Multiple cerebral thrombosis in fletcher factor (prekallikrein) deficiency: A case report

Harris, Margot G.; Exner, Thomas; Rickard, K.A.; Kronenberg, H.

doi:10.1002/ajh.2830190409

Cited by 39 publications

(23 citation statements)

References 26 publications

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“…They belonged to 56 separate kindreds [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47]. A thrombotic event was reported in 9 of these patients belonging to 6 different families (table 1) [5,16,22,23,24,28]. …”

Section: Resultsmentioning

confidence: 99%

Thrombotic Events in Patients with Congenital Prekallikrein Deficiency: A Critical Evaluation of All Reported Cases

et al. 2010

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The occurrence of thrombotic events in patients with congenital bleeding conditions has received considerable attention in recent years. The same is true for asymptomatic defects of factors of the contact phase of blood coagulation, mainly FXII. Anecdotal reports on thrombosis in patients with prekallikrein deficiency have occasionally been reported. These involved both arterial and venous thrombosis. The purpose of the present article is to analyze the stories and the clinical pictures of all 75 cases of prekallikrein deficiency published so far. Among these patients were 9 with thrombosis, 6 arterial (myocardial infarction and ischemic stroke) and 3 venous (deep vein thrombosis with or without pulmonary embolism). In 6 cases acquired thrombosis risk factors were present; in 2 cases no associated risk factors were present and in 1 case no information was supplied in this regard. One patient who presented both a stroke and a pulmonary embolism had a fatal outcome. The article clearly indicates that prekallikrein deficiency does not protect from thrombosis in spite of the severe in vitro coagulation defect.

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Section: Resultsmentioning

confidence: 99%

Thrombotic Events in Patients with Congenital Prekallikrein Deficiency: A Critical Evaluation of All Reported Cases

et al. 2010

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“…Interestingly, FXII and prekallikrein have also been shown to contribute to the development of experimental thrombosis in mice, 22,23 despite the normal to possibly prothrombotic phenotype associated with deficiency of either of these proteins (Hagemen trait and Fletcher trait, respectively) in humans. 14,[24][25][26] We previously demonstrated that FXI deficiency was associated with improved survival and reduced coagulopathy relative to wild-type mice during polymicrobial peritoneal sepsis. 27 The data suggested that FXI activity may have contributed to the pathogenesis of abdominal sepsis by promoting DIC.…”

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confidence: 99%

Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis

Tucker

Verbout

Leung

et al. 2012

Blood

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Severe bacterial sepsis often leads to a systemic procoagulant and proinflammatory condition that can manifest as disseminated intravascular coagulation, septic shock, and multiple organ failure. Because activation of the contact proteases factor XII (FXII), prekallikrein, and factor XI (FXI) can trigger coagulation and inflammatory responses, the contact factors have been considered potential targets for the treatment of sepsis. However, the pathogenic role of contact activation in severe infections has not been well defined. We therefore investigated whether an anticoagulant antibody (14E11) that selectively inhibits prothrombotic FXI activation by activated FXII (FXIIa) modifies the course of bowel perforation-induced peritoneal sepsis in mice. Early anticoagulation with 14E11 suppressed systemic thrombin-antithrombin complex formation, IL-6, and TNF-␣ levels, and reduced platelet consumption in the circulation and deposition in the blood vessels. Treatment with 14E11 within 12 hours after bowel perforation significantly improved survival compared with vehicle treatment, and the saturating dose did not increase tail bleeding. These data suggest that severe polymicrobial abdominal infection induces prothrombotic FXI activation, to the detriment of the host. IntroductionInfection-associated intravascular blood coagulation is common in patients with severe sepsis. The resulting coagulopathy is probably driven by bacterial cell components, including peptidoglycans, teichoic acid, polyphosphates, and lipopolysaccharides (LPSs), which have been shown to activate contact proteases and tissue factor-expressing leukocytes. [1][2][3] The host response to bacteria can also produce a systemic inflammatory response syndrome that can contribute to intravascular coagulation and defective fibrinolysis, resulting in disseminated intravascular coagulation (DIC)-associated consumption of platelets, leukocytes, and coagulation factors that cause both thrombosis and secondary hemorrhage. Activation of the contact protease factor XII (FXII) on negatively charged surfaces, including bacterial components, activates prekallikrein and factor XI (FXI) in terrestrial mammals, 4 which results in thrombin generation through the intrinsic coagulation pathway, activation of the complement system, and release of the inflammatory peptide bradykinin from high-molecular-weight kininogen. 5,6 Although the contact proteases appear to play a significant prothrombotic role as part of the intrinsic coagulation pathway, the importance of contact system activation in infection-related hostresponse remains uncertain.Most persons with inherited contact protease deficiencies, including FXII and its substrate prekallikrein, do not have an obvious abnormal phenotype and have normal hemostasis. 7-9 FXI deficiency (hemophilia C) is associated with excessive traumainduced bleeding in a subset of affected persons, 10,11 indicating that FXI can contribute to normal hemostasis. Despite its apparently modest hemostatic role, persons with high plasma FXI levels a...

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“…Recovery from the operation was normal as expected. A rare case of cerebral thromboses in Fletcher factor was reported by Harris et al (1985).…”

Section: Discussionmentioning

confidence: 99%

Fletcher factor deficiency in a woman requiring emergency caesarean section

Odumosu

Yoong

Fakokunde

2009

Journal of Obstetrics and Gynaecology

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Multiple cerebral thrombosis in fletcher factor (prekallikrein) deficiency: A case report

Cited by 39 publications

References 26 publications

Thrombotic Events in Patients with Congenital Prekallikrein Deficiency: A Critical Evaluation of All Reported Cases

Thrombotic Events in Patients with Congenital Prekallikrein Deficiency: A Critical Evaluation of All Reported Cases

Inhibition of factor XI activation attenuates inflammation and coagulopathy while improving the survival of mouse polymicrobial sepsis

Fletcher factor deficiency in a woman requiring emergency caesarean section

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