H. Graeff

The importance of early laboratory screening methods for maternal and fetal outcome in cases of HELLP syndrome

Over a period of 5 years and 3 months 50 patients with HELLP syndrome were treated at our hospitals. All of these patients fulfilled the criteria of this syndrome described by Weinstein. Pre-eclampsia with HELLP syndrome was either diagnosed correctly by the referring doctor or on admission by the obstetrician on the basis of the laboratory findings. The median time interval between admission and delivery was 3 hours (range: 0.5-40 hours). In 49 patients, Caesarean section was performed, one patient developed a HELLP syndrome 18 hours after vaginal delivery. The median gestational age at delivery was 35 weeks (range: 26-40). Only three of 51 infants died before delivery, and there was one neonatal death, resulting in a perinatal mortality of 7.8%. Apgar scores below 7 occurred in 15 of the newborns after 1 min and in only 2 after 5 min. In 47 cases, Caesarean section and hospital course were free of complications; in three patients postoperative hemorrhages required relaparotomy, in two of these patients puerperal hysterectomy had to be performed. In our experience, the relevant laboratory parameters should be determined in any pregnant women with right upper quadrant pain independent of the severity of pre-eclampsia in order to diagnose HELLP syndrome as soon as possible. Both early control and follow-up of the laboratory parameters and immediate delivery--by Caesarean section, if necessary--may lead to a reduction of maternal mortality and morbidity and to an improvement of perinatal results.

CROSSLINKED FIBRIN DERIVATIVES AND FIBRONECTIN IN ASCITIC FLUID FROM PATIENTS WITH OVARIAN CANCER COMPARED TO ASCITIC FLUID IN LIVER CIRRHOSIS

Ascitic fluid from patients with ovarian cancer and from patients with alcohol induced liver cirrhosis were compared in respect to hematological and related parameters (content of fibrinogen and fibrin (ogen) degradation products, fibrinopeptide A, F-CB3 related antigen, ratio of crosslinked fibrin to non crosslinked fibrin (ogen), fibronectin and total protein). In tumor ascites all parameters except FPA were significantly elevated compared with cirrhosis ascites. Tumor ascites contains a six-fold higher level of fibrin (ogen) degradation products. A considerable portion of it constitute crosslinked (factor XIII induced) high molecular weight fibrin derivatives. Their content is approx. 10 times higher in tumor ascites than in cirrhosis ascites. Characterization of the crosslinked fibrin derivatives revealed the presence of fragments DD, DY, and some other fragments compatible with XY, DXD, DXY, YXY and DXX. The fibronectin content is also significantly higher in tumor ascites compared with cirrhosis ascites. The value ranges showed no overlap. The findings suggest a turnover of fibrinogen in both ascitic fluids via coagulation and fibrinolysis. In tumor ascites however, fibrinogen seems to be catabolized to a higher degree via the degradation of crosslinked fibrin.

Disseminated intravascular coagulation during the continuous infusion of endotoxin in rabbits

Endotoxinemia was produced in rabbits by a continuous intravenous infusion of endotoxin (30 to 50 βg per kilogram per hour) for 8 to 14 hours. Disseminated intravascular coagulation occurred 6 to 14 hours after the onset of the infusion. Fibrin deposition was observed in decreasing order of frequency in kidney, liver, lung, and spleen. Approximately 50 per cent of the treated animals revealed focal glomerular necrosis. The extent of glomerular fibrin deposition was correlated to the occurrence of focal glomerular necrosis. In one group of animals allowed to survive lysis of glomerular fibrin deposition was demonstrated in kidney sections. Hemodynamic studies revealed a rise in central venous pressure during the experiment. The parameters of pH, pCO 2 , serum lactate, and base excess indicated a steady state of metabolic acidosis during the infusion. Renal function revealed a polyuric phase with disturbed medullary function preceding renal failure.

Recent aspects of hemostasis, hematology and hemorheology in preeclampsia-eclampsia

Because intravascular fibrin deposition is found in the glomerular capillaries of patients who have died of eclampsia, it was long assumed that a chronic form of intravascular clotting represents the decisive cause of the condition. Fibrin deposition is also typically observed in the uteroplacental bloodstream. The occurrence of high levels of soluble fibrin and fibrin(ogen) degradation products, which in severe cases can also include fibrin oligomers, in combination with thrombocytopenia and factor VIII consumption were interpreted as additional evidence for the significance of intravascular clotting in the pathogenesis of EPH gestosis. The hemolysis of the microangiopathologic type, which occurs in severe cases, was attributed to the resulting impairment in microcirculation. Doubts regarding this theory arose when it was noted that the course of EPH gestosis is not altered by the use of heparin, and that even in severe cases of eclampsia with hemolysis and thrombocytopenia the plasmatic clotting system is involved only to a small extent and probably only secondarily. More recent investigations have yielded the first evidence of reduced prostacyclin synthesis in maternal and fetal vessels in patients with EPH gestosis. Since prostacyclins lower arterial resistance yet at the same time are strong inhibitors of thrombocyte aggregation, this prostacyclin deficiency could account for the hypertension and the occurrence of platelet thrombi in the placental bloodstream associated with EPH gestosis. The observation of a reduction in the number of thrombocytes as a consequence of increased platelet breakdown, which precedes a rise in the level of fibrin(ogen) degradation products, also points to the significance of an abnormal interrelation between platelets and endothelium. In addition to the plasmatic and thrombocytic hypercoagulability and impaired prostacyclin synthesis, hemoconcentration with increased microvascular permeability is also observed. Early detection of disturbances of the vessel wall and vessel contents may provide a means of prophylaxis.

Amount and distribution pattern of soluble fibrin monomer complexes during the early puerperium

Soluble fibrin monomer complexes (SFMC) were determined in 12 patients following delivery, 2, 4, 6 days and 3 months post partum. Quantitative gel filtration (1 per cent agarose) of the beta-alanine-precipitated plasma samples yielded the relative (per cent of the total fibrinogen content) and absolute (milligrams per 100 ml. of plasma) amount of SFMC. During the early puerperium the amount of SFMC remained essentially constant, with average postpartum values of 6.3 +/- 1.2 per cent and 27.6 +/- 9.1 mg. per 100 ml. (mean and standard deviation). Three months after delivery the level of SFMC was significantly (p less than 0.001) decreased (3.3 +/- 1.3 per cent and 8.4 +/- 3.4 mg. per 100 ml.). The quantitative estimation of SFMC in the early puerperium as presented in this study indicates that a state of hypercoagulability can be evaluated by measuring the thrombin-mediated catabolic products of fibrinogen.

High Molecular Weight Derivatives of Fibrinogen and their Relation to the Total Fibrinogen Content Following the Infusion of Endotoxin in Pregnant Rabbits

High molecular weight derivatives of fibrinogen can be demonstrated in human cases of disseminated intravascular coagulation (DIC) (1, 2) in concentrations of up to 15 % of the total fibrinogen content (3). At least some of these derivatives could also be shown in uncomplicated human pregnancy (4) but the concentrations observed amounted only to 2–3% of the total fibrinogen content. No high molecular weight derivatives could be demonstrated with the methods applied in plasma of healthy male blood donors.

Equipment and General Requirements for the Coagulation Laboratory

Publisher Summary This chapter discusses the equipment and general requirements for the coagulation laboratory. Most coagulation studies are performed at constant temperatures and water baths supplied with a thermostat accurate enough to maintain a water temperature of 37±1°C are widely used. Glass or plastic straight-walled containers are preferable to round containers because they allow observation and magnification without removing tubes. A good light source placed at the side or the bottom of the container is helpful. The prerequisite for reproducable and quantitative results in blood coagulation tests is a clean venipuncture. Minimal contamination with tissue thromboplastin or contact of the blood with human skin or dirty glassware are factors that invariably produce serious errors. Most routine assays are performed in buffer systems covering the physiologic pH range of the blood. The use of compounds capable of binding ionized calcium is indispensable in coagulation work. Trisodium citrate, sodium oxalate, and disodium ethylenediamine tetracetate are all highly effective. Cationic exchange resins such as Dowex 50 or Amberlite IRC-50 can be used to remove ionized calcium from blood.

HELLP-Syndrom@@@HELLP-Syndrome

Summary32 patients suffering from HELLP-syndrome (hemolysis, elevated liver enzymes, low platelets, [pains in the right epigastrium] were treated in the departments of Obstetrics and Gynecology, Universities of Göttingen and Munich (Rechts der Isar) during the last 2 years. The clinical management was the following: 1.Laboratory examinations in each case of “gestosis and asymptomatic placental insufficiency”.2.Patients with HELLP-syndrome were delivered consequently by c.s., if vaginal delivery could not be performed earlier.

Temperature dependent dissociation of soluble fibrin monomer complexes demonstrated by agarose gel filtration

Abstract The temperature dependent dissociation behaviour of soluble fibrin monomer complexes (SFMC) in plasma of post surgical patients was studied using gel filtration chromatography of β-Ala precipitated plasma samples. A temperature dependency in the investigated range between 12° and 37°C was demonstrated with a linear regression y = 5.56−0.07 x and a correlation coefficient r = 0.83. Additional experiments using 125 I-des- A fibrin injected into heparinized rabbits revealed that after gel filtration of whole plasma samples at 20°C 68% of the activity was eluted in front of the fibrinogen elution volume and 32 % with the fibrinogen volume. At 37°C 24 % of the activity was eluted in front of fibrinogen, while 76 % eluted with the fibrinogen peak. The experiments indicate that SFMC are subject to a temperature dependent dissociation behaviour which is also influenced by the type of the complexes.

Blutgerinnungsveränderungen unter der Einnahme von hormonalen Kontrazeptiva

Das Risiko thromboembolischer Erkrankungen als potentielle Nebenwirkung hormonaler Kontrazeption ist seit dem Jahre 1961 bekannt. Damals beschrieb Jordan (6) das Auftreten rezidivierender Embolien bei einer Patientin, die mit Sexualhormonen behandelt wurde. In der Folge wurden eine Vielzahl von kasuistischen Beobachtungen zu diesem Problemkreis veroffentlicht. Man versuchte auserdem den Zusammenhang zwischen thromboembolischer Erkrankung und der Anwendung hormonaler Kontrazeptiva uber grosere epidemiologische Studien zu klaren. Die ersten dieser Studien waren sogenannte Case-Kontrollstudien, bei denen ein Kollektiv von Thrombosepatientinnen (bei Zugrundelegung der klinischen Diagnose) daraufhin untersucht wurde, ob sie die Pille eingenommen hatten oder nicht. Diese retrospektiven Studien zeigten, das das relative Risiko thromboembolischer Erkrankungen bei hormonaler Kontrazeption um das etwa Achtfache ansteigt. Um das Risiko weiter zu prazisieren, versuchte man in prospektiven Kohortenstudien zusatzliche Informationen zu erhalten. Hierbei wird eine Gruppe von Pillenanwenderinnen mit einer vergleichbaren Gruppe prospektiv ausgewahlt und wahrend des Einnahmezeitraums die Haufigkeit thromboembolischer Erkrankungen beobachtet. Auch in diesen Studien bestatigt sich das erhohte relative Risiko, wenngleich die Risikozunahme etwas geringer erscheint. Die absolute Haufigkeit thromboembolischer Erkrankungen liegt bei Pilleneinnahme bei 0,8 auf 1000 Frauen im Jahr und bei den Kontrollen bei 0,2. Die thromboembolische Gefahrdung ist offensichtlich nur whrend der Anwendung gegeben, Rauchen scheint keinen Einflus auf die Entstehung venoser Thrombosen und ihrer Folgeerkrankungen zu haben. Die Summation anderer Risikofaktoren ist unsicher zu beurteilen und kann aus keiner der epidemiologischen Studien wirklich abgeleitet werden. Die Thromboemboliemortalitat steigt nicht uber die Inzidenz einer vergleichbaren Kontrollgruppe und liegt bei etwa 1 auf 100 000 Jahresanwendungen (Ubersicht bei 10).