Type 3 von Willebrand Disease in Pregnancy: A Systematic Literature Review.

OBJECTIVE: von Willebrand disease (VWD) is a hereditary bleeding disorder. Type 3 VWD is the most severe and rare phenotype that presents many challenges for management of pregnant women. The aim of this study was to review the maternal characteristics and complications in pregnant women with Type 3 VWD. STUDY DESIGN: A systematic literature search was performed to include all publications that address Type 3 VWD in pregnancy. RESULTS: Thirteen studies met the inclusion criteria. There were 28 pregnancies with Type 3 VWD in 17 women. All were diagnosed with Type 3 VWD prior to pregnancy. Concentrate treatment was administered before delivery for 19 pregnancies and postpartum for 26 pregnancies. Eight pregnancies required blood products postpartum. Primary postpartum hemorrhage (PPH) was reported in 48% (10/21) and secondary PPH was reported in 56% (5/9). Secondary PPH occurred between 7 and 22 days. No study reported hysterectomies, intensive care unit admissions, or maternal mortality. All 28 pregnancies resulted in 28 live births at term. CONCLUSION: Our review highlights the maternal outcomes in patients with Type 3 VWD and the different approaches in management during pregnancy and delivery. Despite prior knowledge of this bleeding disorder, PPH was still a significant complication.

Lysosomal storage disease spectrum in nonimmune hydrops fetalis: a retrospective case control study.

OBJECTIVES: Nonimmune hydrops fetalis (NIHF) accounts for 90% of hydrops fetalis cases. About 15% to 29% of unexplained NIHF cases are caused by lysosomal storage diseases (LSD). We review the spectrum of LSD and associated clinical findings in NIHF in a cohort of patients referred to our institution. METHODS: We present a retrospective case-control study of cases with NIHF referred for LSD biochemical testing at a single center. Cases diagnosed with LSD were matched to controls with NIHF and negative LSD testing and analyzed according to the STROBE criteria to the extent the retrospective nature of this study allowed. RESULTS: Between January 2006 and December 2018, 28 patients with NIHF were diagnosed with a LSD. Eight types of LSD were diagnosed: galactosialidosis 8/28 (28.6%), sialic acid storage disease (SASD) 5/28 (17.9%), mucopolysaccharidosis VII 5/28 (17.9%), Gaucher 4/28 (14.3%), sialidosis 2/28 (7.1%), GM1 gangliosidosis 2/28 (7.1%), Niemann-Pick disease type C 1/28 (3.6%), and mucolipidosis II/III 1/28 (3.6%). Associated clinical features were hepatomegaly 16/21 (76.2%) vs 22/65 (33.8%), P < .05, splenomegaly 12/20 (60.0%) vs 14/58 (24.1%), P < .05, and hepatosplenomegaly 10/20 (50.0%) vs 13/58 (22.4%) P < .05. CONCLUSION: The most common LSD in NIHF were galactosialidosis, SASD, mucopolysaccharidosis VII, and Gaucher disease. LSD should be considered in unexplained NIHF cases, particularly if hepatomegaly, splenomegaly, or hepatosplenomegaly is visualized on prenatal ultrasound.

Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time.

Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients' lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture.