Currently, there is a paucity of data that addresses the diagnostic utility of D-dimer in pregnant and post-partum populations with suspected PE. Not surprisingly, there is no clear guidance on the management of this specific cohort of patients due to the lack of evidence available.
Before our study, the only available data that directly addressed the above clinical dilemma was by Damodaram et al. [15], a retrospective case study comprising 37 women with suspected PE that underwent ventilation/perfusion diagnostic scanning. There is also a case report based on a single pregnant patient with PE [16]. Hence, our retrospective study comprising 93 pregnant and post-partum patients with recorded D-dimer levels represents the largest study sample to date.
Our study data showed that the sensitivity and specificity of D-dimer as a screening test for suspected PE in pregnant and post-partum patients undergoing emergency diagnostic imaging was 100 and 42%, respectively, while the negative likelihood ratio was 0 (Table 2). These results appear to be principally dictated by the lack of a single positive PE diagnosis when the D-dimer measure was below the 0.5 mg/L cut-off.
By contrast, Damodaram et al. [15] showed the sensitivity of 73% and specificity of 15%, respectively, while the negative likelihood ratio was 1.8. Their D-dimer cut-off point was also 0.5 mg/L. However, a moderate probability V/Q was also considered as a positive diagnostic test for PE. This is against the current guidelines [10, 11, 17]. A single case report by To et al. [16] illustrated a case of a pregnant patient with objectively diagnosed PE, but with a negative D-dimer.
Clearly, we need a larger prospective study to determine with confidence if a negative D-dimer result can safely rule out the diagnosis of PE in pregnancy as our study findings contradict those of the existing smaller retrospective study [15] and of the case report [16].
In the non-pregnant woman, a negative MDA latex agglutination D-dimer test helped to rule out VTE (both DVT and PE) in those with both intermediate and low clinical probability with the pooled sensitivity 97%, specificity 46%, +LR 1.8 and −LR 0.07 [18]. It is likely that the same D-dimer assay, as utilised in our study, could be potentially useful as a means of ruling out PE in pregnant and post-partum patients.
Our D-dimer data appeared to show increasing linear trends throughout gestation for both non-PE and PE groups (Fig. 2), but these trends were not significant in a regression analysis. This lack of significance could be due to the impact of outlying values and a lack of power attributable to the small sample size. Unfortunately, we had insufficient data to apply the results to patients in the individual stages of gestation (trimesters and post-partum).
Our data did not show any significant differences in median HR, MAP, SI and A-a gradient amongst pregnant and post-partum patients between non-PE and PE groups (Table 3). Only the A-a gradient was close to being statistically significant. None of these clinical presentation variables were significant predictors of PE during pregnancy and post-partum periods.
There is no published data that addresses the relationship between the A-a gradient and PE in pregnant and post-partum populations.
Stein et al. examined the data derived from PIOPED I for any potential diagnostic utility of an A-a gradient for PE in non-pregnant patients [19]. They found that normal values of the A-a gradient did not exclude the diagnosis of acute PE.
One needs to recognise a fundamental physiological difference in the population characteristics between those in PIOPED I and II trials [10, 11]—generally older patients with variable baseline cardio-pulmonary function vs. pregnant and post-partum patients and younger patients with healthy baseline cardio-pulmonary function. Hence, an abnormal A-a gradient could prove to be a more significant predictor of PE amongst our study cohort, compared to that of the PIOPED cohorts. Further investigation and more data are needed to assess this relationship further.
Limitations
The study relied on the retrospective data collection with subsequent absence of some data. It is also a single-centred study with a relatively small number of participants. Nonetheless, it is still the biggest study to address the utility of D-dimer in the diagnosis of pregnancy-associated PE.
The study identified only those patients with suspected PE who underwent emergency diagnostic imaging. It is possible that some patients were discharged home from the emergency department or antenatal clinics with a normal D-dimer and no imaging but had subsequently developed PE. Such patients would not have been captured in our data if they had sought health care services elsewhere for treatment.
Finally, it is possible that CTPA or V/Q imaging were considered unnecessary in some patients but still treated for presumed PE, i.e. positive bilateral leg DVT scans or echocardiography findings suggestive of PE. The study focused on CTPAs and V/Q scans as the diagnostic imaging of choice, as this is the accepted practice in the authors’ hospital. However, it is likely that there are other accepted modes of investigation across different healthcare settings. This lack of agreement is due to the absence of consensus in the national or international guidelines.