COVID-19 and acute coagulopathy in pregnancy.

We present a putative link between maternal COVID-19 infection in the peripartum period and rapid maternal deterioration with early organ dysfunction and coagulopathy. The current pandemic with SARS-CoV-2 has already resulted in high numbers of critically ill patients and deaths in the non-pregnant population, mainly due to respiratory failure. During viral outbreaks, pregnancy poses a uniquely increased risk to women due to changes to immune function, alongside physiological adaptive alterations, such as increased oxygen consumption and edema of the respiratory tract. The laboratory derangements may be reminiscent of HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, and thus knowledge of the COVID-19 relationship is paramount for appropriate diagnosis and management. In addition to routine measurements of D-dimers, prothrombin time, and platelet count in all patients presenting with COVID-19 as per International Society on Thrombosis and Haemostasis (ISTH) guidance, monitoring of activated partial thromboplastin time (APTT) and fibrinogen levels should be considered in pregnancy, as highlighted in this report. These investigations in SARS-CoV-2-positive pregnant women are vital, as their derangement may signal a more severe COVID-19 infection, and may warrant pre-emptive admission and consideration of delivery to achieve maternal stabilization.

Ovarian Torsion in the Third Trimester of Pregnancy Leading to Iatrogenic Preterm Delivery.

Ovarian torsion in the third trimester of pregnancy leading to a midline laparotomy and caesarean section for the delivery of a preterm baby is an uncommon event. As the woman is likely to present with nonspecific symptoms of lower abdominal pain, nausea, and vomiting, ovarian torsion can often be misdiagnosed as appendicitis or preterm labour. Treatment and the opportunity to preserve the tube and ovary may consequently be delayed. We report the case of a multiparous woman who had undergone two previous caesarean sections at term, presenting at 35 weeks of gestation with a presumptive diagnosis of acute appendicitis. Ultrasonography described a cystic lesion 6 × 3 cm in the right adnexa, potentially a degenerating fibroid or a torted right ovary. MRI of the pelvis was unable to provide further clarity. The patient was managed by midline laparotomy and simultaneous detorsion of the ovarian pedicle and ovarian cystectomy together with caesarean section of a preterm infant. This report describes that prompt recognition and ensuring intraoperative access can achieve a successful maternal and fetal outcome in this rare and difficult scenario. Furthermore, we would like to emphasise that the risk for a pregnant woman and her newborn could be reduced by earlier diagnosis and management of ovarian masses (Krishnan et al., 2011).

Synergistic intracellular iron chelation combinations: mechanisms and conditions for optimizing iron mobilization.

Iron chelators are increasingly combined clinically but the optimal conditions for cellular iron mobilization and mechanisms of interaction are unclear. Speciation plots for iron(III) binding of paired combinations of the licensed iron chelators desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) suggest conditions under which chelators can combine as 'shuttle' and 'sink' molecules but this approach does not consider their relative access and interaction with cellular iron pools. To address this issue, a sensitive ferrozine-based detection system for intracellular iron removal from the human hepatocyte cell line (HuH-7) was developed. Antagonism, synergism or additivity with paired chelator combinations was distinguished using mathematical isobologram analysis over clinically relevant chelator concentrations. All combinations showed synergistic iron mobilization at 8 h with clinically achievable concentrations of sink and shuttle chelators. Greatest synergism was achieved by combining DFP with DFX, where about 60% of mobilized iron was attributable to synergistic interaction. These findings predict that the DFX dose required for a half-maximum effect can be reduced by 3·8-fold when only 1 µmol/l DFP is added. Mechanisms for the synergy are suggested by consideration of the iron-chelate speciation plots together with the size, charge and lipid solubilities for each chelator. Hydroxypyridinones with low lipid solubilities but otherwise similar properties to DFP were used to interrogate the mechanistic interactions of chelator pairs. These studies confirm that synergistic cellular iron mobilization requires one chelator to have the physicochemical properties to enter cells, chelate intracellular iron and subsequently donate iron to a second 'sink' chelator.