Acute promyelocytic leukaemia: a report of five cases with a comment on the diagnostic significance of serum vitamin B 12 determination.
Explore the source record for details and available documents.
Acute Disease↗
SEARCH · Search PubMed
Results for “AFIBRINOGENEMIA”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Platelet-aggregating activity in neuraminidase-treated human cryoprecipitates: its correlation with factor-VIII-related antigen.
Explore the source record for details and available documents.
Afibrinogenemia↗
Fibrinogen Adelaide: a familial hypodysfibrinogenaemia associated with abnormal alpha chains.
A familial hypodysfibrinogenaemia occurring in four females with occasional haemorrhagic problems in an Adelaide family was investigated. Affected family members had slightly prolonged thrombin time, prothrombin time and Reptilase time tests, and apparently elevated levels of fibrin degradation products (FDPs). Fibrinogen assessed by reactivity with thrombin (Clauss method) was significantly less than fibrinogen determined by various other methods, though even by immunoquantitation fibrinogen levels were only slightly above half normal in affected family members. Isoelectric focussing (IEF) of the reduced patient's fibrinogen in urea/polyacrylamide gel revealed minor components with higher isoelectric points (pI) than present in normal fibrinogen or fibrin. These were shown to have a molecular weight similar to the alpha chain of fibrin by subsequent sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The abnormal species tended to remain in plasma after clotting with Reptilase or thrombin although polymerization of the clotted fibrin was normal. The magnitude of the pI shift relative to normal fibrin alpha chain indicated an increased positive charge on the abnormal species.
Adult↗
Episodes of increased fibronectin level observed in a patient suffering from recurrent thrombosis related to congenital hypodysfibrinogenaemia (fibrinogen Malmoe).
A study has been conducted in a Swedish patient with severe thrombotic disease and repeated miscarriages related to a hypodysfibrinogenaemia with defective thrombin binding to the abnormal fibrin. The hypodysfibrinogenaemia was found in several members of the family. The patient also had an increased concentration of fibronectin in her plasma at two different occasions. This would appear to be unrelated to the abnormal fibrinogen since a normal concentration of fibronectin has been found in her relatives presenting the same fibrinogen anomaly, and in the patient at two other times. In conclusion, the thrombotic disorder in this patient presenting a congenital hypodysfibrinogenaemia may be explained by the defective thrombin binding to fibrin.
Adult↗
Platelet aggregation occurs in congenital afibrinogenaemia despite the absence of fibrinogen or its fragments in plasma and platelets, as demonstrated by immunoenzymology.
Platelet aggregation of an afibrinogenaemic patient's platelet rich plasma (PRP) was greatly decreased when ADP was used for stimulation. In the presence of collagen or arachidonic acid the changes in light transmission recorded during platelet aggregation of patient's PRP were similar to those observed with normal PRP but the size of aggregates appeared to be smaller in comparison with those observed with normal platelets. In addition, thrombin-induced aggregation of washed platelets was similar to normal platelets. The interpretation was made possible because the fibrinogen level in plasma and in platelets was found to be almost nil as demonstrated by both an Elisa procedure described here and the determination of fibrinopeptide A (fpA). Furthermore, fibrinogen fragments, which could result from abnormal synthesis and therefore replace fibrinogen in platelet aggregation, were undetectable by immunological analysis using specific antibodies against A alpha, B beta and gamma chains and 10 different monoclonal antibodies against fibrin degradation products.
Adenosine Diphosphate↗
Binding of von Willebrand factor to glycoproteins Ib and IIb/IIIa complex: affinity is related to multimeric size.
We have separated von Willebrand factor (vWF) multimers of different size into several fractions which were characterized by SDS-agarose gel electrophoresis and by measuring the ratio between ristocetin cofactor activity (Ricof) and von Willebrand antigen (vWF:Ag) content. The pooled fractions contained vWF with multimeric structures and Ricof similar to those in plasma. The pool was labelled with 125I and used for inhibition binding studies with individual fractions to calculate the dissociation constants (Kd values expressed in mol/l) of the individual fractions for ristocetin-dependent binding to GP Ib and thrombin-induced binding to GP IIb/IIIa. Direct binding studies of the 125I-vWF pool gave mean Kd values of 2.02 +/- 0.05 x 10(-8) for GP Ib and 1.15 +/- 0.02 x 10(-8) for the GP IIb/IIIa complex. Inhibition binding studies gave Kd mean values one third to one tenth as high for larger multimers and 3-10 times higher for smaller multimers, for both GP Ib and IIb/IIIa complex. Similar results were observed when binding studies were carried out in the presence of platelets from a patient with afibrinogenaemia. These data on binding correlated very well with ristocetin- and thrombin-induced aggregation of afibrinogenaemic platelets, since equal concentrations of the higher molecular weight forms gave significantly higher aggregation rates. Based on these results, we conclude that the affinity of the vWF molecule for its two platelet receptors is greater for the largest multimers.
Afibrinogenemia↗
Pregnancy in congenital afibrinogenaemia: report of a successful case and review of the literature.
Explore the source record for details and available documents.
Adult↗
Sustained correction of the bleeding time in an afibrinogenaemic patient after infusion of fresh frozen plasma.
We have evaluated the duration of the effect of replacement therapy with two different doses of fibrinogen on the prolonged bleeding time of an afibrinogenaemic patient and the relationship between changes in bleeding time and plasma and platelet fibrinogen concentrations. The infusion of 40 mg/kg fibrinogen, as fresh frozen plasma (FFP), corrected the prolonged bleeding time of the patient from longer that 30 min to 8 min. The bleeding time was still normal 9 d after infusion, at a time when the plasma and platelet fibrinogen levels were low (0.13 g/l and 27 micrograms/10(9) platelets; normal ranges 1.6-4.0 and 60-190). Two months later, the infusion of a smaller dose of fibrinogen (4 mg/kg) also corrected the bleeding time, which remained normal until the second day after infusion, despite the fact that plasma and platelet fibrinogen were very low (0.02 g/l and 3.4 micrograms/10(9) platelets). The bleeding time returned to the prolonged baseline values only by day 6 post-infusion, when plasma and platelet fibrinogen levels were 4 x 10(-4) g/l and 1.4 micrograms/10(9) platelets. Therefore, sustained correction of the prolonged bleeding time may be obtained in afibrinogenaemic patients with a single infusion of fibrinogen at lower doses than usually recommended.
Adult↗
Hypofibrinogenaemia is the commonest congenital fibrinogen abnormality in north India.
Congenital abnormalities of fibrinogen are rare disorders and all the cases reported in the literature indicate that the incidence of afibrinogenaemia is much higher than hypofibrinogenaemia. Of the total of 20 cases reported from other parts of India only one was congenital hypofibrinogenaemia. In contrast, the present study showed eight patients with congenital hypofibrinogenaemia among a total of nine unrelated North Indian patients with a fibrinogen abnormality. This disproportionately high incidence of hypofibrinogenaemia suggests the existence of a distinct genetic defect in the North Indian population.
Adolescent↗
The rare coagulation disorders--review with guidelines for management from the United Kingdom Haemophilia Centre Doctors' Organisation.
The rare coagulation disorders are heritable abnormalities of haemostasis that may present significant difficulties in diagnosis and management. This review summarizes the current literature for disorders of fibrinogen, and deficiencies of prothrombin, factor V, FV + VIII, FVII, FX, the combined vitamin K-dependent factors, FXI and FXIII. Based on both collective clinical experience and the literature, guidelines for management of bleeding complications are suggested with specific advice for surgery, spontaneous bleeding, management of pregnancy and the neonate. We have chosen to include a section on Ehlers-Danlos Syndrome because haematologists may be consulted about bleeding manifestations in such patients.
Afibrinogenemia↗
Fibrinogen Denver: a dysfibrinogenemia associated with an abnormal Reptilase time and significant bleeding.
This paper reports a new dysfibrinogenemia with an unusual pattern of laboratory assays. The patient, a 51-year-old female with a lifelong moderate bleeding history, was initially diagnosed with von Willebrand disease based on routine coagulation assays and the clinical bleeding presentation. During recent testing as part of a preoperative screen and without any current history of treatment, levels of von Willebrand factor (VWF) antigen, VWF activity, and factor VIII activity were all significantly elevated, which was unexpected given her previous diagnosis. Additional testing was performed looking for other heritable causes for her considerable bleeding tendency. Interestingly, the patient had a significantly prolonged Reptilase time, minimally short thrombin time, and an abnormal fibrinogen-crossed immunoelectrophoresis pattern. Clearly, this patient had a fibrinogen abnormality that had been missed when only routine coagulation screening assays were performed. A brief review of the fibrinogen literature revealed no other dysfibrinogenemias reported with a similar pattern of test results, and thus this defect was designated fibrinogen Denver.
Afibrinogenemia↗
Identification of three FGA mutations in two Chinese families with congenital afibrinogenaemia.
Congenital afibrinogenaemia is a rare autosomal recessive disorder, characterized by the complete absence or extremely reduced level of fibrinogen (Fg). We attempted to analyse the phenotype and genotype in two Chinese families with congenital afibrinogenaemia. Coagulation studies including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) and Fg were performed in the patients and other family members. All the exons, exon-intron boundaries and promoter regions of three Fg genes (FGA, FGB and FGG) were screened by direct sequencing. Three patients in two families suffered from moderate to severe haemorrhage. Their APTT, PT and TT were extremely prolonged and plasma Fg levels were undetectable by Clauss method and extremely reduced by immunoassay. Genetic analysis revealed three FGA mutations in three patients including one novel mutation. In family 1, patient 1 was detected compound heterozygous mutations in FGA, g.1892-1899delAGTA/GTAA from her patriline and g.1978-g.3215del1238 bp from her matriline. In family 2, a homozygous Gln203X in Aalpha-chain was found in both patients 2 and 3 due to consanguineous marriage. All these mutations were null mutations, which could produce premature stop codons in FGA. It can be indicated that with more genetic analysis performed on afibrinogenaemia patients all over the world, there is no distinct difference in geographical distribution of Fg gene mutations. Gln203X in Aalpha-chain was first reported in this study, which may help to further understand the function of Aalpha-chain.
Afibrinogenemia↗
Management of acute bleeding in a patient with congenital afibrinogenaemia.
Congenital afibrinogenaemia is a rare bleeding disorder characterized by absence of fibrinogen and varying bleeding tendency. Treatment with fibrinogen concentrates is considered to be the best choice for afibrinogenaemic patients who experience bleeding. We report the case of a 22-year-old Greek patient who presented with large muscular haematomas and was treated with fibrinogen concentrates. The efficacy of this treatment and the problems that arose during his hospitalization are being discussed.
Adult↗
Reduced erythrocyte CR1 (CD 35) receptor function and complement opsonization in factor I-deficient patients is restored by plasma infusion.
Erythrocytes (E) from three factor I-deficient patients were investigated for surface-bound complement factors and CR1 (CD 35) expression and function. The E were coated with C4b, C3b, and factor H. Following plasma infusion or in vitro incubation of the patients' E with normal human serum (NHS) or purified factor I, cell-bound C4b and C3b could no longer be detected. The E now expressed C3d, and factor H was unaffected, indicating that factor H was bound to the C3d part of the C3b molecules, providing the co-factor for effective cleavage of E-bound C3b when purified factor I was added. The binding of monoclonal anti-CR1 antibodies (M710) to the patients' E was markedly reduced compared with control E, and was not normalized by treatment with NHS, probably because covalently bound C3d/factor H interfered with the binding of M710. By contrast, the reduced ability of the patients' E-CR1 to bind complement-opsonized immune complexes (IC) was normalized after plasma infusion. This shows that the impaired CR1 function was acquired and emphasizes the importance of performing functional CR1 assays. Complement opsonization of IC for binding to normal E was severely compromised in the patients' sera due to consumption of factor B and C3. After plasma infusion the opsonization capacity of the patients' sera was restored. Thus, two mechanisms of importance for normal clearance of IC were compromised in factor I-deficient patients: (1) the opsonization of IC for binding to E-CR1, and (2) the capacity of E-CR1 to bind opsonized complexes. Both dysfunctions were temporarily corrected by plasma infusion.
Adult↗
Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H.
The complement system participates in both innate and acquired immune responses. Deficiencies in any of the protein components of this system are generally uncommon and require specialized services for diagnosis. Consequently, complement deficiencies are clinically underscored and may be more common than is normally estimated. As C3 is the major complement component and participates in all three pathways of activation, it is fundamental to understand all the clinical consequences observed in patients for which this protein is below normal concentration or absent in the serum. C3 deficiencies are generally associated with higher susceptibility to severe infections and in some cases with autoimmune diseases such as systemic lupus erythematosus. Here, we review the main clinical aspects and the molecular basis of primary C3 deficiency as well as the mutations in the regulatory proteins factor I and factor H that result in secondary C3 deficiencies. We also discuss the use of animal models to study these deficiencies.
Afibrinogenemia↗
Quantification by ELISA of erythrocyte-bound C3 fragments expressing C3d and/or C3c epitopes in patients with factor I deficiency and with autoimmune diseases.
A sensitive ELISA assay for quantifying erythrocyte (E) bound C3 fragments was developed. The assay employs a double-antibody sandwich technique, using polyclonal anti-C3d or anti-C3c antibodies to quantify C3 fragments, expressing C3d and/or C3c epitopes in washed, detergent-solubilized E. The assay detected 50-120 molecules of C3d per E in healthy individuals. Antigens reacting with anti-C3c antibodies were also detected on E from normal individuals, but the density of C3c-epitopes was 0.9-2.4 times lower than that of C3d-epitopes. In 2 patients with congenital factor I deficiency significantly increased density of E-bound C3c- as well as C3d-antigen was observed. Plasma infusion in one of the patients induced a loss of E-bound C3c-antigens, indicating cleavage of E-bound C3b to iC3b and further to C3c and E-bound C3d. Loss of C3c-antigens also occurred following in vitro treatment with normal human serum of E from one of the patients. Two thirds of 22 patients with systemic lupus erythematosus (SLE) and of 18 patients with rheumatoid arthritis had significantly increased density of E-bound C3d, the highest density being 490 C3d molecules/E in an SLE patient. The density of E-bound C3d correlated with the plasma-C3d concentration, indicating that the coating of E with C3d reflects the degree of complement activation.
Afibrinogenemia↗
Replacement of massive blood loss.
Treatment of massive blood loss has experienced major changes during the recent decade. The transition towards pure component therapy has been the most significant issue, which has compelled the clinician to revise some of their basic strategies in treatment of massively bleeding patients. The importance of adequate volume resuscitation with crystalloids and colloids is still unrefutable, but the therapy of hemorrhagic derangements has changed. Plasma-poor red cells (RC) are now commonly used instead of whole blood (WB) or packed red blood cells (PRBC) to correct oxygen carrying capacity during massive blood loss. As the plasma content of RC is minimal, deficit of plasma and coagulation factors develops earlier than during transfusion of WB and PRBC. Hypofibrinogenemia develops first followed by other coagulation factor deficits and later by thrombocytopenia. Therefore the use of fresh frozen plasma (FFP) is the primary intervention to treat abnormal bleeding encountered in the replacement of massive blood loss with RC. As the development of thrombocytopenia is a highly individual phenomenon, the transfusion of platelets should be guided by repeatedly determined platelet counts.
Adult↗
Use of a monoclonal antibody to measure the surface expression of thrombospondin following platelet activation.
The radiolabelled monoclonal antibody, 5G11, directed against native thrombospondin, has been used to assess the surface expression of secreted thrombospondin on human blood platelets. Emphasis has been placed on studying the role of fibrinogen in this process. Unstimulated platelets bound low amounts of 5G11 (about 2000 molecules/platelet). Binding increased 2-fold and 5-7-fold after stimulation of platelets with ADP or thrombin (or ionophore A23187) respectively. Unstimulated platelets from patients deficient in alpha-granule proteins (gray platelet syndrome) bound baseline levels of 5G11. However, binding was not increased after activation. Thrombospondin expression on thrombin-stimulated normal platelets was for a large part divalent-cation-dependent and was not affected by AP-2, a monoclonal antibody to GPIIb-IIIa complexes. However, binding of 5G11 was some 50% lower when platelets were stimulated in the presence of Fab fragments of a polyclonal rabbit antibody to fibrinogen. This suggested either a direct binding of thrombospondin to surface-bound fibrinogen or a steric inhibition due to a close proximity of the two proteins. The fact that binding of 5G11 was at the lower limit of the normal range to the stimulated platelets of an afibrinogenaemic patient specifically lacking detectable fibrinogen favoured the latter explanation. Thus, a major fibrinogen-independent pathway for thrombospondin expression must exist.
Afibrinogenemia↗