Tuesday, May 31, 2011
COAGULATION CORNER: JUNE 2011
Coagulation and Pregnancy
There are both physiological and chemical changes in pregnancy that affect the coagulation and fibrinolytic systems. Pregnancy is associated with changes in haemostasis, including an increase in the majority of clotting factors, a decrease in the quantity of natural anticoagulants and a reduction in fibrinolytic activity. These changes result in a state of hypercoagulability and are likely due to hormonal changes which increase the risk of thromboembolism. The increase in clotting activity is greatest at the time of delivery with placental expulsion, releasing thromboplastic substances. These substances stimulate clot formation to stop maternal blood loss. As placental blood flow is up to700mlmin, considerable haemorrhage can occur if clotting fails. Coagulation and fibrinolysis generally return to pre-pregnant levels 3–4 weeks postpartum.
Bleeding can occur in the first trimester due to abortions which may be caused by chromosomal abnormalities, or other reasons which will cause cramping and bleeding resulting in a completed abortion or one that requires intervention to remove the remaining tissue. Other conditions such as ectopic pregnancy, or a tubal rupture can result in intrperitoneal bleeding that requires surgery to mange symptoms. Third trimester bleeding is cause by placenta anomalies. Placenta previa occurs when the placenta is improperly implanted in the lower uterine segment. While abruptio placenta is the premature separation of the placenta form the implantation site. It usually occurs after the twentieth week of pregnancy.
The platelet count decreases in normal pregnancy possibly due to increased destruction and hemodilution with a maximal decrease in the third trimester.This is not a pathological process. It is the most common cause of thrombocytopenia during pregnancy and occurs in 5-8% of all pregnant women. The platelet counts are in the lower range of normal and can be as low as 100x109 L-1. The quantitative decrease in platelets is balanced by enhanced platelet activity. Women with this disorder are not at risk of bleeding. It is a diagnosis of exclusion.
Idiopathic/Immunological thrombocytopenic purpura is an immunological disorder in which antiplatelet antibodies are produced resulting in thrombocytopenia with platelet counts are usually = 50x109 L-1 there is an increased incidence of bruising, epistaxis and gingival bleeding. It is important for labor and delivery that platelet counts = 50x109 L-1 for normal vaginal delivery. As there is transplacental transfer of antiplatelet antibodies the neonate may be born with thrombocytopenia. If fetal platelet count is = 50x109 L-1 then delivery should be by a caesarean section.
Factors VIII(FVIII), vonWillebrandfactor(vWf), ristocetincofactor(RCoA) and factors X(FX) and XII (FXII) increase during pregnancy. Levels of factor VII (FVII) increase gradually during pregnancy and reach very high levels (upto1000%) by term. Fibrinogen also increases during pregnancy with levels at term 200% above pre-pregnant levels. Other factors either remain at non-pregnant levels or decrease during pregnancy. Factor XIII(FXIII), increases in the first trimester but by term it is 50% of non- pregnant levels. Factor V (FV) concentrations increase in early pregnancy then decrease and stabilize. Factor II (FII) levels may increase or not change in early pregnancy but are normal by term. There is debate about factor XI (FXI) levels with reports indicating increases or decreases. Similarly,FIX levels are reported as increasing, decreasing or remaining stable through out pregnancy. In one study, 50% of carriers of FIX deficiency had FIX levels 50 IUdl at term.
Protein C levels remain the same or are slightly increased during pregnancy while protein S decreases. Antithrombin levels remain normal during pregnancy.
Fibrinolysis is reduced in pregnancy due to decreases in t-PA activity, which remains low until1-h postpartum when activity returns to normal. This reduction is due to the gradual, eventually threefold, increase in plasminogen activator inhibitor-1(PAI-1)and the increasing levels of plasminogen activator inhibitor-2(PAI-2). The placenta produces PAI-1and is the primary source of PAI-2. PAI-2 levels at term are 25 times that of normal plasma. Postpartum, t-PA levels quickly return to normal as PA-1 levels decrease; however,PA-2 levels remain elevated for a few days. Thrombin activatable fibrinolysis inhibitor(TAFI)(an antifibrinolytic which cleaves the C-terminal lysine in fibrin to render it resistant to cleavage by plasmin) levels are increased in the third trimester. D-Dimer levels increase in pregnancy but are not thought to indicate intravascular coagulation as fibrinolysisis depressed. These D-Dimers may originate from the uterus
It is important to know the expected levels of these factors during pregnancy so as not to misdiagnosis patients. Many of these levels indicate the bodies protective mechanisms during pregnancy against bleeding and clotting.
Venous thromboembolism (VTE)
Pregnancy is a hypercoagulable state and certain disorders increase the risk of thrombosis. Patients with inherited thrombophilia have an increased tendency to venous thromboembolism. VTE is the leading cause of maternal mortality in the developed world. The risk of pulmonary embolism and deep vein thrombosis is increased during pregnancy. VTE occurs in 10 per 100,000 women of child bearing age and affects100 per100000 pregnancies. Pregnancy-related hypercoagulation is maximal immediately postpartum, increasing the risk of VTE at that time Thromboembolism is 20 times more likely to occur following caesarean delivery than vaginal delivery. The thromboplilias with the highest risk of thrombosis are AT, PC or PS deficiency. The most frequently identified deficiency are those patients presenting with Factor V Leiden. Patients presenting with antiphospholipid antibody are at the highest risk for adverse pregnancy outcomes. Heparin prophylaxsis is recommended for high risk categories.
Disseminated Intravascular Coagulation
Acquired coagulopathies are due to uncontrolled activation of the coagulation system causing disseminated intravascular coagulation (DIC). Once triggered the uncontrolled activation of procoagulants leads to widespread intravascular coagulation. This leads to a fall in the levels of clotting factors to such a low level that they are insufficient to stop further bleeding.
The most common causes of DIC during pregnancy are abruption placentae, intrauterine death, missed abortion, amniotic fluid embolism, ruptured uterus, eclampsia/pre-eclampsi, throphoblastic disease, saline abortion and sepsis
Pregnancy clearly unbalances the coagulation scale causing it to be tipped back and forth between bleeding and clotting. Many of these processes are natures way to protect mothers from bleeding or clotting. However understanding these mechanisms and when factors are elevated are important when managing mom and baby.
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