Helge Stormorken

Hereditary α2-antiplasmin deficiency

Le temps de saignement du cas indicateur etait normal, sans allongement important apres acide acetylsalicylique. Les produits de degradation du fibrinogene netaient pas augmente mais chez lindicateur la lyse des englobulines etait notablement plus courte que chez le temoin avant et apres stase. La concentration et lactivite du fibrinogene etaient normales alors que lactivite et la concentration de lα 2 -antiplasmine etaient reduites de plus de moitie, et la sensibilite a la plasmine fortement augmentee chez lindicateur

Lupus Anticoagulant: A Unique Case with Lupus Anticoagulant and Habitual Abortion together with Antifactor II Antibody and Bleeding Tendency

Lupus anticoagulants (LA) are associated with various forms of thrombotic events. Of particular interest to obstetrics is the association with placental infarcts and habitual abortion. In the case described a near full-term viable infant was delivered subsequent to four early miscarriages. However, the mother had then developed an antifactor II antibody leading to grave hypoprothrombinemia with bleeding tendency, indicating efficient autoanticoagulation. This natural experiment indicates that these patients should receive anticoagulation during pregnancy, possibly in combination with steroids to depress the LA level.

Chromogenic Substrate Assay of Plasma Prekallikrein

A method for assaying plasma prekallikrein has been developed applying the chromogenic substrate Chromozym PK. Different variables have been investigated, and the final assay system was found to give

Interrelations between the Clotting and Kinin Systems

A survey is given of the most recent work on interrelations between the coagulation and kinin systems. The recent identification of the Fletcher factor with prekallikrein has established another link between the clotting and kinin systems besides factor XII. Further links are provided by the cold activation of factor VII by factor XII-prekallikrein, and the feedback activation of factor XII by kallikrein. These new apprehensions also have consequences for the theory of intrinsic clotting, and the relation between the intrinsic and extrinsic system, and emphasize the complex function of factor XII.

A new case of total kininogen deficiency

Six families with total kininogen deficiency have been described in the literature. We report herein an additional case in a Pakistanese woman. The defect was discovered accidentally due to lack of normal clot formation in a preoperative routine blood sample. She had a borderline prolonged bleeding time, and reported occasional hematuria, but was otherwise without symptoms. Absence of both kininogen species was proven by functional and immunological methods, and by lack of kinin formation both by plasma kallikrein and hog pancreas kallikrein. Prekallikrein was reduced, probably because the main part circulates complexed to high molecular kininogen. Activation of intrinsic fibrinolysis was grossly hampered, and cold activation of coagulation absent with epsilonaminocaproic acid and greatly retarded by dextran sulfate, kaolin and ellagic acid. Together with other evidence the findings indicate the following order of importance for contact activation in plasma--F.XII, high molecular weight kininogen, prekallikrein.

STUDIES ON COAGULATION AND FIBRINOLYSLS IN BLOOD FROM PUERPERAL WOMEN WITH AND WITHOUT OESTROGEN TREATMENT

Coagulation and fibrinolytic studies were made on 25 women who had a normal puerperium and breast fed their babies and on 32 otherwise healthy women who had lactation suppressed by diethylstilboestrol. In the untreated patients the fibrinogen, Factors VIII and IX, platelet count, and antifibrinolytic activity increased, and the levels of Factors II, VII, and X and of plasminogen and plasminogen proactivator decreased. The incidence of cold activation of Factor VII decreased slowly from the 5th postpartum day onwards. The concentration of antithrombin TI1 which was depressed in pregnancy, increased in the puerperiuin and was the only observed change that counteracted an increased coagulation potential. Oestrogen treatment produced further increases of Factors II, VII, and X, platelet count, and the cold activation of Factor VII while it decreased the concentration of antithrombin III. These changes favoured coagulation but were possibly to some degree counterbalanced by an increased concentration of plasminogen and decreased antifibrinolytic activity.

A novel gene mutation in the 60s loop of human coagulation factor VII - inhibition of interdomain crosstalk.

A novel mutation in the factor VII gene resulting in procoagulant activity of 7.5% and antigen levels of 23% is presented. Single-stranded conformational polymorphism and DNA sequencing analysis revealed heterozygous shifts, and mutations were detected in exons 5, 7 and 8. The mutant L204P in exon 7 was novel, while the common polymorphisms, H115H and R353Q, were located in exons 5 and 8, respectively. The molecular effect of the L204P mutation was characterized using recombinant mammalian expression in Chinese hamster ovary cells. Low levels (4 ng/ml) of secreted mutant protein were found in transiently transfected cells compared to wild-type factor VII (83 ng/ml). Metabolic labeling demonstrated that the rate of mutant protein synthesis was similar to that of wild-type FVII, and the mutant protein accumulated intracellularly with no signs of increased degradation during a four-hour chase. No interaction between secreted P204 protein and immobilized soluble tissue factor was detected using surface plasmon reso-nance. The activation rate of recombinant mutant FVII protein was strongly reduced compared to wild-type FVII. A 9-fold reduction in the rate of FX activation was detected whereas Km was nearly the same for wild-type and the mutant. This slow rate was caused by a correspondingly lowered rate of P204 activation. A synthetic peptide sequence comprising amino acids 177-206 blocked binding of FVIIa to the TF-chip, and the subsequent factor X activation with an IC(50) value of 0.5 micro M in a chromogenic factor Xa assay. Additionally, evaluation of the peptide by surface plasmon resonance analysis resulted in inhibition of complex formation with an apparent K(I) of 7 micro M.