Strengths and Limitations
Our review is the largest reported to date, even following removal of
potential duplicates. The precision of our estimates is therefore
greater.
Many primary studies were case reports or hospital-based series, which
are at risk of bias towards cases or findings of interest, resulting in
potential overestimation of complications. On the other hand, few papers
specifically stated that there were no haemostatic complications in each
case. Our assumption that this means an absence of complications may
result in an underestimate, as theoretically complications may have been
present, but not reported.
The DIC score used to identify cases from laboratory findings is a
composite of prothrombin time, platelet counts and fibrinogen levels
[4]. However, coagulopathy in COVID-19 is associated with a modest
change in these parameters [5], meaning that the DIC score alone may
be less accurate as a measure of COVID-19 coagulopathy in pregnancy. In
addition, many authors did not report fibrinogen levels or prothrombin
time, which will have falsely lowered our rate estimate of coagulopathy.
D-dimer, like C-reactive protein (CRP), is an acute phase reactant,
which can be elevated in trauma or any inflammatory condition. Elevated
d-dimer levels are difficult to interpret, as the etiology of their rise
can be multifactorial. D-dimer elevations can occur during an
uncomplicated pregnancy, though typically they are not as pronounced as
in some of the cases in this study, where the values were reported.
Pneumonia as well has been associated with high D-dimer levels, as have
thromboembolic events. As reported in Pereira et al, pregnant
women who were classified as having severe clinical features of
pneumonia in COVID-19 had higher D-dimer and CRP [7]. On the other
hand, significant elevations of D-dimer were also noted in two reported
cases of COVID-19 associated coagulopathy in pregnancy, neither of which
were complicated by pneumonia or significant respiratory compromise
[43]. While lack of standardisation of D-dimer thresholds in
pregnancy renders interpretation challenging, in these two cases D-dimer
levels were grossly elevated, at 17- and 12- fold the upper limit of
normal [43].
The efficacy of D-dimer in the diagnosis of pulmonary embolism (PE) in
pregnancy has been investigated, with conflicting results. The DiPEP
(diagnosis of PE in pregnancy) group concluded, using D-dimer
measurement by ELISA (counted as negative if <400ng/ml) and
using Innovance technology (reference range 1-1.3mg/L), that D-Dimer was
not useful for the diagnosis of PE in the context of pregnancy [44].
However, Van der Pol et al. reported that D-dimer measurement could be
used in order to rule out PE in this group [45], using a cut of
value of >1000ng/ml if nil clinical criteria were met, or
<500ng/ml where wither there were clinical signs of either
deep vein thrombosis; haemoptysis or where PE was the most likely
diagnosis. Thus, the potential prognostic value of D-dimer in pregnancy
in the setting of COVID-19 cannot be dismissed outright and deserves
further investigation. Additionally, other tools for assessing
hypercoagulability or other forms of coagulopathy such as
Thromboelastography ™ /Thromboelastometry ™ are worth evaluating. An
ISTH review and recommendation for the use of these technologies in
obstetrics has recently been published [46].