Relevance of plasma fibrinogen estimation in obstetric complications.H Parasnis, B Raje, IN Hinduja
Dept of Gynaecology and Obstetrics, Seth GS Medical College, Parel, Bombay, Maharashtra.
We present a study of fibrinogen levels in 133 patients who were prone to develop disseminated intravascular coagulation as a result of an underlying complication of pregnancy such as abruptio placentae, pregnancy-induced hypertension, missed abortion, septic abortion, intrauterine fetal death, vesicular mole and amniotic fluid embolism. A high incidence of hypofibrinogenemia was found in cases of abruptio placentae (43.9%) and pregnancy-induced hypertension (25%). Hypofibrinogenemia occurred in 10% cases of intrauterine fetal death within 4 weeks of fetal demise. The use of this simple investigation makes possible the diagnosis of hemostatic failure and also helps to guide replacement therapy during the fibrinopenic state. There were 4 maternal deaths and 12 perinatal losses in this study.
Keywords: Abruptio Placentae, complications,epidemiology,Disseminated Intravascular Coagulation, blood,complications,epidemiology,Female, Fetal Death, epidemiology,Fibrinogen, analysis,Human, Hypertension, complications,epidemiology,Incidence, Pregnancy, Pregnancy Complications, Cardiovascular, epidemiology,Pregnancy Complications, Hematologic, blood,epidemiology,Pregnancy Outcome, Prospective Studies, Risk Factors,
Hemostatic failure, as an end result of various complications of pregnancy, is an important cause of maternal mortality in India,. The occurrence of disseminated intravascular coagulation (DIC) in various obstetric complications such as abruptio placentae, intrauterine fetal death (lUFD), missed abortion, septic abortion, pregnancy induced hypertension (PIH), and amniotic fluid embolism is known,,,,,,,,,.
The diagnosis of this dreaded complication usually requires complicated laboratory tests, which may not be feasible at all centres.  Estimation of plasma fibrinogen, on the other hand, is a simple and accurate method of diagnosing hemostatic failure.
The present communication deals with our study of fibrinogen levels in various obstetric complications and its correlation with the outcome of pregnancy.
A prospective study was carried out at the University hospital in Bombay where on an average, 4,000 deliveries are conducted every year. During a period of two years (1988-1989), 133 cases presenting with various obstetric complications such as abruptio placentae, PIH, IUFD, missed abortion, septic abortion and amniotic fluid embolism were studied. The mean age of the patients was 24.3 years and the mean parity was 2.4.
Plasma fibrinogen was estimated routinely at the time of admission in these patients. In cases of lUFD, serial fibrinogen estimations were required. Thus, a total of 167 estimations were performed in 133 patients. Clotting time was measured in some cases as part of the routine clinical work-up, on clinical suspicion of DIC, coagulation profile was done.
Plasma fibrinogen was estimated by King's microjeldahl precipitation method, which involved isolation of fibrin from plasma, acid digestion, messlerisation and comparison with a standard,.
Plasma fibrinogen levels were then correlated with the occurrence of clinical manifestations of DIC, the line of therapy followed, and the maternal and perinatal mortalities.
Hypofibrinogenemia (Plasma fibrinogen < 300 mg%) was found in 38 of the 133 cases thus giving an incidence of 28.6%. The hypofibrinogenemia was mild (plasma fibrinogen 150-300 mg%) in 30 of these 38 patients (78.9%) and severe (plasma fibrinogen < 150 mg%),, in the remaining 8 patients (21.1 %).
The incidence of hypofibrinogenemia in various obstetric complications and the correlation with maternal and perinatal mortalities is shown in [Table - 1]. The mean fibrinogen level in cases of abruptio placentae was found to be 209 mg%.
Hypofibrinogenemia occurred within 4 weeks of fetal demise in 3 of the 30 cases with IUFD (10%) and occurred after 4 weeks of fetal death in 6 of the 30 cases (20%). Of the 15 patients with a missed abortion of less than 12 weeks gestational age, only 2 (13.3%) developed hypofibrinogenemia, whereas of the 2 patients with missed abortion of more than 12 weeks gestational age; developed severe hypofibrinogenemia. All the 8 patients of severe hypofibrinogenemia developed clinical manifestations while none of the patients with normal fibrinogen levels developed DIC.
In the cases with mild hypofibrinogenemia, blood transfusions alone sufficed to stabilise the clotting system of the patient clinically. However, in the cases with severe hypofibrinogenemia, fresh frozen plasma and cryoprecipitate were required in addition to blood transfusions to correct the clotting deficiency.
A common terminal event in pregnancy induced complications is the occurrence of DIC,,,,,,,,,, which is responsible for maternal mortality,.
After the onset of clinical manifestations, the diagnosis of DIC is simplified but the treatment becomes difficult. Thus, it is important to diagnose DIC at its subclinicai stage so that early therapeutic measures can be instituted. The estimation of plasma fibrinogen is helpful not only in the early diagnosis of hemostatic failure but also to puide replacement therapy during the fibrinopenic state.
In patients with abruptio placentae, the incidence of hypofibrinogenemia was found to be 43.9% in this study, which is significantly higher than the incidence of 25-38% found in another study. The incidence of severe hypofibrinogenemia in abruptio was found to be 9.7% in this study which compares favourably with the range of 4 - 10% quoted by Sher,. Only 5 patients (13%) with abruptio placentae in this study later developed clinical manifestations of DIC.
In abruptio placentae, hypofibrinogenemia may be associated with increased levels of fibrin degradation products, which are known to inhibit myometrial contractifity,,. Thus, its detection warns the physician of the possibility of postpartum haemorrhage.
A good correlation has been reported between plasma fibrinogen levels and the amount of blood loss in a case of abruptio placentae. The presenting fibrinogen level of < 150 mg% indicates a loss of 2,000 ml of blood. The fibrinogen level helps to calculate the amount of blood required to stabilise a patient's hemodynamic condition. Particularly in concealed haemorrhage, a vast underestimation of blood loss frequently occurs and when the vital signs deteriorate it may be difficult or impossible to catch up.
We found that the mean fibrinogen level in cases of abruptio placentae was 209 mg%, which compares favourably with the figure of 170.8 mg% found by 13hattacharya and Malkani. However, this is stli significantly lower than the normal range (300-600 mg%) for pregnancy.
In the women with IUM, hypofibrinogenemia occurred within 4 weeks of fetal death in 10% and after 4 weeks of fetal death in 20% of the cases thus giving a total incidence of 30%. Earlier, Jimenez and Pritchard reported that hypofibrinogenemia is unlikely to occur within a period of 5 weeks after fetal demise. They also found that only one third of the patients with a dead fetus retained in utero for more than 5 weeks had fibrinogen levels < 1 50 mg%. However, findings of our study are supported by Hatch et al who have shown that the time interval between fetal death and uterine evacuation does not influence the development of coagulopathy.
Furthermore, the balance of evidence indicates primary fibrinogen consumption as the cause of coagulopathy in IUM. From a practical point of view, one should therefore measure the fibrinogen level rather than rely upon other tests as an indirect measure of DIC. Also, the clotting system must be evaluated before initiating therapeutic measures for termination of pregnancy, even if less than 4 weeks have elapsed since fetal demise. Similar precautions are indicated for cases of missed abortion where the underlying pathology responsible for hypofibrinogenemia is similar to that of IUFD. This is especially important in view of the high incidence (17.7%) of hypofibrinogenemia in missed abortion observed in this study.
Although, hypofibrinogenemia occurred in only 1 case each, of vesicular mole (11.1%) and septic abortion (6.7%), it is advisable to order a coagulation screen in all patients of vesicular mole and septic abortion. A similar suggestion was made earlier in a study by Talbert et al.
The incidence of hypofibrinogenemia in cases of pregnancy, induced hypertension was found to be as high as 25%. Most other studies have found fibrinogen levels to be normal in cases of PIH,,. An interesting observation was that in 3 of 15 patients (20%) with normal plasma fibrinogen levels, clotting time was prolonged. The decreased hepatic blood supply in cases of P1H may bring about a qualitative alteration in the fibrinogen molecule and hence the prolonged clotting time in spite of normal plasma fibrinogen levels. This has been termed as ‘dysfibrinogenemia’.
In conclusion, estimation of plasma fibrinogen is a simple method of evaluating obstetric patients prone to hemostatic failure. It's importance lies in the fact that it helps to diagnose a fibrinopenic stage when effective therapeutic measures can completely reverse the condition. We recommend that this estimation be part of the routine work-up of all patients with obstetric complications such as abruptio placentae, pregnancy induced hypertension, missed abortion, septic abortion, vesicular mole, intrauterine fetal death and amniotic fluid emolism.
We are grateful to the Dean, Seth GS Medical College and King Edward Memorial Hospital for allowing us to publish this data.
[Table - 1]