Personal practice: An approach to investigation of easy bruising.
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Accidental Falls↗
SEARCH · PubMed Health
Results for “Coagulation Protein Disorders”
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Deficiency of natural anticoagulant proteins C, S, and antithrombin in portal vein thrombosis: a secondary phenomenon?
BACKGROUND: Hereditary deficiencies of natural anticoagulant proteins are implicated in the pathogenesis of portal vein thrombosis (PVT). Secondary deficiencies of these proteins have also been reported in PVT, making interpretation of concentrations difficult. AIMS: To characterise the coagulation profiles in adult patients with PVT and to investigate the possible mechanisms of natural anticoagulant protein deficiency. PATIENTS: Twenty nine adult patients with portal hypertension caused by PVT, and normal biochemical liver function tests. METHODS: Routine coagulation profiles and concentrations of proteins C, S, and antithrombin were measured; where indicated, corresponding concentrations in parents were also measured. Synchronous peripheral and hepatic or splenic vein concentrations were compared in seven patients undergoing interventional procedures, as were peripheral concentrations before and after shunt surgery in three patients. RESULTS: Deficiencies of one or more of the natural anticoagulant proteins occurred in 18 patients (62%), with six patients having combined deficiency of all three proteins. There were strong correlations between prothrombin and partial thromboplastin time ratios and concentrations of natural anticoagulant proteins. Family studies in nine cases of anticoagulant protein deficiency revealed possible hereditary deficiency in only three cases, and significantly lower concentrations of anticoagulant proteins in all PVT cases compared with parents. Levels of anticoagulant proteins tended to be lower in hepatic veins but higher in splenic veins compared with peripheral vein concentrations. Peripheral concentrations decreased after shunt surgery. CONCLUSIONS: Deficiency of natural anticoagulant proteins is common in PVT and is probably a secondary phenomenon in most cases, occurring as part of a global disturbance of coagulation variables. The mechanism for this remains unclear but may result from a combination of reduced hepatic blood flow and portosystemic shunting itself.
Adult↗
[Randomised clinical trial of an intensive intervention into life-styles of patients with hyperfibrinogenaemia in primary prevention of cardiovascular pathology in primary health care].
OBJECTIVES: To study the effect of an intensive programme to modify life-style on levels of plasma fibrinogen in patients without cardiovascular pathology, with high fibrinogen and normal cholesterol levels. To analyse whether the effect on fibrinogen is independent, or otherwise, of the effect on lipids. DESIGN: Randomised clinical trial with a control. SETTING: 11 health districts in L'Hospitalet de Llobregat and Barcelona. PARTICIPANTS: 436 patients will be included, 218 individuals between 35 and 75 years old in each group, and without cardiovascular pathology (ischaemic cardiopathy, cerebral vascular accident or peripheral arteriopathy), with hyperfibrinogenaemia (fibrinogen > 300 mg/dL) and with plasma control < 250 mg/dL. INTERVENTIONS: One group of patients will receive an intensive intervention (in frequency and intensity of counselling and treatment) for life-style changes, i.e. stopping smoking, low-calorie diet in case of overweight or obesity, and physical exercise. The follow-up of the intervention group will be every 2 months. The control group will follow customary treatments. MEASUREMENTS: Levels of plasma fibrinogen. In addition, other relevant events will be recorded over a 2-year monitoring period: modification of risk factors, changes in quality of life, cardiovascular events or death. DISCUSSION: The introduction of an intensive primary prevention intervention (life-style changes) in patients with hyperfibrinogenaemia could be a more effective measure than the habitual intervention for reducing plasma fibrinogen figures. In addition, these measures could be translated into a reduction of cardiovascular risk and an improvement in the patient s quality of life.
Adult↗
[Pancytopenia and acquired factor IX deficiency in patient with Sheehan's syndrome].
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Anti-Inflammatory Agents↗
Does recombinant factor VIIa, apart from overall hemostasis, regulate TAFI dependent fibrinolysis? In vitro analysis using overall hemostasis potential (OHP) assay.
Using the recently developed overall hemostatic potential (OHP) assay, we investigated the effects of different concentrations of recombinant factor VIIa on overall hemostasis and on thrombin activatable fibrinolysis inhibitor (TAFI) dependent fibrinolysis in different factor deficient plasmas. rFVIIa increased OHP in FV, FVIII and FIX deficient plasmas but not up to the levels in normal pooled plasma (NPP). Maximal levels were found at 2.4 microg/mL of rFVIIa, while higher doses did not further increase OHP. In FXII deficient plasma, OHP is higher than in NPP and addition of rVIIa further increased it. Even very high concentrations of rFVIIa (9.6 microg/mL) did not induce a significant increase of OHP in NPP. Higher concentrations of rVIIa down-regulated fibrinolysis in FVIII, FIX and FXI deficient plasmas to values obtained in NPP. Using potato tuber carboxy-peptidase inhibitor (PTCI), a specific inhibitor of TAFI, it was found that TAFI's influence on fibrinolysis down-regulation in FVIII and FIX deficient plasmas increased after addition of higher concentrations of rFVIIa. From this in vitro study it seems that rFVIIa in a concentration of 2.4 microg/mL improves overall hemostasis in FV, FVIII and FIX deficient plasmas. rFVIIa, even at very high (supra-therapeutic) concentrations, does not induce hypercoagulability either in NPP or in deficient plasmas. Higher concentrations of rVIIa induce, at least partly, TAFI dependent down-regulation of fibrinolysis in FVIII and FIX deficient plasmas. These results, together with some previous ex vivo studies, point to OHP assay as a possible diagnostic tool for evaluating the hemostatic effects of rFVIIa.
Blood Coagulation Tests↗
Decreased coagulability has no clinically relevant effect on atherogenesis: observations in individuals with a hereditary bleeding tendency.
BACKGROUND: Hemostasis affects ischemic cardiovascular disease through its role in formation of occluding arterial thrombi. Several studies suggest that hemostasis also might play a role in atherogenesis. We investigated whether individuals with an inherited bleeding tendency are protected against development of atherosclerosis. METHODS AND RESULTS: A total of 76 individuals with an inherited bleeding tendency (hemophilia and von Willebrand disease) and 142 healthy controls were included in the present study. Early atherosclerotic vessel-wall changes were quantified by measurement of intima-media thickness in the carotid and femoral arteries by B-mode ultrasonography. To validate intima-media thickness measurements, measurements also were performed in 77 individuals with clinically proven atherosclerosis and in 34 healthy, age-matched controls. A large difference in intima-media thickness was found between individuals with proven atherosclerosis and healthy controls, in particular for the femoral artery (difference for carotid artery, 0.16 mm; femoral artery, 0.53 mm). Comparison between patients with a bleeding tendency and healthy controls showed only minimally reduced intima-media in femoral artery in individuals with a bleeding tendency (adjusted difference, -0.078 mm; 95% CI, -0.17 to 0.018 mm). Subgroup analysis revealed that in subjects with moderate to severe hemophilia, vessel walls were thinnest (adjusted difference, -0.10 mm; 95% CI, -0.27 to 0.061 mm). CONCLUSIONS: Hypocoagulability caused by hemophilia or von Willebrand disease has at most a limited effect on atherogenesis.
Adult↗
Studies of the human factor VIII/von Willebrand factor protein. III. Qualitative defects in von Willebrand's disease.
The Factor VIII/von Willebrand factor protein was characterized in two unrelated patients with von Willebrand's disease in whom procoagulant and Factor VIII/von Willebrand factor antigen levels were normal. In both patients evidence of an abnormal protein was observed on crossed antigen-antibody electrophoresis. In one patient the Factor VIII/von Willebrand factor protein eluted from Sepharose 4B in a position and distribution identical to normal with normal levels of procoagulant activity and antigen. However, the partially purified Factor VIII/von Willebrand factor protein had markedly reduced von Willebrand factor activity in a ristocetin assay. In the second patient the peak of Factor VIII/von Willebrand factor protein, antigen, and procoagulant activity eluted from a Sepharose 4B column with an estimated molecular weight of approximately half that of normal. This protein had no von Willebrand factor activity. In both patients the reduced Factor VIII/von Willebrand factor protein subunit was indistinguishable from normal on polyacrylamide gel electrophoresis. These studies indicate that in some patients with von Willebrand's disease there is a qualitative defect of the Factor VII/von Willebrand factor protein; the total amount of protein, antigen, and procoagulant activity are normal while the von Willebrand factor activity is deficient.
Antibodies↗
Activated partial thromboplastin time as a screening test of minor or moderate coagulation factor deficiencies for canine plasma: sensitivity of different commercial reagents.
To determine the sensitivity for detection of coagulation factor deficiencies by commercial reagents for canine plasma, 5 commercial activated partial thromboplastin time (APTT) reagents with different types of contact activator and phospholipid of various origin were examined. Thirty canine plasma samples with minor or moderate deficiencies of coagualition factors that influence the APTT were examined. Significant differences were found for the sensitivity of various reagents, but no correlation was found with the type of contact activator. Following the test instructions provided by the manufacturers, the number of APTT results that were prolonged beyond the reference range varied between 20 and 30 (sensitivity = 0.67-1.00); the number of corresponding results using a standardized test protocol varied between 19 and 28 (sensitivity: 0.63-0.93). The most sensitive reagent contained kaolin as a contact activator and a human placental thromboplastin. The results of this study indicate that the APTT test optimized for human plasma is also a sensitive screening test of the intrinsic system of canine plasma, provided that a suitable reagent is used.
Animals↗
Tissue distribution of fetal liver cells following in utero transplantation in mice.
Transplantation of hepatic stem cells in utero has been advanced as a potential clinical approach to a variety of diseases, including deficiencies of coagulation factors. Although syngeneic transplantation has met with some success, consideration needs to be given to the potential for transplanted cells to colonize nontarget tissues. Liver cells were harvested from Rosa26 embyros at embryonic age 12.5 days postconception (pc) and transplanted into the peritoneal cavity of syngeneic recipients in utero. Tissues were harvested from tissue recipients at various time points ranging from 1 to 328 days pc, and tissues were stained for beta-galactosidase to identify the existence of cells derived from Rosa26 donors. Beta-galactosidase-positive cells were found in the lung, liver, and brain as early as 20 days pc and through 328 days pc. Positive cells in these tissues existed as islands of cells that were morphologically similar to hepatocytes. In the spleen, individual beta-galactosidase-positive cells of both leukocytic and erythrocytic lineages were present, and suggest that hematopoietic cells were transferred to recipients along with hepatocytes. The lack of an inflammatory response to the beta-galactosidase-positive cells suggests that the donor cells were immunologically tolerated. In summary, the possibility that cells administered in utero may inadvertently colonize nontarget tissues suggests that clinical application of this method will need to be approached with diligence.
Animals↗
Predicting abnormal coagulation in ischemic stroke: reducing delay in rt-PA use.
Normal prothrombin time (PT) and partial thromboplastin time (PTT) are recommended for administration of recombinant tissue-plasminogen activator (rt-PA) in stroke, but waiting for results can delay use. We examined the charts of 365 stroke patients to assess predetermined risk factors associated with elevated PT/PTT. Elevated PT/PTT can be predicted in patients taking warfarin or heparin/heparinoid or on hemodialysis, according to emergency department triage, with 100% sensitivity and 94.7% specificity. These results could be applied to rt-PA candidates and reduce potential delays.
Adult↗
Molecular diagnostics in China.
Molecular diagnostics is changing the face of clinical laboratories and laboratory medicine. The case of China is no exception. In the present paper, a brief description on this promising discipline is given first, followed by an overview of the development of molecular diagnostics in China. Work done in the author's own laboratory is introduced in the third part and a short discussion on the challenges ahead is provided last.
Adrenoleukodystrophy↗
Analysis of blood clotting factor activities in canine Legg-Calvé-Perthes' disease.
Legg-Calve-Perthes' (LCP) disease is a noninflammatory aseptic necrosis of the femoral head and neck in small-breed dogs. The etiology of the disease is not known, but ischemia resulting from vascular compression or occlusion has been proposed. A latent ischemic phase during development of the femoral epiphysis seems to be responsible for the onset of the typical clinical features of LCP disease. Ischemia might result from insufficient oxygen supply either caused by a reduced number of afferent arterial vessels or an occlusion of the efferent venous vessels by thrombosis. In humans, LCP disease has been linked to hypercoagulability and hypofibrinolysis caused by deficiencies of protein C, protein S, or resistance to activated protein C. To determine whether canine LCP disease is caused by similar deficiencies, we determined protein C, protein S, activated protein C, factor II, factor V, factor VIII:C, and AT III activities in plasma samples of 18 dogs with clinically and histopathologically verified LCP disease. All dogs had normal plasma activities of these factors, indicating that in these dogs LCP disease was not caused by deficiencies of the analyzed blood clotting factors.
Animals↗
Gene targeting in hemostasis. tissue factor pathway inhibitor.
Tissue Factor Pathway Inhibitor (TFPI) is a serine protease inhibitor of the Factor VIIa/Tissue Factor (FVIIa/TF)-initiated clotting cascade. Mice expressing a mutant form of TFPI, in which its Kunitz-1 domain has been deleted (TFPIKu1delta/delta), die prematurely in embryogenesis between E9.5dpc and birth. These results provide a rationale for the absence of TFPI-deficient patients. This early mortality can be ameliorated by an accompanying heterozygous or homozygous deficiency in FVII. Thus, diminishment of FVII activity precludes the requirement for TFPI-mediated inhibition of the FVIIa/TF pathway during embryogenesis.
Animals↗
Treatment of deep vein thrombosis using temporary vena caval filters after allogeneic bone marrow transplantation.
Bone marrow transplant (BMT) recipients have risk factors for deep vein thrombosis (DVT) including venous stasis caused by immobilization in the sterile unit, vessel wall damage caused by preparative regimen or indwelling catheters, and hypercoagulability caused by decreased natural anticoagulants. We successfully treated a patient who developed massive DVT in the superior vena cava after BMT with anticoagulation and the use of temporary vena caval filters. Considering the delayed complications, permanent filter is not appropriate for BMT recipients, because the risk factors for DVT associated with BMT are transient. We considered that temporary vena caval filter is a safe and useful device to prevent pulmonary embolism after DVT in BMT recipients.
Anticoagulants↗
Abnormalities in thrombin-antithrombin pathway in AL amyloidosis.
Various pathogenic factors have been proposed to explain the abnormal hemostasis observed in AL amyloidosis. Since imbalance between clotting factors and inhibitors could play a pathogenic role in both hemorrhagic and thrombotic manifestations, we investigated the thrombin-antithrombin pathway in 35 patients with AL amyloidosis. Ten patients suffered from bleeding while 3 patients experienced deep venous thrombosis. Thrombin time was prolonged in 29 subjects, the mean values of antithrombin III activity (ATIII Act) were significantly lower than those of antithrombin III antigen (ATIII Ag) with loss of relationship between these two different techniques of ATIII detection, normally observed in healthy controls. In 19 patients increased levels of thrombin-antithrombin (TAT) complexes were present. Crossed immunoelectrophoresis of ATIII, performed in presence of heparin, evidenced ATIII forms with reduced binding capacity to heparin and TAT complexes of various electrophoretic mobilities. In conclusion, the impairment of the thrombin-antithrombin pathway, in association with the low ATIII biological activity, might play a pathogenic role in the hypercoagulable state reported in AL amyloidosis, despite the higher frequency of bleeding manifestations.
Adult↗
Clinical and laboratory management of the prothrombin G20210A mutation.
OBJECTIVE: To make recommendations regarding the appropriate evaluation for the prothrombin G20210A mutation, as reflected by published evidence and the consensus opinion of recognized experts in the field. DAT SOURCES: Review of the medical literature, primarily since 1996. DATA EXTRACTION AND SYNTHESIS: After an initial assessment of the literature, key points defining the condition, and review of the clinical study design, a draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference on Diagnostic Issues in Thrombophilia before the meeting. Each of the key points and associated recommendations were then presented for discussion at the conference. Recommendations were accepted if a consensus of 70% of experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS: Consensus was reached on several recommendations concerning the criteria for testing for the prothrombin G20210A mutation and for the method of testing. First, a major point of consensus was that the prothrombin G20210A mutation is a significant risk factor for venous thromboembolism (VTE) and that testing should be considered in the initial evaluation of suspected inherited thrombophilia. Second, although several analytic methods are commonly used for genetic testing for the prothrombin mutation, all are generally robust and reliable. The recommendations for testing for the prothrombin mutation parallel those for the factor V Leiden mutation and include patients with a history of recurrent VTE, a first episode of VTE before the age of 50 years, a history of an unprovoked VTE at any age, thromboses in unusual anatomic sites, or an affected first-degree relative with VTE. A history of VTE related to pregnancy or estrogen use and unexplained pregnancy loss during the second or third trimesters were also considered to be indications for testing. Other scenarios remain controversial or not recommended, including general population screening.
Adult↗
Elevated hemostatic factor levels as potential risk factors for thrombosis.
OBJECTIVES: To review the state of the art relating to elevated hemostatic factor levels as a potential risk factor for thrombosis, as reflected by the medical literature and the consensus opinion of recognized experts in the field, and to make recommendations for the use of specific measurements of hemostatic factor levels in the assessment of thrombotic risk in individual patients. DATA SOURCES: Review of the medical literature, primarily from the last 10 years. DATA EXTRACTION AND SYNTHESIS: After an initial assessment of the literature, key points were identified. Experts were assigned to do an in-depth review of the literature and to prepare a summary of their findings and recommendations. A draft manuscript was prepared and circulated to every participant in the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia prior to the conference. Each of the key points and associated recommendations was then presented for discussion at the conference. Recommendations were accepted if a consensus of the 27 experts attending the conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS: Consensus was reached on 8 recommendations concerning the use of hemostatic factor levels in the assessment of thrombotic risk in individual patients. Detailed discussion of the rationale for each of these recommendations is presented in the article. This is an evolving area of research. While routine use of factor level measurements is not recommended, improvements in assay methodology and further clinical studies may change these recommendations in the future.
Blood Coagulation Tests↗
Pulmonary embolus after vena cava filter placement.
This report characterizes risk factors in patients who suffer pulmonary embolus (PE) after insertion of vena caval filter (VCF) and formulates an organized diagnostic and therapeutic plan of management. Three hundred eighteen patients were included in a review of patients undergoing insertion of VCF from 1989 to 1995. Ten patients (six men and four women, ages 25-72 years) from this group (3.1%) experienced PE after VCF insertion. Risk factors for deep venous thrombosis were documented in these ten patients. Venacavography was performed after diagnosis of PE. Thrombus length measured from the apex of the filter was used to determine further therapy. Thrombus 5 cm or greater in length was treated with a second VCF (VCF-2). Smaller clots were treated with anticoagulation (AC). All patients treated with AC underwent repeat vena caval study (CT scan or venacavagram) 10 days to 18 months after treatment. PE occurred from 8 days to 5.5 years after original VCF insertion. Five patients suffered PE longer than 6 months (range, 21-66 months; mean, 39 months) after VCF insertion. Venacavagrams demonstrated thrombus in all ten patients with PE. Six patients were treated with VCF-2 and four patients with AC. Dissolution of thrombus was seen on follow-up in all patients given AC. All 10 patients harbored at least two risk factors for deep venous thrombosis. Malignancy was found in only two patients. Five patients were found to have procoagulant states characterized by decreased levels of anti-thrombin III or protein C or S. No postoperative deaths or early recurrent PE occurred. One patient experienced another PE 5 years after treatment with AC when she discontinued warfarin. Contraindications to AC appeared to be self-limited, and all patients were discharged on warfarin. No significant bleeding occurred during early follow-up. Our findings confirm the reliability and low complication rate for VCF. Patients experiencing PE after insertion of VCF mandate an aggressive diagnostic approach that should include venacavography and a search for identifiable risk factors including procoagulant state. Treatment with AC and insertion of a second VCF both give favorable results. All patients appear to benefit from short- or long-term warfarin therapy, and contraindications to AC frequently are self-limited. Therapy based on clot size warrants further study.
Adult↗