ABSTRACT
During normal pregnancy the hemostatic balance changes in the direction of hypercoagulability,
thus decreasing bleeding complications in connection with delivery. The most important
initial factor for acute hemostasis at delivery is, however, uterine muscle contractions,
which interrupt blood flow. Global tests such as Sonoclot;rM signature, the Thromboelastogram;rM,
and a new method analyzing overall plasma hemostasis, all show changes representative
of hypercoagulability during pregnancy. Increased endogenous thrombin generation,
acquired activated protein C resistance, slightly decreased activated partial thromboplastin
time (aPTT) and increased prothrombin complex level (PT) measured as international
normalized ratio (INR) of less than 0.9 have been reported as well. In normal pregnancy,
the platelet count is within normal range except during the third trimester when benign
gestational thrombocytopenia, 80 to 150 × 109/L, can be observed. Platelet turnover is usually normal. Activation of platelets
and release of beta-thromboglobulin and platelet factor 4 are reported. The bleeding
time is unchanged during normal pregnancy. Most blood coagulation factors and fibrinogen
increase during pregnancy. Factor (F) XI is the only blood coagulation factor that
decreases. Blood coagulation inhibitors are mainly unchanged but the level of free
protein S decreases markedly and the level of tissue factor pathway inhibitor increases.
Thrombomodulin levels increase during pregnancy. Fibrinolytic capacity is diminished
during pregnancy, mainly because of markedly increased levels of plasminogen activator
inhibitor-1 (PAI-1) from endothelial cells and plasminogen activator inhibitor-2 (PAI-2)
from the placenta. Thrombin-activated fibrinolysis inhibitor is reported to be unaffected.
The total hemostatic balance has been studied by analyses of prothrombin fragment
1+2, thrombin-antithrombin complex, fibrinopeptide A, soluble fibrin, D-dimer, and
plasmin-antiplasmin complex. There is activation of blood coagulation and a simultaneous
increase in fibrinolysis without signs of organ dysfunction during normal pregnancy.
These changes increase as pregnancy progresses. During delivery, there is consumption
of platelets and blood coagulation factors, including fibrinogen. Fibrinolysis improves
and increases fast following childbirth and expulsion of the placenta, resulting in
increased D-dimer levels. These changes are self-limiting at normal delivery. The
hemostatic changes, noted during pregnancy, normalize after delivery within 4 to 6
weeks. Platelet count and free protein S, however, can be abnormal longer. Hemostasis
should not be tested earlier than 3 months following delivery and after terminating
lactation to rule out influences of pregnancy. PAI-1 and PAI-2 levels decrease fast
postpartum, but PAI 2 has been detected up to 8 weeks postpartum. α2-antiplasmin, urokinase, and kallikrein inhibitor levels have been reported to be
increased 6 weeks postpartum.
KEYWORDS
Hemostasis - pregnancy - clotting factors - inhibitors - fibrinolysis - platelets
