Hemostasis during Normal Pregnancy and Puerperium

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 signature, the Thromboelastogram, 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 x 10 9/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. alpha 2 -antiplasmin, urokinase, and kallikrein inhibitor levels have been reported to be increased 6 weeks postpartum.

Evaluation of Acute Phase Proteins in Clinically Healthy Dairy Cows in Perinatal Period and During Lactation

“…The changes in fibrinogen concentration may be related to pregnancy and delivery. It is known that during pregnancy the activation of blood coagulation panel takes place, and these changes in blood coagulation system, including fibrinogen concentration, are normalized within one month after delivery (Hellgren 2003). In our study the highest concentrations of fibrinogen were observed in cows just before calving.…”

A Review of Hemostasis in Normal Pregnancy and Puerperium

“…Frequency of gestational thrombocytopenia was estimated to be 7-12% at term [12,14,15]. A platelet count of 80 x 10 9 /L is considered to be a safe threshold [20] with no impact on either mother [21] or the fetus [15], unless the thrombocytopenic mother has some comorbids [14]. Mothers having platelet count of 150 x 10 9 /L at 28 th week of gestation have a pre-birth platelet count >100…”

“…As a result, an increase in mean platelet volume (MPV), platelet distribution width and large-size platelets in peripheral film were observed in many [7,9,17,25] but not all reports [18,26]. Large-sized platelets may be pathogenic [27] but since platelet turnover is usually normal [20] and platelet count is low therefore, overall effect is a balanced platelet mass [7]. Usually, the platelet count normalizes within 4-6 weeks after delivery [20].…”

Nonclinical aspects of venous thrombosis in pregnancy

“…Elevated plasma levels of clotting factors (such as fibrinogen and thrombin), and reduced anticoagulants (such as protein S, activated protein C, and antithrombin III), are reported to occur during pregnancy (James, 2009;Patil et al, 2013). In addition, fibrinolysis is impaired by an increase in PAI-1 and PAI-2, the latter synthesized from the placenta, with a net result tilting toward thrombotic state (Hellgren, 2003;Patil et al, 2013).…”

“…Similarly, high levels of estrogen with the use of oral hormone contraceptives or hormone therapy augment the increase in the levels of factor VII, VIII, and X, prothrombin, and fibrinogen (Hellgren, 2003). Multiple mechanisms that activate thrombotic processes and mediators in the endothelium are considered to be amplified during pregnancy.…”