurred in 17% of patients; statistically significant correlation with low preoperative serum albumin (p = 0.005), running suture technique (p = 0.029), high intraoperative blood loss (p = 0.038), and the occurrence of postoperative delayed gastric emptying (p = 0.045) was found. Anastomotic strictures occurred in 31% of patients; a statistically significant correlation was found with preceding anastomotic leak (p = 0.001) and intraoperative blood loss (p = 0.042). Factors including preoperative radiotherapy and diabetes mellitus were not found to be significant.