Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor

Stead, Nancy W.; Bauer, Kenneth A.; Kinney, Thomas R.; Lewis, James G.; Campbell, Elizabeth E.; Shifman, Mark A.; Rosenberg, Robert D.; Pizzo, Salvatore V.

doi:10.1016/0002-9343(83)91115-4

Cited by 96 publications

(22 citation statements)

References 33 publications

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“…A novel, likely pathogenic, nonconservative missense variant in the PLAT gene was identified, which segregated with DVT/PE in his family. Loss of function PLAT variants have been associated with decreased release of the thrombolytic protein tPA and thrombophilia and gain of function variants in this gene have been associated with increased tPA release and hyperfibrinolysis 30–33 . Common variants of PLAT gene have been associated with the risk of CVD 34 and myocardial infarction 35 .…”

Section: Discussionmentioning

confidence: 99%

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults

Seidelmann¹,

Smith²,

Subrahmanyan³

et al. 2017

Circ Cardiovasc Genet

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Background With the advent of high throughput sequencing, the identification of genetic causes of cardiovascular disease (CVD) has become an integral part of medical diagnosis and management and at the forefront of personalized medicine in this field. The utility of whole exome sequencing (WES) for clinical diagnosis, risk stratification and management of inherited CVD has not been previously evaluated. Methods and Results We analyzed the results of WES in first two hundred adult patients with inherited CVD, who underwent genetic testing at the Yale Program for Cardiovascular Genetics. Genetic diagnosis was reached and reported with success rate of 26.5% (53 of 200 patients). This compares to 18% (36 of 200) that would have been diagnosed using commercially available genetic panels (p=0.04). WES was particularly useful for clinical diagnosis in patients with aborted sudden cardiac death (SCD), in whom the primary insult for the presence of both depressed cardiac function and prolonged QT had remained unknown. The analysis of the remaining cases using genome annotation and disease segregation led to discovery of novel candidate genes in another 14% of the cases. Conclusions WES is an exceptionally valuable screening tool for its capability to establish the clinical diagnosis of inherited cardiovascular diseases, particularly for poorly defined cases of SCD. By presenting novel candidate genes and their potential disease associations we also provide evidence for the utility of this genetic tool for identification of novel CVD genes. Creation and sharing of exome databases across centers of care should facilitate the discovery of unknown cardiovascular disease genes.

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Section: Discussionmentioning

confidence: 99%

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults

Seidelmann¹,

Smith²,

Subrahmanyan³

et al. 2017

Circ Cardiovasc Genet

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“…Although deficient tissue plasminogen activator synthesis or release from vessel walls, another possible mechanism of hypercoagulability, were not excluded, they do not seem likely. 14 Cerebral venous thrombosis is a rare complication of these thrombotic diseases. It has been reported in patients with antithrombin III deficiency 2 -15 and protein C deficiency 16 but has been only briefly mentioned in patients with protein S deficiency.…”

Section: Discussionmentioning

confidence: 99%

Superior sagittal sinus thrombosis in a patient with protein S deficiency.

Cros

Beltran

Gum

1990

Stroke

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A 30-year-old man presented with sagittal sinus thrombosis. He had a history of multiple thrombotic events since adolescence, and his father had had a similar history. Laboratory studies revealed the complete absence of free protein S in his plasma. Protein S deficiency, an autosomal dominant disorder, is an identifiable cause of cerebral thrombosis. The literature and our experience with this case suggest that long-term anticoagulant therapy may prevent thrombotic episodes in patients with this disorder. (Stroke 1990;21:633-636)

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“…We identified 12 eligible reports (114-125) on plasminogen deficiency types 1 and 2, 7 on dysfibrinogenemia (126-132), 9 on decreased fibrinolytic activity due to decreased tissue plasminogen activator release or increased plasminogen activator inhibitors (133)(134)(135)(136)(137)(138)(139)(140)(141), 3 on heparin cofactor II deficiency (142)(143)(144), and 1 on increased histidine-rich glycoprotein (145). The result of a review analysis using the Mantel Haenszel test and an estimate of the common odds ratio are shown in Table 1.…”

Section: Other Biochemical Abnormalitiesmentioning

confidence: 99%

Familial Thrombophilia: A Review Analysis

Belt¹,

Prins²,

Huisman

et al. 1996

Clin Appl Thromb Hemost

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The correct approach to the management of the asymptomatic carrier with a recognized inherited thrombophilic disorder is uncertain because reliable in formation of the risk of spontaneous (unprovoked) throm bosis in these disorders is not available. To determine the best available estimate of the annual incidence of spon taneous thrombosis in asymptomatic carriers of disorders that have been linked to familial thrombophilia, we per formed a literature review. Using Medline search from 1965 to 1992, supplemented by manual searches, we re trieved all articles that presented data on antithrombin III, protein C, protein S, dysfibrinogenemia, plasmino gen, histidine-rich glycoprotein, heparin cofactor II, and fibrinolysis in relation to thrombosis. Publications were included in the analysis if they (1) reported one or more probands with thrombotic disease and a heterozygous biochemical abnormality of the hemostatic system, (2) assessed the presence of this abnormality in family mem bers independent of the presence or absence of a history of thrombotic disease, and (3) assessed the presence of a history of thrombotic disease in all available family mem bers. The biochemical status and clinical details of all family members reported were extracted from each eligi ble article. For each abnormality the odds ratio for throm bosis was compared in family members with and without the biochemical abnormality. If applicable, thrombosis- free survival and age-specific incidences of thrombosis were calculated. The thrombotic episodes were classified as spontaneous or secondary to a recognized risk factor, and the proportion of spontaneous episodes was calcu lated. The influence of diagnostic suspicion bias in symp tomatic patients with a family history of thrombosis was reduced by recalculating the absolute incidence of throm bosis from the odds ratio after adjusting the incidence of venous thrombosis in nonaffected family members to that observed in the general population. Statistically signifi cant associations between the presence of a biochemical abnormality and a history of venous thrombosis were found for antithrombin III deficiency types 1 and 2a and 2b, protein C deficiency type 1, and protein S deficiency type I. Dysfibronogenemia was statistically significantly associated with venous as well as arterial thrombosis. Thirty-five to 67% of the events were classified as being provoked, as they occurred following exposure to a rec ognized risk factor for thrombosis. The recalculated an nual incidence of spontaneous thrombosis was 0.6 to 1.6%/year. It is concluded that this relatively low inci dence does not warrant life-long continuous use of anti coagulant prophylaxis since the reported risk of major and fatal bleeding associated with the use of oral antico agulants is 2-3 and 0.4%/year, respectively.

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Venous thrombosis in a family with defective release of vascular plasminogen activator and elevated plasma factor VIII/von Willebrand's factor

Cited by 96 publications

References 33 publications

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults

Superior sagittal sinus thrombosis in a patient with protein S deficiency.

Familial Thrombophilia: A Review Analysis

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