Hemostatic abnormalities in Sneddon's syndrome.

Sneddon's syndrome is a rare condition comprising widespread livedo retucularis and multiple episodes of transient cerebral ischemia. Treatment to date has been empirical. The hemostatic/thrombotic status of 4 patients with Sneddon's syndrome was studied by a unique technique, hemostatometry, which measures primary hemostasis (shear-induced platelet plug formation), the overall coagulation, and thrombolysis (dislodgment of the hemostatic plugs) from nonanticoagulated blood. In all 4 patients, platelet reactivity, which shows itself in the initial phase of the hemostatic reaction, was enhanced. The overall hemostasis, in which the generation of thrombin by activated platelets plays the decisive role, was enhanced in 3 patients. Three of the 4 patients had hypercoagulation, and in 3, spontaneous thrombolysis was inhibited. Treatment was commenced with aspirin and nifedipine, and patients were monitored both clinically and by serial hemostatometry over two years. One patient had one further transient ischemic episode; the other 3 remained asymptomatic. Thus, the observed clinical improvement correlated with improvement of the hemostatic profile.     

Pharmacokinetics of tissue-type plasminogen activator during acute myocardial infarction in men. Effect of a prostacyclin analogue.

BACKGROUND. Coronary reocclusion complicates the thrombolytic therapy of acute myocardial infarction despite the routine use of aspirin. This is consistent with experimental studies demonstrating that multiple agonists, in addition to thromboxane A2, mediate the platelet activation underlying reocclusion. Consequently, a more potent antiplatelet therapy with a broader spectrum of activity than aspirin may be required in this setting. Prostacyclin and its more stable analogue, iloprost, inhibit platelet aggregation to all known agonists and exert an additional effect over aspirin alone. Experiments in animal models have demonstrated, however, that iloprost increases the clearance of tissue-type plasminogen activator (t-PA) and impairs thrombolysis in vivo. This study examines whether a similar interaction occurs in humans. METHODS AND RESULTS. Twelve patients with acute myocardial infarction received t-PA intravenously, 60 mg in the first hour and a maintenance infusion of 13.3 mg/hr for 3 hours. Patients were assigned in a double-blind fashion to iloprost (2 ng/kg/min) or placebo following the initial 90 minutes of the maintenance infusion of t-PA. Iloprost decreased mean arterial blood pressure (-10 +/- 2.9 mm Hg, p less than 0.05) but did not alter heart rate. Steady-state plasma iloprost concentration was 591 +/- 64 pmol/l. At this concentration, iloprost markedly inhibited platelet aggregation in vitro, particularly in the presence of aspirin. Steady-state clearance of t-PA was unchanged by iloprost (454 +/- 65 versus 443 +/- 136 ml/min in controls, p = NS). Furthermore, neither elimination kinetics nor plasma protein binding of t-PA was altered by iloprost. CONCLUSIONS. At plasma levels that exert a potent antiplatelet effect, iloprost did not alter the pharmacokinetics of t-PA in men. Prostacyclin analogues may prove useful as an adjunct to plasminogen activators, particularly in patients at high risk for thrombotic reocclusion.     

Activation of the hemostatic mechanism during thrombolysis in patients with unstable angina pectoris

In patients with myocardial infarction, thrombolytic therapy induces a paradoxical activation of the hemostatic mechanism. In patients with unstable angina, the effect of thrombolysis on the coagulation cascade is unknown. We prospectively measured the plasma concentrations of prothrombin fragment 1 + 2 and fibrinopeptide A in consecutive patients with unstable angina randomized to receive placebo alone (n = 23), streptokinase 1,500,000 IU over 1 hour followed by a 48-hour placebo infusion (n = 21), or streptokinase 250,000 over 1 hour followed by a continuous infusion of 100,000 IU per hour over 48 hours (n = 20). All the patients received intravenous heparin for 72 hours. The plasma levels of the different markers were measured at baseline, 90 minutes, 24 hours, and 48 hours after the start of therapy. The median baseline plasma concentrations of prothrombin fragment 1 + 2 and fibrinopeptide A were similar in the three treatment groups. In comparison with placebo, an increase in plasma prothrombin fragment 1 + 2 and fibrinopeptide A, was observed after 90 minutes in the two groups receiving thrombolysis. After 24 and 48 hours, the prothrombin fragment 1 + 2 levels remained significantly higher only in the patients receiving the 48-hour streptokinase infusion. In patients with unstable angina, thrombolytic therapy induces an activation of the hemostatic mechanism, despite concomitant heparin administration; in those receiving a prolonged streptokinase infusion, the activation of coagulation persists for as long as the drug is administered.     

Hemostatic complications in leukemic patients

With clinical vigilance and laboratory tests of platelet and coagulation factor function, the clinician can promptly recognize and treat hemostatic disorders in leukemic patients. For example, laboratory values are strikingly abnormal in disseminated intravascular coagulation. Prompt neutralization of the underlying cause of the coagulopathy is essential. Platelet and coagulation factors may have to be replaced if the disorder is severe. Diffuse petechiae, purpura, mucous membrane bleeding, and hemorrhage around venipuncture or infusion sites indicate thrombocytopenia. Vigorous platelet replacement is necessary to prevent massive intracranial of gastrointestinal hemorrhage. Platelet dysfunction may cause spontaneous bleeding or immediate or delayed hemorrhage after surgery. The abnormality is often evident in peripheral blood smear or indicated by bleeding time or aggregation studies. If possible, sufficient autologous platelets should be infused to return the bleeding time to normal. Immune thrombocytopenic purpura may be easy to diagnose when the reduction in the circulating platelet count is compared with the normal number of marrow megakaryocytes. But attempts to increase platelet count by platelet transfusions may be frustrating. Treatment involves high doses of corticosteroids, followed by splenectomy if necessary.     

A global platelet test of thrombosis and thrombolysis detects a prothrombotic state in some patients with non-insulin dependent diabetes and in some patients with stroke

Platelet aggregation and spontaneous thrombolytic activity were assessed in patients with non-insulin dependent diabetes and stroke using a shear-induced and agonist-induced platelet aggregation test. The Thrombotic Status Analyser (TSA), induces platelet-rich thrombus formation solely by shear forces, while whole blood platelet aggregometry measures platelet reactivity to different agonists. These tests were employed in the present study because in earlier studies they both demonstrated that platelet aggregability in healthy volunteers was unchanged with age. On the other hand, it is known that thrombolytic activity decreases with age in males, but not in females. In diabetic patients shear-induced platelet aggregability varied according to the stage of nephropathy but platelet aggregation to collagen was suppressed at all stages. Platelet reaction to shear stress was enhanced in stroke patients with haemorrhagic episodes but not in patients with lacunar infarction. In contrast, platelet reactivity to collagen was suppressed and changes in ADP-induced platelet aggregability were inconsistent. Suppressed thrombolysis was observed only in diabetes with minor renal defect. Fibrinogen was increased in diabetes with stage III and IV nephropathy. Fibrinopeptide A (FPA) and D-dimer were increased in stroke. Thus, the observed increase in fibrinogen, FPA and D-dimer is inconsistent with changes in platelet aggregability. Our present findings suggest that a shear-induced platelet aggregation test is superior to other tests such as agonist-induced platelet aggregation and thrombotic markers such as fibrinogen, FPA and D-dimer in detecting a prothrombotic state. It is concluded that elderly males may have a prothrombotic state not because of platelet hyper-aggregability but because of suppressed thrombolytic activity. On the other hand, a prothrombotic state in patients with non-insulin dependent diabetes and after stroke may be due to changes in age-independent platelet aggregability.     

A global platelet test of thrombosis and thrombolysis detects a prothrombotic state in some patients with non-insulin dependent diabetes and in some patients with stroke

Platelet aggregation and spontaneous thrombolytic activity were assessed in patients with non-insulin dependent diabetes and stroke using a shear-induced and agonist-induced platelet aggregation test. The Thrombotic Status Analyser (TSA), induces platelet-rich thrombus formation solely by shear forces, while whole blood platelet aggregometry measures platelet reactivity to different agonists. These tests were employed in the present study because in earlier studies they both demonstrated that platelet aggregability in healthy volunteers was unchanged with age. On the other hand, it is known that thrombolytic activity decreases with age in males, but not in females. In diabetic patients shear-induced platelet aggregability varied according to the stage of nephropathy but platelet aggregation to collagen was suppressed at all stages. Platelet reaction to shear stress was enhanced in stroke patients with haemorrhagic episodes but not in patients with lacunar infarction. In contrast, platelet reactivity to collagen was suppressed and changes in ADP-induced platelet aggregability were inconsistent. Suppressed thrombolysis was observed only in diabetes with minor renal defect. Fibrinogen was increased in diabetes with stage III and IV nephropathy. Fibrinopeptide A (FPA) and D-dimer were increased in stroke. Thus, the observed increase in fibrinogen, FPA and D-dimer is inconsistent with changes in platelet aggregability. Our present findings suggest that a shear-induced platelet aggregation test is superior to other tests such as agonist-induced platelet aggregation and thrombotic markers such as fibrinogen, FPA and D-dimer in detecting a prothrombotic state. It is concluded that elderly males may have a prothrombotic state not because of platelet hyper-aggregability but because of suppressed thrombolytic activity. On the other hand, a prothrombotic state in patients with non-insulin dependent diabetes and after stroke may be due to changes in age-independent platelet aggregability.     

Impaired spontaneous thrombolytic activity in elderly and in habitual smokers, as measured by a new global thrombosis test.

We used a new test (the G?r?g Thrombosis Test) for assessing the effect of aging, smoking and exercise habits on the overall thrombotic status including platelet reactivity and spontaneous thrombolytic activity of 30 healthy young males (mean, 21.1 +/- 0.4 years) and 34 elderly males (64.5 +/- 1.1 years). The occlusion time (OT) and the lysis time (LT) were measured from a single native blood sample. The OT is an index of platelet activation and subsequent occlusive thrombus formation by high shear stress, while the LT is an index of the resumption of blood flow due to thrombolysis. The LTs in the elderly group were significantly longer than in the young group (P < 0.001). The LTs of elderly smokers were significantly longer than those of non-smokers (P < 0.001). Exercise did not affect the LT significantly. Platelet reactivity to shear stress (OT) was not affected either by aging, smoking or exercise habits. Suppressed spontaneous thrombolytic activity in elderly males and smokers could be a mechanism of acute thrombotic events in these people.     

血小板参数和凝血指标与溶栓治疗关系的探讨

目的 动态观察急性脑梗死患者溶栓治疗过程中血小板参数及凝血指标的变化规律,探讨血小板参数和凝血指标与溶栓治疗的关系.方法 应用血细胞分析仪检测180例急性脑梗死患者（实验组）和180例健康体检者（对照组）的血小板计数（PLT）、血小板平均体积（MPV）和大血小板比率（P-LCR）,血凝分析仪检测凝血酶原时间（PT）、部分活化凝血活酶时间（APTT）、纤维蛋白原（Fg）及凝血酶时间（TT）,动态观察溶栓前及溶栓后1、2、4小时和48小时血小板参数和凝血指标的变化.结果 溶栓前脑梗死患者的MPV、P-LCR和Fg含量均高于对照组（P均＜0.05）,PLT、PT和APTT显著低于对照组（P均＜0.05）;溶栓治疗后,MPV、P-LCR和Fg含量显著下降,PLT、PT和APTT显著升高（P均＜0.05）.结论 溶栓治疗过程中,动态监测急性脑梗死患者的血小板参数（PLT、MPV和P-LCR）和凝血指标（PT、APTT、Fg）,可反映患者凝血功能的变化,对脑梗死患者的溶栓治疗具有一定的参考价值.     

Altered in vitro hemostasis, clotting, and thrombolysis after oral nifedipine in normal volunteers

In this study the authors used the Haemostatometer, a new instrument to monitor the pattern of hemostatic plug formation that occurs in holes in polyethylene tubing through which nonanticoagulated blood is flowing under standard conditions. The pattern and speed of blood coagulation, subsequent to hemostasis, was also monitored. Simultaneously, the time until expulsion of hemostatic plugs formed was measured and considered as spontaneous thrombolysis time (STT). In 10 healthy volunteers, blood samples were drawn and tested before and ninety minutes after administration of 10 mg oral nifedipine. After nifedipine, the initial phase of primary hemostasis was delayed (p less than 0.05), the clotting time lengthened (p less than 0.01), and the STT shortened (p less than 0.01). The authors conclude that the effect of nifedipine on hemostasis and thrombolysis could contribute to its therapeutic efficacy.     

Testing various fruits for anti-thrombotic effect: i. Mulberries

Prevention of arterial thrombotic disease has high priority in developed countries. As inappropriate diet predispose to acute thrombotic events, regular intake of an antithrombotic diet may be a convenient and effective way of prevention. The present study was performed to examine antithrombotic effect of mulberry varieties. A shear-induced in vitro platelet reactivity/thrombolysis test (Gorog Thrombosis Test) was used to screen for antiplatelet and thrombolytic activities. In case of effectiveness, it was followed by an in vivo test of laser-induced thrombosis in mice. Antioxidant capacity was assessed by superoxide anion and radical scavenging activities. Total polyphenolics, anthocyanin and citrate contents were also measured. The tested varieties showed different effect in vitro on platelet reactivity and endogenous thrombolytic activity. Varieties inhibiting platelet reactivity were antithrombotic in vivo regardless inhibition or enhancement of thrombolysis. Those mulberry varieties, which enhanced platelet reactivity in vitro, were prothrombotic only if inhibitory activity on endogenous thrombolysis coexisted with the platelet effect. Antioxidant activities and polyphenolics content did not affect platelets and the overall thrombotic status. However, antioxidant activities and polyphenolics content significantly correlated with the endogenous thrombolytic activity. These data showed that mulberry varieties can be grouped into subclasses with either anti- or prothrombotic activities. Antioxidant activities and polyphenolic contents do not affect platelets but may enhance endogenous thrombolysis, thus causing an overall antithrombotic effect.     

Effect of emotional tension on intravascular coagulation in patients with angiographically established ischemic heart disease

The effect of simulated emotional stress (ES) on the platelet/vascular and plasma components of the hemostatic system was examined in normal subjects and coronary patients. In coronary patients, prestress hemostatic platelet/vascular and plasma factors were disturbed, their blood showing a tendency to activated intravascular coagulation. Stress further increased the blood thrombogenic potential of coronary patients, causing intravascular coagulation as evidenced by declining cAMP/cHMP ratio, enhanced release of soluble fibrin and fibrinogen-fibrin degradation products (FDPs), and reduced antithrombin III.     

o-raffinose cross-linked hemoglobin improves the hemostatic defect associated with anemia and thrombocytopenia in rabbits

Several different preparations of cross-linked hemoglobin (CLHb) are being evaluated for their efficacy and safety as red cell substitutes in a variety of preclinical and clinical settings. Because CLHb is known to sequester nitric oxide (NO) and inhibit NO-mediated processes, we hypothesized that CLHb would have a hemostatic effect by enhancing platelet reactivity, inducing vasoconstriction, or both. Infusion of o-raffinose CLHb shortened the prolonged microvascular bleeding time and decreased blood loss from ear incisions in rabbits rendered anemic and thrombocytopenic. Moreover, this hemostatic effect persisted for at least 24 hours after infusion. Phenylephrine induced a degree of vasoconstriction similar to that induced by CLHb but did not shorten the bleeding time or decrease blood loss, suggesting that vasoconstriction alone cannot account for the hemostatic effect of CLHb. There was no evidence of CLHb-induced activation of coagulation in vivo, since infusion of CLHb did not increase circulating levels of thrombin-antithrombin complex. In vitro, CLHb abolished the inhibitory effect of the NO donor 3-morpholinosydnonimine on platelet aggregation and enhanced the aggregation of stimulated but not resting platelets. This potentiating effect was not attenuated by the addition of superoxide dismutase or catalase. To evaluate the potential arterial thrombogenicity of CLHb, a model of carotid artery thrombosis was developed in rabbits without thrombocytopenia or anemia. Compared with albumin infusion, CLHb infusion shortened the time to complete carotid occlusion. These data suggest that CLHb may shift the thromboregulatory balance toward clot formation, resulting in decreased bleeding in anemic and thrombocytopenic rabbits and possibly increasing arterial thrombogenicity in normal rabbits.     

A Comparison of Hemostatic Parameters in Hypothermic Versus Normothermic Cardiopulmonary Bypass

Ten patients who underwent PCPS (group A) at our institution were evaluated for hemostatic abnormalities and compared to an age matched population undergoing open CPB (group B) to study the effects of CPB independent of the effects of hypothermia. Both groups had hemostatic parameters measured prior to, 1 hour after, and 16–24 hours following completion of the procedure. The mean duration of perfusion for group A was 53.7 ± 13.5 minutes and group B 108.1 ± 26.5 minutes (P < 0.0001). There were no significant differences in hemoglobin, platelet count, coagulation factors, and tests of in vitro platelet function between groups A and B at the different time points. While bleeding times for group B returned to baseline within an hour following bypass, they remained significantly prolonged in group A 24 hours later (P = 0.02). Conclusion: Normothermic bypass used during PCPS results in platelet function abnormalities similar to open hypothermic CPB suggesting the dominant role of the membrane oxygenator over hypothermia in inducing the platelet dysfunction .     

Simultaneous measurement of all thrombosis parameters from native human blood: usefulness in monitoring efficacy and complications of thrombolytic therapy

The sequelae of thrombus formation, both by shear forces and by collagen fiber, the subsequent coagulation, and the dislodgement of thrombi (thrombolysis) were measured from a small volume of nonanticoagulated blood sample, by a new instrument. Addition of streptokinase (SK) or tissue-type plasminogen activator (rt-PA) to the blood sample eliminated the need for anticoagulation for thrombolysis measurement: clot lysis preceded and allowed thrombolysis to occur. The test revealed activation of platelets and coagulation by SK and rt-PA. Apart from this general trend, platelet reactivity in response to plasminogen activator showed great individual variation. Whether the greatly enhanced (42%) or prolonged hemostasis (13%), observed in different blood samples with rt-PA, could be used as a predictor of reocclusion or bleeding complications remains to be established. Thrombolysis did not occur in 12% of the samples tested. These thrombolysis models may be useful for developing new agents for the dissolution of platelet-rich thrombi. It is suggested that this technique be used for monitoring thrombolytic therapy.     

Coagulation/fibrinolysis balance and lung cancer

Forty-eight patients with freshly diagnosed carcinoma of the lung (40 males, 8 females) were evaluated for a coagulation profile including activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, F VIII R:Ag, fibrin monomers (FM), thrombin-antithrombin-III complex (TAT-III), D-dimers and the platelet count. Thirty-eight patients had a normal aPTT and 37 patients a normal PT. None of the patients had clinical or laboratory indications of serious hemorrhage or thrombosis. On the other hand, high percentages of increased values were found for fibrinogen and F VIII R:Ag, which can be seen as prethrombotic factors. The very high percentages of elevated results for the FM, TAT-III and D-dimer are strongly indicative for low-grade coagulation activation with reactive fibrinolysis. Nevertheless, most lung cancer patients are able to maintain a normal or near normal hemostatic function. The results shown here are indicative of a coagulation and fibrinolysis equilibrium at an enhanced level and demonstrate why an unbalance between the two systems can result in thrombotic complications in (lung) cancer patients as earlier reported.     

Enhanced platelet reactivity and hypercoagulability in the steady state of sickle cell anaemia.

A prospective controlled study was undertaken to investigate the haemostatic and coagulation status of 18 adult subjects in the steady state of sickle cell anaemia (SCA), using a relatively new in vitro technique. Shear induced haemostasis, whole blood dynamic coagulation, and spontaneous thrombolysis were measured using nonanticoagulated blood. As expected, the haemoglobin levels were significantly lower and platelet counts significantly higher in subjects with SCA compared with controls. Haemostasis and coagulation were significantly enhanced in SCA. No correlation was found between the raised platelet count and enhanced haemostasis or the reduced haemoglobin and hypercoagulation, respectively. Hyperactivity of the haemostatic system may have a pathogenic role in vaso-occlusive microthrombotic events and in the leg ulcers, both of which occur frequently in SCA.     

Multiscale prediction of patient-specific platelet function under flow

During thrombotic or hemostatic episodes, platelets bind collagen and release ADP and thromboxane A(2), recruiting additional platelets to a growing deposit that distorts the flow field. Prediction of clotting function under hemodynamic conditions for a patient's platelet phenotype remains a challenge. A platelet signaling phenotype was obtained for 3 healthy donors using pairwise agonist scanning, in which calcium dye-loaded platelets were exposed to pairwise combinations of ADP, U46619, and convulxin to activate the P2Y(1)/P2Y(12), TP, and GPVI receptors, respectively, with and without the prostacyclin receptor agonist iloprost. A neural network model was trained on each donor's pairwise agonist scanning experiment and then embedded into a multiscale Monte Carlo simulation of donor-specific platelet deposition under flow. The simulations were compared directly with microfluidic experiments of whole blood flowing over collagen at 200 and 1000/s wall shear rate. The simulations predicted the ranked order of drug sensitivity for indomethacin, aspirin, MRS-2179 (a P2Y(1) inhibitor), and iloprost. Consistent with measurement and simulation, one donor displayed larger clots and another presented with indomethacin resistance (revealing a novel heterozygote TP-V241G mutation). In silico representations of a subject's platelet phenotype allowed prediction of blood function under flow, essential for identifying patient-specific risks, drug responses, and novel genotypes.     

Platelet reactivity and streptokinase resistance following antecedent streptokinase therapy for myocardial infarction.

AIMS: To assess the efficacy of second-time administration of streptokinase (SK). First-time thrombolysis with SK in myocardial infarction (MI) is established but the efficacy of subsequent SK is unknown. METHODS AND RESULTS: Platelet reactivity to shear stress, spontaneous and SK-induced thrombolysis were measured in vitro in 28 patients who had received SK for MI and compared to 15 controls. SK antibody (Ab) titres were inversely related to time from MI. Platelet reactivity was greatly enhanced in patients (p < 0.0001). Spontaneous thrombolysis in patients was poor and in 17 failed to occur. In contrast, thrombolysis occurred in all but 1 control. In patients platelet reactivity was strongly related to thrombolytic activity (r = -0.516; p = 0.0029). SK in vitro was at least 4 times more effective in controls than in patients. CONCLUSION: The chances of achieving patency with second administration of SK are poor. Ab titre is not a reliable predictor of resistance.     

Bleeding and thrombosis in multiple myeloma and related plasma cell disorders

A variety of disease- and treatment-related factors affect the coagulation system and the risk of bleeding and thrombotic complications in patients with multiple myeloma (MM) and related plasma cell disorders (PCD). As commonly observed in other cancer settings, the malignant clone induces a cytokine environment responsible for a hypercoagulable state. The increase of blood viscosity and impairment of platelet and coagulation function due to circulating monoclonal proteins are considered key mechanisms in the hemostatic abnormalities frequently detected in patients with PCD. However, clinically significant bleeding is relatively rare and poorly correlated with these abnormalities. Management is often challenging because of the multifactorial pathogenesis and underestimation or misdiagnosis of acquired bleeding disorders, particularly acquired von Willebrand syndrome. In recent years, growing interest in thromboembolic risk has emerged after the introduction of novel and more effective antimyeloma agents (thalidomide and lenalidomide), which was associated with increased risk of venous thromboembolism, particularly when associated with dexamethasone and multiagent chemotherapy in newly diagnosed patients. The clinical impact of bleeding and thrombotic complications in patients with PCD, with emphasis on MM, will be discussed in this review, reporting the current knowledge about pathophysiologic mechanisms and implications for management.     

Significance of plasma fibrinogen in coronary arterial disease: marker or causative risk factor for arterial thrombosis?

The relationship between fibrinogen and severity of disease was measured in patients with coronary arterial disease (n = 301) prior to surgical coronary revascularisation. Platelet reactivity (shear-induced haemostasis) was measured from non-anticoagulated blood, in vitro. Coagulation was assessed by the clotting time of flowing native blood (dynamic) and by the conventional (stagnant) tube tests. Significantly enhanced platelet reactivity to shear-stress was observed when patients with one-vessel disease were compared to those with two- or three-vessel disease (P = 0.003). Neither coagulation nor fibrinogen were significantly related to the severity of disease. Furthermore, patients who had myocardial infarction (n = 144) showed enhanced platelet reactivity (P = 0.02) as compared to those who had not (n = 157). Again, neither coagulation nor fibrinogen discriminated between these groups of patients. Relationship between plasma fibrinogen and platelet reactivity was also investigated in vitro. Identical blood samples with normal (220-280 mg/dl) and elevated plasma fibrinogen (approximately 500 mg/dl) were compared by measuring platelet reactivity and coagulation from native blood and platelet aggregation in whole blood. The in vitro studies suggested that plasma fibrinogen and platelet reactivity are inversely associated. Furthermore, increased fibrinogen prolonged dynamic coagulation. These findings do not support the assertion that elevated plasma fibrinogen is a true causative factor for coronary arterial disease and arterial thrombosis.