Platelet behaviour on von Willebrand Factor changes in pregnancy: Consequences of haemodilution and intrinsic changes in platelet function

Abstract

Platelet function in pregnancy is poorly understood. Previous studies of platelet function in pregnancy have used non-physiological assays of platelet function with conflicting results. This study using a physiological assay of platelet function investigated platelet interactions with von Willebrand Factor (VWF) in blood from healthy pregnant women and healthy non-pregnant controls. Blood samples (200 µl) from third-trimester pregnancies (n = 21) and non-pregnant controls (n = 21) were perfused through custom-made parallel-plate flow chambers coated with VWF under arterial shear (1,500 s−1). Multi-parameter measurements of platelet interactions with the immobilized VWF surface were recorded by digital-image microscopy and analysed using custom-designed platelet-tracking software. Platelet interactions with VWF decreased in healthy third-trimester pregnant participants relative to controls. This effect is most likely due to haemodilution which occurs physiologically during pregnancy. Interestingly, platelets in blood from pregnant participants translocated more slowly on VWF under arterial-shear conditions. These decreases in platelet translocation speed were independent of haemodilution, suggesting intrinsic changes in platelet function with pregnancy.

Blood group alters platelet binding kinetics to von Willebrand factor and consequently platelet function

“…Because initiation of thrombosis in the arterial circulation is mediated primarily through the platelet GPIb and GPIIbIIIa receptors, we sought to characterize the dynamic interaction of platelets in flowing blood on VWF using a well-characterized assay of platelet function that mimics arterial shear conditions. [16][17][18] This assay, which we have termed the dynamic platelet function assay (DPFA), measures the motional parameters of individually tracked platelets as they tether, translocate, and adhere to VWF.…”

Recombinant vs plasma-derived von Willebrand factor to prevent postpartum hemorrhage in von Willebrand disease

“…The question is why VWF at a higher dose (ie, 80 IU/kg), whether rVWF or pdVWF, failed to prevent PPH. Some potential explanations include the concomitant bleeding risk in patients with an underlying bleeding disorder together with well-established acquired coagulopathies associated with pregnancy, including the dilutional coagulopathy associated with the increased blood volume of pregnancy, 11,14 rapid hormonal-associated decrease in VWF and FVIII at delivery, 3,21 platelet functional defects associated with pregnancy, 22 and/or activation of the fibrinolytic system within the first 3 hours of delivery. 23 If PPH in women with VWD is a combined coagulation disorder (ie, a result of defective hemostasis associated with VWD and defective hemostasis associated with pregnancy), perhaps a combined approach is needed to prevent PPH.…”

Case-based discussion on the implications of exogenous estrogens in hemostasis and thrombosis: the hematologist’s view

“…27 In the WOMAN trial, a large randomized double-blind placebo-controlled trial of .15 000 women from low-to middle-income countries, tranexamic acid was shown to reduce PPH and mortality when given 28 Iron deficiency 29 Uterine atony 27,37 Dilutional coagulopathy 44 Prolonged hospitalization 28 II. Current approach to management Transfusion of PRBCs 28 Fluid resuscitation 47,48 Uterotonics, uterine compression 29 Iron supplementation 29 Antifibrinolytic agents [30][31][32][33][34] VWF concentrates 27,[35][36][37][38][39][40][41][42][43] PRBCs, red cell transfusions.…”

“…Hemostatic support with clotting factor is the recommended approach to PPH prevention in women with VWD (Table 4). Based on expert guidance, 27,[35][36][37][38][39][40][41][42][43] a VWF level . 50 IU/dL is recommended before epidural analgesia.…”