Viscoelastic Hemostatic Assays for Postpartum Hemorrhage.

This article discusses the importance and effectiveness of viscoelastic hemostatic assays (VHAs) in assessing hemostatic competence and guiding blood component therapy (BCT) in patients with postpartum hemorrhage (PPH). In recent years, VHAs such as thromboelastography and rotational thromboelastometry have increasingly been used to guide BCT, hemostatic adjunctive therapy and prohemostatic agents in PPH. The three pillars of identifying hemostatic competence include clinical observation, common coagulation tests, and VHAs. VHAs are advantageous because they assess the cumulative contribution of all components of the blood throughout the entire formation of a clot, have fast turnaround times, and are point-of-care tests that can be followed serially. Despite these advantages, VHAs are underused due to poor understanding of correct technique and result interpretation, a paucity of widespread standardization, and a lack of large clinical trials. These VHAs can also be used in cases of uterine atony, preeclampsia, acute fatty liver of pregnancy, amniotic fluid embolism, placental abruption, genital tract trauma, surgical trauma, and inherited and prepartum acquired coagulopathies. There exists an immediate need for a point-of-care test that can equip obstetricians with rapid results on developing coagulopathic states. The use of VHAs in predicting and treating PPH, although in an incipient state, can fulfill this need.

Targeted Thromboelastographic (TEG) Blood Component and Pharmacologic Hemostatic Therapy in Traumatic and Acquired Coagulopathy.

Trauma-induced coagulopathy (TIC) is a recently described condition which traditionally has been diagnosed by the common coagulation tests (CCTs) such as prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), platelet count, and fibrinogen levels. The varying sensitivity and specificity of these CCTs have led trauma coagulation researchers and clinicians to use Viscoelastic Tests (VET) such as Thromboelastography (TEG) to provide Targeted Thromboelastographic Hemostatic and Adjunctive Therapy (TTHAT) in a goal directed fashion to those trauma patients in need of hemostatic resuscitation. This review describes the utility of VETs, in particular, TEG, to provide TTHAT in trauma and acquired non-trauma-induced coagulopathy.

Atypical protein kinase C induces cell transformation by disrupting Hippo/Yap signaling.

Epithelial cells are major sites of malignant transformation. Atypical protein kinase C (aPKC) isoforms are overexpressed and activated in many cancer types. Using normal, highly polarized epithelial cells (MDCK and NMuMG), we report that aPKC gain of function overcomes contact inhibited growth and is sufficient for a transformed epithelial phenotype. In 2D cultures, aPKC induced cells to grow as stratified epithelia, whereas cells grew as solid spheres of nonpolarized cells in 3D culture. aPKC associated with Mst1/2, which uncoupled Mst1/2 from Lats1/2 and promoted nuclear accumulation of Yap1. Of importance, Yap1 was necessary for aPKC-mediated overgrowth but did not restore cell polarity defects, indicating that the two are separable events. In MDCK cells, Yap1 was sequestered to cell-cell junctions by Amot, and aPKC overexpression resulted in loss of Amot expression and a spindle-like cell phenotype. Reexpression of Amot was sufficient to restore an epithelial cobblestone appearance, Yap1 localization, and growth control. In contrast, the effect of aPKC on Hippo/Yap signaling and overgrowth in NMuMG cells was independent of Amot. Finally, increased expression of aPKC in human cancers strongly correlated with increased nuclear accumulation of Yap1, indicating that the effect of aPKC on transformed growth by deregulating Hippo/Yap1 signaling may be clinically relevant.