June 29, 2022

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Relationship between ionized calcium and postpartum hemorrhage

The relationship between ionized calcium and the severity of postpartum hemorrhage

Relationship between ionized calcium and postpartum hemorrhage.  The Ca2+ level at the time of PPH diagnosis is related to the risk of severe bleeding.

Postpartum haemorrhage (PPH) is often associated with coagulation dysfunction. The purpose of this study is to determine whether the level of ionized calcium (Ca2+) in the diagnosis of PPH is related to the severity of bleeding, which is an important coagulation cofactor. The results of the study will be published in the BJA Journal in May 2021.

Relationship between ionized calcium and postpartum hemorrhage



This is a retrospective cohort study of women who were diagnosed with PPH during vaginal delivery between January 2009 and April 2020.

The Ca2+ levels of women who progressed to severe PPH (the main research target) and those with lighter bleeding were compared at the time of PPH diagnosis.

Severe PPH is defined as 2 units of blood transfusion, arterial embolism or emergency surgery, admission to ICU, or death. The relationship between other variables (such as fibrinogen concentration) and the severity of bleeding was also evaluated.


Among the 436 patients included in the analysis, hypocalcemia was more common in patients with severe postpartum hemorrhage (51.5% vs. 10.6%, P<0.001).

In the multivariate logistic regression model, only Ca2+ and fibrinogen are parameters independently related to the severity of pulmonary hypertension. For every 10 mg/dl decrease in fibrinogen, the odds ratio (OR) is 1.14 (95% confidence interval) , 1.05-1.24; P=0.002) and 1.97 (95%CI, 1.25-3.1; P=0.003). There was no statistical difference in the changes of Ca2+ or fibrinogen (area under the curve [AUC]=0.79[95%CI, 0.75-0.83] vs. AUC=0.86[95%CI, 0.82-0.9]; P=0.09).

The addition of calcium to fibrinogen improved the model, causing the AUC to become 0.9 (95% confidence interval, 0.86-0.93), P=0.03.

Relationship between ionized calcium and postpartum hemorrhage

Table 1 The relationship between clinical and laboratory characteristics and outcomes of 436 women


Relationship between ionized calcium and postpartum hemorrhage

Figure 1 The relationship between fibrinogen, ionized calcium and clinical outcome.



Relationship between ionized calcium and postpartum hemorrhage

Figure 2 The receiver operating characteristic (ROC) curve of fibrinogen, ionized calcium and the combination of the two can be used to predict severe postpartum hemorrhage



The Ca2+ level at the time of PPH diagnosis is related to the risk of severe bleeding. Ca2+ monitoring helps identify and treat high-risk patients.



Expert comments:

The results of this study show that in high-risk patients with PPH (blood gas analysis is required), low calcium levels at the time of diagnosis of PPH are associated with a high risk of severe bleeding, independent of other laboratory and clinical indicators. Therefore, calcium ion concentration as an independent parameter or combined with fibrinogen level can help identify women with high-risk PPH.

Postpartum hemorrhage is the main cause of preventable perinatal death. As many as 70% to 93% of these deaths are considered preventable. Rapid diagnosis and early multidisciplinary treatment can improve maternal prognosis. Most cases of PPH are caused by weak uterine contractions, abnormal placenta, and damage to the reproductive tract. However, fast-developing coagulopathy may lead to an increase in the degree and duration of bleeding. The use of tranexamic acid can reduce mortality and blood loss. The decrease in fibrinogen level is the first sign of impaired coagulation function during PPH, and it is also an important predictor of severe bleeding at the time of PPH diagnosis. The early low fibrinogen level of PPH indicates multiple blood transfusions, the need for surgery and angiographic intervention, admission to the ICU, and death. It is unclear whether this relationship is related or causal.

Studies on healthy volunteers have shown that Ca2+ >0.56 mmol/L is unlikely to cause significant in vitro coagulation abnormalities. Ho and Yip et al. conducted studies on patients with bleeding risk or active bleeding and found that there is a concentration-dependent relationship between the Ca2+ level and the in vitro coagulation intensity measured by the thromboelastogram. Vasudeva et al. described the connection between calcium ions and coagulopathy in severely injured adults without pre-infusion of any blood product. However, neither of these two studies can rule out that hypocalcemia may be a sign of decreased coagulation function due to other reasons. There are no studies to evaluate the in vitro effects of Ca2+ on bleeding or critically ill patients.

Although there are some changes in calcium homeostasis during pregnancy, calcium ion levels remain stable during pregnancy. Ca2+ may play a role in uterine contractions. In an in vitro study, the normal blood calcium state is strongly correlated with the contraction ability of uterine tissue induced by oxytocin, while the contraction induced by oxytocin is different in uterine tissue with abnormal calcium ions. These differences disappeared in the myometrium pretreated with oxytocin. In another trial, the combined use of oxytocin and calcium chloride after cesarean section did not record changes in uterine tone or blood loss. However, a recent study showed that higher doses of calcium chloride (1g) can reduce the incidence of uterine weakness in high-risk patients. If it is true, the dose-dependent effect of calcium ions on uterine tension may become another therapeutic target for PPH treatment.

The Ca2+ concentration at the time of PPH diagnosis is a sign of the risk of severe bleeding. The identification of hypocalcemia may help to quickly identify high-risk patients who require rapid multidisciplinary assistance in obstetric management. This marker may have great clinical value because it can be quickly determined by blood gas analysis. The results of this study indicate that it is necessary to conduct a randomized controlled trial to evaluate the effect of calcium supplements on the clinical course of women with PPH and reduced serum Ca2+ concentration. Further research is also necessary for the reduction of serum Ca2+ concentration and uterine weakness and coagulopathy.



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