Occurrence Of Thrombotic Complications Research Articles

Effect of Intraoperative Tranexamic Acid on Perioperative Major Hemorrhage Requiring Transfusion in Patients Undergoing Elective Spine Surgery: A Propensity Score-Matched Analysis Using a National Inpatient Database.

Retrospective cohort study. This study aimed to examine whether the use of intravenous TXA in elective spine surgery is associated with reduced perioperative massive hemorrhage requiring transfusion. We extracted all patients who underwent decompression with or without fusion surgery for the cervical, thoracic, and lumbar spine between April 2012 and March 2019. The primary outcome was the occurrence of massive hemorrhage requiring transfusion, defined as at least 560mL of blood transfusion within 2 days of spine surgery or the requirement of additional blood transfusion from 3-7days postoperatively. Secondary outcomes were the occurrence of thrombotic complications (pulmonary embolism, acute coronary syndrome, and stroke) and postoperative hematoma requiring additional surgery. We identified 83,821 eligible patients, with 9747 (12%) patients in the TXA group. Overall, massive hemorrhage requiring transfusion occurred in 781 (.9%) patients. Propensity score matching yielded 8394 pairs. In the matched cohort, the TXA group had a lower proportion of massive hemorrhage requiring transfusion than the control group (.7% vs 1.1%; P = .002). There was no significant difference in the occurrence of thrombotic complications and postoperative hematoma requiring additional surgery between both groups. The multivariable regression analysis also showed that the use of TXA was associated with significantly lower proportions of massive hemorrhage requiring transfusion (odds ratio, .62; 95% confidence interval, .43-.90; P = .012). In this analysis using real-world data, TXA use in elective spinal surgery was associated with reduced perioperative massive hemorrhage requiring transfusion without increasing thrombotic complications. Prognostic Level Ⅲ.

Thromboembolic complication among COVID-19 patients in the intensive care unit (ICU): a single-centre study from a Malaysian perspective

Funding AcknowledgementsType of funding sources: None.IntroductionThe emerging complications of thromboembolism (TE) in COVID-19 patients have led to severe consequence such as death. Nonetheless, the prevalence of TE complications among COVID-19 patients in the Intensive Care Unit (ICU) in Malaysia is unknown.ObjectiveTo investigate the prevalence of thromboembolic (TE) complications including venous [deep vein thrombosis (DVT), pulmonary embolism (PE), and line related thrombosis] and arterial [stroke, peripheral arterial disease and myocardial infarction (MI)] thrombosis and mortality among COVID-19 patients admitted to an ICU at a single centre hospital. The proportions of patients with TE complication who died, and factors associated with the occurrence of thrombotic complications were explored.MethodsIn this retrospective Malaysian cohort study, patients admitted to a single centre ICU with PCR confirmed of SARS-CoV-2 virus and received adequate thromboprophylaxis within February 2020-2021 were included. Thromboembolic (TE) event is a combination of venous and arterial thrombosis.ResultsMean (SD) age 56.6 (13.7), 63.5% were male, 61.6% Malays, median (IQR) 7 (3-14) days of ICU admission, 64.2%, 53.2% and 20.9% had underlying hypertension, diabetes and obesity respectively. Of 534 patients, 4 (0.7%) developed DVT, 198 (37.1%) PE and 2 (0.4%) line related thrombosis. Meanwhile, 21 (3.9%) developed stroke, 39 (7.3%) MI, 1(0.2%) PAD and 22.8% died despite adequate thromboprophylaxis. In total, 240 (44.9%) developed TE event during their ICU admission. Significantly higher proportions of COVID-19 patients who developed complications of DVT (2.5% vs. 0.2%; p = 0.013), PE (47.5% vs 34.0%; p = 0.006), stroke (12.3% vs. 1.5; p < 0.001) and MI (16.4% vs. 4.6%; p < 0.001) died. Age, duration of ICU admission, obesity, white cell count (WCC), troponin, D-Dimer and corticosteroid use were significantly greater among those with TE events. Demographics, co-morbidities, other laboratory parameters and inflammatory markers were similar in COVID-19 patients with and without TE events. Predictors of TE events on multivariate logistic regression analysis were age [OR 1.02 (95% CI 1.00-1.03)], obesity [OR 2.84 (95% CI 1.93-4.18)], WCC [OR 1.04 (95% CI 1.00-1.07)], and duration of ICU admission [OR 1.04 (95% CI 1.02-1.06)].ConclusionIn this cohort of severely ill COVID-19 patients, the overall prevalence of TE complication was high (44.9%) with the overall mortality of 22.8% despite adequate thromboprophylaxis. Key predictors of TE events included age, obesity, white cell count, and duration of ICU admission. Perhaps a more aggressive treatment (combination of thromboprophylaxis and enhanced anti-inflammatory treatment) may be needed among COVID-19 patients admitted to ICU with high risk factors to prevent further increase in the incidence of thromboembolism and death.

Incidence of thrombotic complications related to weight-based dosing of activated prothrombin complex concentrate (aPCC) for reversal of apixaban and rivaroxaban in obese patients.

Factor eight inhibitor bypassing activity (aPCC) is recommended as a non-specific reversal agent for direct oral anticoagulants (DOACs) according to the 2017 American College of Cardiology (ACC) guidelines for reversal of anticoagulation. Factor eight inhibitor bypassing activity carries a black box warning for thrombotic events such as stroke, pulmonary embolism, deep vein thrombosis, and myocardial infarction, particularly at high doses. This was a retrospective, single-center, cohort investigation that included patients who received a weight-based dose of aPCC for reversal of apixaban and rivaroxaban between January 1, 2015, and December 31, 2020. Patients were grouped by BMI as obese (BMI ≥ 30kg/m2) or non-obese (BMI < 30kg/m2) for analysis. The primary outcome of this investigation was the occurrence of thrombotic complications [venous thromboembolism (VTE), myocardial infarction, stroke] documented in the medical record at any point during hospitalization after administration of aPCC. Secondary outcomes included bleeding complications, in-hospital mortality, ICU and hospital length of stay. Patients in the obese group were younger [76.4 years (SD +/- 11.3 years) vs. 69.6 years (SD +/- 12.4 years); p < 0.0001] and a higher proportion had a diagnosis of diabetes mellitus prior to admission [37 (19.2%) vs. 35 (36.8%); p = 0.0011]. There was no difference in the primary outcome of thrombotic events between non-obese and obese patients [12 (6.2%) vs. 5 (5.3%); p = 0.75], or for any of the secondary outcomes of bleeding, in-hospital mortality or length of stay. This investigation did not reveal a difference in rates of thrombosis or bleeding events between obese and non-obese patients who received aPCC for reversal of apixaban and rivaroxaban.

Large Biventricular Thrombosis in Acute Myocardial Infarction Assessed at CT Scan

Background: Ventricular thrombosis represents a not uncommon complication of Acute Myocardial Infarction (AMI) and Left Ventricular (LV) thrombosis may complicate large anterior ST-elevation myocardial infarction with anteroapical aneurysm. Right ventricular thrombosis is a more rare complication of inferior infarction. Transthoracic echocardiogram is routinely performed in patients with AMI to assess left ventricular function and the occurrence of thrombotic complications. However, other imaging techniques are occasionally required to more clearly evaluate thrombus extent and endocardial border line. Methods: We report a case of biventricular thrombosis firstly found at echocardiograph examination; the exact extension of biventricular thrombosis, however, was more clearly defined at CT scan. Results: In case of large ventricular thrombosis, CT scan may be useful in the exact definition of thrombus extension when cardiac magnetic resonance is not feasible. Conclusion: When transthoracic ultrasonography does not allow adequate characterization of the thrombus and cardiac magnetic resonance is not feasible, CT scan can provide additional definition of cardiac walls and the extent of the thrombus.

Non-Overt Coagulopathy in Non-ICU Patients with Mild to Moderate COVID-19 Pneumonia.

Introduction: Aim of the study is to assess the occurrence of early stage coagulopathy and disseminated intravascular coagulation (DIC) in patients with mild to moderate respiratory distress secondary to SARS-CoV-2 infection. Materials and methods: Data of patients hospitalized from 18 March 2020 to 20 April 2020 were retrospectively reviewed. Two scores for the screening of coagulopathy (SIC and non-overt DIC scores) were calculated. The occurrence of thrombotic complication, death, and worsening respiratory function requiring non-invasive ventilation (NIV) or admission to ICU were recorded, and these outcomes were correlated with the results of each score. Chi-square test, receiver-operating characteristic curve, and logistic regression analysis were used as appropriate. p Values < 0.05 were considered statistically significant. Results: Data of 32 patients were analyzed. Overt-DIC was diagnosed in two patients (6.2%), while 26 (81.2%) met the criteria for non-overt DIC. Non-overt DIC score values ≥4 significantly correlated with the need of NIV/ICU (p = 0.02) and with the occurrence of thrombotic complications (p = 0.04). A score ≥4 was the optimal cut-off value, performing better than SIC score (p = 0.0018). Values ≥4 in patients with thrombotic complications were predictive of death (p = 0.03). Conclusions: Overt DIC occurred in 6.2% of non-ICU patients hospitalized for a mild to moderate COVID-19 respiratory distress, while 81.2% fulfilled the criteria for non-overt DIC. The non-overt DIC score performed better than the SIC score in predicting the need of NIV/ICU and the occurrence of thrombotic complications, as well as in predicting mortality in patients with thrombotic complications, with a score ≥4 being detected as the optimal cut-off.

ВИВЧЕННЯ ВПЛИВУ ВІКУ ТА ІНДЕКСУ КОМОРБІДНОСТІ НА РИЗИК ТРОМБОТИЧНИХ УСКЛАДНЕНЬ У ХВОРИХ НА РАК ЕНДОМЕТРІЯ НА ДООПЕРАЦІЙНОМУ ЕТАПІ

Endometrial cancer (EC) is the most common gynecological malignancy in women over 50 years of age. Age is a specific, significant predictor of the survival outcome in EC. Thrombotic complications (TC) are the other frequencies due to death in cancer patients. The problem of thrombosis is relevant and occupies a large proportion of the immediate causes of death in patients with oncological practice. Identification of risk groups, the implementation of a personalized approach to the prevention of TB is very practical in patients with EC.The aim of the study – to conduct an assessment of the Charleson Comorbidity Index and identify the link between an increased risk of thrombotic formation in patients with EС and associated pathology at the preoperative stage.Materials and Methods. The study used general clinical methods of examination: laboratory, specific for determining the state of hemostasis (D-dimer, antithrombin III, protein C, fibrinogen B, ACTH , IF, PM ), ultrasound examination (abdominal organs, small pelvis, lower vessels limbs and pelvic plexus; elastography of the vessels of the lower extremities and pelvic plexus). Histologic methods of tumor investigation – to determine the relationship between histological type, depth of invasion, degree of malignancy of the tumor. Mathematical, statistical – for analysis and generalization of data in the package "Statgraph" (v.3.0).Results and Discussion. On the basis of the obtained data and analysis of the risk factors of the occurrence of TC on the scale of Caprini, we came to the conclusion that the whole surveyed group of patients in the EC referred to the high risk of TC since they had 6 or more points. This is due to age, overweight, increased body surface area and body mass index, cancer pathology, concomitant pathology, which coincides with the data of world literature. Based on the integrated assessment of the Charleson Comorbidity Index and the assessment of the risk of developing TC on the Caprini scale, we noted that the most common risk factors for thrombosis are: abnormal fat metabolism, hypertonic disease, atherosclerosis, vascular disease. The combination of two or more risk factors for thrombosis was noted at 46.25 %. Relevant statistical discrepancies (p &lt;0.05) in the hemostasis system in patients, depending on anthropometric indices, were confirmed by correlation bonds. We established a statistically significant (0.001 &lt;p &lt;0.05) positive relationship (r2&gt; 0.17) between pelvic vein thrombosis and weight, age, BM I, Caprini scale, PPT , proper weight and PPT , PM , ACTCH Fibrinogen, D-dimer and a reliable negative (r2 &lt;-0.17) relationship between thrombosis of the veins of the small pelvis and: the relation between the level of the MS and the level of D-dimer; PM / D-dimer; AT III / D-dimer.Conclusions. Based on the correlation data, it can be argued that the calculation of the Charleson Comorbidity Index is an important element in predicting survival rates in patients, but it does not provide an opportunity to predict the risk of thrombotic complications in patients with PE . The parallel compilation of the Charleson Comorbidity Index and the determination of the risk of developing thrombotic complications in endometrial cancer patients at the preoperative stage allows the isolation of high and high-risk groups of TU , especially in women over the age of 50 with existing comorbidity.

Treatment of bleeding in acquired hemophilia A with the proper administration of recombinant activated factor VII: single-center study of 7 cases

Recombinant activated factor VII (rFVIIa) is the bypassing agent used in the first-line hemostatic therapy for acquired hemophilia A (AHA); however, the occurrence of thrombotic complications in rFVIIa-treated AHA patients was recently reported to be 2.9–6.5%. Therefore, the investigation of the proper administration of rFVIIa for AHA is needed. In the present study, we retrospectively investigated the clinical features of AHA with regards to the use of rFVIIa (presence or absence of use and total amount) in 7 AHA patients encountered in our department for 7 years between January 2008 and December 2014. Ages were 63–89 years old (median: 79 years old), and there were 5 male and 2 female patients. The coexistence of cardiovascular risk factors and arteriosclerotic diseases, such as hypertension, diabetes mellitus, and cerebral infarction were present in 6 patients. Anemia progressed to less than 7 g/dL of hemoglobin and required red blood cell transfusion in 5 patients, showing “severe” hemorrhage. Factor VIII inhibitors were removed by immunological treatments in 6 patients. As a hemostatic therapy, rFVIIa was used in 4 patients. rFVIIa was not administered or was administered at a very low dose (20 mg) to 3 and 1 patient, respectively, and bleeding stopped as inhibitor titers decreased and disappeared in these patients. Inhibitors did not disappear in 1 patient and the control of hemostasis became poor and was accompanied by intestinal hemorrhage. Although a large amount of rFVIIa (265 mg in total) was administered, the patient bled to death. Therefore, bleeding may be stopped without the administration of rFVIIa in some AHA cases, while the dose of rFVIIa is not necessarily related to hemostatic effects in other cases. Since the main aim of AHA treatments is the removal of inhibitors, caution is needed to ensure that more than the necessary amount of rFVIIa is not administered.

Rare coagulation disorders: an emerging issue.

Rare coagulation disorders: an emerging issue.

Anesthetic management of a patient with polycythemia vera undergoing emergency repair of a type-A aortic dissection and concomitant coronary artery bypass grafting: a case report.

Polycythemia vera is a chronic progressive myeloproliferative disease characterized by increased circulating red blood cells, and the hyperviscosity of the blood can lead to an increased risk of arterial thrombosis. In a previous survey regarding postoperative outcomes in polycythemia vera patients, an increased risk of both vascular occlusive and hemorrhagic complications have been reported. Aortic surgery involving cardiopulmonary bypass may be associated with the development of a coagulopathy, and as a result, the occurrence of thrombotic complications should be avoided after coronary anastomosis. Thus, optimizing the hemostatic balance is an important concern for anesthesiologists. However, only a few cases of anesthetic management in polycythemia vera patients undergoing concomitant aorta and coronary arterial bypass surgery have ever been reported. Here, we experience a polycythemia vera patient who underwent an emergency repair of a type-A aortic dissection and concomitant coronary artery bypass grafting, and report this case with a review of the relevant literature.

Antiphospholipid Syndrome in a Neonate

Antiphospholipid syndrome presenting in the neonatal period is very rare. Although antiphospholipid antibodies from mothers with antiphospholipid syndrome can cross the placenta and put their neonates at risk, the occurrence of thrombotic complications in these neonates is uncommon. We present a 10-day-old neonate who developed Klebsiella sepsis with arterial gangrene of the left lower limb. Investigations revealed thrombosis of the left femoral artery with both the mother and the neonate positive for antiphospholipid antibodies. In conclusion, passive transfer of antiphospholipid antibodies from mothers to their offspring can be associated with significant complication in the presence of secondary risk factors.

Elevated Circulating Platelet-Derived Microparticles in Ph1 Negative Chronic Myeloproliferative Disorders.

Abstract 1906Poster Board I-929Microparticles (MP) are plasma membrane vesicles bearing potent procoagulant proteins and released into the circulation by various blood and endothelial cells during cellular activation and apoptosis. Their concentration has been shown markedly increased in vascular and thromboembolic diseases and in several types of cancer. Essential Thrombocythemia (ET), Polycythemia Vera (PV) and Primary Myelofibrosis (PM) are Bcr-Abl-negative chronic myeloproliferative disorders (MPD) with common biological and clinical features, especially thrombocytosis and more or less effective megakaryocytic proliferation. ET, PV and PMF are also characterized by an increased risk of thrombotic complications. Given the involvement of megacaryocytopoiesis in this group of diseases, we chose to focus on circulating platelet-derived microparticles (PMP) whose count can be established by flow cytometry. Our goals were to look for an increased release of PMP in MPD and if so, try to establish a correlation between thrombotic events recorded retrospectively and PMP level. Patients and methods:Plasma samples were collected from 85 patients with MPD (40 ET, 28 PV, 17 PMF) at any time of the disease course except blastic phase and 31 healthy age-paired controls ; the quantity of PMP (positive for the platelet marker CD41 and the microparticle marker AnnexinV) was measured by flow cytometric analysis using the FC500 cytometer from Beckmann-Coulter™. Pre-analytic and testing procedures complied with the recommendations of the ISTH Standardization Subcommittee and besides, our laboratory participates in a multicenter program to standardize the enumeration of cellular microparticles. Results:The number of PMP is significantly higher in ET, PV and MFP patients (median: 4862 MPP/mL, 3289 MPP/mL and 6114 MPP/mL respectively) than in controls (median 1310 MPP/mL) [p=0.000018, p=0.0013, p=0.0009]. Neither in MPD patients nor in control group PMP correlates with platelet count and appears thus as an independent parameter. ROC method allows to fix a cut-off at 3121 MPP/mL to discriminate MPD from controls. This value has a sensibility of 75 % and a specificity of 94%. Interestingly, the total number of PMP is not different between untreated patients (mean=7246 MPP/mL) and those who received myelosuppressive therapy (mean=6320 MPP/mL). Regarding thrombotic events, we failed to demonstrate any significant difference between patients with previous thrombosis and those without; however, the small size of the series and the retrospective assessment are possible bias. Conclusion:Patients with Phi negative MPDs have a high number of circulating PMP, irrelevant to platelet count or treatment by Hydroxy-urea or aspirin. A role for microparticles in the development of these diseases and in the occurrence of thrombotic complications can be hypothesized but requires further studies -;preferably prospective- on larger cohorts of patients. Disclosures:Charpentier:Schering-Plough: Research Funding.

Performance of a New Global Chromogenic Assay for Protein C Pathway (HemosIL ThromboPath) in the Diagnosis of Lupus Anticoagulant and Antiphospholipid Antibodies.

Background: The HemosIL ThromboPath assay (Instrumentation Laboratory) is a new chromogenic assay designed to globally evaluate the functionality of the PC pathway. It is based on the ability of endogenous APC generated after activation of PC by a snake venom extract (Protac) to reduce the thrombin generation induced by a reagent containing tissue factor. Briefly, optical density is measured after addition of a thrombin-specific chromogenic substrate in the presence (OD A) or absence (OD B) of Protac. It is recommended by the test manufacturer to express results as the Protac-Induced Coagulation Inhibition percentage (PICI%) which corresponds to the ratio [OD B - OD A]/OD B x 100. Previous studies demonstrated a high sensitivity (over 96%) for PC pathway abnormalities i.e. PC/PS deficiency, and FV Leiden-related APC Resistance, but also for lupus anticoagulant (LA), known to be associated with acquired APC Resistance.The aim of the present study was to evaluate the sensitivity of that assay for antiphospholipid antibodies (APL), especially in connection with the occurrence of thrombotic complications. Actually, APL is a heterogeneous family of antibodies which have a significant impact on coagulation tests (LA) or could be detected using ELISA anticardiolipin assays (ACL).Methods: We retrospectively evaluated the frozen plasma samples from 178 patients previously diagnosed as positive for LA or as having high ACL levels. There were 48 M and 130 F with a mean age=43 years (range 14 – 87). None was on vitamin K-antagonist. Screening for LA, performed according to the ISTH criteria (Thromb Haemost 1995; 74:1185), was positive in 126 patients (LA+ patients) and negative in 52 patients, all of the latter having high ACL levels (LA- patients). Among LA+ patients, 41 had antiphospholipid syndrome (APS) i.e. 18 with a history of venous thrombosis (VT), 10 with arterial thrombosis (AT), 7 with obstetrical complication (OB) and 6 with combined vascular complications (CVC). The same applied to 39 LA- patients with high APL levels i.e. VT (n=13), AT (n=8), OB (n=12) and CVC (n=6). The control group consisted of 29 age- and sex-matched healthy subjects without a history of vascular or auto-immune disease. The HemosIL ThromboPath assay was performed by an operator blinded of the specific biological test results and of the clinical status of the patients.Results: Test result was significantly lower in LA+ patients than in LA- patients or in healthy controls (Table). Similarly, the percentage of abnormal test results i.e. PICI% below 85.0% as the cut-off value, was significantly higher in LA+ patients than in the two other groups (p<0.0001 in both cases). That cut-off value for the PICI% was determined, according to the recommendations of the reagent manufacturer, as the mean minus 1 SD of the values measured in the plasma of 29 healthy control subjects. Despite significantly lower PICI% in LA- patients than in controls (p<0.05), the proportion of abnormal test results was not significantly different (p<0.10) in these two groups.LA+ Patients (n=126)LA-Patients (n=52)Controls (n=29)Test Result (PICI%)74.5 ± 13.186.7 ± 9.490.3 ± 5.3PICI%<85% (n, %)99 (78.6%)15 (28.8%)3 (10.3%)Moreover, test result was not significantly different in LA+ patients with and without a history of vascular thrombosis (PICI%=74.4 ± 12.9, n=51 vs. 74.5 ± 13.5 n=75, p=0.91) and the same applied for the percentage of abnormal test results (n=41/51 (80.4%) vs. n=58/75 (77.3%); p=0.83). There was no significant difference between LA+ patients with venous, arterial thrombosis and obstetrical complications.Conclusion: The HemosIL ThromboPath assay was highly sensitive for LA (78.6%) but it did not allow to distinguish between LA+ patients those with APS. It was found to be weakly sensitive (28.8%) to high ACL levels without LA activity, despite a higher percentage of abnormal test results. The potential interest of the HemosIL ThromboPath assay as part of the screening strategy of LA deserves to be further investigated prospectively.

Inflammatory Bowel Disease and Cerebrovascular Arterial and Venous Thromboembolic Events in 4 Pediatric Patients: A Case Series and Review of the Literature

Inflammatory bowel disease has been linked to cerebrovascular lesions, but the mechanisms of these vascular complications and their frequency among children with inflammatory bowel disease are unclear. We present 4 children with inflammatory bowel disease who developed ischemic or hemorrhagic stroke or cerebral sinovenous thrombosis. All 4 patients were female; 3 had Crohn's disease and 1 had indeterminate colitis. All of the patients had additional risk factors for thrombosis including thrombocytosis, severe dehydration attributable to an inflammatory bowel disease exacerbation, and, in 2 instances, genetically mediated coagulation defects. It is believed that the occurrence of thrombotic complications in individuals with inflammatory bowel disease is attributable to multifactorial causes. The current literature on cerebrovascular complications and treatment in the setting of pediatric inflammatory bowel disease is reviewed.

The Prothrombotic Paradox of Hypertension

Despite increased pulsatile stress, thrombotic rather than hemorrhagic events represent a major complication of hypertension. The pathophysiology of thrombosis in hypertension involves the interaction among vascular endothelium and particularly the renin-angiotensin and kallikrein-kinin systems. Because hypertension is often associated with some degree of inflammation, the combination of chronic inflammation and chronic shear stress may convert the normal anticoagulant endothelium into a procoagulant surface, expressing tissue factor. Activation of the renin-angiotensin system leads to activation of nuclear factor kappaB-dependent proinflammatory genes, also accelerating the expression of tissue factor. Renin-angiotensin and kallikrein-kinin systems interact at several levels to modulate coagulation, fibrinolysis, and vasodilatation in such a way that these 2 systems could have a major influence on the occurrence of thrombotic complications. Treatment with angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists may favorably influence the balance between the renin-angiotensin and kallikrein-kinin axis, regulating blood pressure as well as reducing the risk of thrombosis, which may explain part of the clinical efficacy of these drugs.

Antiphospholipid syndrome accompanying systemic lupus erythematosus.

The aim of the study was the assessment of the prevalence of antiphospholipid syndrome (APS) in patients with systemic lupus erythematosus (SLE). 72 patients with SLE had been investigated, 66 females and six males, aged 17 to 70 years, average 37.03. The presence of APA was determined using both ELISA assay for antiphospholipid antibodies, ASSERACHROM APA by Diagnostica Stago and clotting tests for lupus anticoagulant: activated partial thromboplastin time (aPTT), tissue thromboplastin inhibition test (TTI) and dilute Russell viper venom time (dRVVT). Antiphospholipid antibodies have been found in 24 patients (33.44%), 10 of them were with positive lupus anticoagulant tests, 6 of them were with positive ELISA test, while 8 of them had positive coagulation and immunological tests. Clinical manifestations that could be related to antiphospholipid syndrome were present in 22 patients (30.5%). The most common were thrombotic complications in 16 patients (22.25), recurrent spontaneous abortions in 7 patients (9.7%) and thrombocytopenia in 1 patient (1.39%). Presence of antiphospholipid syndrome was determined in 15 patients (20.83%). We can conclude that there is a significant correlation between presence of antiphospholipid antibodies and both thrombotic events and recurrent spontaneous abortions in SLE patients. Occurrence of thrombotic complications is in direct correlation with the level of antiphospholipid antibodies.

High plasma level of plasmin-α2-plasmin inhibitor complex is predictor of poor prognosis in patients with lung cancer

The occurrence of thrombotic complications is commonly associated with poor prognosis in patients with malignancy. However, the prognostic significance of the subclinical activation of the clotting system, frequently observed in cancer patients, is unknown. The purpose of the present study was to evaluate the value of the pre-thrombotic state for predicting survival of lung cancer patients. This investigation comprised 70 lung cancer patients without clinical or laboratory diagnosis of intravascular coagulation. There were 49 cases with non-small and 21 with small cell carcinomas. Samples taken in controls were available for comparison. The clotting system was assessed measuring thrombin-antithrombin III complex (TAT) and plasmin-α2-plasmin inhibitor complex (PAP). The independent value of these clotting markers to predict survival was evaluated in relation with previously well-established prognostic factors for lung cancer patients. Plasma concentration of each parameter was significantly higher in cancer patients as compared to that of controls. The plasma level of PAP was a predictor of survival independently from the stage of disease, sex, age, histological type, performance status, tumor size and the presence of distant metastasis. Discriminant analysis of PAP plasma concentration identified 2 groups with significant difference in survival rate in all patients, cases in advanced stages of disease and in those with small and non-small cell lung cancer. The results of the present study showed prognostic significance of the subclinical activation of the clotting system, particularly of the fibrinolytic pathway, in lung cancer. Newly developed markers of fibrinolysis might be potentially applicable for predicting outcome in malignancy.

The effect of desmopressin acetate on postoperative hemorrhage in patients receiving aspirin therapy before coronary artery bypass operations

It has been suggested that desmopressin acetate has been effective in reducing hemorrhage after coronary artery bypass grafting in patients receiving aspirin before operation. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine the effectiveness and safety of desmopressin in these patients. Sixty-five patients pretreated with aspirin within 7 days before their scheduled elective coronary artery bypass grafting were randomized to receive desmopressin (0.3 micrograms/kg) or placebo after cessation of bypass and reversal of heparin with protamine. The demographic characteristics and last dose of aspirin were similar in both groups. There was a significant reduction in postoperative blood loss noted between groups for both chest tube blood loss (833 +/- 311 ml for the 1-desamino-8-D-arginine vasopressin [desmopressin] group versus 1176 +/- 674 ml for the placebo group; p = 0.016) and total blood loss (1215 +/- 381 ml for the desmopressin group versus 1637 +/- 761 ml for the placebo group; p = 0.0097). Despite the differences in blood loss between the two groups, the red cell transfusions were not significantly different, but the use of platelets was less in the desmopressin group and almost achieved statistical significance (p = 0.053). Neither was there a difference in the occurrence of thrombotic complications between groups. It appears that desmopressin in this specific subgroup of patients receiving preoperative aspirin is effective as a prophylactic agent for reduction of postsurgical hemorrhage.

Does desmopressin acetate prophylaxis reduce blood loss after valvular heart operations?

The effectiveness of prophylactic desmopressin acetate in reducing hemorrhage after cardiopulmonary bypass operations is controversial. We conducted a prospective, randomized, placebo-controlled, double-blind trial to determine its effectiveness and safety in such patients. Eighty-three evaluable patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 microgram/kg) (41) or placebo (42) after cardiac bypass. Demographic characteristics were similar in both groups. There was no significant difference in total 24-hour blood loss between groups (desmopressin 1064.8 +/- 647.1 ml versus placebo 844.4 +/- 507.6 ml; p greater than 0.05), or in the requirement for red blood cell, platelet, or fresh frozen plasma transfusion, or for reexploration for control of hemorrhage. Neither was there a difference in the occurrence of thrombotic complications between groups. Analysis of factor VIII activity, von Willebrand factor, or von Willebrand factor multimers failed to show significant correlations with blood loss or differences between groups except for factor VIII activity, which was significantly higher in the desmopressin group 1 hour after operation than in the placebo group. A detailed comparative analysis of similar trials to determine the reasons for different outcomes suggests that desmopressin should not be used routinely as a prophylactic agent to reduce postsurgical hemorrhage, but that it may be beneficial when used in patients who already manifest excessive bleeding postoperatively.

New Approaches to the Prevention of Thrombotic Restenosis After Angioplasty or Thrombolysis

Percutaneous transluminal coronary angioplasty (PTCA) and early coronary thrombolysis are now widely used to treat selected patients with atherosclerotic coronary artery disease and acute myocardial infarction, respectively. However, the efficacy of these procedures may be limited by the occurrence of thrombotic complications. Restenosis of the dilated vessel, which occurs in about 30% of the patients, is considered the Achilles' heel of PTCA. Experimental and clinical data suggest that restenosis after PTCA may be mediated by platelet attachment at the site of balloon dilation, with a consequent release of platelet-derived mitogen factors able to stimulate intimal hyperplasia. Similarly, a thrombotic reocclusion of the infarct-related coronary artery may significantly reduce the potential benefits of early thrombolysis. This reocclusion occurs in up to 30-35% of the patients successfully reperfused after suspension of the thrombolytic agent, despite the concomitant use of heparin. Increasing evidence indicates that intracoronary platelet activation and aggregation play a major role in the pathophysiology of reocclusion. First, it has been demonstrated that a marked increase in thromboxane A2 production occurs at the moment of reperfusion in patients with acute myocardial infarction undergoing successful thrombolysis. Second, in experimental models of coronary thrombosis, reocclusion after thrombolysis can be prevented or markedly delayed by antiplatelet interventions, such as administration of a monoclonal antibody against the platelet glycoprotein (GP) IIb and IIIa--the putative fibrinogen receptor on platelet membrane whose exposure seems to be an obligatory step for platelet aggregation to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of venous thrombosis after total knee arthroplasty. Comparison of antithrombin III and low-dose heparin with dextran.

In a prospective, randomized trial, we compared the efficacy of a combination of antithrombin III and heparin with that of dextran 40 as prophylaxis against venous thrombosis after total knee arthroplasty. Ascending venography identified thrombosis in about one-third of the patients who received the combination of antithrombin III and heparin, compared with about four-fifths of those who received dextran (p less than 0.001). In both groups, the patients who had venous thrombosis had a significantly lower concentration of antithrombin III postoperatively than those who did not have thrombosis. Venous thrombosis occurred in all patients in whom the concentration of antithrombin III was less than 65 per cent postoperatively. These findings demonstrated that, after total knee replacement, the combination of antithrombin III and heparin effectively reduces the incidence of postoperative venous thrombosis and is significantly better than dextran. Furthermore, the findings suggested a relationship between postoperative deficiency of antithrombin III and the occurrence of thrombotic complications.