High coagulation factor VIII and von Willebrand factor in patients with lymphoma and leukemia.

The risk of venous thromboembolism is increased in patients with lymphoma and leukemia; however, little is known about the potential underlying hereditary or acquired thrombophilia. We prospectively analyzed procoagulant markers and gene mutations in patients with lymphoma (n = 35) and leukemia (n = 10) at diagnosis and over the course of treatment. Global coagulation tests were normal in all patients, as were antithrombin and protein S. Activated protein C resistance caused by the factor V Leiden mutation was found in four patients, one patient had the G20210A mutation of the prothrombin gene, and one patient had protein C deficiency. The most striking findings were sustained very high levels of factor VIII (>150 %) in 30 patients (68 %), which correlated with high von Willebrand factor. An acute phase response in these patients was ruled out by absence of fever and normal IL-6 and -α. Elevated factor VIII is an independent thrombophilic risk factor and may play an etiologic role in thromboembolic complications in patients with malignant lymphoma. Since high von Willebrand factor is most likely caused by endothelial cell injury, an additional, unknown pathophysiological association with malignant lymphoma and acute leukemia is possible.

[Hemophilia B (factor IX deficiency) with concomitant factor XII degradation in a male crossbreed cat]. / Hämophilie B (Faktor-IX-Mangel) mit begleitender Faktor-XII-Erniedrigung bei einem Mischlingskater.

A male cat suffered from a severe haemorrhagic disorder manifesting as deep, partly infected cutaneous haematomas, enhanced and prolonged bleeding after injuries and subsequent lameness at several occasions. Bleeding resulted in severe anaemia with haematocrit falling to as low as 0.10 L/L. Haemophilia B was diagnosed based on factor IX deficiency with a functional residual activity of 5% and factor IX antigen of 8%, respectively. Additionally, factor XII activity was reduced to 32% of normal. The mutation 31217G==>A in exon 8 of the factor IX gene, predicting the amino acid exchange G366R was identified as the cause of moderate factor IX deficiency. This is the first mutation identified in cats with haemophilia B. Treatment was limited to local therapy and palliation, insufficient to prevent lethal outcome due to severe anaemia.

Effect of physical exercise on platelet activity and the von-Willebrand-factor in patients with persistent lone atrial fibrillation.

BACKGROUND: The risk of stroke is of great clinical importance in patients with atrial fibrillation (AF). It is not known whether physical exercise influences plasma coagulation and platelet aggregability during AF. The purpose of this study was to assess the effect of physical exercise on platelet activity, thrombin generation, and levels of von-Willebrand-factor in patients with persistent AF. METHODS: Thirteen patients with lone AF (>or=1 year) were compared with 13 matched patients in sinus rhythm. Patients with AF were anticoagulated effectively with coumarin. All patients underwent bicycle ergometry using a respiratory gas exchange technique for 20 min at one-third of the age-adjusted maximal workload. Thereafter, workload was increased until maximal exercise capacity was reached. Platelet factor-4 (PF-4), beta-thromboglobulin (beta-TG; marker for platelet activation), von-Willebrand-factor (vWF; marker for endothelial dysfunction), prothrombin fragment F1 + 2 (F1 + 2; marker for thrombin generation) and fibrinogen levels were determined throughout the study in all patients. RESULTS: Gas exchange variables, hemodynamic parameters and norepinephrine levels were comparable in the groups during moderate (45 +/- 5 W) and heavy exercise (198 +/- 38 W). In contrast to moderate exercise, PF-4 and beta-TG levels increased to 212 +/- 56% ( p < 0.05) and to 145 +/- 24% ( p < 0.05), respectively, in patients with AF during heavy exercise. In contrast, physical exercise had no significant effect on platelet activity in patients with sinus rhythm. Levels of vWF increased by delta24% ( p < 0.05) in all patients during maximal exercise, whereas F1 + 2 levels increased only in patients with sinus rhythm. CONCLUSIONS: Heavy physical activity increases platelet activity and vWF levels during AF, whereas moderate exercise has no procoagulatory effect. Coumarin therapy prevents exercise-induced thrombin generation only. Future studies are needed to prove the hypothesis that heavy physical exercise is a risk factor for thromboembolic events in patients with AF.

[Prekallikrein (Fletcher Factor) Deficiency and Prolongation of APTT Reaction]. / Präkallikrein-(Fletcher-Faktor-)Defekt als Ursache einer präoperativen APTT-Verlängerung.

BACKGROUND: Prekallikrein (Fletcher factor) is a protein of the contact phase of the blood coagulation system. A deficiency is a very rare event. The clinical meaning is still unknown. CASE REPORT: In a 24-year-old patient of Croatian nationality, who has never suffered from any kind of proneness to hemorrhage, a considerable prolongation of activated partial thromboplastin time (APTT) was diagnosed preoperatively. The prothrombin time (PT) was normal. The patient had to be subjected to horseshoe-kidney surgery. CLOTTING TESTS: A very seldom Fletcher factor (prekallikrein) deficiency type II was detected. The activity was < 1%, but the prekallikrein concentration was normal, comparable to that in normal plasma. THERAPY AND COURSE: Complications were neither noticed during renal surgery nor postoperatively. The patient did not show clinical symptoms. This fact corroborates reports about similar cases published earlier. CONCLUSION: Nevertheless, attention has to be paid to these exceptionally rare symptoms, as in some publications, thromboembolic or even bleeding complications were reported.

Fibrinogen Magdeburg I: a novel variant of human fibrinogen with an amino acid exchange in the fibrinopeptide A (Aalpha 9, Leu-->Pro).

INTRODUCTION: The exchange of Aalpha 16, Arg for Cys or His is the most common molecular defect in dysfibrinogenemia directly affecting the thrombin cleavage site involved in fibrinopeptide A (FPA) release. Other amino acid exchanges within the fibrinopeptide A have been only rarely reported. MATERIALS AND METHODS: In clinically asymptomatic dysfibrinogenemic patients with low functional plasma fibrinogen (Fg) levels and prolonged thrombin time but normal or slightly prolonged batroxobin (reptilase) time, mutation analysis was carried out by direct sequencing of the coding regions of the three fibrinogen genes. Isolated fibrinogen was functionally characterized for thrombin- or batroxobin-induced fibrinopeptide release and fibrin formation. Fibrinogen and fibrinopeptides were structurally studied by electrophoretic techniques or high-performance liquid chromatography. RESULTS AND CONCLUSIONS: Molecular analysis revealed heterozygosity for a novel missense mutation T1182C in the FGA gene causing the amino acid exchange Aalpha 9, Leu-->Pro. Fibrin generation induced by thrombin was moderately impaired, whereas batroxobin-induced fibrin formation was almost normal. Release of the abnormal fibrinopeptide A by thrombin was delayed but fibrin monomer aggregation was almost normal. Cleavage of Aalpha chains by batroxobin was only slightly delayed. Fibrinopeptides A of the patient fibrinogen did not show any gross abnormality in chromatographic behaviour. This new molecular variant designated fibrinogen Magdeburg I supports the view that amino acid residue Leu-9 in the Aalpha chain as part of a small hydrophobic cluster is involved in the interaction with an apolar binding site of thrombin, thus adding to our understanding of the thrombin-fibrinogen interaction crucial in coagulation.

[Determination of clotting factor VIII activity in mammals using the one-stage clotting and the chromogenic methods]. / Bestimmung der Aktivität des Gerinnungsfaktors VIII beim Säugetier mit der koagulometrischen und der chromogenen Methode.

Two different laboratory assays exist for the determination of clotting factor VIII activities in human plasma. One method is based on the one-stage clotting principle, the other one on the chromogenic principle. To evaluate the suitability for veterinary medicine human plasma and plasma of ten mammalian species (pig, cattle, dog, cat, zebra, llama, snow leopard, greater kudu, horse-like antelope, mink) were examined with each method. Factor VIII activities in human plasma determined using both assays were in a good agreement. Results of factor VIII activities in plasma of mammals obtained with both methods were similar, if a species-specific reference plasma was used. The practicability of the chromogenic method was reduced. However, the factor VIII activities differed nonsystematically up to 500% between both methods, if a human plasma was used as a reference plasma. Determination of factor VIII activities in plasma of mammals using the chromogenic assay cannot be recommended.