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Results for “Coagulation Protein Disorders”

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At least 469 records · Page 26Linked to original sources
PubMed2001

Vascular thrombohemorrhagic disorders: hereditary and acquired.

This review has summarized the more important diseases that may be accompanied by or lead to a disorder of hemostasis or thrombosis via alterations of the vasculature. It is to be stressed that the vascular component of hemostasis is often overlooked by clinicians caring for patients with disorders of hemostasis and thrombosis. It should be appreciated that the vasculature is intricately related to the coagulation protein system and to platelets when involved in thrombohemorrhagic diatheses. Although many vascular disorders may lead to hemorrhage or thrombosis, it must be appreciated that often it is impossible to discern between a primary vascular defect/damage and a defect that has been induced by platelet activation/dysfunction or procoagulant abnormalities.

Amyloidosis↗
PubMed1984

Disseminated intravascular coagulopathy in a patient undergoing total hip arthroplasty for carcinoma. A case report.

A 78-year-old man was treated by total hip arthroplasty (THA) for metastatic carcinoma of the proximal femur. After operation, disseminated intravascular coagulopathy (DIC) developed. DIC is a known complication of malignancy but is reported infrequently as a complication of THA. Its occurrence in this patient may have been triggered by the release of coagulant proteins from surgical manipulation of the tumor. The disorder was characterized clinically by profuse uncontrollable hemorrhage from the surgical wound. Laboratory abnormalities indicated a consumptive coagulopathy. Guidelines for the diagnosis and management of a patient with DIC are available. Orthopedic surgeons should be alerted to the potential of this serious complication in patients treated by THA for metastatic bone abscess of the hip.

Aged↗
PubMedDate not supplied

Protein C activators from snake venoms and their diagnostic use.

Proteinases converting the zymogen protein C (PC) of vertebrates into activated PC have been detected in several snake venoms. Most PC activators have been purified from venom of snake species belonging to the genera of the Agkistrodon complex. Unlike the physiological, thrombin-catalyzed PC activation reaction which requires thrombomodulin as a cofactor, most snake venom activators directly convert the zymogen PC into the catalytically active form which can easily be determined by means of coagulation or chromogenic substrate techniques. Due to this feature, the fast-acting PC activator Protac from Agkistrodon contortrix contortrix (southern copperhead snake) venom has found a broad application in diagnostic practice for the determination of disorders in the PC pathway. Recently, screening assays for the PC pathway have been introduced, based on the observation that the PC pathway is probably the most important physiological barrier against thrombosis.

Agkistrodon↗
PubMed2003

Coagulation and inflammation.

The protein C anticoagulant pathway is critical for controlling microvascular thrombosis and is initiated when thrombin binds to thrombomodulin (TM) on the surface of the endothelium. Protein C activation is augmented by an endothelial cell protein C receptor (EPCR). EPCR is shed from the vasculature by inflammatory mediators and thrombin. EPCR binds to activated neutrophils in a process that involves proteinase 3 and Mac-1 and appears to inhibit leukocyte extravasation. EPCR can undergo translocation from the plasma membrane to the nucleus where it re-directs gene expression. During translocation, EPCR can carry activated protein C (APC) to the nucleus, possibly accounting for the ability of APC to modulate inflammatory mediator responses in the endothelium. TNF-alpha and other inflammatory mediators can down-regulate EPCR and TM. Inhibition of protein C pathway function increases cytokine elaboration, endothelial cell injury and leukocyte extravasation in response to endotoxin and infusion of APC reverses these processes. In vitro, APC has been reported to inhibit TNF-alpha elaboration from monocytes and to block leukocyte adhesion to selectins. Since thrombin can elicit many inflammatory responses in microvascular endothelium, loss of control of microvascular thrombin generation due to impaired protein C pathway function probably contributes to microvascular dysfunction in sepsis.

Animals↗
PubMed2004

Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemia.

OBJECTIVE: Clinical trials show that interleukin (IL)-6 represents a predictive marker in human sepsis. Furthermore, IL-6 has been proposed as a candidate mediator for endotoxin (lipopolysaccharide)-induced coagulation activation: In a primate model, an (alphaIL-6 antibody (alphaIL-6 Ab) almost abolished lipopolysaccharide-induced coagulation activation. Therefore, we wished to determine if an alphaIL-6 Ab (B-E8) may also attenuate lipopolysaccharide-induced activation of coagulation in humans. DESIGN: The study was a randomized, double blind, placebo-controlled parallel group trial (n = 12 per group). SETTING: University medical center. PATIENTS: Healthy volunteers. INTERVENTIONS: Healthy volunteers were randomized to receive either 80 mg of a monoclonal anti-IL-6 Ab (B-E8) or placebo intravenously before bolus infusion of 2 ng/kg lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: B-E8 effectively decreased IL-6 bioactivity as measured by a Bg-bioassay in vitro and concentrations of C reactive protein. However, B-E8 did not decrease lipopolysaccharide-induced tissue factor-messenger RNA transcription or plasma concentrations of downstream coagulation variables (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes, and D-dimer concentrations). Similarly, tumor necrosis factor-alpha concentrations, fibrinolytic activity (plasmin-antiplasmin complexes), endothelial activation (soluble E-selectin), and IL-10 were unaffected. CONCLUSION: IL-6 does not appear to mediate early-phase lipopolysaccharide-induced coagulation activation in humans.

Adult↗
PubMed1998

Protein Z in healthy human individuals and in patients with a bleeding tendency.

Protein Z is a vitamin-K-dependent plasma glycoprotein; its physiological function is not clear. Low protein Z levels were found in patients with otherwise unexplained bleeding disorders. It was therefore suggested that low protein Z levels might be associated with a bleeding diathesis. In the present study we measured protein Z levels in plasma samples of 48 patients with a suspected bleeding disorder and in plasma samples of 200 healthy adult individuals. We found protein Z to have a wide normal range in healthy men and women. Significantly lower protein Z levels were observed in women compared to men, whereas no correlation was found with age or other vitamin-K-dependent coagulation proteins. None of the 48 patients with a bleeding disorder had a protein Z level below the normal range. However, protein Z was significantly lower in the group of male patients with a bleeding history as compared to healthy men. In conclusion, our data indicate that low-normal protein Z levels are not associated with a bleeding tendency. However, it remains to be determined whether a low protein Z level is a weak cofactor associated with an increased bleeding tendency and whether decreased or absent protein Z (conditions not detected in our patients) might constitute a haemorrhagic diathesis.

Adolescent↗
PubMed1990

Studies of natural anticoagulant proteins and anticardiolipin antibodies in patients with the lupus anticoagulant.

Components of the natural anticoagulant system (NAS) and anticardiolipin antibodies were examined in 21 patients with lupus anticoagulant (LA), 13 of whom had past histories of thrombotic episodes. No relationship could be shown between the antigenic levels of protein C and S (PC, PS) and a history of thrombosis. Inhibition of the anticoagulant activity of activated protein C (APC) was observed using plasma from 20/21 patients when phospholipid vesicles were used as the surface for the coagulation reaction. This effect was not affected by the addition of PS. When platelet membranes were employed only 2/21 patients demonstrated inhibition of APC. Under the latter condition, PS functional activity was inhibited in 7/21 patients, six of whom had a past history of thrombosis. Reduced antithrombin III or heparin cofactor II levels were observed in a total of 4/21 patients and may have contributed to the development of thrombosis in three of these patients. Antibodies specifically directed against these proteins were not detected suggesting the possibility of an associated constitutional deficiency. Anticardiolipin antibodies, though elevated in 17/21 patients, did not serve as a useful marker for an increased risk of thrombosis, and the level did not correlate with inhibition of the activity of APC or PS. We conclude that the mechanism of thrombosis in patients with LA is multi-factorial. A subset of patients in whom LA specifically inhibits PS function may represent patients who are at significant risk from thrombosis.

Antibodies↗
PubMed1994

Multicenter evaluation of a kit for activated protein C resistance on various coagulation instruments using plasmas from healthy individuals. The APC Resistance Study Group.

Recently a new hemostatic disorder has been described which appears to be an important risk factor for familial thromboembolism. The disorder is characterized by a poor anticoagulant response to activated Protein C (APC) and has been shown to be due to lack of an APC cofactor activity which is a property of factor V. A kit for determining the response of plasma samples towards addition of APC in an APTT-based assay--COATEST APC Resistance-has been evaluated on 35 coagulation instruments in a multicenter study involving 32 laboratories. A lyophilized normal plasma and identical plasma aliquotes from 20 individuals, one of whom had a borderline resistance to APC, were analysed in each laboratory and the sensitivity of each plasma to APC was determined as the ratio between the clotting times obtained in the presence and absence of APC (APC ratio). The plasma from the individual with a borderline resistance to APC activity was correctly classified as the lowest responder in each laboratory, with an APC ratio in the range 1.6-2.4. In comparison, plasmas from individuals with a pronounced response to APC activity resulted in APC ratios above 3.4 in most cases. Interestingly, although the actual APT time for a plasma from a given individual showed a more than 10s difference due to the type of instrumentation used, the variation in the APC ratio was limited. A similar discrimination was also obtained from evaluation of the actual prolongation of the clotting time in the presence of APC.(ABSTRACT TRUNCATED AT 250 WORDS)

Automation↗
PubMed2005

Identifying novel genetic determinants of hemostatic balance.

Incomplete penetrance and variable expressivity confound the diagnosis and therapy of most inherited thrombotic and hemorrhagic disorders. For many of these diseases, some or most of this variability is determined by genetic modifiers distinct from the primary disease gene itself. Clues toward identifying such modifier genes may come from studying rare Mendelian disorders of hemostasis. Examples include identification of the cause of combined factor V and VIII deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1 and MCFD2. These proteins form a cargo receptor that facilitates the transport of factors V and VIII, and presumably other proteins, from the ER to the Golgi. A similar positional cloning approach identified ADAMTS-13 as the gene responsible for familial TTP. Along with the work of many other groups, these findings identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for hemostasis. Recent advances in mouse genetics also provide powerful tools for the identification of novel genes contributing to hemostatic balance. Genetic studies of inbred mouse lines with unusually high and unusually low plasma VWF levels identified polymorphic variation in the expression of a glycosyltransferase gene, Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans.

ADAM Proteins↗
PubMed1984

[Nutrition--a factor in preventing arteriosclerosis, coronary disease and blood coagulation disorders. II. The effect of nutritional imbalance on atherogenesis and the blood coagulation system].

The presented data show that nourishment balanced with respect to fats, carbohydrates, proteins and also containing the necessary vitamins, mineral, salts and microelements is an effective way of prevention and treatment of atherosclerosis and its complications as well as of restoration and preservation of the function of anticoagulative system when its failure is caused by disbalanced food.

Aging↗
PubMed1996

On the value of menorrhagia as a predictor for coagulation disorders.

The value of menorrhagia as a predictor for mild bleeding disorders has been very little studied and the results are divergent. In the present study on 30 women with objectively verified menorrhagia, we found a significantly increased prevalence of von Willebrand's disease (20%). By keeping a strict sampling and laboratory routine, and by restricting sampling to cycle days 5-7, we also obtained a very low interindividual variation of von Willebrand factor and coagulation factor VIII. We conclude that menorrhagia is a valuable predictor for coagulation and platelet disorders, and that time of sampling is of importance. This should be considered in the investigation of menorrhagia, and can be a guideline in looking for mild bleeding disorders.

Adult↗