Acquired Dysfibrinogenemia Secondary to Multiple Myeloma
ABSTRACT Abnormal coagulation properties indicative of a dysfibrinogen were found in the plasma of a 72-year-old male with multiple myeloma (IgGkappa, stage IIIA). The patient had high paraprotein concentration (85.75 g/l) and prolonged thrombin time (76.8 s), activated partial thromboplastin time (39.5 s), prothrombin time (23.5 s) and reptilase time (72.0 s). The fibrinogen level was increased. The fibrin polymerization induced by both thrombin and reptilase was impaired. Scanning electron microscopy revealed abnormal clot morphology. After six months of treatment, the paraprotein level decreased (19.48 g/l) and coagulation normalized as well as fibrin polymerization and fibrin clot morphology. It was found that the paraprotein interacts with the gamma-chain of fibrinogen. Acquired dysfibrinogenemia associated with multiple myeloma was diagnosed in the 72-year-old patient.
- Acta Haematologica 02/2014; 132(2):140-143. DOI:10.1159/000356781 · 0.99 Impact Factor
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ABSTRACT: Congenital dysfibrinogenemia is a rare disease characterised by inherited abnormality in the fibrinogen molecule, resulting in functional defects. Two patients, a 26-year-old woman and a 61-year-old man, both with history of thrombotic events, had abnormal coagulation test results. DNA sequencing showed the heterozygous gamma Y363N mutation (Fibrinogen Praha III) and the heterozygous Aalpha N106D mutation (Fibrinogen Plzen), respectively. Fibrin polymerisation, after addition of either thrombin or reptilase, showed remarkably delayed polymerisation in both cases. Fibrinolysis experiments showed slower tPA initiated lysis of clots. SDS-PAGE did not show any difference between normal and Praha III and Plzen fibrinogens. Both mutations had a significant effect on platelet aggregation. In the presence of either ADP or TRAP, both mutations caused the decrease of platelet aggregation. SEM revealed abnormal clot morphology, with a large number of free ends and narrower fibres of both fibrin Praha III and Plzen. Praha III mutation was situated in the polymerisation pocket "a". The replacement of the bulky aromatic side chain of tyrosine by the polar uncharged small side chain of asparagine may lead to a conformational change, possibly altering the conformation of the polymerisation pocket. The Plzen mutation is situated in the coiled-coil connector and this replacement of polar uncharged asparagine residue by polar acidic aspartate changes the alpha-helical conformation of the coiled-coil connector; and may destabilise hydrogen bonds in its neighborhood. Although both mutations are situated in different regions of the molecule, both mutations have a very similar effect on fibrinogen functions and both are connected with thromboses.Thrombosis and Haemostasis 10/2009; 102(3):479-86. DOI:10.1160/TH08-11-0771 · 5.76 Impact Factor
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ABSTRACT: Plasma cell dyscrasias are characterized by a malignant clonal proliferation of plasma cells. Due to the excessive production of abnormal clonal gammaglobulins, or paraproteins, there are major hemorheologic changes in the circulation. As a result, clinical manifestations of the hyperviscosity syndrome become a major cause of morbidity and mortality. Pathogenic factors for the hyperviscosity are due both to increased plasma viscosity and to increased erythrocyte aggregation, leading to increased whole blood viscosity. These changes are dependent on the plasma concentration as well as the molecular size of the paraprotein with the threshold for onset of hyperviscosity for IgG >15 g/dl, for polymerized IgG3 >4-5 g/dl, for IgA >10-11 g/dl; for polymerized IgA >6-7 g/dl and for IgM >3 g/dl. Correspondingly, the incidence of symptomatic hyperviscosity in Waldenstrom's macroglobulinemia is 10-30%, while that in IgG myeloma is 2-6%. Clinically, the syndrome has neurologic features of headache and dizziness, visual changes, renal failure, and cardiac failure from increased plasma volume. Thrombotic complications are frequent. Paradoxically, there can be bleeding complications due to impairment of platelet function. Removal of the paraprotein by plasma exchange (plasmapheresis) can effectively reduce the hyperviscosity. Long-term control of paraprotein production can be achieved by chemotherapy. The early recognition of the symptoms of hyperviscosity, confirmed by laboratory findings of increased paraproteins and of increased blood viscosity, is essential for the proper management of this group of disorders.Clinical hemorheology and microcirculation 03/2013; DOI:10.3233/CH-131691 · 2.22 Impact Factor