Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The records of all patients to whom heparin was dispensed by the pharmacy of the University of California Medical Center, San Diego, during the year 1979 were reviewed. A total of 131 patients above age 15 met the inclusion criteria-they had received more than 10,000 units of heparin per 24 hours for at least 24 hours. All 131 patients were administered heparin by continuous intravenous infusion by peristaltic pump. All heparin was porcine heparin from a single commercial source. The daily mean minimum dose averaged 19,700 units, the maximum, 25,600 units. The activated partial thromboplastin time, usually measured once a day, was the only test used to monitor the dose. Major complicating events occurred in 13 patients (10 percent), and minor complicating events occurred in 10 patients (7.6 percent). All major complicating events occurred in patients with serious concurrent diseases. In subpopulations of 58 patients without concurrent disease, and of 24 in whom heparin was initiated for suspicion of thromboembolism that was not confirmed, no major complicating events occurred. These data indicate that continuous, intravenous administration of heparin is associated with minimal risk, and that risk is concentrated among older patients with serious concurrent disease.
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PMID:Risk of complications during intravenous heparin therapy. 709 Mar 67

Three members of a San Antonio, Texas, family were identified with prothrombin activity levels half the normal level but to have normal levels of antigen. All exons of the prothrombin gene from the proband were sequenced. A G-to-A mutation at nucleotide 7543 was found that resulted in the substitution of His for Arg at residue 320. The Arg320-Ile321 bond is 1 of 2 sites in prothrombin cleaved by Factor Xa in the prothrombinase complex to form thrombin. Substitution of His for Arg at this site resulted in the blockage of Factor Xa cleavage, forming a dysfunctional molecule. The proband, her mother, and her maternal aunt were found to be heterozygous for this mutation. This is the first known observation of an amino acid substitution at this site that resulted in dysprothrombinemia. (Blood. 2000;95:711-714)
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PMID:Prothrombin San Antonio: a single amino acid substitution at a factor Xa activation site (Arg320 to His) results in dysprothrombinemia. 1062 84

A synthetic selective inhibitor of factor Xa, the pentasaccharide SR90107A/Org31540 is in clinical development for the prophylaxis of postsurgical deep vein thrombosis. Another synthetic pentasaccharide with even more sustained inhibition of factor Xa, SanOrg34006, has also been developed. Both of these agents were tested in comparison to unfractionated heparin and a low molecular weight heparin (enoxaparin) for their relative platelet activation potential in heparin-induced thrombocytopenia assays. Sera from patients (n = 30) with heparin-induced thrombocytopenia were pooled and validated for heparin-dependent aggregation responses. Using heparin-platelet factor 4 Sepharose columns, antibodies to heparin-platelet factor 4 were purified from the same pool. The effects of heparin, enoxaparin, SR90107A/Org31540, and San-Org34006 were evaluated in a platelet aggregation assay using platelet donors (n = 10). At comparable concentrations, heparin and enoxaparin consistently produced platelet activation, whereas both pentasaccharides failed to produce a response at a concentration up to 100 micrograms/mL (approximately 50 microM). Similarly, in the 14C-serotonin release and flow cytometric assays, heparin and enoxaparin produced positive responses (n = 30), whereas the two pentasaccharides consistently failed to produce any effect. These observations suggest that the two pentasaccharides with highly selective anti-Xa activity are devoid of generating antiheparin-platelet factor 4 antibody, do not produce heparin-induced thrombocytopenic responses and may inhibit active heparin-induced thrombocytopenia antibody platelet activation.
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PMID:Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies. 1072 24

New treatments in hematological malignancies were a focal point of sessions and presentations at the 42nd Annual Meeting of the American Society of Hematology, held December 15, 2000, in San Francisco, California, U.S.A. The meeting also provided discussion on pathogen inactivation in blood banking, stem cell transplantation in leukemia as well as nonmalignant diseases, the reparative potential of stem cells, a new oral antithrombotic therapy and a new class of highly selective factor Xa inhibitors.
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PMID:Latest advances from basic and clinical research in hematology. 1281 8

Hypercoagulation often occurs in type 2 diabetes, suggesting pleiotropy of the genes that influence disease liability and hemostasis-related phenotypes. To better understand the relationship between hemostasis and diabetes, we first used maximum-likelihood methods to estimate the relative contribution of additive genetic, measured environmental, and shared household effects to the normal variance of 16 hemostasis-related traits in 813 individuals participating in the San Antonio Family Heart Study. We estimated moderate to high heritabilities (0.20-0.60) for each phenotype. Von Willebrand factor (VWF), thrombin activatable fibrinolysis inhibitor, activated protein C (APC) ratio, factor V, and prothrombin time had heritabilities greater than 0.50. The correlation between type 2 diabetes status and the hemostasis-related traits was then partitioned into genetic and environmental components using bivariate variance-components methods. Significant (p < or = 0.05) positive genetic correlations (0.37-0.51) occurred with factors II and VIII, VWF, total protein S (tPS), and tissue factor pathway inhibitor. Significant negative genetic correlations were estimated for activated partial thromboplastin time (-0.49) and APC ratio (-0.38). By contrast, significant environmental correlations occurred only with factor II (-0.40) and tPS (-0.31). Our results suggest that genes are important contributors to the normal variation in hemostasis-related traits and that genes influencing hemostasis-related traits pleiotropically influence diabetes risk.
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PMID:Heritability of hemostasis phenotypes and their correlation with type 2 diabetes status in Mexican Americans. 1611 12

Necrotizing soft tissue infections are potentially fatal infections that often involve extremities. Studies of mixed anatomic sites suggest several factors increase mortality (eg, age, medical comorbidities, laboratory values, treatment timing). We hypothesized that patients with necrotizing soft tissue infections of the extremities would have similar factors associated with mortality. We retrospectively reviewed 150 patients with necrotizing soft tissue infections of the extremities treated at San Francisco General Hospital from 1993-1997. We recorded cofactors, treatment, physical findings, radio- graphs, and laboratory findings at presentation. No cofactor or examination finding was associated with increased mortality. Compared with survivors, nonsurvivors had a higher leukocyte count, blood urea nitrogen, creatinine, potassium, partial thromboplastin time, and aspartate aminotransferase, but had lower pH and bicarbonate. Nonsurvivors did not have delays in treatment relative to survivors. Univariate analysis showed an increased risk of mortality in patients with hypotension, hypothermia, Clostridium species in the wound culture, low leukocyte count and bicarbonate levels, and elevated blood urea nitrogen, aspartate aminotransferase, creatinine, and potassium levels. Several signs of shock and organ dysfunction were associated with mortality in patients with necrotizing soft tissue infections of the extremities. The overall mortality rate (9.3%) was lower than in some other reports.
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PMID:Necrotizing soft tissue infections of the extremities and back. 1667 2

The direct oral anticoagulants (DOACs) have gained popularity recently among both patients and providers for their comparable or better efficacy and safety profiles compared with warfarin and the lack of need for routine monitoring of anticoagulant effect. One obstacle for the more widespread use of the DOACs in clinical practice has been the lack of a reversal agent. Most DOACs act by directly binding to and inhibiting the effects of factor Xa. Andexanet alfa (Andexxa, Portola Pharmaceuticals, San Francisco, CA) is a modified form of factor Xa that acts as a decoy binding entity for DOACs, thereby allowing endogenous factor Xa to perform its normal clotting functions. Andexanet has proven efficacious in clinical trials for reversing the anticoagulant effects of apixaban, edoxaban, and rivaroxaban, although its impact on clinical outcomes has not been adequately studied. Andexanet has a boxed warning for thromboembolic risks, ischemic risks, cardiac arrest, and sudden death, with these adverse events occurring in up to 18% of patients in clinical trials. However, the occurrence of these adverse events needs to be considered in relation to the fragile nature of patients who receive this agent. Because the duration of the DOACs is much less than that of warfarin, it is unclear how many patients would actually need andexanet in clinical practice, because cessation of the DOAC may be all that is needed to effectively manage bleeding. Nonetheless, having andexanet available in cases of DOAC-associated severe or life-threatening bleeding represents a therapeutic advance and should provide an added level of comfort with the clinical use of DOACs.
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PMID:Andexanet Alfa for Reversing Factor Xa Inhibition. 3036 66

Heparin resistance is an uncommon phenomenon defined as the need for high-dose unfractionated heparin (UFH) of more than 35,000 IU/day to achieve the target activated partial-thromboplastin time ratio or the failure to achieve the desired activated clotting time after a full UFH dose. This rare phenomenon is being more commonly observed in Covid-19 patients in a hypercoagulable state. We describe a Covid-19 patient confirmed by reverse-transcriptase polymerase chain reaction assay, with acute limb ischemia, who developed heparin resistance. The patient was managed by the departments of vascular surgery, anesthesia and intensive care, and the Coagulation Service and Thrombosis Research from San Raffaele Scientific Institute, Milan, Italy.
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PMID:A Case of Covid-19 Patient with Acute Limb Ischemia and Heparin Resistance. 3258 31