Kulkarni, AA; (2013) Changes in the coagulation system of the mother and fetus: pregnancy, labour and puerperium. Doctoral thesis , UCL (University College London).

Abstract

Aim of this thesis is to study the changes in the maternal coagulation system during pregnancy and puerperium. The effect of labour and mode of delivery on the fetal coagulation system was also studies. A study of 191 women with inherited bleeding disorders showed a significant increase in mean FVIII (p <0.0001), VWF:Ag (p <0.0001) and VWF:CB (p <0.0001) levels in third trimester of pregnancy compared to mean pre pregnancy values, in women with von Willebrand disease (VWD). However, there was no increase in mean factor levels in those with severe VWD. A significant increase in mean FVIII levels (p <0.0001) in third trimester was also observed compared to mean pre pregnancy levels, in haemophilia A carriers, with FVIII level >50 IU dL-1 in 96% pregnancies. A significant increase in mean FIX levels in third trimester (p <0.0001) compared to mean pre pregnancy values was observed in carriers of haemophilia B. However, 29% pregnancies in carriers of haemophilia B had levels below 50 IU dL-1 at term. In women with FXI deficiency, there was only 19% increase in FXI level during third trimester over pre pregnancy level. Pregnancy associated rise in coagulation factors returns to pre pregnancy level after delivery. To assess the exact time when the factor levels start to decline in the immediate postnatal period, a study of FVIII, VWF:Ag and VWF:CB on days 1, 2 and 3 of the puerperium was conducted in 95 healthy pregnant women. There was no significant decrease in mean FVIII, VWF:Ag and VWF:CB levels on days 1 (p=0.17, p=0.36, p=0.21 respectively) and day 2 (p=0.064, p=0.97, p=0.46 respectively) of the puerperium compared to mean factor levels at the onset of labour or immediately prior to elective caesarean section (CS). A significant decrease in mean VWF:Ag and VWF:CB level (p=0.009 and p=0.04 respectively) was seen on day 3 postpartum. In another study, cord blood was obtained from 154 normal full term pregnancies, to study the level of coagulation factors and inhibitors of coagulation and to assess the effect of labour on these parameters. There was a significant difference in mean cord blood levels of FVIII:C (p<0.0001), VWF:Ag (p<0.0001), VWF:CB(p<0.0001), FIX(p=0.0002), FXI(p=0.0008), FXII(p<0.0001) and plasminogen (p=0.01) between cord blood of fetuses who went through labour, compared to those who were born by an elective caesarean section; levels being higher in those who laboured. Babies with meconium stained liquor, had significantly lower levels of FII (p=0.003), FV (p=0.009), FVII (p=0.0004) and FX (p=0.0009) in cord blood compared to those with clear liquor. In conclusion: This study has refined data on the changes of coagulation factor in pregnancy in women with inherited bleeding disorders. There was a significant increase in mean FVIII, FIX and VWF levels in third trimester compared to pre pregnancy level. All women with mild VWD and 96% of carriers of haemophilia A had factor normal (>50 IU dL-1) at term. However, 29% haemophilia B carriers, continue to have factor levels below 50 IU dL-1 at term, thus required prophylactic cover for labour/delivery as well as regional block. The changes in coagulation factors in first trimester in women with IBDs were also been defined in this study. 29% pregnancies with VWD and 24% pregnancies in carriers of haemophilia in this study, had factor levels below 50 IU dL-1 in the first trimester. They require haemostatic measures such as factor replacement, to reduce the risk of haemorrhagic complications in the event of miscarriage, termination of pregnancy and invasive prenatal diagnosis. Epidural catheters are generally removed within 12 h of delivery and it has been recommended that factor levels are reassessed before removal of the catheter. Study of postnatal changes in VWF and FVIII showed a significant drop in mean VWF level on day 3 compared to levels during early labour and FVIII:C levels did not show any statistically significant decrease on day 1, day 2 and day 3 after delivery. Thus, it seems unnecessary to repeatedly check coagulation profiles and factor levels prior to the removal of the epidural catheter, avoiding delay in removal of the catheter and mobilisation and limiting infection risk. The findings may provide an explanation for secondary PPH which most commonly occurs in the second week following delivery. Cord blood levels of FVIII:C, VWF:Ag, VWF:CB, FIX, FXI, FXII and plasminogen were significantly higher in women who laboured, compared to women who had elective caesarean section. Significantly lower values of FII, FV, FVII and FX were found in the cord blood of babies with meconium stained liquor compared to those with clear liquor. The current study provides valuable information on the effect of labour on the coagulation system of the fetus and indicates that, in cord blood, the results of coagulation parameters in the newborn baby should be considered in light of mode of delivery and events of labour.

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