Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recurrent retinal branch artery occlusions, carotid thromboembolism, cerebral venous thrombosis, transient brainstem ischemia, and massive brainstem and cerebral infarction complicated the course of inflammatory bowel disease in 5 patients. Three patients had ulcerative colitis and 2 had regional enteritis. The usual risk factors for stroke were absent. Neuropathological examination in 1 patient showed in situ thrombosis of small cerebral and brainstem arteries and veins. Coagulation studies showed thrombocytosis, short partial thromboplastin times, and elevation of fibrinogen and Factor VIII levels. Platelet counts and coagulation factors returned toward normal after control of intestinal inflammation in each of the 4 surviving patients. Inflammatory bowel disease can be accompanied by a hypercoagulable state that predisposes to stroke.
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PMID:Cerebral and retinal vascular complications of inflammatory bowel disease. 44 68

Ten clinically healthy subjects (5 men and 5 women), 31 +/- 11 yrs of age, were studied at six timepoints (0800, 1200, 1600, 2000, 0000, 0400) distributed over a 1-week span. Circadian rhythms in platelet aggregation in response to adenosine diphosphate (ADP) and adrenalin (A), platelet adhesiveness measured as retention in a glass bead column, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, Factor VIII activity and alpha-1-antitrypsin antigen showed circadian rhythms. The plasma concentrations of plasminogen, alpha-2-macroglobulin, and antithrombin III (AT III) antigen, Factor V and fibrinogen degradation products showed no circadian rhythm by ANOVA or cosinor analysis. The phase relations of the rhythms of different coagulation parameters are of interest in the physiology and pathobiology of the coagulation-fibrinolytic system. The extent of the circadian rhythm (range of change) described is not of a magnitude to lead to diagnostic problems in the clinical laboratory. The timing of these rhythms, however, may determine transient risk states for thromboembolic phenomena, including myocardial infarction and stroke. Several but not all coagulation parameters suggest a transient state of hypercoagulability during the morning hours. The recognition of these rhythmic, and thus in the time of the occurrence predictable temporary risk states for thromboembolic phenomena, may lead to timed treatment and/or effective prevention.
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PMID:Circadian variations in blood coagulation parameters, alpha-antitrypsin antigen and platelet aggregation and retention in clinically healthy subjects. 212 46

Coagulation parameters were initially monitored in 8 patients receiving whole body hyperthermia (WBH). Patients were heated by the warm water blanket technique to 41.8 degrees C (Tmax), maintained at this temperature for 2 hours, then allowed to cool. A fall in platelets was apparent by the time Tmax was achieved and continued during the 18 hours after WBH. Levels of beta-thromboglobulin (BTG) and platelet factor 4 rose by 56% and 191% by the end of treatment but returned to baseline 18 hours later. Fibrinogen, plasminogen and alpha 2-antiplasmin levels declined and FDP and fibrinopeptide A (FPA) levels increased during WBH. Factor XII and Factor VIII:C fell moderately during WBH while Factors VIII R:Ag, VIII:RC and V did not change or showed a late rise. Factor VII levels fell in 7 of 8 patients, reaching levels of 30% of normal in four. To better define the sequence of these coagulations perturbations, earlier and more frequent timepoints were studied in an additional 3 patients. This revealed that decreases in fibrinogen and plasminogen and increases in FPA and BTG occur very early (by the time the patient reaches 39 degrees C). On the other hand, a decrease in Factor VII activity was not apparent until patients had reached Tmax. WBH is therefore associated with a consumption coagulopathy. Possible mechanisms are discussed and extrapolations to the situation seen in heat stroke are suggested.
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PMID:Activation of coagulation during therapeutic whole body hyperthermia. 373 68

A sample of in all 119 young adults below the age of 55, with ischemic cerebrovascular disease (TIA and minor stroke), was investigated later than three months after acute disease. Factor VIII biological activity and antithrombin antigen were significantly (p less than 0.001) increased as compared to 80 healthy controls. In combination, these two variables correctly classified 85 percent of patients and controls at a stepwise discriminant analysis. Factor VIII related antigen was increased (p less than 0.02) in patients with atherosclerotic signs at cerebral angiography and in postmenopausal female patients (p less than 0.001). It is suggested that high levels of factor VIII might predispose for thrombosis/atherosclerosis. Antithrombin biological activity was normal in spite of high antithrombin antigen levels, possibly indicating a relative insufficiency in the antithrombin defense line. It is concluded that young stroke patients provide good opportunities to look for early operating factors and predictors in human atherosclerosis and arterial thromboembolism.
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PMID:A study of hemostasis in ischemic cerebrovascular disease. I. Abnormalities in factor VIII and antithrombin. 681 Apr 96

An analysis was made of 41 cases of disseminated intravascular coagulation in dogs, with the objective of evaluating routine and nonroutine laboratory tests used in making the diagnosis. The dogs were grouped on the basis of underlying disease, which included neoplasia (39%), pancreatitis (30%), chronic active hepatitis (15%), heat stroke (12%), and sepsis (4%). Of the diagnostic tests evaluated, those for determination of activated partial thromboplastin time, antithrombin III activity, prothrombin time, and the platelet count were the most valuable. Of the clotting factors, factor V activity was decreased more frequently than the activity of factor VIII:C (factor VIII: procoagulant). The factor VIII:C activity was in conflict with prevailing dogma that reflects depression of this factor in disseminated intravascular coagulation. Factor VIII:C activity was decreased in only 29% of dogs studied. Activation of the fibrinolytic system was manifested by decreased plasminogen activity in 49% of the dogs studied. Sixty-one percent of the dogs had increased amounts of fibrin (ogen) degradation products.
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PMID:Disseminated intravascular coagulation: antithrombin, plasminogen, and coagulation abnormalities in 41 dogs. 726 67

The mechanisms leading to the hyperacute rejection of a vascularized xenograft are still incompletely understood. The first stage of the rejection process is when blood of the recipient comes into contact with the endothelium of the xenograft. A working heart model was used to examine endothelium-related processes and their impact on organ function. Pig hearts were perfused with porcine (autologous) or human (xenogeneic) blood. Cardiac function was evaluated by calculating the stroke work index, arteriovenous oxygen, coronary flow, and resistance. PgF1a as a marker of endothelial activation, its antagonist TXB2, and myoglobin reflecting myocardial damage were measured in the hemoperfusate. H&E and PAS staining and immunohistological demonstration of factor VIII-related antigen was performed. Xenogeneic perfused porcine hearts showed significantly less stroke work, a higher arteriovenous oxygen difference, and an increased coronary resistance. Factor VIII-related antigen could not be demonstrated immunohistologically on the endothelium after xenogeneic perfusion. PgF1a levels were significantly higher in the xenogeneic hemoperfusate, indicating endothelial cell activation. The concentration of myoglobin in the hemoperfusate remained within normal values and was similar during autologous and xenogeneic perfusion. Therefore endothelium-related processes are likely to affect the coronary circulation--thus being one mechanism leading to diminished cardiac performance during hyperacute rejection.
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PMID:The contribution of endothelial cells to hyperacute rejection in xenogeneic perfused working hearts. 831 May 18

When a blood vessel is injured, control of bleeding starts with the rapid adhesion of circulating platelets to the site of damage. Within seconds, the adhered platelets are activated, secrete the contents of storage organelles, spread out over the damaged area and recruit more platelets to the developing thrombus. However, if this same process occurs in a diseased, sclerotic or occluded vessel, the resulting platelet thrombus may break away and block the coronary artery, causing a heart attack, or restrict blood supply to the brain, causing a stroke. The glycoprotein (GP) Ib-IX-V complex, a member of the leucine-rich protein family, is a constitutive platelet membrane receptor for von Willebrand Factor (vWF), a multimeric adhesive glycoprotein found in the matrix underlying the endothelial cell lining of the blood vessel wall and in the plasma. Binding of vWF to the GP. Ib-IX-V complex regulates adhesion of platelets to the subendothelium at high shear flow, and initiates signal transduction leading to platelet activation. The GP Ib-IX-V complex also constitutes a binding site for alpha-thrombin, an interaction that facilitates thrombin-dependent platelet activation. This review will focus on recent detailed analysis of the GP Ib-IX-V complex and vWF that has identified discrete amino acid sequences that mediate their interaction. An anionic/sulfated tyrosine sequence of the GP Ib alpha-chain that is critical for binding of the GP Ib-IX-V complex to both vWF and alpha-thrombin is analogous to sulfated anionic amino acid sequences mediating interactions of other adhesive proteins, including P-selectin binding to PSGL-1 and Factor VIII binding to vWF.
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PMID:Molecular mechanisms of platelet adhesion and activation. 907 44

Little is known about the prospective associations of fibrinogen, factor VII, or factor VIII with cardiovascular disease (CVD) and mortality in the elderly. At baseline in the Cardiovascular Health Study (5888 white and African American men and women; aged >/=65 years), we measured fibrinogen, factor VIII, and factor VII. We used sex-stratified stepwise Cox survival analysis to determine relative risks (RRs) for CVD events and all-cause mortality (up to 5 years of follow-up), both unadjusted and adjusted for CVD risk factors and subclinical CVD. After adjustment, comparing the fifth quintile to the first, fibrinogen was significantly associated in men with coronary heart disease events (RR=2.1) and stroke or transient ischemic attack (RR=1.3), and also with mortality within 2.5 years of follow-up (RR=5.8) and later (RR=1.7). Factor VIII was significantly associated in men with coronary heart disease events (RR=1.5) and mortality (RR=1.8), and in women with stroke/transient ischemic attack (RR=1.4). For both factors, values were higher in those who died, whether causes were CVD-related or non-CVD-related, but highest in CVD death. Factor VII exhibited associations with incident angina (RR=1.44) in men and with death in women (RR, middle quintile compared with first=0.66). However, in general, factor VII was not consistently associated with CVD events in this population. We conclude that, if confirmed in other studies, the measurement of fibrinogen and/or factor VIII may help identify older individuals at higher risk for CVD events and mortality.
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PMID:The relationship of fibrinogen and factors VII and VIII to incident cardiovascular disease and death in the elderly: results from the cardiovascular health study. 1039 98

Factor VIII (FVIII) is key component of the fluid phase of the blood coagulation system. Recent evidence suggests a direct relationship between high plasma levels of FVIII and an increased risk for arterial and venous thrombosis. Thus material reviews the most important clinical and epidemiological evidence about this prothrombotic association. Main function of FVIII is to activate FX functioning as a cofactor for activated FIX in the presence of phospholipids and calcium. Since its deficiency has been historically associated with a hemorrhagic disease (namely hemophilia A), it was never studied its role in thrombosis. In order to explain the association FVIII and thrombosis, defects in its synthesis that increase its plasma concentration as well as postranslational modifications that allow a higher activity, have been proposed. Since 1977 it was suggested that increased plasma concentrations of FVIII and thrombosis may be associated. Shortly after, several other studies confirmed this association. Indeed, patients with stroke of acute myocardial infarction having high plasma levels of FVIII have a shorter survival. On the other hand, deep venous thrombosis is more frequent in patients with high plasma levels of FVIII. This rise in plasma FVIII concentration is also associated with recurrent venous thrombosis. The increment of plasma FVIII concentration is not due to an acute phase reaction. Plasma concentrations of FVIII above 100-150 IU/dL increase 3-fold the risk of thrombosis while concentrations above 150 IU/dL increase the the same risk 6-fold. While it is established the real importance of FVIII as a cause of thrombosis, every patient at risk of thrombosis must have a quantification of this factor. Evaluation of plasma FVIII concentration must be performed in patients with suspected thrombophilia since there is evidence that shows that high plasma FVIII levels is an independent thrombophilic risk factor. There are not effective therapeutic interventions able to normalize the high concentrations of FVIII. Therefore, appropriate prophylaxis during high thrombosis risk clinical episodes is the best alternative for the patient.
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PMID:[A new thrombophilia risk factor: the increase of plasma factor VIII]. 1463 11

Current treatments for preventing thrombotic diseases are associated with a significant risk of bleeding. Improved anticoagulant agents are therefore still required. The specificity and pharmacokinetics properties of monoclonal antibodies to coagulation factors allow novel anticoagulation approaches. Treatment with human antibodies or humanized mouse monoclonal antibodies should avoid unacceptable side effects due to immune response to the drug. Such antibodies were developed against three coagulation factor: Tissue factor (TF), Factor IX (FIX) and Factor VIII (FVIII). A fully humanized antibody was successfully derived from a mouse monoclonal antibodies to TF. In vivo studies with monoclonal antibodies to TF demonstrated efficient antithrombotic activity. Anti-TF antibodies may also prove useful in cardiovascular disorders and cancer, given the role of TF in these diseases. Mouse and human monoclonal antibodies to FIX were also efficient to prevent thrombosis in animal models of venous and arterial thrombosis and in stroke. A humanized anti-FIX antibody was tested in phase I study in healthy volunteers. The pharmacokinetics of the antibody were determined by the rapid formation of stable complexes with newly synthesised FIX. Human anti-FVIII antibodies inhibiting only partially FVIII activity were recently described. Investigations in mice have established that treatment with such anti-FVIII antibodies is efficient to prevent deep vein thrombosis. Given the low concentration of FVIII in plasma and the long half-life of antibody, treatment with anti-FVIII antibody could be very convenient, allowing one administration every month. Altogether, monoclonal antibodies to coagulation factor appear as promising novel antithrombotic drugs.
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PMID:The use of antibodies to coagulation factors for anticoagulant therapy. 1537 13


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