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PubMed2003

Prothrombotic and antithrombotic pathways in acute coronary syndromes.

The acute coronary syndromes arise from procoagulant changes in complex plaques, which trigger both platelet activation and coagulation pathways. These 2 pathways intersect at a number of points that form positive-feedback loops to sustain and accelerate thrombus formation. In normal hemostasis and with a healthy endothelium, intravascular thrombosis is prevented, and vascular patency is protected by the fibrinolytic system and a number of antithrombotic factors, such as antithrombin, thrombomodulin, and tissue factor pathway inhibitor. However, atherosclerosis is characterized by a hypercoagulable state, and the fibrinolytic balance is skewed toward occlusive thrombus formation at critical sites on vulnerable plaques. This review focuses on cellular and humoral mechanisms and the antithrombotic strategies that are important during the acute phase of an ischemic coronary syndrome, both in patients managed conservatively and in patients scheduled for an interventional procedure. These strategies include fibrinolytic therapy, antiplatelet therapies (aspirin, clopidogrel, glycoprotein IIb/IIIa receptor inhibitors), and low-molecular-weight heparin.

Acute Disease↗
PubMed1998

Activation of blood coagulation in patients with mitral stenosis and sinus rhythm.

The aim of this study was to assess whether there is blood coagulation activation in patients with mitral stenosis (MS) and sinus rhythm (SR) and to investigate the value of left atrial spontaneous echo contrast (LASEC) as a predictive sign of increased coagulation activity. Using thrombin-antithrombin III complexes and prothrombin fragment 1+2 as in vivo hemostatic markers, we concluded that there is a hypercoagulable state in patients with MS and SR when LASEC is present.

Adult↗
PubMed1987

Hereditary protein C deficiency during pregnancy.

Hereditary protein C, a primary hypercoagulable state, has not been previously associated with preeclamptic toxemia. A woman with previous preeclamptic toxemia and fetal deaths presented with recurrent deep vein thrombosis during her third pregnancy. Hereditary protein C was diagnosed but full heparinization followed by low-dose heparin failed to prevent preeclamptic toxemia.

Adult↗
PubMed1997

The procoagulant activity of red blood cells from patients with severe preeclampsia.

OBJECTIVE: Our purpose was to determine whether red blood cells from patients with severe preeclampsia may exhibit increased membrane exposure of procoagulant phospholipids (i.e., phosphatidylserine), which may initiate intravascular clotting and platelet activation. STUDY DESIGN: The study group comprised 28 women: 9 with severe preeclampsia in the third trimester of pregnancy, 10 normotensive with uncomplicated pregnancies, and 9 age-matched, nonpregnant, healthy women. The exposure of phosphatidylserine on the outer membrane phospholipid layer was analyzed with use of isolated, washed red blood cells that were added as a source of phospholipids to a "prothrombinase" coagulation complex. RESULTS: The resultant thrombin formed was measured by an amidolytic assay. Thrombin generation significantly increased on the addition of red blood cells from women with preeclampsia (741 +/- 132 mU/ml/min) compared with red blood cells from normotensive pregnant (422 +/- 228 mU/ml/min) and nonpregnant women (316 +/- 268 mU/ml/min, p = 0.0008). CONCLUSION: This study indicates that in patients with preeclampsia the red blood cells exhibit a significant procoagulant surface that may trigger thrombin formation, thereby playing a role in the hypercoagulable state.

Adult↗
PubMed1999

Hemostatic effects of smoking and oral contraceptive use.

This review addresses current knowledge of the effects of lower dose oral contraceptives (containing 35, 30, or 20 micrograms of ethinyl estradiol) on hemostasis in smoking and nonsmoking women. Evidence suggests that formulations containing 30 and 35 micrograms ethinyl estradiol induce a significant activation of coagulation, whereas oral contraceptive preparations with 20 micrograms ethinyl estradiol appear to have a negligible effect or no effect. In nonsmokers who take oral contraceptives any procoagulatory effects that may occur are counterbalanced by fibrinolytic effects. In smokers, however, compensatory fibrinolytic effects to offset the procoagulatory effects seen with 30-micrograms ethinyl estradiol oral contraceptive formulations are absent, shifting the hemostatic profile toward a hypercoagulable state. This suggests that a formulation with the lowest dose of ethinyl estradiol may be most suitable for smokers who wish to use this form of contraception.

Blood Coagulation↗
PubMed2003

Antiphospholipid antibody syndrome in a six-year-old female patient.

PURPOSE: To report the first instance of primary antiphospholipid antibody (APA) syndrome in an otherwise healthy 6-year-old female patient with retinal venous thromboses. DESIGN: Observational case report. METHODS: A 6-year-old girl with poor vision in the left eye and preretinal hemorrhage underwent testing for infectious, autoimmune and embolic disease, diabetes, and hypertension. Testing for factor V Leiden and prothrombin G20210A mutations, homocysteine, anticardiolipin antibodies (ACAs), lupus anticoagulant, and functional assays for protein S, protein C, and antithrombin III were performed to detect a hypercoagulable state. No IRB approval was necessary. RESULTS: Only a positive lupus anticoagulant and moderately elevated ACA IgG were found. The ACA IgG was moderately elevated on repeat testing 18 months later. Laser to nonperfused retina caused some regression of retinal neovascularization. Aspirin was recommended to reduce the risk of future thromboses. CONCLUSIONS: Although uncommon, retinovascular thrombosis in children can occur in APA syndrome. Testing for ACA and lupus anticoagulant should be considered.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

Retinal arterial occlusions in young adults.

PURPOSE: To determine the cause, associated factors, visual results, and systemic morbidity in patients less than 40 years old with retinal arterial occlusions. METHODS: We studied 27 eyes with nontraumatic retinal arterial occlusions in 21 patients less than 40 years old (range, 22 to 38 years; mean, 28 years). RESULTS: Of the 21 patients, branch retinal artery (arteriolar) occlusion occurred in 15 (71%), central retinal artery occlusion occurred in five (24%), and cilioretinal artery occlusion occurred in one (5%). Retinal artery occlusions were bilateral in six patients (29%) and occurred in 14 women (67%). Emboli were identifiable in seven patients (33%). Cardiac valvular disease was the most commonly recognized etiologic agent and was present in four patients (19%). Various associated factors leading to a hypercoagulable state or embolic condition were identified in 19 patients (91%). CONCLUSION: Retinal arterial occlusions in young adults occur via multiple mechanisms. Systemic evaluation allows detection of a risk factor for retinal arterial occlusive disease in most patients.

Adult↗
PubMed1999

In situ detection of tissue factor within the coronary intima in rat cardiac allograft vasculopathy.

Cardiac allograft vasculopathy is a major cause of morbidity and mortality of cardiac transplant recipients. The underlying cause of this disease remains unclear. Histological studies have implicated accelerated hemostasis and intravascular fibrin deposition in its pathogenesis. In the present study a defined model of this disease in the rat was used to elucidate the implication of tissue factor in the production of the hypercoagulable state observed in cardiac allograft vessels. Tissue factor protein and mRNA expression were studied in rat heart allografts developing allograft vasculopathy resembling human disease. Immunohistochemistry demonstrated tissue-factor-positive cells present in the allograft coronary intima and adventitia. Significant staining for tissue factor was detected in the endothelium lining coronary lesions in cardiac allografts and in interstitial mononuclear cells, respectively. Both transplant coronary endothelial cells and mononuclear cells contained tissue factor mRNA as indicated by oligo-cell reverse transcription polymerase chain reaction after laser-assisted cell picking. In contrast, tissue factor mRNA and protein were not or negligibly detectable within the coronary intima of nontransplanted control hearts. Thus, the present study clearly demonstrates that aberrant tissue factor expression occurs within the coronary intima after cardiac transplantation. Tissue factor, activating downstream coagulation mechanisms, may account for the intravascular clotting abnormalities observed in cardiac allografts and may represent a key factor in transplant atherogenesis.

Animals↗
PubMed1990

Management of variceal bleeding in patients with extrahepatic portal vein thrombosis.

Patients with extrahepatic portal vein thrombosis may present from infancy through adulthood with variceal bleeding. Physiologically, such patients differ from patients with cirrhosis and variceal bleeding in that they have a normal liver and maintain good portal perfusion through hepatopedal collaterals. Complete evaluation of these patients requires identification of the bleeding site by endoscopy, definition of the anatomy by angiography, and confirmation of a normal liver by biopsy examination. Causative factors, including hypercoagulable states, should be evaluated. Therapeutic options range from noninterventive, through ablative procedures, to shunt operations. The goal should be definitive control of bleeding and return to a normal lifestyle. Distal splenorenal shunt offers the best option if technically feasible, but if no shuntable veins are patent, ablative procedures and sclerotherapy may be required. A noninterventive, noninvestigational approach is inappropriate in patients who can be offered definitive therapy. Splenectomy for hypersplenism should not be done in these patients.

Esophageal and Gastric Varices↗
PubMed1990

An outpatient anticoagulation protocol managed by a vascular nurse-clinician.

Lifetime anticoagulation has become a therapeutic option for surgical patients with hypercoagulable states or prosthetic arterial bypass grafts. However, physicians may not achieve optimal anticoagulation or may attempt to limit the length of the therapy period because of the perceived morbidity from hemorrhagic complications of Coumadin therapy. A protocol for anticoagulant therapy monitored and regulated by a vascular nurse-clinician was reviewed. Coumadin was prescribed for 1,891 patient-months to 93 patients to maintain their prothrombin time 1.5 to 2 times control (range: 18 to 24 seconds). The mean (+/- SD) prothrombin time for the study population was 19.8 +/- 1.8 seconds. During follow-up, 472 (14%) of 3,479 prothrombin times measured were below the therapeutic range (n = 232) or prolonged (n = 240), prompting an adjustment in the Coumadin dose in 82 (88%) patients. Four patients developed recurrent vascular graft thrombosis while receiving anticoagulation. There were 6 major and 11 minor hemorrhagic complications. Patients with a chronic risk for arterial or venous thrombosis can have out-patient anticoagulant therapy administered at optimal intensity and regulated safely with a low incidence of hemorrhagic and thrombotic events.

Adolescent↗
PubMed1998

Etiology of peripheral arterial thromboembolism in young patients.

BACKGROUND: No prior studies have explored the etiology of peripheral arterial thromboembolic events (PATE) in younger patients. Therefore, we analyzed the sources of these events in patients <50 years of age over a recent 10-year period. Diagnostic and work-up strategies will be proposed based on the presence of cardiac or atherosclerotic risk factors. PATIENTS AND METHODS: The sources of emboli were classified as (1) conventional (cardiac or arterioarterial), (2) unconventional, or (3) unknown. A statistical analysis of risk factors that, if absent, would suggest an unconventional cause was performed. Risk factors included those for cardiac and atherosclerotic disease: coronary artery disease (CAD), valvular disease, smoking, arrhythmia, hypertension, or diabetes mellitus. RESULTS: Overall, 51 patients were identified. Twenty-nine patients (57%) had unconventional causes (8 paradoxical emboli, 4 possible paradoxical emboli, 12 hypercoagulable states, 3 white clot syndromes, and 2 cervical ribs), 17 (33%) had conventional causes, and 5 (10%) were unknown. When the number of cardiac risk factors was < or =1, excluding smoking, the probability of a conventional source was zero, in contrast to 100% if the number of risk factors was >1. When the following risk factors were absent, there were significantly more unconventional than conventional sources of emboli (P < 0.001): smoking (100% versus 0%), CAD (93% versus 7%), arrhythmias (83% versus 17%), hypertension (93% versus 7%), and diabetes mellitus (81% versus 19%). Patients with a conventional source were significantly older (44 versus 38 years). CONCLUSIONS: The "unconventional" causes of PATE were responsible for a higher percentage of cases in young patients. An analysis of the number of risk factors was useful in predicting which patients suffered embolic events from conventional sources, with the critical number being >1 (excluding smoking). Therefore, when younger patients present with PATE, and are found to have < or =1 identifiable cardiac risk factor, their work-up should be directed toward the unconventional sources first.

Adult↗
PubMed2002

[Duration of oral anticoagulant therapy in deep venous thrombosis of the lower limbs].

The optimal duration of oral anticoagulant therapy is a matter of debate. It is essential to balance the desired effect of the anticoagulants in reducing recurrences against the risk of major bleeding. Recent data suggest that it is necessary to tailor the duration of anticoagulation individually according to the topography of deep vein thrombosis (DVT) and the presence of risk factors. A six-week treatment for patients with isolated calf DVT is sufficient. For proximal DVT and/or pulmonary embolism, a short anticoagulant course seems sufficient in patients with temporary risk factors (three months) and a longer anticoagulant course (six months at least) is recommended for cases with permanent risk factors or idiopathic DVT. The inherited or acquired hypercoagulable states can be divides into those that are common and associated with a modest risk of recurrence (i.e. isolated factor V Leiden or G20210A prothrombin gene) and those are uncommon but associated with a high risk of recurrence (i.e. antithrombin, protein C or S deficiencies and anticardiolipin antibodies). Thus, the presence of one of these last abnormalities favours more prolonged anticoagulant therapy. For the high-risk of recurrence patients, there is a paucity of evidence based medicine particularly for patients with biological thrombophilia, and randomised controlled trials in this population are required. An assessment of low- or fixed-dose oral anticoagulation is also necessary in order to reduce the bleeding risk.

Administration, Oral↗
PubMed2003

[Pediatric priapism associated with pulmonary infection].

Priapism is a rare urologic emergency in pediatric population. It is usually a consequence of sickle cell disease. Leukemia is another important cause of priapism in children. We present a case of priapism associated with an acute pulmonary infection. To our knowledge, this is the second case describing this association. In the other reported case, pulmonary infection was related to Mycoplasma Pneumoniae. The hypothesis is that infection with Mycoplasma Pneumoniae can produce a hypercoagulable state, especially in selected areas of the circulation.

Child↗
PubMed2003

Left ventricular thrombus sans overt cardiac pathology.

A 25-year-old man presenting with peripheral and cerebral emboli was incidentally detected as having a left ventricular mass on two-dimensional echocardiographic examination of the heart. In absence of any obvious structural heart disease or hypercoagulable state, the mass was presumptively diagnosed as left ventricular myxoma. The patient was operated on, and histopathology revealed the mass to be a thrombus. The cause and pathogenesis of the left ventricular thrombus, differential diagnosis, and management are discussed. The rarity of the case is highlighted.

Adult↗
PubMed1982

Hyperlipoproteinemia as a significant risk factor for pulmonary embolism in patients undergoing coronary artery bypass grafting.

A five-year (1975 through 1979) retrospective analysis of all cardiac surgical patients who sustained a postoperative pulmonary embolism was undertaken, and lipoprotein profiles of these patients were evaluated. Twenty-six patients (20 men and 6 women) were identified who had definite clinical, laboratory, and radiological evidence of pulmonary embolism in the postoperative period. Twenty had undergone coronary artery bypass grafting, and the remaining 6 had undergone other cardiac surgical procedures. Of the 20 patients who had coronary bypass, 19 (95%) were found to have hyperlipoproteinemia (14 patients with type II and 5 with type IV). There were 4 hospital deaths (15%), all related to pulmonary embolism. The 4 patients had undergone coronary bypass procedures, and all had type II hyperlipoproteinemia. Since patients with hyperlipoproteinemia made up less than 10% of the coronary bypass population, the incidence of pulmonary embolism in this group is highly significant (p less than 0.001). Experimental evidence has shown that patients with hyperlipoproteinemia, especially type II, have increased platelet adhesiveness and aggregation, and coagulation abnormalities consistent with a hypercoagulable state. This retrospective study clinically confirms that finding and suggests that early postoperative anticoagulation therapy may be indicated in patients with hyperlipoproteinemia, particularly type II, to reduce thromboembolic complications.

Coronary Artery Bypass↗
PubMed1998

Activation of coagulation and fibrinolysis during cardiothoracic operations.

BACKGROUND: During open cardiac operations using cardiopulmonary bypass, there is activation of coagulation and fibrinolysis. We assessed the separate contributions of the surgical procedure itself and cardiopulmonary bypass to this, by studying sequential samples from patients undergoing routine open cardiac operations or thoracic operations without cardiopulmonary bypass. METHODS: Activation of coagulation and the extent of fibrinolysis were measured from sequential samples obtained before the operation to 48 hours after the operation for 7 thoracic patients and 8 cardiac patients. RESULTS: In the thoracic group operation length was shorter (p = 0.002), and there was no significant increase in thrombin-antithrombin III complexes or D-dimers until 24 hours postoperatively. In contrast, there was a highly significant increase in thrombin-antithrombin III complexes (p = 0.0043) and D-dimer levels (p = 0.009) during cardiopulmonary bypass. The increase in fibrinolytic activity was caused by an increase in tissue plasminogen activator (p = 0.013). At 48 hours postoperatively, the cardiac patients had a more hypercoagulable state than thoracic patients with significantly higher levels of thrombin-antithrombin III complexes (p = 0.041) and plasminogen activator inhibitor-1 activity (p = 0.0033). CONCLUSIONS: This study suggests the major activation of coagulation and fibrinolysis seen during cardiac operations is caused by the use of cardiopulmonary bypass.

Adolescent↗
PubMed2003

Risks of acute hospital transfer and mortality during stroke rehabilitation.

OBJECTIVE: To identify demographic, medical, and functional factors associated with transfer of stroke patients to acute hospital services and/or mortality during stroke rehabilitation. DESIGN: Two case-control studies in which logistic regression was used to control for clinical traits associated with differences in likelihood. SETTING: A total of 542 US inpatient and rehabilitation units. PARTICIPANTS: A total of 64,471 patients discharged during 1995. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Transfer to an acute hospital service and death. RESULTS: There were 5847 (9.1%) acute hospital transfers and 320 (0.5%) deaths. Greater disability at admission was associated with higher odds of both acute hospitalization and mortality. Cardiopulmonary arrest, chest pain, gastrointestinal problems, bleeding disorders, hypercoagulable states, and acute renal difficulties increased the relative odds of acute hospitalization from 3.1 (95% confidence interval [CI], 2.3-4.2) to 12.7 (95% CI, 9.2-17.6). The likelihood of mortality for patients 85 years of age or older was more than 2-fold (2.5; 95% CI, 1.7-3.6) that of patients 65 years of age or younger for blacks, it was nearly 2-fold (1.7; 95% CI, 1.3-2.3) compared with whites, after adjusting for clinical differences. CONCLUSION: Higher likelihoods of mortality among older patients versus younger, black patients versus white, and patients with more rather than less disability at admission suggest the need for greater vigilance in monitoring medical status.

Activities of Daily Living↗
PubMed2003

Comparative study of the effects of two once-a-month injectable contraceptives (Cyclofem and Mesigyna) and one oral contraceptive (Ortho-Novum 1/35) on coagulation and fibrinolysis.

A randomized controlled multicenter study was undertaken to monitor the effects on hemostasis of two once-a-month injectable contraceptive preparations, Mesigyna (50 mg norethisterone enanthate and 5 mg estradiol valerate) and Cyclofem (25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate) in comparison with a well-known oral contraceptive (OC) Ortho-Novum 1/35 (norethisterone 1 mg and ethinyl estradiol 35 microg). A total of 378 volunteers from four centers (Bangkok, Hangzhou, Santiago and Singapore) were monitored. Blood sampling took place in one pretreatment cycle, the third and ninth injection intervals and one posttreatment cycle. In each of the three treatment groups, a rise in hemoglobin, and increases in platelet count and in prothrombin time were observed. With treatment there was a significant increase in activated partial thromboplastin time among Mesigyna users, no change among Cyclofem users and a significant decrease among OC users. OC use led to increases in plasma levels of fibrinogen, factor VII, factor X, plasminogen, protein C and decreases in plasma levels of t-PAI and antithrombin. Use of combined injectables induced no change (Cyclofem) or decreases (Mesigyna) in plasma levels of fibrinogen, factor VII, factor X and antithrombin. Use of both combined injectables led to decreases in protein C, slight decreases in plasminogen and increases in plasminogen and fibrinogen. Overall, the injectable preparations may be more beneficial than the oral preparation in not enhancing a hypercoagulable state because of the reduced synthesis of fibrinogen, factors VII and X; however, decreases in antithrombin and protein C, which are potent coagulation inhibitors, may raise some concern. Whether these changes can lead to modifications in the risk of arterial or venous disease can only be ascertained by conducting epidemiological studies.

Adolescent↗