D-dimer levels in normal pregnancy : Learnt something Important recently !
Have we ever wondered how six liters of blood in our body flows like a live stream, maintaining the fluidity life long, in spite of an active coagulation system in situ, ready to freeze at the slightest provocation (Invisible vascular wear & tear!) This housekeeping job, within the vast network of the human vascular tree, is silently accomplished by a less apparent system called fibrinolytic system. D-dimer is a physiological breakdown product of this system . D-dimer comes from fibrin monomer. The D in D-dimer stands for the domain. (See below) The ability to detect the D-dimer in the bedside has given us a good opportunity to monitor intravascular thrombus formation and subsequent dissolution in health and disease.
Learning from a false alarm of pulmonary embolism
Recently I came across a pregnant woman in the third trimester with sudden onset dyspnea. Ongoing panic and a hyper response ER protocol ended up in D-dimer estimation. It was 2600μg/ml, which created a false alarm among obstetricians. She was started on heparin by then. Though her saturation was 95%, ECG was normal.An emergency bedside echo revealed normal right atrium and ventricle, no pulmonary HT. The diagnosis of PE was now rejected confidently. The much-dreaded dyspnea turned out to be some patient anxiety. Unnecessary exposure of a fragile pregnant lady to heparin was reverted with much difficulty as no one was willing to discount jacked-up D-dimer still. (Such is the power of sophisticated biomarkers and numbers! I asked them to report the elevated D-dimer as false-positive in bold letters in the case sheet and applied the break to bring the high voltage obstetrical -cardiac consult to a halt )
What is the normal D-dimer levels in blood?
In the strict sense, D- dimer can’t have normality. It is flushed-out molecular debris from clots, levles of which fluctuates depending upon the fibrinolytic load on a given day. It is further limited by lab standardization issues and methodology. (ELISA vs latex ) Currently, a level of <500μg/ml is considered diagnostically useful to rule out DVT/PVE (Good sensitivity /low specificity)
What happens to D-dimer levels in pregnancy?
D-dimer levels are nornally high in pregnancy, and can reach very high levels as well.
What is this source of D-Dimer In pregnancy?
- Pregnancy is a procoagulant condition. (Estrogen Induced effect on fibrinogen and other clotting factors especially factor 2 & 7 ) We presume it is due to more microthrombus activity in materno placental capillary circulation. When there is a pro-coagulant activity, fibrinolytic activity is also high hence elevating FDP and D dimers.
- Pregnancy-associated with diabetes /PIH/preeclampsia elevate it further due to subclinical endothelial dysfunction
- Placental source for D-dimer is documented. (Might be a marker for partial abruption as well)
- The role of the fetus in generating or triggering maternal procoagulant activity is possible with a reverse breach in the placental maternal barrier. (Many of stillbirth, Intrauterine deaths / DIC in mother could reflect pathological faces of hypercoagulation states)
Normality redefined in pregnancy
This paper has something important. Didn’t knew this till now. In the third trimester, D-Dimer can reach up to 4400 in diabetic mothers. It is also worthwhile to note the other common causes for high D- dimers sepsis, autoimmune disorders* and occult malignancy,
*In fact, every normal pregnancy can be termed as a relative autoimmune disorder, as it is impossible for the mother to go through the pregnancy without immunological modification of the host (by fetus or host itself)
Never rely on elevated D-dimer in isolation to diagnose DVT/Pulmonary embolism. This is especially true in pregnancy where even very high levels are physiological. The commonest cause for dyspnea in pregnancy will continue to be anxiety, anemia, PIH & physical deconditioning, and weight gain (not the mitral valve stenosis /PE/or peripartum cardiomyopathy). Yes, It may appear rewarding to think like a specialist, but please realize if we diagnose rare entities, we are “rarely likely” to be correct and the consequences of that are not always pleasant.
1.Siennicka A, Kłysz M, Chełstowski K, et al. Reference Values of D-Dimers and Fibrinogen in the Course of Physiological Pregnancy: the Potential Impact of Selected Risk Factors-A Pilot Study. Biomed Res Int. 2020;2020:3192350.
2.Gutiérrez García I, Pérez Cañadas P, Martínez Uriarte J, García Izquierdo O, Angeles Jódar Pérez M, García de Guadiana Romualdo L. D-dimer during pregnancy: establishing trimester-specific reference intervals. Scand J Clin Lab Invest. 2018 Oct;78(6):439-442.