Reference Ranges of Coagulation Parameters in Pregnancies of Healthy Women and Women with Mild Bleeding Disorders
Authors: Halimeh Susan , Rott Hannelore , Osseiran Ihsan , Kappert Guenther , Siebert Manuela 
Published: October 2019

Abstract
Introduction:
It is well know that most of the coagulation factor increase during pregnancy in healthy women. Nevertheless the uninterrupted course of coagulation parameters from the beginning until the end of a pregnancy in healthy women has not been described yet. Only reference ranges for the third month and the sixth month of pregnancy are evaluated. There aren't any data available for the course of coagulation parameters during pregnancy in women with known coagulation disorders.
In 2012 we started a study to investigate reference ranges during pregnancy for all coagulation factors, anticoagulants and activation markers of coagulation in 100 healthy pregnant women and 100 pregnant women with a previously known mild bleeding disorders.
The study has been approved by the Ethics Committee Nordrhein.
Samples and Methods:
We analysed samples of pregnant women by conducting the following tests: Blood count, VWF:RCo, VWF:Ag, VWF:CB, Fibrinogen (Clauss), activities of FII, FV, FVII, FVIII (clotting and chromogenic), FIX, FX, FXI, FXII, FXIII. d-dimer, prothrombin fragment 1.2, Quick, partial thromboplastin time, plasma thrombin time , CRP, proteine S, proteine C, antithrombin, Lupus antigoaculant, ACA, ß2-GP in week 10, 16, 22, 28, 34, 40 and 6 weeks post partum (max. +/- 1)
Interim Results:
Currently 21 pregnant women were included in our study. 16 obviously healthy women were used to calculate the reference ranges for pregnancy. Because of strict inclusion and exclusion criteria (no previous spontaneous abortion, no previous placenta haematoma, no previous pre-eclampsia and only natural pregnancies) most of the women are in the group of the no known coagulation disorder so far.
Discussion/Conclusion:
There are signs that defects in the coagulation system can be associated to complications during pregnancy like child loss, intrauterine haematoma and genital bleeding. The evaluation of reference ranges helps to detect and to value coagulation disorders during pregnancy.
It might be possible to explain the higher abortion rate in women with mild bleeding disorders
by determination of reference values of all pro- and anticoagulants during pregnancy. If a treatment with coagulation factor concentrates can help to prevent miscarriage is still subject of ongoing studies.
Determination of reference ranges for coagulation factors in the third trimenon might help to determine the peripartum bleeding risk of women with mild coagulation disorders and to help to decide whether a women needs coagulation factor concentrate during labour.
Limitation:
Based on the strict inclusion and exclusion criteria the number of patients is small.

Disclosures
Halimeh: Biotest: The authors declare that they receive research grant from Biotest AG Other. Rott:Biotest: The authors declare that they receive research grant from Biotest AG Other. Osseiran:Biotest: The authors declare that they receive research grant from Biotest AG Other. Kappert:Biotest: The authors declare that they receive research grant from Biotest AG Other. Siebert:Biotest: The authors declare that they receive research grant from Biotest AG Other.