Coagulation disorders

Abstract

The risk of severe haemorrhage in pregnancy is well recognized, and uncontrolled bleeding remains a major cause of maternal death throughout the world, including the British Isles. The haemochorial system of human placentation carries with it an inherent risk of haemorrhage and this probably explains why the serious congenital disorders of haemostasis are predominantly found in the male. In pregnancy, complex physiological changes occur in the systems responsible for the control of blood loss from the vascular tree. Coagulation and Fibrinolysis during Normal Pregnancy COAGULATION SYSTEMThe effect of pregnancy on the clotting factors can be detected from as early as the first trimester. Plasma fibrinogen gradually increases and levels ranging between 400 mg and 600 mg per cent are usually present in late pregnancy and labour. This elevation of fibrinogen is much greater than occurs in women taking high doses of oestrogen and progestational steroids, and is thus not explained by the effect of these hormones. Factors VII and X likewise show a definite increase and in the third trimester are usually in the range 120-180 per cent. Cold-promoted activation of factor VII when the plasma is exposed to low temperatures for almost 20 hours is a phenomenon which can readily be shown in the plasma of pregnant women and in women using oestrogen/ progestogen contraception; factor VII activity is enhanced as much as ten-fold and activation may be mediated through the kallikrein system (Gj0nnaess, 1973).Factor VIII, as measured by two-stage techniques, has an average value of around 200 per cent in late pregnancy, with a range from 80 to 450 per cent. During pregnancy, Bennett and Ratnoff (1972) found that factor VIII-related antigen (factor VIlI-RA)increased in proportion to factor VIII activity, but our own investigation and that of Bouma et al (1973) showed that the ratio of factor VIII-RA to factor VIII activity, as measured by a clotting assay, slightly increased during pregnancy and the ratio was considerably higher in patients with severe preeclampsia. An increase of factor VIII activity during pregnancy has also been noted in women with congenital deficiency of factor VIII, as found in some carriers of classical haemophilia and in Von Willebrand's disease. Postpartum haemorrhage is a common complication in women severely affected by these congenital deficiencies, particularly where the factor VIII level is seriously depressed and does not increase during pregnancy. In such patients, the administration of factor VIII concentrates or fresh plasma before delivery and during the first three or four days of the puerperium will obviate the risk of uterine haemorrhage. Several authors have reported slight elevations of factor IX during pregnancy. Studies on factor XI reported a decrease during pregnancy, with average levels between 60 and 70 per cent (Nossel et al, 1966). The level of fibrin-stabilizing factor (factor XIII) was investigated by Coopland et al (1969) and a gradual decrease was found during pregnancy with the leve...

Hemostasis in Pregnant Saudi Women

“…14 Weenink et al, 24 using the chromogenic substrate (S 2238) assay we used in this study, found no significant variation in the antithrombin III concentration throughout pregnancy and Puerperium compared to nonpregnant levels. A similar conclusion was reported more recently by Stirling et al 14 Our finding of a slight but statistically significant decrease in antithrombin III levels in the second and third trimesters of pregnancy confirms other reports 22,25 and could be other indirect evidence of thrombin generation. Reports on platelet count in pregnancy have provided discordant results.…”

“…11,15,[17][18][19][20][21] In the present study, the vWFAg/VIII:C ratios in the first, second, and third trimesters are 1.23, 1.7, and 1.6, respectively. Such elevated ratios are common in normal pregnancy 14,22,23 and are indicative of thrombin-induced loss of factor VIII:C activity as a consequence of activation of the coagulation system and thrombin generation. 14 Weenink et al, 24 using the chromogenic substrate (S 2238) assay we used in this study, found no significant variation in the antithrombin III concentration throughout pregnancy and Puerperium compared to nonpregnant levels.…”

α2‐Antiplasmin and α2‐Macroglobulin—The main inhibitors of fibrinolysis—During the Menstrual Cycle, Pregnancy, Delivery, and Treatment with oral contraceptives

“…There is a decrease in the spontaneous fibrinolytic activity and of the vein wall activator activity (6,21). During parturition and placental separation there are changes indicative of activation and consumption of coagulation factors (5,20). A normalization of the low spontaneous fibrinolytic activity and the low vein wall activator activity found during pregnancy takes place almost immediately after placental separation (20, 22).…”

Low Molecular Weight Heparin Novo (LHN-1) Does Not Cross the Placenta During the Second Trimester of Pregnancy

“…Oral anticoagulants are contraindicated because they cross the placenta and may cause fetal abnormalities and death (1 -3 ). Unfractionated heparin (U F -H ) does not cross into the fetal circulation (4,5) and is the anticoagulant o f choice during pregnancy. L ow molecular weight heparins (L M W -H ) present some advantages over U F-H : Their absorption after s. c. administration is more complete and anti-Xa activity is maintained for a longer time (6 -8 ).…”