P047 Acquired dysfibrinogenemia associated with multiple myeloma

Kotlín, Roman; Sobotková, Alžběta; Suttnar, Jiřı́; Salaj, Peter; Riedel, Tomáš; Dyr, Jan E.

doi:10.1016/s0268-960x(07)70122-4

Cited by 13 publications

(25 citation statements)

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“…Prolonged TT was most likely a result of acquired dysfibrinogenemia secondary to multiple myeloma. Fibrin polymerization induced by thrombin was impaired by paraprotein, which interacts with the g chain of Fbg [4]. In addition, some people found that light chain had lupus anticoagulant activity, which could be responsible for the correlation between TT and lightchain concentration [9].…”

Section: Discussionmentioning

confidence: 99%

“…heparin-like activity) [17,18]; and paraprotein disturbs the function of coagulation factor or accelerates the clearance of coagulation factor by forming complexes with specific clotting factors [4,19].…”

Section: Discussionmentioning

confidence: 99%

“…Hyperviscosity of blood, platelet dysfunction, fibrinogen (Fbg) dysfunction, inhibition of coagulation factors or von Willebr and factor, circulating proteins with heparin-like activity have played a part in this process [4,5]; however, the high concentration of paraproteins has always been considered as an important contributor to these mechanisms.…”

Section: Introductionmentioning

confidence: 99%

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Effect of serum monoclonal protein concentration on haemostasis in patients with multiple myeloma

Huang

Li²,

Li³

2015

Blood Coagulation &Amp; Fibrinolysis

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Abnormalities in haemostasis are often detected in patients with multiple myeloma and the fundamental factors that lead to these abnormities are worthy of exploration. The objective of this study was to investigate bleeding diathesis and coagulopathy in different multiple myeloma types or stages and assess how paraprotein concentration contributes to differences in these conditions. Haemostasis screening tests and serum monoclonal protein (M protein) concentration were retrospectively analysed in 101 patients newly diagnosed with multiple myeloma from January 2012 to April 2014. No significant differences were found between bleeding diathesis and types or International Staging System (ISS) stages of multiple myeloma; however, prolonged thrombin time (TT) was found in most of patients (77.7%) and was positively related to light-chain concentration (P ≤ 0.01). Prolonged prothrombin time (PT) was more obvious in IgA and IgG-type multiple myeloma than in the light-chain type (P ≤ 0.01). With increased clinical staging, PT remarkably increased (P ≤ 0.01). M protein concentration was significantly higher in patients with prolonged PT than in those with normal PT (P ≤ 0.01). The D-dimer mean was significantly higher than normal (>0.5 μg/ml) (P ≤ 0.01). Fibrinogen was negatively related to M protein levels (P ≤ 0.01); however, there was no correlation between activated partial thromboplastin time (APTT) and multiple myeloma stages or types, M protein levels and serum light-chain concentration (P ≥ 0.05). Patients with light-chain type multiple myeloma were more likely to have prolonged TT than patients with other types. M protein levels had an obvious effect on PT. Prolonged PT was more common in IgA and IgG-type multiple myeloma. Abnormal haemostasis test results are not always accompanied by clinically apparent haemostatic complications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of serum monoclonal protein concentration on haemostasis in patients with multiple myeloma

Huang

Li²,

Li³

2015

Blood Coagulation &Amp; Fibrinolysis

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“…There is increased in bleeding complications due to defect in the hemostatic function. First, the polymerization of fibrin monomers, an essential step in fibrin formation, is inhibited by the paraproteins [19]. Blood coagulation can also be impaired by the presence of heparin-like inhibitor [41].…”

Section: Increased Risk Of Bleeding Complicationsmentioning

confidence: 99%

Hyperviscosity in plasma cell dyscrasias

Kwaan

2013

Clinical Hemorheology and Microcirculation

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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 IgG 3 >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.

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“…Fibrin polymerization curve measurement Fibrin polymerization was measured in plasma samples after the addition of either human thrombin (0.1 NIH U/ ml, final concentration) or reptilase (0.1 mg/ml; TEClot BAT Reptilase, TECO, Neufahrn, Germany), as described earlier [15][16][17].…”

Section: In-gel Digestion Of Isolated Fibrinogen Chainsmentioning

confidence: 99%

Dysfibrinogenemia in childhood: two cases of congenital dysfibrinogens

Kotlín

Blažek

Suttnar

et al. 2010

Blood Coagulation &Amp; Fibrinolysis

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A 2-year-old asymptomatic boy and his relatives were investigated for a suspected fibrinogen mutation after coagulation tests revealed a decreased functional fibrinogen level (family A). Eight-year-old and 1-year-old asymptomatic brothers were investigated for a suspected fibrinogen mutation after coagulation tests revealed a decreased functional fibrinogen level and prolonged thrombin time (family B). To identify whether genetic mutations were responsible for these dysfibrinogens, DNA extracted from the blood was analyzed. Fibrin polymerization and fibrinolysis were measured by a turbidimetric method at 450 nm. DNA analysis was performed by the Sanger method. Mass spectroscopy was performed on a Biflex IV mass spectrometer. DNA sequencing showed the heterozygous point mutation Aα Arg16His in the fibrinogen of family A and the heterozygous point mutation Aα Arg16Cys in the fibrinogen of family B. Kinetics of fibrinopeptide release, fibrinolysis, and fibrin polymerization were impaired in the carriers of the mutations in both families. Mass spectroscopy showed the presence of mutant fibrinogen chains in circulation. Scanning electron microscopy revealed thicker fibrin fibers, differing significantly from the normal control in both cases. Two cases of asymptomatic dysfibrinogenemias, found by routine coagulation testing, were genetically identified as new cases of fibrinogen variants Aα Arg16His and Aα Arg16Cys.

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P047 Acquired dysfibrinogenemia associated with multiple myeloma

Cited by 13 publications

References 0 publications

Effect of serum monoclonal protein concentration on haemostasis in patients with multiple myeloma

Effect of serum monoclonal protein concentration on haemostasis in patients with multiple myeloma

Hyperviscosity in plasma cell dyscrasias

Dysfibrinogenemia in childhood: two cases of congenital dysfibrinogens

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