Tranexamic acid and obstetric hemorrhage: give empirically or selectively?

Antifibrinolytic agents such as tranexamic acid (TXA) inhibit the fibrinolytic pathway and protect blood clots from being degraded, thereby promoting hemostasis. They have been used to reduce blood loss in various settings including obstetrics. Based on current evidence, TXA can be considered as a therapeutic adjunct to control postpartum hemorrhage (PPH) after vaginal and cesarean deliveries, with earlier administration preferred. This strategy has been demonstrated to reduce mortality due to bleeding (but not the incidence of transfusion) in developing countries. On the other hand, the benefit-risk ratio of TXA has not been fully assessed in developed countries which have much lower PPH-related mortality rates and better access to other management modalities. As a proposed prophylactic agent to prevent PPH, the level of evidence is currently insufficient to recommend the routine use of TXA to prevent blood loss after vaginal and cesarean deliveries. The results of large new multicenter studies assessing the impact of TXA on maternal blood loss-related outcomes after cesarean delivery are awaited. While most studies to date have focused on empirical and one-size-fit-all dosing of TXA, more selective and individualized treatment protocols (possibly guided by functional coagulation assays) are needed to pave the way for safer and more effective use of this inexpensive and widely used medication.

Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.

The effect of a novel intravenous fluid (Oxsealife®) on recovery from haemorrhagic shock in pigs.

Blood transfusion is given according to haemoglobin thresholds aimed at restoration of arterial oxygen-carrying capacity. Patient survival after severe haemorrhagic shock depends on restoration of microvascular perfusion, tissue oxygen delivery, endothelial function and organ integrity. We investigated a novel crystalloid fluid designed for tissue oxygen delivery, Oxsealife® , with components that generate microvascular nitric oxide and scavenge reactive oxygen species generated during ischaemia-reperfusion injury. The amount of dissolved oxygen in blood progressively increased during step-wise in vitro haemodilution with this fluid, suggesting that the oxygen solubility coefficient of blood is dynamic, not static. We performed a pilot safety and efficacy study to compare resuscitation with this novel crystalloid vs. whole blood transfusion in a swine haemorrhagic shock model with animals bled to an arterial lactate oxygen debt target. Despite contributing no haemoglobin, viscosity nor oncotic potential, resuscitation with Oxsealife after severe haemorrhagic shock restored central haemodynamic parameters comparable to stored allogeneic blood transfusion. Tissue perfusion, oxygenation and metabolic outcomes were equivalent between treatment groups. Increased consumption of bicarbonate in animals given Oxsealife suggested greater capillary recruitment and enhanced clearance of acidic tissue metabolites. Serum markers of organ function, animal activity during recovery and histological analysis of tissue morphology and endothelial glycocalyx integrity confirmed functional recovery from haemorrhagic shock. We conclude that recovery of tissue oxygen delivery and organ function after haemorrhagic shock may not be dependent on treatments that increase haemoglobin levels. Oxsealife shows promise for treatment of severe haemorrhagic shock and may reduce the requirement for allogeneic blood products.

'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.

In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources.

What is really dangerous: anaemia or transfusion?

Summary While complex physiological mechanisms exist to regulate and optimize tissue oxygenation under various conditions, clinical and experimental evidence indicates that anaemia, unchecked, is associated with organ injury and unfavourable outcomes. More data (especially from human studies) are needed to answer questions regarding the optimal approaches to the treatment of acute and chronic anaemia. Meantime, allogeneic blood transfusions remain the most common treatment, particularly in surgical/trauma patients and those with moderate-to-severe anaemia. Clinical studies emphasize the paradox that both anaemia and transfusion are associated with organ injury and increased morbidity and mortality across a wide span of disease states and surgical interventions. Further characterization of the mechanisms of injury is needed to appropriately balance these risks and to develop novel treatment strategies that will improve patient outcomes. Here, we present the current understanding of the physiological mechanisms of tissue oxygen delivery, utilization, adaptation, and survival in the face of anaemia and current evidence on the independent (and often, synergistic) deleterious impact of anaemia and transfusion on patient outcomes. The risks of anaemia and transfusion in the light of substantial variations in transfusion practices, increasing costs, shrinking pool of donated resources, and ambiguity about actual clinical benefits of banked allogeneic blood demand better management strategies targeted at improving patient outcomes.

Laddering through pedigrees: family history of malignancies in primary breast cancer patients.

A family history (FH) of breast cancer (BC) is a long recognized risk factor for developing the disease. Also, there have been some reports of links between an FH and some other malignancies (mostly uterus, ovary, and prostate cancers), and an increased risk of developing BC. In this paper we present descriptive report of the occurrence pattern of malignancies in families of BC afflicted patients through 4 generations. Patients included 542 Iranian primary BC cases, presenting at an outpatient clinic for treatment and follow-up. Detailed pedigrees were drawn for each patient, and data for a total of 6220 relatives were gathered. Among the probands, 29.9% and 53.9% had a positive FH of BC and other malignancies (OM) respectively. Mean number of breast cancers was nearly double in maternal-lines versus paternal-line relatives. Also, occurrence of brain, uterus, and colorectal cancers was significantly higher in maternal-line relatives, but conversely, liver cancer showed a tendency toward paternal-line relatives (1st degree relatives excluded). The highest frequency of BC involvement was noted in 2nd degree/2nd generation, and 3rd degree/3rd generation relatives. For OMs, although gastric cancer was by far the most frequent OM across pedigrees, uterus cancer, and hematopoeitic system lesions (leukemia) predominated over gastric cancer through the 3rd and 4th generations respectively. We did not find any relation between having a positive FH of BC, and developing early-onset BC. The findings discussed in this paper were partially presented at the 18th UICC International Cancer Congress, Oslo-Norway, 30 June-5 July 2002.

Linking Histopathology and Family History in Breast Cancer.

In order to assess the prognostic value of family history (FH) of malignancies in patients afflicted with breast cancer (BC), we examined FH and histopathologic characteristics of 542 Iranian primary BC patients. Cases with distant metastasis at the time of diagnosis were excluded. Mean age of the studied population was 49 and the most common presenting stage was stage IIA followed by stage IIB. Data on a total of 6089 relatives (1st to 4th generations with the assumption of probands as the 3rd generation) were gathered. FH of BC and other malignancies (OM) was positive in 29 and 54% of cases, respectively. The most common OM's were gastric (67), lung (52) and uterus (47) cancers. We found that a FH of BC does not have any significant correlation with proven prognostic factors but a history of BC among relatives at or before the age of 36 is associated with more aggressive tumours. On the other hand, although FH of OM was associated with an older age of the probands (which is generally associated with a favourable prognosis), tumours of the cases with FH of OM had higher grades, lymphatic invasion being detected more frequently. Also we noted that the younger the age of the relatives diagnosed with cancer, the higher the stage of the probands themselves. All together our study indicates the possibility of a relation between FH of BC and OM, and histopathologic characteristics of the probands' tumours which would put forward FH as a prognostic factor rather than a simple risk factor in BC.