Successful treatment of life-threatening bleeding after cesarean section with recombinant activated factor VII.

Hemorrhagic shock developed in a 29-year-old nullipara without coagulopathy after emergency caesarean section. Treatment with uterotonic drugs, prostaglandins, and conservative procedures with transfusion of packed red cells and fresh-frozen plasma failed to control the diffuse vaginal and uterine bleeding. Finally an intravenous bolus injection of 90 microg/kg recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark), was given and showed success within 20 minutes after administration, without any side effects.

Red cell deformability in gestational hypertension.

Erythrocyte deformability and red cell characteristics (MCV, MCHC, Hct) were studied in 18 patients with gestational hypertension, 24 normotensive primigravidae and 20 nonpregnant nulliparous women. The deformability of red cells was determined by red cell filtration in a filtrometer MF4 after prefiltration through cotton wool. We found a statistically reduced deformability in patients with gestational hypertension compared with normal pregnancy and nonpregnant controls. Our data suggest a strong correlation between red cell filterability and newborn weight (r = 0.59, p < 0.02). The deformability of erythrocyte in gestational hypertension mainly depends on the fluidity of the cell membrane (lipid content). Other factors are the hemoglobin viscosity and the cell membrane surface area/cell volume ratio.

[Hemoglobin--an obstetric risk factor]. / Das Hämoglobin--ein geburtshilflicher Risikofaktor.

The relationship between haemoglobin values (14th to 30th week of gestation), pregnancy outcome and perinatal morbidity was investigated in a prospective study. Subsequently, haemoglobin values, blood pressure, proteinuria and perinatal risk factors, together with the foetal cardiotocogram were abstracted from the obstetrician's records. Preterm birth (25%), intrauterine growth retardation (7.6%) gestational hypertension (31.5%) and low birth weight babies (10.3%) were seen significantly more often in women with haemoglobin > or = 13 g/dl in the 2nd trimester (14-30 wk). We observed a high perinatal morbidity from RDS (9.3%) and newborn hyperviscosity (23.9%) in women with a high haemoglobin level. These results were in agreement with the hypothesis, that a higher blood viscosity or a lack of haemodilution are risk factors for poor placental perfusion.

[Clinical experiences with passive immunotherapy in habitual abortion]. / Klinische Erfahrungen mit der passiven Immuntherapie beim wiederholten Abort.

In a pilot study, 25 patients with histories of repeated abortion were treated by passive immunotherapy with high-dosage immunoglobulin administration (Sandoglobulin). Plasma viscosity, RBC aggregation, hematocrit, PAI, D-dimer and Factor VIIIR:AG were studied in order to detect risks. By September 1, 1992, 16 women had given birth; abortion had recurred in 2 women and 7 were pregnant between the 10th and 37th GW. Five pregnancies terminated in premature/small-for-date births and one neonate had a congenital malformation syndrome. Under immunoglobulin therapy no hyperviscosity or excessive fibronolysis defects with a tendency to thrombosis or restriction of intervillous perfusion were observed. Besides safety for mother and fetus, intravenous immunoglobulin administration has the added advantage that it can be used in cases of primary and secondary abortion and for women with deficient immune response.

[Accumulation of two different hydroxyethyl starch preparations in the placenta after hemodilution in patients with fetal intrauterine growth retardation or pregnancy hypertension]. / Die Speicherung von zwei unterschiedlichen Hydroxyäthylstärke-Präparaten in der Plazenta nach Hämodilution bei Patientinnen mit fetaler Mangelentwicklung oder Schwangerschaftshochdruck.

In a prospective clinical study the safety of two hydroxyethylstarch preparations (HES steril 10%, Fresenius AG, Oberursel = HES-A; Haemufusin, Kabi-Pfrimmer, Erlangen = HES-B) were assessed. In 60 patients with fetal growth retardation and/or gestational hypertension, hematocrit, aPTT, factor VIIIR: Ag, fibrinogen, uric acid, cord blood hemoglobin, hematocrit, pH-value and the fetal/maternal hydroxyethylstarch concentration before and after eight (HES-B) or nine (HES-A) days of treatment were monitored. 500 ml HES-A (n = 36) or HES-B (n = 24) together with the same volume electrolyte solution, were infused daily. Both substances lowered significantly the maternal and fetal hematocrit. Histopathological changes of placenta (trophoblast cells and stroma) taking place after the infusion of HES-A or HES-B were depicted by light microscopy. Administration of HES-A or HES-B was associated with lower values of factor VIIIR: Ag and a prolongation of aPTT, but only HES-B demonstrated a significant effect (31% vs. 12%, p less than 0.01). We observed in 4 (16.7%) cases severe uterine bleeding complications and one woman (4.2%) with abruptio placentae in the group HES-B. Light microscopy shows vacuoled trophoblast and stroma cells after HES infusions. The marked vacuolisation of the placenta after HES-B is due to differences in the physicochemical characteristics of HES-A and HES-B. For this reason, we prefer to administer HES-A in the dilution treatment of patients with placental insufficiency.

Fc receptor blocking antibodies after active immunization for the treatment of recurrent spontaneous abortion.

In a prospective study 140 couples who had at least three spontaneous abortions (RSA) were studied for the presence of Fc receptor blocking antibodies detected by the erythrocyte antibody rosette inhibition (EAI) assay, for anti-paternal cytotoxic antibodies (APCA), and for mixed lymphocyte culture inhibiting (MLCI) antibodies before and after active immunization with paternal lymphocytes. The comparative analysis revealed the EAI assay to possess a higher sensitivity than the APCA and/or MLCI tests in monitoring the specific immune response after active immunization. The success of pregnancy in EAI positive post-immunization patients was not influenced by the presence or absence of APCA or MLCI. In the light of a successful pregnancy outcome of 85.7% (n = 37) in this study we conclude that the monitoring of Fc receptor blocking antibodies is useful in active immunization protocols for RSA patients.

[Changes in plasma coagulation and fibrinolysis following cesarean section and relationship to deep venous thrombosis. Results of a randomized prospective comparative study with 6% hydroxyethyl starch 0.62 and low-dose heparin as thrombosis prophylaxis]. / Veränderungen der plasmatischen Gerinnung und der Fibrinolyse nach Kaiserschnitt-Operationen und die Beziehungen zur tiefen Beinvenenthrombose. Ergebnisse einer randomisierten prospektiven Vergleichsstudie mit 6% Hydroxyäthylstärke 0.62 und low dose Heparin als Thromboseprophylaxe.

Routine postoperative monitoring of plasma coagulation and fibrinolysis system values after cesarean delivery in 191 women who did not develop thrombosis and 16 who did revealed a preoperative defect in the fibrinolysis (PAI, TAT) and inhibitor (AT III) systems. Significant postoperative correlations in the drop in antithrombin levels could not be explained solely by hemodilution. Moreover, a disturbance of the equilibrium of the alpha-2 increase and plasminogen was observed, favouring alpha-2 antiplasmin. Hydroxyethyl starch is capable of simultaneously influencing hypercoagulability and postoperative status. The only difference noted between the two groups of drugs was in the course of the PAI concentration (P less than 0.02). It would therefore appear logical in clinical practice to extend preoperative tests to include determination of the plasminogen activator inhibitor and the thrombin-antithrombin complex.

[Hemostasis and pre-eclampsia]. / Hämostase und Präeklampsie.

A longitudinal study has been undertaken in 125 pregnant women between 25 and 40 weeks of gestation, to provide systematic information on the changes that occur in a wide range of haemostasiological and haemorheological variables. Fibrinogen, D-Dimer, Factor VIIIR: Ag, erythrocyte aggregation and plasma viscosity rose markedly throughout pregnancy. Antithrombin III and alpha 2-antiplasmin were unchanged during pregnancy. There were no significant differences between women in the pre-eclamptic group (N = 16) and the control group. HELLP syndrome (N = 7) was associated with high D-Dimer (p less than 0.05), and TAT (p less than 0.05), low antithrombin III (p less than 0.03), protein C (p less than 0.01) and platelets (p less than 0.001). Our results demonstrate that during pregnancy (also, however, in pre-eclamptic women) alterations of the coagulation system occur, but these changes do not affect the overall haemostatic balance. Findings in patients with "true" HELLP syndrome are consistent with an increased tendency for intravascular coagulation.

[Value of hemodilution therapy in pregnancy]. / Die Bedeutung der Hämodilutionstherapie in der Schwangerschaft.

The ability to produce a large increase in plasma volume is one of the hallmarks of a successful pregnancy. Data from Garn et al. (5), Knottnerus et al. (14) and Murphy et al. (15) have shown, that hemoglobin levels above 13 g/dl or hematocrit 38% before admittance to hospital are associated with a high incidence of IUGR (intrauterine growth retardation), gestational hypertension and with a greater perinatal mortality. Patients with an elevated viscosity and hematocrit have increased perinatal risks. In these cases the hemodilution with hydroxy- ethylstarch (HES) improves the blood flow and decreases the incidence of dysmature babies and pregnancy complications. The effect of HES on certain coagulation assays seems qualitatively similar to those of Dextran. In a prospective trial we evaluated the effect of HES in the incidence of thrombosis after cesarean section and we found a 5.9% incidence of thrombosis in patients treated with 6% HES 0.62 compared with a 7.8% incidence in heparin treated patients. Treatment with 1500 ml 6% HES 0.62 before and after cesarean section is similarly effective in preventing deep vein thrombosis as heparin prophylaxis.

[Deep venous thrombosis in pregnancy: risk factors and possibilities for prevention]. / Die tiefe Venenthrombose in der Schwangerschaft: Risikofaktoren und Präventionsmöglichkeiten.

Twenty-two cases of acute venous thrombosis in pregnancy (0.64%) were studied. Concomitant pulmonary embolism was documented in 0.23%. Prophylactic heparinization was performed in 32 gravidae. In the acute thrombosis group therapy was instituted in the 26th week, and in the prophylaxis group in the 20th week of pregnancy. Recurrent thromboses after cesarean section occurred in 4.5% of the patients with acute venous thrombosis and in 5.6% of those in the prophylaxis group. Reduced red blood cell deformability, low antithrombin III and high leukocyte count were identified as risk factors. Heparinization did not prevent increased red blood cell aggregation and plasma viscosity at birth. Rheologic factors played only a secondary role in the prophylaxis group. Prophylactic heparinization in pregnancy is currently the only means of reducing the thrombosis recurrence rate in patients with a history of thromboembolism.