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PubMed2001

[Atherothrombosis and inflammation].

Alterations of coagulation, fibrinolysis, platelets and low grade inflammation are causal pathophysiological factors in atherosclerosis. Considerable activation of several involved pathways occurs during the acute progression of atherosclerotic lesions, which is characterized by an occluding thrombus, and local and systemic inflammatory reactions as in patients with acute coronary syndromes. These patients become clinically compromised due to the reduction in coronary flow. Furthermore, a frequent occurrence of non-occluding thrombi may be assumed as a progression factor in atherosclerotic diseases. Both the extrinsic and the intrinsic pathway of coagulation are involved, resulting in a hypercoagulative state. Furthermore, an inflammatory acute phase reaction occurs in addition to the activation of several other inflammatory pathways in patients with unstable angina pectoris or acute myocardial infarction. Exposure of tissue factor by the ruptured plaque together with a systemic hypercoagulative state, local and systemic inflammation as well as stimulated platelets and endothelial dysfunction are involved in the pathophysiology of acute coronary syndromes. In the following paper the current knowledge on activation of these pathways and on the various complex interactions is discussed.

Coronary Artery Disease↗
PubMed2003

Modifiable patient factors are associated with reverse vein graft occlusion in the era of duplex scan surveillance.

OBJECTIVE: Modifiable patient factors that contribute to graft occlusion may be addressed after surgery. To determine risk factors associated with reverse vein graft (RVG) occlusion, we examined the characteristics and duplex scan surveillance (DS) patterns of patients with RVGs. METHODS: Patients treated with RVG from January 1996 through December 2000 were identified from a prospective registry. The study population consisted of all patients with RVGs performed during the study period with grafts that subsequently occluded. Patients whose grafts remained patent served as age-matched and gender-matched control subjects. The prescribed DS regimen was every 3 months for the first postoperative year and every 6 months thereafter. Early DS failure was defined as having no DS within the first 3 months. Cox proportional hazards analysis was used to compare the two groups. Hazard ratios were calculated. RESULTS: During the study period, 674 patients underwent RVG. Fifty-five patients with occluded RVGs were compared with 118 with patent RVGs. The follow-up period for occluded grafts was 13.40 +/- 12.59 months and for patent grafts was 32.40 +/- 15.61 months. Dialysis therapy, a known hypercoagulable state, continued smoking, and DS failure were independent factors associated with RVG occlusion. The hazards ratio for dialysis was 6.45 (95% CI, 3.07 to 13.51; P <.001), for current smoking was 4.72 (95% CI, 2.5 to 8.85; P <.001), for hypercoagulable state was 2.99 (95% CI, 1.47 to 6.10; P =.003), and for early DS failure was 2.43 (95% CI, 1.29 to 4.59; P =.006). CONCLUSION: Continued smoking and failure to undergo DS within the first three postoperative months are modifiable factors associated with RVG occlusion. Smoking cessation and graft surveillance must be stressed to optimize patency of infrainguinal RVGs.

Aged↗
PubMed1990

[Clinical research of hypercoagulation in patients with diabetes mellitus, glomerular diseases and pregnancy induced hypertension].

The hypercoagulable state in patients with diabetes mellitus, glomerular diseases and pregnancy induced hypertension was studied by using new methods. The research items included platelet function, coagulation, anti-coagulation system, fibrinolysis and TEG examination. The results showed that there was a hypercoagulable state in patients with diabetes mellitus, pregnancy induced hypertension and glomerular diseases, especially in those with uremia and nephrotic syndrome.

Adolescent↗
PubMed2005

Identification of a novel gene, HCR2, in aorta of hypercoagulable rats using suppression subtractive hybridization.

Screening and identification of novel genes involved in hypercoagulable state (HCS) is important in understanding the underlying mechanisms of development of atheroslerosis, which implicated in critical vascular diseases such as coronary heart disease and stroke. HCS was induced in rats with high carbohydrate diet. Subtractive hybridization experiments between aorta tissues from hypercoagulable rats and controls showed that a novel cDNA (GenBank Accession No. AY234417), designated as hypercoagulability related gene-2 (HCR2), was highly expressed in aorta tissue. The predicted protein encoded by HCR2 contains 78 amino acids, which has a theoretical isoelectric point (pI) of 8.59 and molecular weight (MW) of 8841.7 based on sequence analysis. Our data suggest that HCR2 may be involved in HCS and identification of the gene may contribute to our understanding of the mechanisms for the production of a hypercoagulable state of several critical clinical disorders.

Amino Acid Sequence↗
PubMed1992

Influence of suction-assisted lipectomy on coagulation.

Suction-assisted lipectomy is the most commonly performed surgical aesthetic procedure in North America today. The procedure is not without significant morbidity, as death as well as serious nonfatal complications have been reported. Thromboembolic disease as a complicating factor of various types of surgical procedures and trauma has been well documented in the literature. Stasis, injury, and hypercoagulation--the limbs of Virchow's triad--contribute to predisposition for morbidity. The effects of stasis and injury are experienced with most operative procedures. We questioned whether suction-assisted lipectomy, in the appropriately selected and managed patient, would demonstrate a predisposition toward a hypercoagulable state and subsequent thromboembolic disease. In our group of ten female patients who underwent large-volume liposuction, a carefully selected assay of hematological factors demonstrated alterations consistent with a controlled response to tissue injury, but did not demonstrate a predisposition to a hypercoagulable state or subsequent increased risk of thromboembolic sequelae.

Adult↗
PubMed1995

Pseudotumor cerebri in systemic lupus erythematosus.

OBJECTIVE: To assess the association between pseudotumor cerebri (PC) and systemic lupus erythematosus (SLE), and to seek a pathogenic mechanism that may elucidate the appearance of PC in patients with SLE. DATA SOURCE: Original English articles having the terms SLE, PC, or benign intracranial hypertension in their titles were identified by Medline search. In addition we report three new patients with this association. STUDY SYNTHESIS: Thirteen articles were found and 21 patients were analyzed. DATA EXTRACTION: Of the reported 21 patients, 18 were previously reported and 3 new patients with coexisting PC and SLE are described. The clinical characteristics of the patients is presented. Patients with PC and SLE generally had a more severe course of SLE; renal involvement occurred in 79%, massive proteinuria in 47%, and hematologic abnormalities were detected in a third. A hypercoagulable state manifest by either recurrent thromboembolic events or a high anti-cardiolipin antibody titer was detected in 58% of the patients described. CONCLUSIONS: The association of PC and SLE is probably not coincidental. The high prevalence of serologic or clinical evidence of a hypercoagulable state suggests that microscopical thromboembolic events play a role in the genesis of PC.

Adolescent↗
PubMed1995

A case of non-insulin-dependent diabetes mellitus with vertebral osteomyelitits: usefulness of imaging diagnosis.

A 63-year-old woman with NIDDM poorly controlled by insulin therapy was admitted to our hospital because of fever and severe lumbago. Laboratory data revealed diabetic ketosis and a hypercoagulable state with infection. Bone and gallium scintigrams revealed an abnormal accumulation of the isotopes at L4-L5, where magnetic resonance imaging showed inflammatory changes. The patient was then diagnosed as having pyogenic vertebral osteomyelitis. Antibiotic chemotherapy and the administration of gebexate mesilate improved the inflammation and hypercoagulable state. When diabetic patients suffer from severe lumbago with sustained fever, and show segmental knock pain along the spine, pyogenic vertebral osteomyelitis should be considered. Bone and gallium scintigrams, and MRI are of clinical value for the early diagnosis of the disease.

Blood Coagulation Disorders↗
PubMedDate not supplied

Trousseau's syndrome in the head and neck.

Thromboses in Trousseau's syndrome are typically confined to the vascular system of the extremities and viscera. The authors report a case of sequential bilateral internal and external jugular-vein thromboses secondary to this paraneoplastic hypercoagulable state. The etiologies of commonly encountered head and neck venous thromboses are infection, trauma, and obstruction. This article purports that head and neck venous thromboses without a proximal inflammatory or mechanical cause may be the initial manifestation of an occult malignancy. Upon establishing the presence of a hypercoagulable state, further evaluation may lead to the early diagnosis of such an occult malignancy.

Adenocarcinoma↗
PubMed2004

Diminished response to activated protein C is not correlated with severity of peripheral arterial occlusive disease.

INTRODUCTION: Poor response to activated Protein C (APC) is a well established risk factor for venous thromboembolism. More recently, the hypercoagulable state which results from diminished response to APC has also been associated with arterial thrombosis. Some studies showed a clear association between low response to APC with advanced arterial disease, others, however, failed to support these data. Thus, there is ongoing dispute about the impact of a hypercoagulable state upon progression of atherosclerosis. MATERIAL AND METHODS: We investigated APC ratios and the existence of Factor V Leiden in 800 patients with documented peripheral arterial occlusive disease (PAD). Clinical symptoms according to Fontaine stages II (intermittent claudication), III (rest pain) and IV (gangrene) and the ankle/brachial index served as parameters for the severity of PAD. RESULTS: There was no association between low response to APC or existence of Factor V Leiden and the clinical stage of PAD or ankle/ brachial index. CONCLUSION: Our data suggest that poor response to APC is not correlated with the severity of peripheral arterial occlusive disease.

Activated Protein C Resistance↗
PubMedDate not supplied

Review of the Multicenter Trial Committee report: a prospective, randomized study on the prophylaxis of postoperative deep venous thrombosis.

The etiology of postoperative deep venous thrombosis (DVT) is thought to be due to a combination of factors including stasis, a hypercoagulable state and venous endothelial damage. Methods of prophylaxis are directed toward correcting one or more of these pathologic events. Methods counteracting more than one of these factors can be expected to be even more effective. The combination of dihydroergotamine (DHE) and heparin was anticipated to minimize stasis and the hypercoagulable state respectively. Based upon current experimental evidence and current theory, an additional benefit might include minimizing venous endothelial injury by controlling venomotor tone. A prospective, randomized, double-blind, multicenter trial was designed and performed in the United States evaluating the prophylactic efficacy of DHE 0.5 mg plus heparin 5000 U, DHE 0.5 mg plus heparin 2500 U, heparin 5000 U, and DHE 0.5 mg versus placebo. General surgical patients including those undergoing noncardiac thoracic and pelvic operations who were identified at moderate to high risk for postop DVT were included. Study medications were injected subcutaneously two hours preoperatively and every 12 hours postoperatively for 5-7 days or until the 125I-fibrinogen-uptake test (RFUT) became positive. Eight hundred and eighty eight patients were entered into this trial and 744 (85%) completed the study. Results showed a statistically significant benefit from DHE/Hep 5000 compared to placebo (p less than 0.01) and compared to other active agents (p less than 0.05). None of the other active agents showed a statistically significant prophylactic benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1995

Thrombin generation in plasma: its assessment via the endogenous thrombin potential.

Thrombin generation is a pivotal function of plasma in haemostasis and thrombosis. Its mechanism is essentially the classical cascade, the velocity of which is governed by the availability of factors Va and VIIIa and that is confined to the surface of the procoagulant membranes which appear at the site of injury. There is no routine test that quantitatively renders the thrombin forming capacity of a plasma sample. Clotting times (PT-prothrombin time, APTT-activated partial tromboplastin time) do not reflect the over all thrombin generation and are insensitive to hypercoagulative states. The endogenous thrombin potential (ETP), i.e. the area under the thrombin generation curve, better represents this function. We developed a method to assess the ETP in the routine laboratory. The first results suggest that it is a sensitive indicator for every form of anticoagulation. It is increased in hypercoagulable states thus far studied, both congenital and acquired and can be designed to indicate deficiencies in protein C and S and APC (activated protein C) resistance.

Animals↗
PubMed1993

Amaurosis fugax, Crohn's disease and the anticardiolipin antibody.

Crohn's disease is associated with a hypercoagulable state due to platelet or clotting abnormalities which may be responsible for the thromboembolic episodes seen in this condition. We report the occurrence of anticardiolipin antibodies in a patient with Crohn's disease who presented with Amaurosis fugax and suggest that these antibodies may be a further cause of the hypercoagulable state of Crohn's disease in some patients.

Aged↗
PubMed1992

[Syndromes of venous mesenteric ischemia: infarction and transient ischemia].

The reports of 8 patients with acute or subacute abdominal pain related to venous mesenteric ischemia were reviewed. None of the patients presented local or regional predisposing factors for venous thrombosis. In 4 patients, a localized segment of ischemic small bowel (median length 125 cm; range: 30-350) was resected without immediate anastomosis and postoperative anticoagulation therapy was given. Two of these patients developed recurrent ischemia involving the bowel adjacent to the stoma, treated successfully in 1 case by a repeat resection. The 4 other patients hospitalized with intestinal obstructive symptoms (1 case) or abdominal angina (3 cases) were treated by long term anticoagulation in 3 cases and artificial nutrition in 2 cases. None of them developed mesenteric infarction with a median follow up of 34 months. In 7 of the 8 patients, a coagulopathy was found: primary myeloproliferative disorder (1 case), hypercoagulation state (5 cases), autoimmune hemolytic anemia (1 case). These observations suggest that venous mesenteric ischemia included two different entities on the basis of clinical and morphological criteria: mesenteric infarction and subacute transient ischemia without bowel infarction. Most of apparently idiopathic cases of acute or subacute venous mesenteric ischemia are related to hypercoagulation states requiring a long term anticoagulation.

Abdominal Pain↗
PubMed1988

Protein C and the endothelium.

With the continued accumulation of clinical and animal studies, it is becoming abundantly clear that the protein C anticoagulant pathway plays a critical role in the regulation of coagulation. Investigations also indicate that this pathway is intimately involved in the interaction of the coagulation and inflammatory systems. Although no direct information is presently available, the function of this pathway is likely depressed in the regions of atherosclerotic plaque. It is clear that monocytes accumulate in this region and release many growth factors and monokines that are capable of endothelial function perturbation. Perturbation of the protein C anticoagulant pathway is one viable mechanism for the hypercoagulable state in this disease. As indicated here, the endothelial cells of the vessel wall play a critical role in the initiation, and possibly expression, of this pathway. Any injury to these cells that affects the proper expression of thrombomodulin, synthesis of protein S, or Factor Va inactivation complex formation could potentially lead to a hypercoagulable state and thrombotic complications. As has been discussed, several inflammatory mediators are already known that fulfill the criteria of endothelial cell perturbants that may lead to such a state. What other entities might have similar effects, either directly or indirectly through induction of cytokines, is not known at this time. A more complete understanding of this critical pathway and the effects of vascular disease on it should lead to a better understanding of many diverse disease processes and potential therapeutic strategies in the future.

Animals↗
PubMed2003

Atrial fibrillation and hypercoagulability: dependent on clinical factors or/and on genetic alterations?

UNLABELLED: It is well known that atrial fibrillation is associated with high incidence of thromboembolic events, propably due to a prothrombotic or hypercoagulable state. However, it is unclear whether or not there is any difference of this prothrombotic state in the clinical subgroups of atrial fibrillation patients, that is, in those with paroxysmal, persistent or permanent atrial fibrillation. From the other side the role of the arrhythmia duration on the changes of coagulative variables in atrial fibrillation patients is not clearly enough. The contribution of genetic and functional alterations in factors of the coagulation and fibrinolytic pathways (that is hemostatic risk factors) to the development of hypercoagulation state in atrial fibrillation requires clarification. We investigated therefore (1) if there are differences in the prothrombotic state between patients with different clinical status of the arrhythmia, (2) if the arrhythmia duration per se could be an independent determinant of the prothrombotic state in all atrial fibrillation patients and (3) if coexistent genetic alterations in haemostatic risk factors in patients with atrial fibrillation could contribute to the development of prothrombotic abnormalities. METHODS: Over a period of 23 months, we studied 55 patients with chronic non-valvular atrial fibrillation. We recruited 18 consecutive patients (13 men, mean age 59 +/- 10 years) with paroxysmal atrial fibrillation 17 patients (11 men, mean age 61 +/- 7 years) with persistent atrial fibrillation who underwent elective successful DC and remained in sinus rhythm at the 3 month visit and 20 patients (14 men mean age 64 +/- 9) with permanent atrial fibrillation. Blood results were compared to 17 age-sex- and race-matched controls. The prothrombotic state was quantified by measurement of plasma levels of fibrinogen, soluble P -selectin (an index of platelet activation) and von Willebrand factor (a marker of endothelial dysfunction). We assessed the frequencies of factor V Leiden and prothrombin variant G20210A to determine whether particular inherited haemostatic risk factors may have contribution to the development of prothrombotic state in atrial fibrillation patients. RESULTS: Permanent atrial fibrillation was associated with significant raised levels of von Willebrand factor, fibrinogen levels and soluble P -selectin compared to matched controls (all p < 0.001) and matched patients with paroxysmal and permanent AF (all p ranged between <0.003 and <0.002). Patients with persistent atrial fibrillation had significantly elevated von Willebrand factor levels (p = 0.0064) and fibrinogen levels (p = 0.002), but not Soluble P -selectin (p = 0.509). when compared to controls. Patients with paroxysmal atrial fibrillation had significantly elevated levels of P -selectin (p = 0.005) and fibrinogen (p = 0.003), but not von Willebrand factor (p =.0.61) compared to controls. Stepwise multiple regression analyses demonstrated that the arrhythmia duration (approximately 3 years) was an independent predictor of abnormal von Willebrand factor, fibrinogen and soluble P -selectin levels. Restoration of sinus rhythm in paroxysmal atrial fibrillation subgroup and successful electrical cardioversion of patients with permanent fibrillation atrial fibrillation did not significantly alter levels of the affected factors. The frequency of factor V Leiden was 8.9 in all studied patients with atrial fibrillation, versus 2.4% in the control group (odds ratio [OR] 4.6 [95% confidence (CI) 1.4-17.5], p = 0.02). The frequency of the prothrombin variant G20210A was 6.4.% compared with control group 1.6% (OR 4.9 [95% confidence interval (CI) 1.2-2.9], p = 0.04). There was a trend towards an increased frequency of factor V Leiden and/or prothrombin variant G20210A in patients age <55 years and in patients living at a particular area of Thrace mountains. CONCLUSIONS: Our results showed that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched that there were significant differences in the prothrombotic state when patients with paroxysmal, and persistent atrial fibrillation were compared to matched patients with permanent atrial fibrillation and controls in sinus rhythm. The duration of the arrhythmia (about 3 years) was an independent predictor of abnormal measured factors. We found for the first time that some genetic alterations in haemostatic risk factors could be coexist in atrial fibrillation patients and may be a contributor to the development of hypercoagulability in atrial fibrillation patients.

Aged↗
PubMedDate not supplied

Non-atherosclerotic aorto-arterial thrombosis: A study of 30 cases at autopsy.

BACKGROUND: Aorto-arterial thrombosis is very often associated with atherosclerotic and/or aneurysmal changes. Thrombosis, unrelated to these changes is infrequent. AIMS: To evaluate the clinical presentation and aetiopathogenesis of aorto-arterial thrombosis, unrelated to atherosclerosis and aneurysms. SUBJECTS AND METHODS: A retrospective study of 30 autopsied cases of non-atherosclerotic and non-aneurysmal aorto-arterial thrombosis collected over a period of 14 years was carried out. RESULTS: There were 23 males and seven females and majority presented in the third to fourth decades of life with clinical features of acute abdomen or lower limb gangrene. Abdominal aorta as the site of thrombosis was observed in 46.5% cases. The causes were attributed to hypercoagulable states and changes in the aortic wall. No aetiology could be identified in 5 patients (16.6%. Associated tuberculosis was seen in six cases. CONCLUSIONS: Non-atherosclerotic aortic thrombosis is a heterogeneous group of disorders. Young and even elderly patients with symptoms related to abdominal ischaemia or peripheral vascular disease should be investigated thoroughly for hypercoagulable states and aortic pathology.

Adolescent↗
PubMed2001

[Mesenteric venous thrombosis: early diagnosis with abdominal CT scan and screening for coagulopathies. Six observations].

PURPOSE: Mesenteric venous thrombosis is an uncommon entity whose diagnosis is difficult because the symptoms are nonspecific. Yet early recognition of this disease helps avoid the evolution towards mesenteric infarction. METHODS: We describe clinical symptoms and hypercoagulable states discovered in six patients with superior mesenteric venous thrombosis. RESULTS: Five of six patients were admitted to hospital for abdominal pain whose mean duration was 9 days before the diagnosis of venous thrombosis was made. Three of them had a fever. Two patients had a past history of deep venous thrombosis. All patients had a hypercoagulable state and three of them had two associated disorders of coagulation. In all cases, abdominal CT scan had permitted the diagnosis of mesenteric venous thrombosis. An anticoagulant therapy was conducted successfully in five of six patients. CONCLUSION: A CT abdominal scan done early in the case of nonspecific abdominal pain, since the patients had a previous history of venous thrombosis, may permit a nonsurgical treatment of mesenteric venous thrombosis. A screening for thrombophilia must always be carried out since coagulation disorders are very frequently the recognised causes in mesenteric venous thrombosis.

Adult↗
PubMed2006

[Haemocoagulative modifications correlated with pregnancy].

AIM: The aim of this paper was to establish the physiologic changes in the coagulation and fibrinolytic systems during normal pregnancy. METHODS: One-hundred and twenty normal pregnant women were investigated in a longitudinal study involving 3 measurements: blood samples were collected at 12, 24 and 36 weeks of gestation and were assayed for prothrombin time, antithrombin III (ATIII) activity, protein C activity, protein S (PS) activity, prothrombin fragments 1+2, type 1 plasminogen activator inhibitor activity, tissue plasminogen activator antigen, plasminogen, activated protein C resistance, factors VII and VIII levels and D dimer. Student t-test, one way analysis of variance (ANOVA) and Fisher test were used for statistical analysis. RESULTS: Factor VII and factor VIII were always increased with respect to controls. Variance analysis showed a statistically significant reduction for anticoagulants (PS) and a rise for F1+2 and D dimer. With regard to fibrinolysis, there was an increase both for t-PA and PA1-1 during pregnancy. Moreover, the increased activity of factors of haemostasis was accompanied by an increase of activity and concentration of ATIII and acquired activated protein C resistance. CONCLUSIONS: These findings suggest that normal pregnancy is associated with an hypercoagulable state, resulting into a moderate risk for thrombosis during the different trimesters of pregnancy. Also broad spectrum assays which measure a range of trombin/fibrin formation in serum have become an established mean to identify activation of blood coagulation and/or fibrinolysis. There is a considerable interest in the application of these assays to the diagnosis of other acquired hypercoagulable states; such as thrombophilia during pregnancy. From the viewpoint of coagulation/fibrinolysis changes, the follow-up of thrombophilia markers could be recommended when levels of coagulation parameters exceed the normal values during pregnancy.

Adult↗