Up-date on solitary plasmacytoma and its main differences with multiple myeloma.

Solitary plasmacytoma is plasma cell neoplasm. It is a localized bone disease and for this reason it is different from multiple myeloma (systemic plasma cell neoplasm). Sometimes, solitary plasmacytoma precedes a following multiple myeloma. Clinical findings of solitary plasmacytoma are related to the univocal localization on damaged bone, while laboratory findings could be similar to multiple myeloma (i.e. M component, kidney dysfunction, blood calcium alterations, increased beta-2-microglobulin). However, during a solitary plasmacytoma, laboratory findings could not be present contemporaneously such clinical complications (i.e. kidney failure, immunological disorders with a trend toward infectious disease and/or autoimmunity, neurological disorders, haematological disorders, amyloidosis, POEMS syndrome). These raise the reason because solitary plasmacytoma has better prognosis compared to multiple myeloma.

Porins from Salmonella typhimurium accelerate human blood coagulation in vitro by selective stimulation of thrombin activity: implications in septic shock DIC pathogenesis.

The effect of porins, major hydrophobic outer membrane proteins purified from Salmonella typhimurium, on human blood coagulation was investigated. It was found that micromolar concentrations of porins accelerated markedly human blood coagulation in vitro. Using appropriate experiments, data were obtained showing that the main target of the porin-induced procoagulant effect was thrombin. A possible binding of porins with thrombin has been suggested to be the basis of this effect. The implications of this finding in the pathogenesis of the disseminated intravascular coagulation syndrome (DIC) occurring during the Gram-negative septic shock is discussed.

Synthesis of novel anti-inflammatory peptides derived from the amino-acid sequence of the bioactive protein SV-IV.

SV-IV is a basic, thermostable, secretory protein of low Mr (9758) that is synthesized by rat seminal vesicle (SV) epithelium under strict androgen transcriptional control. This protein is of obvious pharmacological interest because it has potent nonspecies-specific immunomodulatory, anti-inflammatory, and pro-coagulant activities. In evaluating the clinical relevance and the possible use in medicine of SV-IV, we became interested in the study of its structure-function relationships and aimed to identify in its polypeptide chain specific peptide fragments possessing the marked anti-inflammatory properties of the protein not associated with other biological activities (pro-coagulation and immunomodulation) typical of this molecule. By using two different experimental approaches (the fragmentation of the protein into peptide derivatives by chemical methods and the organic synthesis on solid phase of selected peptide fragments), data were obtained showing that in this protein: (a) the immunomodulatory activity is related to the structural integrity of the whole molecule; (b) the anti-inflammatory activity is located in the N-terminal region of the molecule, the 8-16 peptide fragment being the most active; (c) the identified anti-inflammatory peptide derivatives do not seem to possess pro-coagulant activity, even though this particular function has been located in the 1-70 segment of the molecule.

Alteration of haemostasis in non-metastatic gastric cancer.

BACKGROUND: Cancer is one of the most common acquired causes of venous thromboembolism. AIM: To evaluate haemostasis disorders in patients with non-metastatic gastric cancer. PATIENTS AND METHODS: We studied 11 patients with non-metastatic gastric cancer (9 males and 2 females, median age 54 years) and 20 healthy subjects (15 males and 5 females, median age 48 years) control. We measured prothrombin time, activated partial thromboplastin time, coagulation time, clot lysis time, fibrinogen, clotting factors (II, VII, VIII, IX, X), C protein, S protein, AT III, activated protein C resistance, prothrombin 1+2 fragment, tissue plasminogen activator and D-Dimer in all subjects. RESULTS: Fibrinogen plasma levels were significantly higher in patients with non-metastatic gastric cancer than in control group (505+/-24 mg/dl vs 336+/-30 mg/dl, p<0.001). We also found a significant increase in prothrombin 1+2 fragment plasma concentration compared with controls (3.8+/-0.6 nM vs 0.83+/-0.09 nM, p<0.001). Plasma D-dimer levels were 20-fold higher in patients with non-metastatic gastric cancer compared with controls (9.57+/-0.4 ng/dl vs 0.4+/-0.05 ng/dl, p<0.001). Also tissue plasminogen activator was significantly higher in gastric cancer patients than in controls (20.8+/-2.32 ng/ml vs 9.1+/-1.37 ng/ml, p<0.01). Finally clot lysis time was significantly accelerated in gastric cancer patients compared with control subjects (81+/-37 min vs 233+/-74 min, p<0.01). CONCLUSIONS: Patients with non-metastatic gastric cancer are at risk for thrombotic events due to the combined increase in fibrinogen plasma levels and thrombin formation.

Inhibition of antithrombin by protein SV-IV normalizes the coagulation of hemophilic blood.

The aim of the study was to evaluate the effect of the protein Seminal Vesicle Protein No. 4 (SV-IV), a potent inhibitor of antithrombin III (antithrombin), on the coagulation of blood obtained from patients affected by hemophilia A. In the coagulating blood of these patients, the antithrombin/thrombin ratio was found to be markedly higher (about 44) than in normal individuals (about 4. 4). This high ratio was related to the low efficiency of thrombin-generating reactions induced by the factor VIII deficiency and to the high levels of free (not bound to serine proteases) antithrombin present in the hemophilic serum (antithrombin concentration was the same in normal and hemophilic plasma). The elevated concentration of free antithrombin in hemophiliacs was primarily a consequence of a reduced consumption caused by the scarce availability in the hemophilic serum of factors Xa and IIa, which are serine proteases possessing strong binding affinity for antithrombin. Addition of SV-IV to coagulating hemophilic blood reduced markedly the serum antithrombin and thrombin-antithrombin complexes, normalizing, as a consequence, the clotting time and other coagulation parameters. Similar results were obtained by using appropriate concentration of factor VIII.

A peptide derivative (1-70 fragment) of protein SV-IV accelerates human blood coagulation in vitro by selective inhibition of the heparin-induced antithrombin III activation process.

The effect of two peptide derivatives of the rat SV-IV (SV-IV/A: 1-70 fragment; SV-IV/B: 71-90 fragment) on human blood coagulation was investigated. The SV-IV/A fragment was found to possess the same procoagulant activity of the native protein, whereas SV-IV/B retained only a very small fraction of the activity. The results obtained strongly suggest that the procoagulant activity of SV-IV/A is due, like SV-IV, to a selective inhibition of the antithrombin III (AT III) activation process induced by heparin, an essential cofactor of AT III. The main data supporting this hypothesis are the following: 1) the concentration of active serum AT III decreases when SV-IV/A is present in the clotting system; 2) the plasma treatment with SV-IV/A reduces the concentration of AT III, but not that of other plasma serine protease inhibitors; 3) the recalcification time (RT) of the plasma treated with a rabbit anti-AT III polyclonal antiserum is not modified by SV-IV/A; 4) the presence of SV-IV/A in a reaction mixture containing pure fibrinogen, alpha-thrombin, heparin, and AT III neutralizes the thrombin inhibition induced by AT III; 5) the concentration of the thrombin-AT III complexes, occurring in sera obtained from CaCl2-coagulated plasma, is markedly reduced in the presence of SV-IV/A; 6) appropriate concentrations of heparin neutralize the inhibitory effect of either SV-IV/A or SV-IV on the AT III activity in vitro.

Rat protein SV-IV (seminal vesicle protein No. 4) accelerates human blood coagulation in vitro by selective inhibition of antithrombin III.

The seminal vesicle protein No. 4 (SV-IV) secreted from the rat seminal vesicle epithelium, possesses immunosuppressive and anti-inflammatory properties and it is a potent inhibitor of platelet aggregation both in vivo and in vitro. This research aimed to investigate the possible effect of SV-IV on the process of human blood coagulation. Preliminary experiments showed that the recalcification time (RT) of platelet-poor plasma (PPP) samples, obtained from both normal subjects and patients affected by some hemorrhagic disorders, was found to be markedly reduced in the presence of micromolar amounts of SV-IV. It was demonstrated that the concentration of free antithrombin III (AT III) occurring in blood sera obtained from PPP samples recalcified in the presence of SV-IV was significantly decreased in comparison with sera obtained from PPP recalcified in the absence of SV-IV. It was also shown that PPP treatment with SV-IV significantly reduced the concentration of free AT III without affecting the levels of other plasma serine protease inhibitors, such as alpha 2-macroglobulin, alpha 1-antitrypsin and C1-inhibitor. In addition, the RT of PPP treated with a specific rabbit anti-AT III polyclonal antiserum (anti-AT III treated PPP) was not modified by SV-IV. These findings were confirmed by the observation that the addition of SV-IV into an in vitro coagulation system, containing pure fibrinogen, alpha-thrombin and AT-III, resulted in complex suppression of thrombin inhibition by AT III. No other steps of the blood clotting process (prothrombinase complex, factor XIII, fibrinogen concentration) were affected by SV-IV.