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  • American Society of Hematology  (3)
  • English  (3)
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  • American Society of Hematology  (3)
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  • English  (3)
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  • 1
    Online Resource
    Online Resource
    Impaired fibrinolysis and increased clot strength are potential risk factors for thrombosis in lymphoma
    American Society of Hematology ; 2023
    In:  Blood Advances
    Details
    In: Blood Advances, American Society of Hematology
    Abstract: Thrombosis and bleeding are significant contributors to morbidity and mortality in patients with hematological cancer, and the impact of altered fibrinolysis on bleeding and thrombosis risk is poorly understood. In this prospective cohort study, we investigated the dynamics of fibrinolysis in hematological cancer patients. Fibrinolysis was investigated prior to treatment and three months after treatment initiation. A dynamic clot formation and lysis assay was performed beyond the measurement of plasminogen activator inhibitor 1, tissue- and urokinase-type plasminogen activators (tPA and uPA), plasmin-antiplasmin complexes (PAP), α-2-antiplasmin activity, and plasminogen activity. Clot initiation, clot propagation, and clot strength were assessed using thromboelastometry (ROTEM®). A total of 79 patients were enrolled. Lymphoma patients displayed impaired fibrinolysis with prolonged 50% clot lysis time compared to healthy controls (p = 0.048). They also displayed decreased clot strength at follow-up compared to at diagnosisp (p = 0.001). A patient with amyloid-light-chain amyloidosis having overt bleeding at diagnosis displayed hyperfibrinolysis, indicated by a reduced 50% clot lysis time, α-2-antiplasmin activity, and plasminogen activity and elevated tPA and uPA. A patient with acute promyelocytic leukemia also displayed marked hyperfibrinolysis with very high PAP indicating extreme plasmin generation, and clot formation was not measurable probably due to the extremely fast fibrinolysis. Fibrinolysis returned to normal after treatment in both patients. In conclusion, lymphoma patients showed signs of impaired fibrinolysis and increased clot strength, whereas hyperfibrinolysis was seen in patients with acute promyelocytic leukemia and light-chain amyloidosis. Thus, investigating fibrinolysis in hematological cancer patients could have diagnostic value.
    Type of Medium: Online Resource
    ISSN: 2473-9529 , 2473-9537
    URL: Article
    DOI: 10.1182/bloodadvances.2023011379
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2023
    detail.hit.zdb_id: 2876449-3
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  • 2
    Online Resource
    Online Resource
    Citrate Anticoagulant Artificially Masks the Hemostatic Effect of Recombinant Factor VIIA in Dilutional Coagulopathy.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 3160-3160
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3160-3160
    Abstract: Introduction: Dilutional coagulopathy may develop in massively bleeding patients who are substituted with synthetic colloid plasma expanders. A series of recent studies have demonstrated that synthetic colloids may induce abnormal function of fibrinogen by compromising fibrin polymerization and substitution with a fibrinogen concentrate appeared to reverse this coagulopathy and arrest traumatic bleeds. Clinical experiences, several case reports as well as a randomised trial point toward a beneficial effect of rFVIIa in control of massive bleeding associated with hemodilution caused by excessive volume substitution. Our haemostasis center recently put forward that rFVIIa, in vitro, was unsuccessful in correction of dilutional coagulopathy induced by HES 130/04. In addition, other investigations utilising a rabbit model have indicated that colloid hemodilution may attenuate the haemostatic potential of rFVIIa. For half a Century laboratory coagulation tests have been carried out using re-calcified citrated blood. However, recent experimental work has revealed that citrate dependent calcium chelation significantly changes the dynamic course of thrombin generation, suspectedly due to interference with the enzymatic properties of coagulation factors. In addition it has been documented that citrate and calcium chelation interferes with the metabolism in platelets. In the present study we aimed at investigating the haemostatic effect of rFVIIa in a laboratory whole blood model of colloid hemodilution using citrate as well as iso-citrate stabilized blood comparing to native whole blood and whole blood stabilized with corn trypsin inhibitor (CTI) that specifically blocks factor XIIa. Materials and Methods: Following informed consent 11 healthy male volunteers with a mean age of 30 years (range 26–38 years) delivered blood for study. Dynamic whole blood coagulation profiles were recorded using thrombelastography activated with minute amounts of tissue factor in a model of ex vivo hemodilution with HES 130/0.4 in a prospective approach. Analyses were evaluated at 30% dilution level, and following ex vivo addition of rFVIIa to whole blood collected into tubes containing citrate, iso-citrate, CTI, or no stabilizer. Results: Hemodilution with HES 130/0.4 induces a coagulopathy characterized by a reduced maximum rate of clot formation and a pronounced reduction in the final clot firmness. With all test mediums investigated, rFVIIa significantly shortened the clot initiation phase. In cases of native whole blood and CTI stabilized whole blood rFVIIa shortens the clotting time but also demonstrated an acceleration of the maximum velocity of clot formation. Conclusion: When citrate or iso-citrate is used as anticoagulants in thromboelastographic clotting assays, these anticoagulants may artificially mask the haemostatic effect of rFVIIa in colloid hemodilution blood. The effect in vitro of rFVIIa in citrated blood samples may significantly underestimate the haemostatic potential of rFVIIa. In cases where the hemostatic potential of rFVIIa is tested in vitro a potentially efficacious rescue treatment may be delayed or excluded.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.3160.3160
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    Fibrinogen Concentrate Corrects Dilutional Coagulopathy: A Prospective, Randomized Placebo Controlled Clinical Trial.
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 1227-1227
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 1227-1227
    Abstract: Introduction: Infusion of artificial colloids such as hydroxyethyl starch (HES) induces a coagulopathy, beyond simple dilution. Laboratory and animal studies have suggested that the coagulopathy could be corrected by substitution with a fibrinogen concentrate. Aims and Hypotheses: The present prospective randomized placebo controlled trial aimed to: verify the development of a coagulopathy following in vivo infusion of HES, and investigate the haemostatic effect of a fibrinogen concentrate patients experiencing sudden excessive bleeding during elective cystectomy. We hypothesized that HES induces a coagulopathy characterized by dysfunctional fibrin polymerization and thereby compromised maximum clot firmness (MCF). Furthermore, we hypothesized that fibrinogen corrects the coagulopathy caused by HES and reduce blood product transfusion requirements. Materials and Methods: Based on sample size calculation a total of twenty patients undergoing cystectomy were included in the study. Approval was granted by the Danish Medicines Agency, Human Ethics Committee, and the Danish Data Protection Agency. Monitoring of the study was performed by the GCP-Unit at Aarhus University Hospital. During the cystectomy operation persisting bleeding was substituted 1:1 with hydroxyethyl starch 130/0.4. At a level of dilution of 30% patients were randomly assigned for intra-operative administration of a fibrinogen concentrate (45 mg/kg) (Haemocomplettan® CSL Behring, Germany) or placebo. The primary endpoint was MCF as assessed by whole blood thromboelastometry. Other pre-specified secondary endpoints blood loss and transfusion requirements as well as other thrombelastometry parameters, platelet function, and thrombin generation. Data were parametric and paired analysis was performed using student’s t-test and ANOVA. Data are presented as mean (95%CI), p & lt;0.05 was considered statistical significant. Results: Whole blood MCF was significantly reduced from 59.2 (SD; 5.8) mm to 50.6 (SD; 4.7) mm following in vivo 30% dilution with HES. Placebo resulted in a further decline of the MCF of −1.2 (SD; 1.4) mm, whereas randomized administration of fibrinogen significantly increased the MCF with +3.1 (SD; 1.7) mm (p & lt;0.001). Furthermore, patients randomized to fibrinogen substitution only needed postoperative red blood cells transfusions in 2 out or 10 cases, as compared with 8 out of 10 in the placebo group (p=0.023). Both platelet function and thrombin generation was reduced following in vivo 30 % haemodilution and fibrinogen administration induced no significant changes. Discussion/Conclusion: Fluid resuscitation with hydroxyethyl starch 130/0.4 as a result of sudden excessive bleeding during cystectomy induces a coagulopathy characterized by reduced whole blood maximum clot firmness. Randomized administration of fibrinogen concentrate significantly improved maximum clot firmness and reduced postoperative transfusion requirements.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.1227.1227
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Location Call Number Limitation Availability
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    Online Resource
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