Obstetric Medicine >
Volume 1, Number 2 >
Pp. 92-94
Original articles |
* Obstetrics and Gynaecology, University Hospitals of Leicester;
Women's Services, Royal Victoria Infirmary;
Obstetrics and Gynaecology, Royal Shrewsbury Hospital;
Haematology, University Hospitals of Leicester
Correspondence to: H J Maybury Email: helenamaybury{at}yahoo.com
Key Words: puerperium • hypercoagulable state • coagulation • pregnancy • thromboelastography
 | INTRODUCTION |
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 TOP INTRODUCTION METHODSRESULTSDISCUSSIONREFERENCES |
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Understanding the rate of change after delivery and the time at which coagulation returns to non-pregnant levels in a population of healthy women with uncomplicated vaginal deliveries, would provide a baseline of normal physiological changes and a standard against which clinical situations associated with higher risk of thromboembolic disease can be compared. This may then inform the use of selective thromboprophylaxis to reduce morbidity and mortality related to thromboembolic disease.
We used thromboelastography to investigate the time taken for the hypercoagulable state of pregnancy to resolve in a population of healthy women with uncomplicated vaginal deliveries.
| METHODS |
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TOPINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Women were visited at home and gave blood samples weekly for up to 10 weeks postdelivery. A control group of 50 non-pregnant women was also recruited. These women were healthy volunteers, between 18 and 40 years of age who had no personal or family history of thromboembolism, had no medical illness and who were not taking the combined oral contraceptive pill. A single blood sample was taken from this group during the follicular phase of the menstrual cycle.
Blood sampling and analysis
Venepuncture was performed with a 21-gauge needle using minimum stasis into two 3 mL Sarstedt Monovett bottles, containing 0.3 mL of 3.2% sodium citrate. The bottles were not prevacuumed and a conventional syringe technique was used. The first sample was discarded to avoid contamination with tissue thromboplastin and the second was used for analysis by thromboelastography.
Thromboelastography
Twenty microlitres of 0.2 mol/L of calcium chloride were pipetted into a disposable plastic cup, which had been loaded in a prewarmed thromboelastogram. The citrated blood sample was inverted five times to ensure mixing of the sample and then 340 µL of native blood was added to the cup. Five thromboelastographic parameters were analysed: R time, k time, 
angle, maximum amplitude (MA) and coagulation index (CI).
R time (reaction time) is the time from placing the blood in the cup until the first significant levels of detectable fibrin formation. This is the point at which most traditional clotting assays, including prothrombin time and activated thromboplastin time, reach their endpoints.
k Time is the time for achievement of a defined level of clot ‘firmness’. It is the time from R time (beginning of clot formation) until a fixed level of clot firmness is reached (amplitude = 20 mm), giving a measure of the velocity of clot formation.
Angle reflects the kinetics of clot development and the rate of polymerization. The angle is more comprehensive than k time, since there are hypocoagulable conditions in which the final level of clot firmness does not reach an amplitude of 20 mm, in which case k is undefined.
MA is the greatest vertical amplitude of the TEG trace. It measures the maximum strength of the developed clot, being dependent on both fibrin and platelets.
CI describes the overall coagulation and is derived from R time, k time, angle and MA of native or kaolin-activated whole blood tracings. It is determined by the equation, CI = –0.2454R + 0.0184K + 0.1655MA – 0.0241 – 5.022.
Statistical analysis
Statistical analysis was performed using MINITAB version 15 (Minitab Inc., PA, USA). To determine the time point at which coagulation in the postpartum women returned to that of the non-pregnant controls, non-parametric, two independent sample Mann-Whitney U tests were performed. A P value of <0.05 was considered statistically significant.
| RESULTS |
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TOPINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Sixty-one women had between two and eight samples taken, the average number of samples being 5.2. Ten women only had one sample taken due to difficult venous access (two), inability to contact patients (three) and patient choice to withdraw from study (five).
R time
The R time was significantly shorter in the first postpartum week (9.6 minutes vs. 13.9 minutes, P < 0.0001) and remained shortened in the second week (12.2 minutes vs. 13.9 minutes, P < 0.05) (Table 1, Figure 1). By the third week postpartum there was no significant difference when compared with the non-pregnant controls.
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Angle
The angle is increased in the first week postpartum (59.1 vs. 43.3, P < 0.0001), but returns to non-pregnant values by the second postpartum week.
Maximum amplitude
MA took four weeks to return to non-pregnancy levels. It was maximally increased in the first week postpartum (67.1 mm vs. 52.7 mm, P < 0.0001) (Table 1, Figure 2), reduced steadily in the second week (61.2 mm vs. 52.7 mm, P < 0.0001) and the third week (56.6 mm vs. 52.7 mm, P < 0.05), but remained significantly elevated at three weeks compared with the non-pregnant controls.
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By the fourth postpartum week none of the parameters differed from the non-pregnant control population, indicating resolution of the hypercoagulable state of pregnancy.
| DISCUSSION |
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TOPINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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We chose to use thromboelastography as this gives a cumulative measure of the numerous and varied changes in individual coagulant, anticoagulant and fibrinolytic factors that occur after childbirth. Furthermore, studies have confirmed correlation of TEG parameters with clinical risk of thrombosis in a number of clinical settings, including following elective abdominal surgery,2 emergency hip fracture surgery3 and elective major non-cardiac surgery.4 In this study, the R and k times had recovered by three weeks postpartum but the MA remained elevated until four weeks. These results are in keeping with previous observations that fibrinogen, upon which MA is partly dependent, takes four weeks to return to baseline.5
The recent guidelines from the Royal College of Obstetricians and Gynaecologists, recommend risk assessment of all women in labour and after vaginal delivery has resulted in increased vigilance and more widespread use of postpartum thromboprophylaxis.6 However, the required duration of treatment is less certain. Currently, lower risk women receive three to five days of low molecular-weight heparin and for those at higher risk, such as with inherited thrombophilia and/or history of thrombosis, treatment is extended to six weeks. If postpartum TEG parameters do provide an accurate assessment of the totality of coagulation and correlate with clinical events, as they have been shown in other clinical settings, our data would suggest that three to five days thromboprophylaxis may be insufficient and six weeks unnecessarily excessive. Studies giving a global assessment of coagulation status in these higher risk settings and large studies to confirm a correlation with clinical events, are needed to clarify the optimum duration of postpartum thromboprophylaxis. In the meantime, this observational study of low-risk deliveries potentially provides valuable information about the resolution of the hypercoagulable state in a timeframe that has been previously ignored.
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  M Martineau and C Nelson-Piercy Venous thromoboembolic disease and pregnancy Postgrad. Med. J., September 1, 2009; 85(1007): 489 - 494. [Abstract] [Full Text] [PDF]
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