Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 73-year-old woman with metastatic transitional cell carcinoma of the bladder developed vaginal bleeding a few days after undergoing radical cystectomy. She had no other signs of mucocutaneous bleeding. Coagulation studies revealed a markedly prolonged thrombin time (greater than 600 seconds), a slightly prolonged reptilase time (20 seconds), and mildly elevated fibrinogen (4.39 g/L), and fibrin D-dimer (200 to 500 ng/mL) levels. Treatment of the patient's plasma in vitro with protamine or barium sulfate normalized the thrombin time. The anticoagulant activity corresponded to 0.15 heparin U/mL when measured by a thrombin time assay using normal plasma as substrate and standardized with porcine heparin. The anticoagulant was quantitatively bound to and subsequently eluted with 1 mol/L NaCl from quaternary aminoethyl (QAE) Sephadex, and then isolated by affinity chromatography on immobilized antithrombin III. The isolated anticoagulant was shown to be sensitive to heparinase digestion. Therefore, the inhibitor has functional and chemical properties similar to those of high-affinity heparin. Thus far, this is the only anticoagulant of this type isolated from the plasma of a patient bearing a tumor other than plasma cell myeloma.
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PMID:Isolation of a heparin-like anticoagulant from the plasma of a patient with metastatic bladder carcinoma. 275 13

We have identified a circulating, heparin-like anticoagulant in a patient with multiple myeloma (IgG4 lambda) who had serious clinically evident bleeding that contributed to his death. Purification of the patient's circulating coagulation inhibitor was accomplished by ammonium sulfate concentration, anion exchange chromatography, and affinity chromatography on protamine sulfate. Analysis of the purified inhibitor showed that it was a proteoglycan that comigrated with heparan sulfate on lithium acetate-agarose-gel electrophoresis and that it contained 39 per cent L-iduronic acid. Control samples of heparan sulfate and heparin contained 29 and 68 per cent L-iduronic acid, respectively. Functional coagulation studies revealed that the purified inhibitor had cofactor activity with antithrombin III that could be abolished by prior incubation with protamine sulfate or platelet factor 4. Recognition of the existence of this or of other similar inhibitors in bleeding patients is important because of the potential for treatment with agents such as protamine sulfate and platelet factor 4, which neutralize the anticoagulant effects of proteoglycans.
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PMID:Circulating heparan sulfate anticoagulant in a patient with a fatal bleeding disorder. 623 89

There is evidence that polymorphonuclear granulocytes release neutral proteinases such as elastase (E) and cathepsin G in the course of acute leukemia. These proteinases may inactivate clotting factors by unspecific degradation before they are eliminated via complex formation with endogenous inhibitors, e.g. the alpha 1-proteinase inhibitor (alpha 1-PI). In this study it was attempted to correlate plasma levels of the E-alpha 1-PI complex with factor XIII and antithrombin III in acute leukemia. Using a newly developed, sensitive enzyme-linked immunoassay the concentration of E-alpha 1-PI in patients with various types of leukemia, malignant lymphoma or multiple myeloma was determined. Only patients with acute myelocytic or promyelocytic leukemia (AML, APL) and chronic myelocytic leukemia with and without blastic transformation (CML) showed moderate to high levels of E-alpha 1-PI (2- to 20-fold of normal). However, coagulation factor concentration observed in the different types of leukemia seemed to be independent of elastase liberation. Most of the AML-patients with elevated E-alpha 1-PI levels showed peroxidase positive blood cell smears.
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PMID:Plasma levels of human granulocytic elastase alpha 1-proteinase inhibitor complex (E-alpha 1-PI) in leukemia. 637 1

A woman, aged 68, with multiple myeloma (immunoglobulin[Ig]A kappa type) developed an anticoagulant with properties suggestive of heparin. The anticoagulant prolonged the thrombin time but not the reptilase time and was resistant to boiling, proteolytic enzyme digestion, and trichloracetic acid precipitation. The thrombin time was corrected by the addition (in vitro) of protamine sulfate or the addition of purified platelet Factor 4 (PF4) to the plasma. The anticoagulant was isolated by PF4-Sepharose affinity chromatography and analyzed in terms of its molecular weight, uronic acid, and amino acid composition. The proteoglycan isolated had a mol wt of 116,000 and appears to consist of two 38,000 dalton polysaccharide units interconnected by peptide material totaling 39,000 daltons. Electrophoretic analysis of the pronase digested peptidoglycan using the lithium acetate-agarose technique suggested the material was of the heparan sulfate type. The peptidoglycan had about one-tenth the specific activity of commercially available heparin on a weight basis. The isolated proteoglycan was indistinguishable from commercial heparin when analyzed in terms of its ability to act as a cofactor in the antithrombin III inhibition of thrombin.
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PMID:Circulating heparan sulfate proteoglycan anticoagulant from a patient with a plasma cell disorder. 644 19

Hemostasis was studied in 55 patients with myeloma, grouped in three groups according to the clinical stage of the disease. Thrombocytic adhesion, aggregation, activity of TF3 and TF4, of antithrombin III, FMDC level, FDP titre and fibrinolysis test were determined on the background of the screening coagulation tests. The studies were carried out before the treatment and were followed up after the therapeutic response or in the absence of improvement. Thirty per cent of the patients had manifestations of hemorrhagic diathesis, and 5 per cent - thromboembolism. Essential hemostatic deviations were found: progressive thrombocytopenia and thrombopathia and DIC syndrome that correlate with the stage of the disease, being most severe among the stage III patients. The patients that responded to the treatment had a great part of the hemostatic disorders corrected, and in case of no effect from the treatment - the deviations persisted, intensified and in 5 of the patients were responsible for the fatal end. The pathogenesis of the hemostatic deviations is complex and is associated with the characteristics of the basic disease and the concomitant complications.
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PMID:[Proceedings of the 7th Congress of Internal Medicine]. 665 83

A 66-old-male admitted to our hospital was diagnosed multiple myeloma (IgA kappa type, Durie & Salmon stage IIIA) and squamous cell lung cancer (c-T2N0M0 stage I). The function of platelets was within a normal range (11.7 x 10(4)/mm3 and the bleeding time of two minutes), but the function of coagulation was reduced (prothrombin time, 13.1 seconds; activating prothrombin time, 45.1 seconds; and antithrombin III, 65%). The hyperviscosity syndrome was anticipated because of high IgA M protein (6,551 mg/dl). Plasmapheresis with 800 ml of fresh frozen plasma was performed before the left lower pulmonary lobectomy and R1 lymph node dissection. Then the function of coagulation was improved (prothrombin time, 12.6 seconds; activating prothrombin time, 31.3 seconds; and antithrombin III, 75%). IgA M protein was also decreased to 4,696 mg/dl. Postoperative bleeding necessitated a second thoracotomy. The cause of postoperative bleeding was the ablasion of the pleural adhesion due to tuberculous pleuritis as well as bleeding tendency of multiple myeloma. The plasmapheresis performed in this case did not fully improve the bleeding tendency. Cases of cancer complicated with multiple myeloma have been increasing and if an operation is needed, plasmapheresis should be considered. The indication and the extent of hematologic restoration to be achieved should be further investigated.
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PMID:[Preoperative plasmapheresis for lung cancer with multiple myeloma]. 855 Oct 81

Investigation of recurrent venous thromboembolic events in a 46-year-old man with progressive IgG kappa (total serum IgG, 74.3 mg/ml) multiple myeloma revealed profound reductions in free protein S (PS) antigen (<0.l U/ml) and PS activity (0.33 U/ml). Total PS antigen, protein C, antithrombin III, and C4b-binding protein levels were within normal limits. The patient had no family history suggestive of a congenital PS deficiency and no history of thrombosis predating the diagnosis of his plasma cell dyscrasia. Patient IgG was isolated from serum using a protein A-sepharose affinity column and characterized. PS-dependent clotting assays (Staclot Protein S, Diagnostica Stago, Asnieres sur-Seine, France) performed on normal pooled plasma mixed with dilutions of patient IgG (0.0-33.0 mg/ml) revealed a dose-dependent neutralization of PS activity by 43%. Total and free PS antigen levels were measured using Laurell rocket electroimmunodiffusion (Assera-Plate Protein S, Diagnostica Stago), which revealed a similar dose-dependent reduction in free PS antigen but preserved normal total PS antigen. Free PS antigen was reduced by 77% to 0.23 U/ml using an IgG concentration (16.5 mg/ml) less than one-fourth of that of the patient at time of serum collection. Specific binding of the patient IgG to commercially available purified human PS was demonstrated by Western immunoblot analysis. Whereas acquired free PS deficiency has been previously reported in association with nephrotic syndrome, inflammatory bowel disease, HIV infection, and varicella infection, this is the first reported case of a hypercoagulable syndrome associated with acquired free PS deficiency and multiple myeloma.
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PMID:Acquired free protein S deficiency associated with multiple myeloma: a case report. 860 34

During recent years, there has been substantial advance in our knowledge of the etiology, pathogenesis, laboratory diagnosis, and management of hematologic disorders. In this symposium, the discussion includes the following six topics: (1) some problems of automatic blood cell analyzer and flow cytometer for the diagnostic use of hematologic disorders, (2) usefulness of fluorescence in situ hybridization techniques for the diagnosis of leukemias, (3) recent advance in pathogenesis and management of multiple myeloma, (4) usefulness of the thrombin-antithrombin III complex, plasmin-antiplasmin complex, and tissue factor activity for the diagnosis of disseminated intravascular coagulation syndrome, (5) detection of activated platelets, and (6) molecular diagnosis of hereditary coagulation disorders.
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PMID:[Recent advances in laboratory approaches to hematologic disorders]. 881 57

We have investigated the possible interaction of paraprotein (pp) with anticoagulation mechanisms and fibrinolysis. Eighty four patients with monoclonal gammapathy (MG) were included to the study, 59 of them with multiple myeloma (MM). In 48.8% cases some defect was found. Decreased levels of antithrombin III (AT III) was observed in 13.3%, protein C (PC) in 18.3% and protein S (PS) in 13.5% of patients. Distribution between the free and the bound PS fraction remained normal. The most frequent abnormality found was the reduction of plasminogen (PLG) activity, which was observed in 35.1% and elevated levels of plasminogen activator inhibitor, detected in 42.3% of cases, respectively. Decreased plasminogen activator activity was observed in only one patient. The relationship between isotype and concentration of paraprotein and frequency of factor levels abnormalities was not found. The incidence of arterial and/or venous thrombosis was higher in patients with laboratory defect in comparison with the unaffected, however, the difference was not statistically significant. In contrast, the incidence of hemorrhagic complications was significantly lower in these patients (p < 0.01), although in most of them simultaneous defect of plasmatic coagulation and/or platelet functions was detected. We suggest, the interaction with both hemostatic and anticoagulation systems could result to "elimination" of inauspicious effect of pp on hemostasis. The impairment of anticoagulation systems and fibrinolysis is another type of paraprotein interference with hemostasis. It is also considered to be another pathogenetic mechanism of secondary deficiency of AT III, PC, PS and PLG.
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PMID:[Disorders of anticoagulation and fibrinolysis in monoclonal gammopathies--another mechanism of paraprotein interference with hemostasis]. 923 17

Monoclonal gammopathies (MG) may be associated with unique monoclonal immunoglobulin (MIg)-induced disturbances of either primary hemostasis or plasma coagulation. We have investigated the possible interference of MIg with antithrombotic systems in 49 patients with MG. Although an increase of tissue-type plasminogen activator (t-PA) activity was the most frequent abnormality in our group, defect of anticoagulation factors was found in 26.5% of patients. The relationship between MIg type and concentration and frequency of antithrombotic factor abnormalities was not found. The risk of venous thrombosis was higher in patients with the defect in comparison with the unaffected group (46% vs. 22%), but the difference was not statistically significant. Bleeding complications were markedly less frequent in the group of patients with defect of anticoagulation mechanisms (0% vs. 17%). In conclusion, we have found abnormalities in anticoagulation and/or fibrinolytic system, analogous to well-known disturbances of hemostatic mechanisms, in more than a quarter of patients with MG. The interference of M-protein with antithrombotic pathways is supposed to be another mechanism of secondary deficiencies of antithrombin III (AT III), protein C (PC), protein S (PS), plasminogen and APC resistance. Together with other factors, it could contribute to higher risk of thromboembolism in myeloma patients.
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PMID:Disturbances of anticoagulation and fibrinolytic systems in monoclonal gammopathies-another mechanism of M-protein interference with hemostasis. 1504 Dec 73


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