Increased fibrin monomer plasma concentration in stable coronary artery disease in patients without oral anticoagulation.

Blood coagulation has been shown to play a role in the pathogenesis of local thrombus formation in coronary arteries. Increased plasma concentrations of thrombin activation markers such as fibrin monomers (FM) indicate coagulation activation. Therefore, we investigated FM plasma levels in 194 patients (127 nonanticoagulated and 67 anticoagulated) with stable coronary artery disease (CAD) and in 96 healthy controls. FM levels were significantly higher (P<0.0001) in nonanticoagulated patients compared with healthy controls, whereas anticoagulated patients showed significantly lower (P<0.0001) FM levels, respectively. FM levels above 0.50 mg/ml were associated with an odds ratio (OR) of 3.0 (95% confidence interval (CI), 1.7--5.5) for the presence of stable CAD in nonanticoagulated patients. However, the association lost significance after correction for possible confounders such as age, body mass index, total cholesterol, fibrinogen, sex, smoking, arterial hypertension and diabetes mellitus. In conclusion, we found elevated FM plasma levels in nonanticoagulated patients as compared with healthy controls. Elevated FM plasma levels were associated with an OR of 3.0 for the presence of stable CAD in nonanticoagulated patients.

Protein Z in ischaemic stroke.

Many risk factors associated with ischaemic stroke are known, including high levels of fibrinogen or factor VII. Protein Z is a vitamin K-dependent coagulation factor, which was found to promote the assembly of thrombin with phospholipid vesicles that might promote coagulation. Indeed, a low protein Z level may be associated with a varying bleeding tendency. Therefore, we hypothesized that high protein Z levels could induce a hypercoagulable state and performed a case-control study to investigate a potential association between high protein Z plasma levels and ischaemic stroke. We measured protein Z in plasma samples from 157 patients with stroke of unknown aetiology and 192 control subjects. All patients had survived an ischaemic stroke or transient ischaemic attack (TIA) for at least 2 months. We found an increased relative risk of ischaemic stroke with increasing protein Z levels, with an odds ratio of 4.3 [95% confidence interval (CI): 1.7--11] for protein Z plasma levels > or = 160%. Excluding patients with a history of venous thromboembolism from the analysis, the same result was obtained (odds ratio 4.2; 95% CI: 1.6--11.2). Using a logistic regression model, this association also remained significant (P = 0.04) after adjustment for established risk factors. Our data indicated that a high plasma level of protein Z is an independent risk factor for ischaemic stroke.

Rapid D-dimer testing and pre-test clinical probability in the exclusion of deep venous thrombosis in symptomatic outpatients.

We assessed the performance of three rapid D-dimer tests (Auto Dimertest, VIDAS and Tinaquant) in combination with a pretest clinical probability model for deep venous thrombosis (DVT) in 106 consecutive outpatients with suspected DVT. Contrast venography or colour-coded duplex ultrasonography demonstrated the presence of DVT in 47 patients (14 distal DVT and 33 proximal DVT). First, we assessed the accuracy indices for different cut-off levels of the rapid D-dimer tests. Sensitivity was found to be 97.9-100%, negative predictive value (NPV) was 96.3-100%, and the exclusion rate was 24.5-31.1%. Next, the patients were grouped according to the pre-test clinical probability model in categories with low, moderate or high probability. In patients with a low pre-test probability, DVT would have been directly ruled out and the patients would not have undergone further investigations. In patients with a moderate probability, D-dimer testing and, in the case of a positive result, objective testing would have been performed and, in the case of a negative result, they would have been ruled out of having DVT. Patients with high probability would directly have undergone objective tests for DVT. The combination with the pre-test clinical probability model improved the exclusion rate (43.5-44.6%), whereas sensitivity (97.5-100%) and NPV (97.6-100%) remained roughly unchanged. The combination of rapid D-dimer tests with a pre-test clinical probability model may help to reduce unnecessary work-up in patients with suspected DVT.

Hemostatic and fibrinolytic parameters in survivors of myocardial infarction: a low plasma level of plasmin-alpha2-antiplasmin complex is an independent predictor of coronary re-events.

Abnormalities of coagulation or fibrinolysis play a role in the pathogenesis of coronary artery disease (CAD). Elevated plasma levels of fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1 and tissue-type plasminogen activator were reported to be predictive for reinfarction and death in patients with CAD. We investigated the risk for coronary re-events associated with 18 hemostatic and fibrinolytic parameters in a prospective study including 200 survivors of myocardial infarction (MI). During a 2-year follow-up, 37 patients suffered one of the following predefined re-events: fatal MI (n = 2), non-fatal MI (n = 5), percutaneous transluminal coronary angioplasty (n = 17) or coronary artery bypass grafting (n = 13). Low plasmin-alpha2-antiplasmin complex (PAP) plasma levels were associated with an up to fivefold (95% confidence interval, 1.6-15.3) increase in relative risk. The association between decreasing PAP levels and coronary re-events remained significant (P = 0.004) after correction for possible confounders using multiple logistic regression analysis. Our data indicate low PAP plasma levels to be associated with subsequent coronary events in patients with a history of MI.

Coagulation factors II, V, VII, and X, prothrombin gene 20210G-->A transition, and factor V Leiden in coronary artery disease: high factor V clotting activity is an independent risk factor for myocardial infarction.

Increased levels of hemostatic factors and genetic mutations of proteins involved in coagulation may play a role in the pathogenesis of coronary artery disease. We investigated clotting activity of factors II (FII:C), V (FV:C), VII (FVII:C), and X (FX:C), the prothrombin gene 20210G-->A transition, and the factor V Leiden mutation in 200 survivors of myocardial infarction and in 100 healthy controls. FV:C (P<0.0001) and FVII:C (P<0.0001) were found to be independent risk factors for myocardial infarction. High FV:C or high FVII:C combined with smoking or arterial hypertension increased the relative risk for myocardial infarction up to 50-fold. One of 177 patients (0.6%) and 4 of 89 controls (4.5%) had the prothrombin 20210 AG genotype. Eleven of 177 patients (6.2%) and 6 of 89 controls (6.7%) were heterozygous for the factor V Leiden mutation. No homozygous carrier for these mutations was found. Neither the prothrombin gene 20210G-->A transition (odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01 to 1.1) nor the factor V Leiden mutation (OR, 1.0; 95% CI, 0.4 to 2.8) were associated with an increased relative risk for myocardial infarction. In conclusion, our data indicate that neither the prothrombin gene 20210G-->A transition nor the factor V Leiden mutation are risk factors for myocardial infarction. High FVII:C was confirmed to be an independent risk factor for myocardial infarction. Moreover, we describe for the first time that high FV:C is an independent risk factor for myocardial infarction.

Congestive hypersplenism: treatment by means of radioembolization of the spleen with Y-90.

Radioembolization of the spleen with yttrium-90 was performed in a patient with severe thrombocytopenia attributable to congestive hypersplenism. Follow-up included performance of serial contrast material-enhanced computed tomographic studies for 13 months. Splenic volume decreased from 1,400 to 470 cm3. The platelet count increased to almost normal levels. No complications were observed. Splenic radioembolization merits further investigation in selected patients.

[Prevention of venous thromboembolism--in whom, when and how?]. / Prophylaxe venöser Thromboembolien--bei wem, wann und wie?

Venous thromboembolic diseases are of major importance with respect to morbidity and mortality. Therefore, efficient prophylaxis is essential. Indication for thromboprophylaxis has to be made individually: In high risk situations, especially in orthopedic surgery, every patient should receive medical prophylaxis, e.g. with heparin, in addition to other preventive measures such as the wearing of elastic stockings or physiotherapy until full mobilization. For high-risk patients having a history of recurrent venous thromboembolism or which are suffering from a thrombogenic disease (e.g. myeloproliferative disorder, especially polycythemia vera, paroxysmal nocturnal hemoglobinuria, systemic lupus erythematosus, homocystinuria) or a hereditary thrombophilia (e.g. deficiency of antithrombin III, protein S, protein C or APC resistance), prophylactic measures should be more generally applied. In these patients, risk factors (e.g. oral contraceptive medication) or risk situations (e.g. long-distance travelling by car or airplane) have to be avoided whenever possible. In inevitable risk situations (e.g. perioperative or peripartal period) prophylaxis is mandatory. It is generally limited to the period of elevated thrombogenic risk and is often effected by application of a low molecular weight heparin. Patients with a history of recurrent thromboembolic events despite elimination of all avoidable risk factors should get a lifelong prophylaxis, usually with oral anticoagulants.

[Fibrinogen Bern III: a further case of hereditary fibrinogen variants with substitution A alpha 16 Arg----Cys]. / Fibrinogen Bern III: ein weiterer Fall der hereditären Fibrinogenvariante mit Substitution A alpha 16 Arg----Cys.

A heterozygous hereditary fibrinogen variant, fibrinogen Bern III, has been characterized. The proposita and her daughter showed prolonged thrombin time and reptilase time, as well as a markedly reduced fibrinogen concentration as determined by functional clotting assay. Fibrinogen was purified from the proposita's plasma and subjected to biochemical characterization. The delayed fibrin formation was shown to result from impaired release of fibrinopeptide A. Thrombin was found to cleave an extended fibrinopeptide A (A alpha 1-19) from the reduced polypeptide chains of the abnormal fibrinogen. Amino acid analysis of this fragment indicated that the arginine residue, located at the physiological thrombin cleavage site, was replaced by cysteine. The functional defect of the fibrinogen variant Bern III is due to the amino acid substitution A alpha 16 Arg----Cys.