A Tail Vein Bleeding Time Model and Delayed Bleeding in Hemophiliac Mice

Broze, George J.; Yin, Zheng-Feng; Lasky, Nina

doi:10.1055/s-0037-1615666

Cited by 98 publications

(1 citation statement)

References 11 publications

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“…The mouse tail clip assay is the most commonly used bleeding model to measure bleeding time and the amount of blood loss, and it is one of only a few in vivo murine assays. This assay has proven useful to compare the differences between mouse models of hemostatic and thrombotic disorders, especially for evaluating hemostasis in genetically deficient mice (Broze, Yin, & Lasky, 2001;Sambrano et al, 2001) and for testing antihemostatic (Bi et al, 1995;Broze et al, 2001) or antithrombotic (Saito et al, 2016) compounds or drugs. Both total blood loss and time to cessation of blood flow are used as measures of the hemostatic system.…”

Section: In Vivo Clotting Time By Tail Clip Assaymentioning

confidence: 99%

Assessing Blood Clotting and Coagulation Factors in Mice

et al. 2019

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The mammalian blood coagulation system was designed to restrict blood loss due to injury as well as keep the blood fluid within the blood vessels of the organism. Blood coagulation activity in inbred mouse strains varies widely among strains, suggesting that many genomic variants affect hemostasis. Some of these molecules have been discovered and characterized; however, many are still unknown. Genetically modified mouse technologies are providing a plethora of new mouse models for investigating the regulation of blood coagulation. Here we provide a protocol for the tail bleeding time as a primary assessment of in vivo blood coagulation, as well as in vitro methods such as the prothrombin time, activated partial thromboplastin time, and thrombin generation assay. We also provide protocols for the assessment of the activities of specific known factors involved in blood coagulation. © 2019 by John Wiley & Sons, Inc.

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Section: In Vivo Clotting Time By Tail Clip Assaymentioning

confidence: 99%

Assessing Blood Clotting and Coagulation Factors in Mice

et al. 2019

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APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice

Uluçkan

Eagleton

Floyd

et al. 2008

J of Cellular Biochemistry

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Platelets contribute to the development of metastasis, the most common cause of mortality in cancer patients, but the precise role that anti-platelet drugs play in cancer treatment is not defined. Metastatic tumor cells can produce platelet aIIbb3 activators, such as ADP and thromboxane A2 (TXA2). Inhibitors of platelet b3 integrins decrease bone metastases in mice but are associated with significant bleeding. We examined the role of a novel soluble apyrase/ ADPase, APT102, and an inhibitor of TXA2 synthesis, acetylsalicylic acid (aspirin or ASA), in mouse models of experimental bone metastases. We found that treatment with ASA and APT102 in combination (ASA + APT102), but not either drug alone, significantly decreased breast cancer and melanoma bone metastases in mice with fewer bleeding complications than observed with aIIbb3 inhibition. ASA + APT102 diminished tumor cell induced platelet aggregation but did not directly alter tumor cell viability. Notably, APT102 + ASA treatment did not affect initial tumor cell distribution and similar results were observed in b3−/− mice. These results show that treatment with ASA + APT102 decreases bone metastases without significant bleeding complications. Anti-platelet drugs such as ASA + APT102 could be valuable experimental tools for studying the role of platelet activation in metastasis as well as a therapeutic option for the prevention of bone metastases.

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Sustained and Complete Phenotype Correction of Hemophilia B Mice Following Intramuscular Injection of AAV1 Serotype Vectors

et al. 2001

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We previously reported that direct intramuscular injection of non-serotype-2 AAV vectors, especially AAV serotype 1 (AAV1), resulted in expression of supranormal levels of canine F9 in immunodeficient mice. Here we test the ability of the AAV1-F9 vector to deliver sustained expression and correction of factor IX (FIX) deficiency in genetically engineered hemophilic mice. Intramuscular injection of AAV1-F9 resulted in 100-1000 times more canine F9 in plasma of recombinant AAV1-F9 mice compared with injection of AAV2-F9. Assessment of clotting activity by activated partial thromboplastin time confirmed that circulating canine FIX was indeed functional. Moreover, phenotypic correction assayed by tail clip challenge resulted in survival of all AAV1-F9 treated animals, in contrast to naive mice and 50% of AAV2-treated hemophilia B mice, which failed to survive. Administration of cyclophosphamide (CTX) was required to suppress formation of anti-canine FIX antibodies for AAV2-treated animals, whereas it was dispensable for those treated with AAV1-F9. This difference in immunogenicity further emphasizes the usefulness of serotype-specific vectors. Finally, we report that correction of the hemophilia phenotype using AAV1-F9 was complete and persistent (over 8 months), a result that underscores the value of continued exploration of alternative AAV serotype vectors.

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A Tail Vein Bleeding Time Model and Delayed Bleeding in Hemophiliac Mice

Cited by 98 publications

References 11 publications

Assessing Blood Clotting and Coagulation Factors in Mice

Assessing Blood Clotting and Coagulation Factors in Mice

APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice

Sustained and Complete Phenotype Correction of Hemophilia B Mice Following Intramuscular Injection of AAV1 Serotype Vectors

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