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M Wramsby

Publications and source records attributed to M Wramsby.

3 recordsLinked to original sources

Decrease in protein C inhibitor activity and acquired APC resistance during normal pregnancy.

BACKGROUND: Since protein C inhibitor (PCI) inhibits activated protein C (APC) and a number of proteases, one would expect lower concentrations of PCI in a hypercoagulable state due to increased consumption of the inhibitor. Normal pregnancy is associated with a state of activated hemostasis, where response to APC is depressed. We aimed to study whether PCI function varies during normal pregnancy, and assess the relationship between this inhibitor and acquired APC resistance. METHODS: PCI activity in plasma was tested during pregnancy and postpartum in 28 healthy pregnant women without factor V Leiden Arg(506) - Gln mutation and in 14 non-pregnant female controls. The PCI levels determined in the present study was compared to the APC ratio (APC-r), we investigated previously, in the same samples. RESULTS: The levels of PCI in the pregnant group, as compared to that in the control group (4.74 +/- 0.48), gradually decreased from the first to the third trimester, i.e., 3.30 +/- 1.31 microg/mL in week 12 (p < 0.001), 2.66 +/- 1.44 microg/mL in week 20 (p < 0.001), 1.92 +/- 1.18 microg/mL in week 28 (p < 0.001), 1.30 +/- 0.94 microg/mL in week 32 (p < 0.001) and 1.49 +/- 1.12 microg/mL in week 37 (p < 0.001). After delivery, they rose to 5.02 +/- 1.93 microg/mL, similar to that in the controls (p > 0.05). The values of APC-r showed the same tendency during gestation and postpartum. CONCLUSION: With advance of normal pregnancy, decreasing PCI function corresponds to increasing APC resistance, probably due to that activated hemostasis acts as a link connecting the two variables.

Activated Protein C Resistance↗

Reactivity against phospholipids during pregnancy.

Antibodies against phospholipids (PLa) are often thought to be associated with the development of activated protein C (APC) resistance. In the present study, PLa were followed throughout 29 healthy pregnancies and compared to APC resistance. The level of PLa did not change during pregnancy [6.9 +/- 3.7 GPL week 12 versus 6.3 +/- 2.8 GPL week 37; 3.3 +/- 1.8 MPL versus 3.2 +/- 1.5 MPL; and lupus anticoagulant (LA) coefficient 0.99 +/- 0.11 versus 0.94 +/- 0.09], in contrast to the APC resistance, which was suppressed (0.96 +/- 0.22 versus 0.78 +/- 0.13, P < 0.05), but both parameters elevated after delivery (up to 8.7 +/- 4.2 GPL; 1.13 +/- 0.1 LA coefficient; 1.11 +/- 0.22 nAPC ratio; P < 0.05). Three women possessed PLa (1 CLa IgG +/- IgM; 1 IgG CLa +/- PSa +/- PEa; 1 PSa), no LA activity was registered. In the PLa-positive women, dynamics of the nAPC ratio during pregnancy was not related to PLa.

Activated Protein C Resistance↗

Variability of the response to activated protein C during normal pregnancy.

The response to activated protein C (APC) was investigated in 28 healthy women, non-carriers of the Arg506-Gln mutation in factor V, throughout pregnancy (gestation weeks 12, 20, 28, 32 and 37) and after the delivery. A suppression of APC response was observed which reached lowest values by week 28 (nAPC-ratio 0.78 +/- 0.13), sustained low up to the end of pregnancy and rose after delivery (1.11 +/- 0.22; P < 0.05). APC resistance (nAPC ratio < 0.75) was registered in 16 of the 28 women (57%). A reduction of APC ratio was directly related to its value in the non-pregnant state, being most pronounced in the women with the highest APC ratio. Factor VIII increased during pregnancy and correlated inversely to APC ratio (Z coefficient = -0.645, P < 0.0001). The correlation became weaker in the course of pregnancy, losing significance by week 32. This was explained by the differences in profiles of the two variables: the lowest measured APC ratio preceded the peak of factor VIII in most cases. The most pronounced rise of factor VIII was found in the women with minimal levels of APC ratio between 0.8 and 0.7. These results allowed us to speculate that APC response is closely regulated during pregnancy, aiming to maintain a certain relevant level. Transitory reduction of APC response is connected to factor VIII and discussed as a prevalent mechanism of functional APC resistance during pregnancy.

Adult↗