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PubMed2026

Nonbacterial Thrombotic Endocarditis Unmasking Concomitant Monoclonal Gammopathy of Undetermined Significance (MGUS) by Manifesting as Stroke.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition characterized by sterile platelet-fibrin vegetations on cardiac valves in the absence of systemic infection. The pathogenesis of marantic endocarditis is driven by endothelial dysfunction and a systemic hypercoagulable state. In contrast to infective endocarditis, vegetations in NBTE lack significant inflammatory infiltrates and do not yield positive blood cultures. NBTE typically comes to clinical attention via systemic embolic events, with cerebrovascular accidents serving as a clinical hallmark and constituting over 50% of cases. While NBTE is commonly associated with mucin-producing adenocarcinomas of the lung, pancreas, and gastrointestinal tract, its occurrence secondary to hematological malignancies or precursor plasma cell dyscrasias like monoclonal gammopathy of undetermined significance (MGUS) is exceedingly rare, particularly in young individuals. We report the case of a previously healthy 35-year-old woman who presented with acute-onset blurred vision. Neuroimaging via magnetic resonance imaging (MRI) revealed an acute left occipital infarct along with multiple chronic infarcts, raising a strong suspicion of a recurrent embolic process. A transesophageal echocardiogram (TEE) demonstrated two vegetations on the aortic valve with moderate transvalvular regurgitation; in the context of persistent negative blood cultures, these findings supported the diagnosis of NBTE. The patient was managed with systemic anticoagulation. A comprehensive hypercoagulable and autoimmune workup revealed an elevated lambda free light chain level with a decreased kappa/lambda ratio. Subsequent bone marrow biopsy and cytogenetic analysis established a diagnosis of MGUS featuring high-risk genomic aberrations, specifically an immunoglobulin heavy chain/musculoaponeurotic fibrosarcoma (IGH/MAF) rearrangement and the loss of chromosome 13 in a polyploid (3n, 4n) background, findings consistent with plasma cell neoplasia. The prevalence of MGUS in individuals under the age of 40 is exceptionally low, estimated at less than 0.3%. This case underscores NBTE as a critical finding that can unmask underlying, atypical plasma cell neoplasms. It highlights the necessity of an exhaustive diagnostic evaluation for occult hematological disorders and high-risk cytogenetic features in young patients presenting with multi-territory embolic strokes.

igh/maf rearrangement↗
PubMed2000

Prognostic significance of markers of thrombin generation in the acute and chronic phases of non cardioembolic ischemic stroke.

BACKGROUND: Previous studies have shown there is activation of the hemostatic system, with thrombin generation, in the acute phase of stroke. Such an activation has unfavourable effects. It is still not known whether there is also a persistent hypercoagulability state in these patients as well as in subjects affected by acute coronary syndromes. METHODS: To know more about the issue, we measured plasma levels of the prothrombin fragment 1 + 2 (F1 + 2) and the thrombin-antithrombin III complex (TAT) in 40 consecutive patients with first ischemic non-cardioembolic stroke; 16 matched involutive cardiomyopathy patients served as the control group. TATs and F1 + 2 were also assessed six months after the onset of stroke symptoms. RESULTS: At baseline stroke patients had higher values than controls of both F1 + 2 and TAT (F1 + 2: 2.38 +/- 2.30 nmol/l vs 1.20 +/- 0.50; p < 0.03; TAT 16.11 +/- 19.60 ng/ml vs 5.51 +/- 4.29; p < 0.05) and these measurements were not related to the typical acute phase reactants. After 6 months F1 + 2 levels in stroke patients were still higher than controls (F1 + 2: 1.68 +/- 0.80 nmol/l vs 1.20 +/- 0.50; p < 0.05), but there were no differences from the baseline levels of F1 + 2 and TAT. According to survival curves mortality was significantly higher in patients with hypercoagulability (defined as F:1 + 2 and TAT levels more than two standard deviations above the mean). CONCLUSIONS: These data confirm that for stroke patients there is sustained activation of the blood coagulation system like in unstable angina and myocardial infarction these abnormalites may have unfavourable prognostic significance.

Acute Disease↗
PubMed2003

Pre-thrombotic state and impaired fibrinolytic potential in coronary heart disease patients with left ventricular dysfunction.

Patients with coronary heart disease (CHD) are at considerable risk for recurrent ischaemic events. A pre-thrombotic state and/or impaired fibrinolysis might play an important role in causing recurrent ischaemic events. Two hundred and fifty-seven CHD patients underwent the dobutamine stress echocardiography test (DSE) to investigate the possible presence of inducible ischaemia; 89 patients showed evidence of stunned and/or necrotic myocardium (resting wall motion abnormalities). Factor VIII activity and fibrinogen levels were significantly higher in patients with stunned/necrotic myocardium than in CHD patients with normal resting wall motions (factor VIII activity, P = 0.004; fibrinogen, P = 0.04). Of interest, after stimulating the fibrinolytic system with the DSE test, plasminogen activator inhibitor-1 activity was significantly higher in patients with necrotic/stunned myocardium than in patients with resting normal wall motion (P = 0.03), whereas tissue-type plasminogen activator activity after the DSE test was significantly lower in patients with stunned/necrotic myocardium than in patients with normal wall motion (P = 0.001). Overall, 30 CHD patients developed induced ischaemia (new wall motion abnormalities) during the DSE test. CHD patients with stunned and/or necrotic myocardium presented decreased fibrinolytic potential and the presence of a hypercoagulable state due to increased factor VIII activity, and fibrinogen levels. Therefore, these CHD patients must be considered at high risk of re-developing coronary thrombosis and might benefit from a more aggressive anticoagulant therapy.

Aged↗
PubMed1993

Laboratory methods for detecting disseminated intravascular coagulation (DIC): new aspects.

The objective was to diagnose a hypercoagulative state or "pre-DIC" with new laboratory tests. APACHE II score was used as a measure of primary illness. Ventilator time was used as a reflexion of secondary complications. Twenty-three ICU patients were divided into two groups depending on time on the ventilator: Group 1 > 7 days and Group II < or = 7 days. If, after admittance patients deteriorated or complications occurred, new quantitative coagulation tests were done: soluble fibrin, prothrombin fragment 1 + 2, thrombin-antithrombin complex, D-dimer and elastase. We found a positive correlation between SF levels, the APACHE II score and the ventilator time. Diagnostic efficacy for SF was 87%, sensitivity 91%, specificity 83%, the predictive value of a positive result was 87% and the predictive value of a negative result 91%. The levels of the other new tests were also generally higher in the clinically worse group, although not significantly. Prothrombin complex, APTT, platelet count and AT III were pathologic to the same extent in both groups. The patients who developed most secondary complications, resulting in longer ventilator treatment (Group I), were also hypercoagulative. Soluble fibrin, in particular, seems to be valuable in the diagnosis of "pre-DIC" and possibly of predictive value for organ system complications.

Adult↗
PubMed2006

Microscopic intrarenal particles after pulsatile machine preservation do not adversely affect outcomes after renal transplantation.

INTRODUCTION: Our center has recently observed foreign carbohydrate-appearing particles (FP) on transplant postreperfusion biopsy specimens: (PRBx). METHODS: To further characterize FPs, we reviewed all renal transplant RBx (30-45 minutes) performed between September 1, 2004 and December 3, 2005. Donor, preservation, and outcome variables were collected among patients with FP. RESULTS: A total of 135 PRBx were performed (45 deceased donors [DD] and 90 live donors [LD]). Fifteen PRBx demonstrated FP. All 15 cases were DD kidneys that underwent machine perfusion (MP) on the Waters RM3 (Waters Medical Systems, Rochester, Minn, United States) with Belzer MP solution (Trans Med, Elk River, Minn, United States). Donor age was 39.8 +/- 15.7 years. Terminal creatinine level was 1.45 +/- 0.8 mg/dL. Two of 15 were flushed in situ with HTK solution (no starch). Cold ischemia time was 28.8 +/- 9.1 hours with 14.3 +/- 5.1 hours of MP. In 13 of 15 patients, perfusion parameters were excellent (flow > 100 mL; resistance < .35). CHARACTERISTICS OF FP: Particles were 10-30 mu and globular in shape. FP were not visible on hematoxylin and eosin stain, but stained strongly periodic acid-Schiff-(PAS) positive and were refractile under polarized light. FP were seen segmentally within glomerular capillaries in all cases and in peritubular capillaries in 3. In 11 of the 15 cases with FP, focal glomerular fibrin thrombi or intracapillary neutrophil margination was seen. Ten of 15 patients with FP had a biopsy within the first week with no identifiable FP. OUTCOMES: Recipient age was 45.3 +/- 11.6 years. Eight patients (53.3%) had delayed graft function. Biopsy-proven rejection occurred in 3 patients (20%). Three-month creatinine level was 1.59 +/- 0.35 mg/dL. One graft was lost to early thrombosis in a patient with a hypercoagulable state and 1 patient died of sepsis at 2 months. All remaining 13 patients are alive with excellent graft function at a median follow-up of 6.7 months (range, 3-17 months). CONCLUSIONS: Microscopic intrarenal particles may be seen on DD kidney PRBx after MP. These FPs likely originate from surgical gloves. FPs are too small to be captured by standard filters but clear spontaneously and do not have deleterious effects on renal function or outcomes.

Adult↗
PubMed1997

[Venous thrombosis of the legs and cancer. Evaluation of risk factors of venous thrombosis in the medical environment].

In medical patients, risk factors of leg venous thrombosis are not well evaluated. Cancer is considered as an important one. The aim of this study was to evaluate the role of intrinsic thrombotic risk (tumor hypercoagulable state) and external thrombotic risk (associate factors). We have made a prospective analysis of thrombotic venous risk factors in two medical populations with leg venous thrombosis: patients with cancer and patients without cancer. Risk of thrombosis depends on the thrombogenic importance of the risk factor and its chronicity or not. We assessed cancer and thromboembolic disease at the time of diagnosis and during a median follow up of 125.2 days. We included 31 consecutive cases of cancer (21 men, 10 women, mean age 63.8 years), and 50 consecutive cases of non cancer patients (32 men, 18 women, mean age 65.5 years), these two populations were not different. The classic risk factors of venous thrombosis were not frequent in cancer patient. Analysis of thrombotic risk showed that 61% of cancer patient group had venous thrombosis without classic thrombotic risk, as compared to 32% in non cancer patient group, showing the direct role of cancer in thrombosis (p < 0.01). The cancer was often aggressive and metastatic adenocarcinoma of various origins. The effect of chemotherapy is not clear, only hormonotherapy seemed to be responsible in two cases. Cancer hypercoagulability, defined by clinical characteristics, is a real risk factor of venous thrombosis but of low frequency. Indeed, the incidence of venous thrombosis in oncologic unit is rare (0.4%). Finally, thromboembolic disease in cancer patients is not different than in no cancer patients, Trousseau's syndrome is unfrequent. Prognosis is poor (40% death with 44.5 days of median survival), and antithrombotic therapy complications are frequent (bleeding 16%, oral anticoagulants resistance 20%).

Aged↗
PubMed1999

Can the laboratory assay of protein C activity assist in monitoring the hemostatic function in pre-eclampsia?

Published reports do not agree about whether protein C activity is non-significantly changed or decreased in a hypercoagulable state induced by pre-eclampsia without hemolysis-elevated liver enzyme/low platelet (HELLP) syndrome. In order to assess the relationship between this anticoagulant and enhanced hemostasis, levels of protein C activity, thrombin-antithrombin complexes, soluble fibrin, fibrin D-dimers and antithrombin were determined in 30 pre-eclampsia patients without the HELLP syndrome, in 22 normal pregnant women in gestational weeks 30-35, and in 13 non-pregnant controls. Levels of thrombin-antithrombin complexes, soluble fibrin and D-dimers increased (P < 0.05) whereas antithrombin decreased (P < 0.05) in patients with pre-eclampsia, compared with normal pregnant women. Levels of protein C did not differ significantly between patients with pre-eclampsia, normal pregnant women and controls (P > 0.05). The 5th and 95th percentiles of protein C levels in normal pregnant women were 0.53 and 1.30 U/ml, respectively; levels between these two values could be considered physiological. When the pre-eclampsia patients were subdivided according to these percentiles, none belonged to the subgroup with protein C < or = 5th percentile; 23% (seven of 30) fell into the subgroup with protein C > or = 95th percentile. Elevated levels of hypercoagulation markers were shown in the groups whose protein C fell within 5th-95th or > or = 95th percentiles (P < 0.05), compared with normal pregnant women. Concentrations of protein C and thrombin-antithrombin complex were significantly correlated (r = 0.69, P > 0.05) in patients with pre-eclampsia. In summary, in subjects with pre-eclampsia without the HELLP syndrome, protein C activity may be similar to that in normal pregnant women. However, such a 'physiological' anticoagulant level in association with the enhanced thrombin generation and fibrin formation does not necessarily reflect a physiological capability of coagulation. Thus, assays of protein C activity might not always assist in monitoring the hemostatic function during pre-eclamptic pregnancy.

Adult↗
PubMed2006

Increased thromboembolic events after lung transplantation.

BACKGROUND: Lung transplantation is a good therapeutic option for end-stage lung disease. Data on thromboembolic complications following lung transplantation are scarce. STUDY OBJECTIVES: To evaluate the incidence of thromboembolic events following lung transplantation, and to determine their possible association with hypercoagulable state. DESIGN: Retrospective study in a single, tertiary-care, university-affiliated referral center. SUBJECTS AND METHOD: The records of 70 patients who underwent lung transplantation in our institution between September 1997 and September 2003 were reviewed for thromboembolic complications. Parameters pertaining to risk of thrombophilia were measured in the patients with thromboembolic complications. RESULTS: Thromboembolic complications developed in 6 of the 70 patients (8.6%) at 4 to 24 months after transplantation: deep vein thrombosis (DVT) in 2 patients, pulmonary embolism (PE) in 1 patient, both DVT and PE in 1 patient, and retinal vein thrombosis in 2 patients. The fibrinogen level was elevated in all six patients, and factor VIII, IX, and/or XI levels were elevated in five patients. Heterozygosity for 5 10-methylene tetrahydrofolate reductase was documented in two patients, and mutation for factor II or factor V-Leiden mutation was found in one patient. Levels of protein C and protein S and activated protein C resistance were within normal range in all patients. Four patients had mildly elevated levels of at least one antiphospholipid antibody; none had a positive lupus anticoagulant test result. Overall, all patients demonstrated abnormalities on hypercoagulability tests. CONCLUSIONS: Thromboembolic complications occur at a high rate (8.6%) in lung transplant recipients and are associated with abnormalities in hypercoagulability. The cause remains unclear. Our results should prompt a high index of suspicion for these potentially fatal complications, which would lead to early diagnosis and successful treatment.

Adolescent↗
PubMedDate not supplied

Principle mechanisms underlying venous thromboembolism: epidemiology, risk factors, pathophysiology and pathogenesis.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are distinct but related aspects of the same dynamic disease process known as venous thromboembolism (VTE). An estimated 200,000 new cases occur in the United States every year, including 94,000 with PE, resulting in an incidence of 23 per 100,000 patients per year-cases. Without treatment, pulmonary embolism is associated with a mortality rate of approximately 30%, causing nearly 50,000 deaths per year. Moreover, based on post-mortem studies, two-thirds of the patients with pulmonary emboli remain undiagnosed. Clinically, PE may present as (1) isolated dyspnea, (2) pleuritic pain and/or hemoptysis, and (3) circulatory collapse. However, clinical history and examination can be notoriously misleading in reaching a diagnosis. A number of acquired etiologic risk factors (predispositions) are associated with a tendency to develop VTE. These include increasing age, immobilization, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, as well as certain types of oral contraception and hormone replacement therapy. In addition, a variety of genetic risk factors, such as factor V Leiden, protein S or C deficiency have also been identified. However, in at least half of the instances, no predisposing factors can be identified (idiopathic PE). In the majority of cases thromboemboli originate in the deep veins of the calf or pelvis. The pathogenic conditions for VTE comprise a triad of factors and include (1) venous stasis, (2) hypercoagulable states, and (3) vascular endothelium injury. Occlusion of pulmonary arteries has variable and transient clinical and pathophysiologic consequences, involving both mechanical and reflex effects of vascular occlusion with a consecutive perfusion defect as well as the release of vasoactive and other inflammatory mediators. The objectives of this article are to present an overview of the etiologic and pathogenic factors promoting VTE as well as the pathophysiologic and inflammatory processes following PE.

Comorbidity↗
PubMedDate not supplied

Altered blood coagulation in patients with posttraumatic stress disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) has been associated with an increased cardiovascular risk, though the pathophysiologic mechanisms involved are elusive. A hypercoagulable state before occurrence of coronary thrombosis contributes to atherosclerosis development. We investigated whether PTSD would be associated with increased coagulation activity. METHODS: We measured resting plasma levels of clotting factor VII activity (FVII:C), FVIII:C, FXII:C, fibrinogen, and D-dimer in 14 otherwise healthy patients with PTSD and in 14 age- and gender-matched, trauma-exposed non-PTSD controls. Categorical and dimensional diagnoses of PTSD were made using the Clinician-Administered PTSD Scale (CAPS) interview. We also investigated to what extent the relationship between PTSD and coagulation measures would be confounded by demographics, cardiovascular risk factors, lifestyle variables, time since trauma, and mood. RESULTS: Coagulation factor levels did not significantly differ between patients with a categorical diagnosis of PTSD and controls while controlling for covariates. In all subjects, FVIII:C was predicted by hyperarousal severity (beta = 0.46, p = .014) independent of covariates and by overall PTSD symptom severity (beta = 0.38, p = .045); the latter association was of borderline significance when separately controlling for gender, smoking, exercise, and anxiety (p values <.07). In patients, fibrinogen was predicted by hyperarousal severity (beta = 0.70, p = .005) and by overall PTSD symptom severity (beta = 0.61, p = .020), with mood partially affecting these associations. FVII:C, fibrinogen, and D-dimer showed no independent association with PTSD symptoms. CONCLUSIONS: PTSD may elicit hypercoagulability, even at subthreshold levels, offering one psychobiological pathway by which posttraumatic stress might contribute to atherosclerosis progression and clinical cardiovascular disease.

Adult↗
PubMed1997

Effect of advanced glycation end product-modified albumin on tissue factor expression by monocytes. Role of oxidant stress and protein tyrosine kinase activation.

Diabetes is associated with a hypercoagulable state that contributes to macrovascular complications, including cardiovascular events. The glycation reaction, a consequence of chronic hyperglycemia, has also been implicated in the pathogenesis of diabetic complications. Glycated proteins have receptors on monocytes and generate reactive oxygen species that can regulate the expression of a number of genes. As abnormal monocyte expression of tissue factor (TF), the main initiator of the coagulation cascade, is responsible for thrombosis in a number of clinical settings, we studied the effect of glycated albumin on monocyte TF expression. Mononuclear cells were incubated with glycated albumin for 24 hours, and monocyte TF activity was measured with a plasma recalcification time assay; TF antigen was measured by ELISA and TF mRNA by RT-PCR. Glycated albumin induced blood monocyte expression of the procoagulant protein TF at the mRNA level. Oxidative stress appeared to be involved in this effect, as the antioxidant N-acetylcysteine diminished TF mRNA accumulation in stimulated monocytes. Hydroxyl radicals, which may be generated inside cells from H2O2 via the Fenton reaction, also appeared to be involved in this effect, as hydroxyl radical scavengers downregulated TF activity and antigen levels (but not TF mRNA). Finally, the involvement of activated protein tyrosine kinase in the transmission of the signal from the membrane to the nucleus was suggested by the inhibitory effect of herbimycin A. These results point to a new mechanism for the hypercoagulability often described in diabetic patients and suggest that antioxidants or protein tyrosine kinase inhibitors might be of therapeutic value in this setting.

Acetylcysteine↗
PubMed1999

Infant cardiopulmonary bypass: a procoagulant state.

BACKGROUND: Procoagulant activity after cardiopulmonary bypass (CPB) in infants may predispose to thrombotic and bleeding complications. The induction of tissue factor and prothrombinase activity on endothelial cell membranes is a primary step in the activation of the extrinsic clotting cascade. The purpose of this study is to characterize the fibrinolytic and endothelial procoagulant state in infants undergoing congenital cardiac repairs with and without CPB. METHODS: Fourteen infants (aged 1 to 12 weeks) underwent repair of congenital cardiac defects. Two patients had closed procedures (controls) and 12 had open cardiac procedures. Serum samples were taken before and after CPB, 1, 4, and 24 hours after CPB. Tissue plasminogen activator, plasminogen activator inhibitor-1, interleukin-1beta, interleukin-6, plasma tissue factor, and factor V levels were measured. Human umbilical vein endothelial cell cultures were incubated with serum taken from the above time points and assayed for induction of tissue factor and prothrombinase activity. RESULTS: Control patients had no change from preoperative values in any of the parameters examined. In experimental patients, tissue plasminogen activator levels peaked at 1 hour after CPB and then decreased to normal by 24 hours. Plasminogen activator inhibitor-1 levels peaked at 4 hours after CPB and returned to baseline by 24 hours. The plasma of all patients had no intrinsic tissue factor activity. Induction of tissue factor activity on umbilical vein endothelial cells peaked immediately and again at 24 hours, whereas prothrombinase activity peaked early and stayed elevated. Serum factor V levels were significantly reduced after CPB, but returned to near baseline levels by 24 hours. CONCLUSIONS: Cardiopulmonary bypass is associated with derangement of the coagulation and fibrinolytic systems in infants. The serum of these patients promotes the induction of endothelial procoagulant activity, suggesting that there may be a hypercoagulable state in the postbypass period.

Blood Coagulation Factors↗
PubMed2003

Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: a link between angiogenesis and thrombogenesis?

Increasing evidence points towards a prothrombotic state in atherosclerosis and its manifestations, such as peripheral artery disease (PAD), which is associated with thrombosis-related complications, such as acute limb ischaemia, graft thrombosis and stroke. We hypothesized that the increased risk of thrombogenesis in PAD may be related to abnormal angiogenesis and, thus, an increased risk of future vascular disease. To test this hypothesis, we measured plasma levels of tissue factor (TF) and related levels to indices of angiogenesis, that is vascular endothelial growth factor (VEGF) and its soluble receptor sFlt-1. We studied 234 patients (145 males; mean age 68.6+/-10 years) with proven PAD (ankle brachial pressure index <0.8) and compared them with 50 healthy controls. Levels of VEGF ( P =0.001) and TF ( P =0.043) were increased in patients compared with controls. There were significant correlations between VEGF and TF levels in both patients (Spearman r =0.351, P <0.001) and healthy controls (Spearman r =0.335, P =0.017). Amongst PAD patients, levels of VEGF were related to gender, with women having higher levels than men. There was no difference in the levels of sFlt-1 between the patients and controls, or between the subgroups of patients. There were however significant correlations between the levels of sFlt-1 and TF (Spearman r =0.268, P <0.001) and between sFlt-1 and VEGF (Spearman r =0.499, P <0.001). In conclusion, patients suffering from proven PAD have higher plasma levels of TF and VEGF compared with controls, with a significant correlation between the two. This suggests a link between the hypercoagulable state in PAD and the process of angiogenesis.

Adult↗
PubMed1995

Effect of cigarette smoking on outcome after thrombolytic therapy for myocardial infarction.

BACKGROUND: Smoking is known to be a strong risk factor for premature atherosclerosis, myocardial infarction, and sudden cardiac death. Unexpectedly, in the reperfusion era, investigators have reported that patients who smoke have a more favorable prognosis after thrombolysis compared with non-smokers. Since smoking is associated with a relatively hyper-coagulable state, we hypothesized that the coronary occlusion responsible for infarction may be primarily thrombotic, with improved outcome relating to enhanced patency or the absence of a residual stenosis after thrombolytic therapy. METHODS AND RESULTS: To examine this issue, we evaluated 1619 patients treated with TPA, urokinase, or both in six consecutive myocardial infarction trials, of whom 878 (54%) were currently smoking. Patients underwent 90-minute and predischarge catheterizations, which were quantified blinded to the patients' smoking status. As expected, baseline fibrinogen (2.8 [2.5,3.6] versus 2.7 [2.4,3.5] g/dL, P = .003) and hematocrit (44% [41%, 47%] versus 43% [40%, 45%], P = .0001) levels were greater in smokers. Although there were no differences between smokers and nonsmokers with regard to 90-minute patency (73% versus 74%), smokers were more likely to have TIMI-3 flow (41.1% versus 34.6%, P = .034), with a larger minimum lumen diameter of the infarct stenosis both acutely (0.82 [0.51, 1.11] versus 0.72 [0.43, 1.04] mm, P = .0432) and at follow-up (1.2 [0.8, 1.74] versus 1.0 [0.7, 1.5], P = .002). Although smokers tended to have reduced in-hospital mortality compared with nonsmokers in univariate analysis (4.0% versus 8.9%, P = .0001), after adjustment for baseline differences between smokers and nonsmokers in age (54 [47, 62] versus 60 [54, 68] years, P < .0001), inferior infarct location (60% versus 53%, P < .0001), three-vessel disease (16% versus 22%, P < .001), and baseline ejection fraction (53% [44%, 60%] versus 50% [42%, 58%], P = .0069), smoking history was of no independent prognostic significance. CONCLUSIONS: Therefore, smokers have a relatively hypercoagulable state, documented by increased hematocrit and fibrinogen levels. Quantitative coronary angiographic analysis suggests that the mechanism of infarction in smokers is more often thrombosis of a less critical atherosclerotic lesion compared with nonsmokers. Enhanced perfusion status, as well as favorable baseline clinical and angiographic characteristics, may be responsible for the more benign prognosis of current smokers.

Adolescent↗
PubMed2006

Livedoid vasculopathy associated with plasminogen activator inhibitor-1 promoter homozygosity (4G/4G) treated successfully with tissue plasminogen activator.

BACKGROUND: Livedoid vasculopathy (LV) is an occlusive thrombotic disease that affects primarily the small blood vessels of the lower extremities and often is associated with recurrent painful ulcerations. The pathogenesis of LV is unclear, but the disease is largely attributed to a hypercoagulable state. Factor V Leiden mutation, heterozygous protein C deficiency, homozygous hyperhomocysteinemia, and other inherited thrombophilias have been associated with LV. Plasminogen activator inhibitor-1 (PAI-1) is an important inhibitor of the fibrinolytic system. Elevated levels of PAI-1 are found in some patients with thrombotic diseases. Some of these patients are homozygous for an allele of PAI-1 containing a stretch of 4 guanines at base -675 in the promoter region. This variant is associated with elevated PAI-1 protein levels, impaired fibrinolysis, and increased risk of thrombosis. OBSERVATIONS: A 33-year-old white woman had a 3-month history of painful enlarging ulcers on both ankles. Various therapies, including administration of oral antibiotic agents and prednisone up to 100 mg/d, to treat presumed vasculitis, were unsuccessful. Skin biopsy specimens revealed numerous thick-walled small blood vessels, many of which were filled with fibrin thrombi, in association with minimal perivascular inflammatory infiltrate, extensive epidermal necrosis, and focal ulceration. A diagnosis of thrombotic vasculopathy was made. Clinical workup revealed an elevated plasma level of PAI-1 (31 microM/mL; reference range, <25 microM/mL) and PAI-1 promoter 4G/4G homozygosity detected at DNA sequencing. Treatment with heparin sodium and tissue plasminogen activator dramatically improved the lesions, resulting in complete healing of the ulcerations. Continuation of anticoagulant therapy with warfarin sodium and episodic administration of tissue plasminogen activator was required for symptomatic control. CONCLUSIONS: Patients with LV may have elevated plasma PAI-1 levels. This may be associated with the PAI-1 promoter 4G/4G genotype, which has not previously been linked with LV. Further studies in patients with LV are warranted to determine how frequently this genotype is present because it may identify responsiveness to fibrinolytic therapy.

Adult↗
PubMed2006

Superficial venous thrombophlebitis as the initial manifestation of hypereosinophilic syndrome: study of the first 3 cases.

BACKGROUND: Superficial venous thrombophlebitis (SVT), often perceived as benign, can coexist with hypercoagulable states. Predisposing risk factors for SVT are similar to those observed for deep venous thrombosis. Association of eosinophilia with SVT is a rare situation that can reveal neoplasia, malignant blood disorders, or vasculitis, but it has never been described in hypereosinophilic syndrome (HES). We herein describe the clinical and biological features, outcome, and response to therapy of 3 patients with SVT associated with eosinophilia that revealed HES. OBSERVATIONS: Superficial venous thrombophlebitis was the initial manifestation of HES in all 3 patients. The mean eosinophil count at diagnosis was 2.4 x 10(3)/muL. All patients received corticosteroids and anticoagulants as the initial treatment, with marked improvement of SVT and return of the eosinophil count to reference limits. All patients experienced relapse and remained dependent on corticosteroid therapy. Two patients received interferon alfa with dramatic regression of SVT, allowing a decrease in the dose of corticosteroids. CONCLUSIONS: We report, to our knowledge, the first 3 cases of SVT related to HES. Superficial venous thrombophlebitis was difficult to treat, with dependence on corticosteroid therapy and partial efficacy of anticoagulant and antiplatelet therapy. Interferon alfa was effective in preventing relapse of SVT related to HES. Mechanisms implied in this thrombogenesis are multiple and remain speculative.

Adult↗
PubMed1999

A randomized trial comparing 5-mg and 10-mg warfarin loading doses.

BACKGROUND: Warfarin sodium therapy is usually initiated with a loading dose to reduce the time required to elevate the international normalized ratio (INR). Warfarin loading doses are associated with early overanticoagulation and the development of a potential hypercoagulable state; they also may not hasten achieving an INR value between 2.0 and 3.0. This study was designed to prospectively confirm our observation that a 5-mg warfarin sodium loading dose is as effective as a 10-mg loading dose in achieving a therapeutic INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy. METHODS: Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were randomly allocated to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses were based on dosing algorithms. The INR was measured daily for 5 days. The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 consecutive daily determinations on days 3, 4, or 5 of the study and whose INR did not exceed 3.0 at any point during the study. RESULTS: Five (24%) of 21 patients in the 10-mg group and 21 (66%) of 32 patients in the 5-mg group achieved the primary end point (relative risk 2.22, 95% confidence interval 1.30-3.70 [P < .003]). A trend toward less overanticoagulation was seen in the 5-mg warfarin group. CONCLUSION: A 10-mg loading dose of warfarin is unlikely to be more effective than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy.

Aged↗
PubMed2001

Fibrinogen and factor VII levels improve with glycemic control in patients with type 1 diabetes mellitus who have microvascular complications.

To determine whether the hypercoagulable state of patients with complications of diabetes can be reversed toward normal, a group of insulin-dependent individuals with proteinuria was treated with intensive insulin protocols. A statistically significant (P<.001) improvement in control of diabetes was achieved (mean +/- SEM glycosylated hemoglobin, 9.51% +/- 0.35% at baseline to 8.36% +/- 0. 39% at 12 months; and mean +/- SEM advanced glycosylated end products, 14.8 +/- 2.8 U/mL at baseline to 8.4 +/- 1.5 U/mL at 12 months). There were statistically significant decreases in 2 procoagulant factors: mean +/- SEM baseline elevated plasma factor VII, 128.69% +/- 5.63% at baseline to 106.24% +/- 3.43% at 12 months (P =.002); and mean +/- SEM plasma fibrinogen, 12.3 +/- 0.7 micromol/L (417.3 +/- 24.7 mg/dL) at baseline to 10.2 +/- 0.7 micromol/L (348.8 +/- 22.6 mg/dL) at 12 months (P =.04). Throughout the study, lipid fractions did not change significantly. Because plasma factor VII and fibrinogen concentrations were elevated while cholesterol and triglyceride concentrations were not, more attention should be paid to procoagulants as markers for thromboembolic complications in diabetic patients undergoing intensive insulin therapy.

Adult↗