[Plasma blood coagulation in mammals (domestic and zoo animals). Experience with screening tests and determinations of individual factor activities]. / Plasmatische Blutgerinnung bei Säugetieren (Haus- und Zootiere). Erfahrungen mit Globaltesten und Aktivitätsbestimmungen von Einzelfaktoren.

Plasma coagulation in mammals shows an essentially uniform structure. Differences are in species specific composition and quantity of coagulation factors. Many of the coagulation disorders occurring in humans have been observed in other mammals. Almost all the coagulation studies performed to date have been in domestic animals. For the majority of mammalian species, e.g. zoo animals, therefore, we have either no data at all or only isolated results. The methods used for coagulation testing in veterinary medicine have not yet been standardized. The significance and informative value of the screening tests are limited in animals compared with humans. The activities of individual factors in animals are determined by coagulometric tests. The results can be determined in relation to the activity in humans with the help of a human normal plasma or in relation to the activity of the respective animal with the help of a normal plasma from the same species. The problem is the parallelity of the dilution curves used as reference curves. The coagulation factor activities given for mammals usually differ more or less markedly from those in humans.

[Hereditary factor V deficiency and factor V inhibitor without bleeding. Rare causes of pathological screening tests of coagulation]. / Hereditärer Faktor-V-Mangel und Faktor-V-Inhibitor ohne Blutungsneigung. Seltene Ursachen pathologischer Globaltests.

Isolated reduction in factor V activity either occur in form of a hereditary deficiency of factor V as an acquired inhibitor against factor V. Diagnosis can not be made by bleeding alone because in both cases it can occur or not occur. Two patients were investigated showing pathological screening tests of coagulation without bleeding. A hereditary and an acquired deficiency of factor V were proved.

[Modified platelet aggregation test in patients on ASA and/or clopidogrel]. / Kontrolle der Thrombozytenaggregations-hemmung unter Therapie mit Azetylsalizylsäure und/oder Clopidogrel mit einem modifizierten Thrombozytenaggregationstest.

Therapy with acetylsalicylic acid (ASA) and/or clopidogrel is used to achieve prophylactic inhibition of platelet aggregation in patients with arterial thrombosis. We examined if aggregometry can be used to see the effect of antiplatelet drugs (ASA 30, 50, 100, 300 mg/d, clopidogrel 75 mg/d or ASA 100 + clopidogrel 75 mg/d). A modified platelet aggregation test was used to investigate maximum aggregation in response to ADP, collagen, adrenalin and arachidonic acid. Reference values were established based on healthy individuals. We devised a simple scoring system for detection of inadequate platelet inhibition. Compared with the control group, we detected a significant delay of maximum aggregation in response to all agonists in patients on ASA and combination therapy ASA + clopidogrel. Patients on clopidogrel alone were found to have prolonged aggregation when induced with ADP, collagen and arachidonic acid. The failure rate to achieve adequate platelet inhibition on 100 mg/d ASA, 75 mg/d clopidogrel or combination therapy was 27%, 26% and 7%, respectively. Our results demonstrate that platelet inhibition in aggregometry is inadequate in many patients with arterial thrombosis.

Multicenter evaluation of a new capillary blood prothrombin time monitoring system.

The analytical performance of the new capillary blood prothrombin time monitoring system CoaguChek was examined in a multicenter evaluation at six hospitals. The coefficients of variation of the INR obtained in the CoaguChek imprecision study were approximately 7% in the control plasma provided (within-run and day-to-day) and 4% in blood (within-run). The prothrombin times were ascertained in capillary blood (CoaguChek PT Test) and citrated venous plasma (Hepato Quick, Thromborel S) from 359 patients under oral anticoagulation therapy with phenprocoumon, acenocoumarin or warfarin. The agreement with the test results obtained with the comparison methods was acceptable versus Hepato Quick assay (n = 359; y = 1.23 x -0.49, r = 0.888) and good versus Thromborel S method (n = 359; y = 1.09 x -0.28, r = 0.895). A simplified assessment of all test results (n = 795) in a nine-field comparison table showed a concordance with the comparison methods of more than 80 (Hepato Quick: 81%, Thromborel S: 83%). The concordance between Hepato-Quick and Thromborel S was slightly higher (88%). Its good analytical performance and convenient handling recommend the CoaguChek system as a suitable system for decentralized prothrombin time testing.

[Case report. Phenprocoumon (Marcumar, Falithrom) as an unusual reason for coumarin poisoning in a dog]. / Phenprocoumon (Marcumar, Falithrom) als ungewöhnliche Ursache einer Kumarinvergiftung beim Hund.

Coumarin poisoning in dogs is not unusual and is in most cases caused by warfarin, a coumarin derivative which is used as a rodenticide. Competitive inhibition of vitamin K with an incomplete synthesis of the coagulation factors II, VII, IX and X can lead to a significant bleeding tendency. We observed a 3-year old male West Highland White Terrier with a reduced general condition and dyspnoea together with a massive haemothorax. Administration of vitamin K1 (3 mg/kg) led to a rapid improvement of the condition. Coagulation analysis revealed a prolonged activated recalcification time (ARCT), prothrombin time (PT) and aPTT with uncharacteristic thrombin time (TT); factor II, VII and X activities were reduced while factor V activity was normal, all of which are characteristic for coumarin poisoning. HPLC did not reveal the presence of warfarin but of phenoprocoumon, a drug used for thromboembolic prophylaxis in humans. This observation has not been described for dogs to date.

Increased risk of venous thromboembolism in patients with acute leukaemia.

Patients with malignancies have an increased risk for venous thromboembolisms (VTE), but data on patients with acute leukaemia are very limited so far. We found VTE in 12% of 455 patients with acute leukaemia, half of which occurred in association with central venous catheters, with equal risk of ALL and AML.

Increased risk of thromboembolism in patients with malignant lymphoma: a single-centre analysis.

An increased risk for thromboembolism in cancer patients has been observed in patients with solid tumours, whereas little data exist on malignant lymphoma. We found an overall thromboembolic event incidence of 7.7% in 1038 lymphoma patients treated in our institution, with a statistically significantly higher incidence in high-grade than in low-grade lymphoma.

[Studies on the demonstration of a factor VIII or IX deficiency by means of partial thromboplastin time]. / Untersuchungen über den Nachweis eines Gerinnungsfaktor VIII- oder IX-Mangels mit Hilfe der partiellen Thromboplastinzeit

A report is presented on the performance of the correction of PTT by means of factor VIII and IX deficiency plasma, which may be used at least one year, when preserved in liquid nitrogen. The method allows reliable, qualitative statements to be made about disturbances in the area of the coagulation factors VIII, IX, XI and XII; the small amount of time required for preparing and carrying out these works representing an essential advantage.

[Precision control of a single step determination of blood coagulation factor VIII in the plasma]. / Präzisionskontrolle bei einer einstufigen Bestimmung des Gerinnungsfaktors VIII im Plasma.

The findings of a precision control are reported for a one-stage determination of the factor VIII activity in the plasma for a period of 6 months. The storage property of the reagents was achieved by storing them in fluid nitrogen. Coefficients of variation under 55 were achieved at controlling the normal range as well as the pathological one. Thus the precision of this method may be compared with that of clinicochemical examinations.

[Factor VIII inhibitors in patients suffering from severe haemophilia A: problems of "very low" responders]. / Faktor VIII-Inhibitoren bei Patienten mit schwerer Hämophilie A: Problematik der "very low" Responder.

Without recognition of any inhibitor until now, low concentrations of factor VIII inhibitors (< 1 Bethesda unit (BU)/mL plasma) can be occasionally measured in patients with severe haemophilia A. The existence of so-called "very low" responders is assessed contradictorily due to a methodically caused inhibitor increase. Plasma from 10 patients with severe haemophilia A was incubated with human plasma or animal plasma from pig, cattle, or cat and assayed for factor VIII inhibitors. No signs of inactivation could be detected in five specimen (0 BU/mL plasma). However, measurable signs of factor VIII inactivation (< 1 BU/mL plasma) did occur in the other five. Therefore, the existence of yet not defined unknown inhibitory substances in certain haemophilic plasmas must be assumed. They are directed against human factor VIII as well as partly against animal factor VIII. These "very low" inhibitors are not identical with factor VIII antibodies of "low" and "high" responding haemophiliacs. The clinical importance of "very low" inhibitors is insignificant because they do not tend to increase after exposure to factor VIII. In fact, a effect of factor VIII therapy is the neutralization of this kind of inhibitors.

[The plasma coagulation system of domestic cats]. / Untersuchungen zum plasmatischen Gerinnungssystem der Hauskatze.

Haemostaseological investigations of the animals need improvement. Usual methods in human medicine have to be reconsidered with regard to their qualification for veterinary medicine. A standardization of methods and accurate haemostaseological characterization of the reagents used are necessary for an appropriate interpretation of the results and interlaboratory comparative studies. Results of global tests (ARZ, PTT, TZW, TZ, RZ) and determinations of activity of single blood clotting factors (I, II, V, VII-XII) in healthy cats are presented and discussed in view of the mentioned.

[Rare causes of decreased thromboplastin values]. / Seltene Ursachen erniedrigter Thromboplastinzeitwerte.

Rare causes of decreases of the thromboplastin time value are hereditary coagulopathies, coagulation inhibitors and application of acetyl salicylic acid. They require a special diagnostic approach including other global and group tests, functional tests of thrombocytes, analyses of individual factors as well as methods of inhibitor proofs.

[Factor XI deficiency--a rare coagulopathy in the GDR]. / Faktor-XI-Mangel--eine seltene Koagulopathie in der DDR.

The authors report on a kin affected with PTA deficiency. The person with homozygous features and a factor XI content below 1% is solely characterized by prolongations of ART and PTT, which were clinically correlated as severe secondary hemorrhages after injuries and surgical treatments. Three heterozygous persons had normal results in global and group tests at 40-50% of factor XI with objectively unambiguous bleeding episodes being absent. As a peculiarity of the recessive heredity of this kin the marriage of two descendants in the fourth generation deserves to be mentioned.

[A suggestion for the uniform laboratory diagnosis of hemophilia]. / Ein Vorschlag zur einheitlichen Labordiagnostik der Hämophilie.

The laboratory diagnosis of the haemophilia is performed in a different way in the individual laboratories. Differences in the selection and the performance of the methods used render differences in evidence, comparability and expenditure of time. The following proposition for a unitary laboratory diagnostics of haemophilia is made: 1. performance of a basic programme, 2. localisation of the coagulation defect with the help of the PTT using correction plasmas, 3. quantitative estimation of factors (possibly inhibitors) after one-step method, in which cases usual test sets of instruments with standardized directive for the performance are prerequisite for comparable results and a subdivision in degrees of severity.

[Hageman factor deficiency (factor XII)--hemorrhage or thrombosis?]. / Hageman-Faktor-Mangel (Faktor XII)--Blutung oder Thrombose?

Four generations of a kin with congenital Factor XII deficiency were examined for coagulation and fibrinolysis, with the homozygous female carrier of features with a Factor XII below 1% also revealing certain indications of a disturbed fibrinolysis. The other members of the family had to be evaluated as heterozygous ones, showing values of Factor XII between 40 and 60%. The findings are discussed by referring to data from literature.

[Diagnosis of hemophilia and von Willebrand-Jürgens syndrome. 3. Results of studies on patients with vWJS, heterozygotes of vWJS and patients with Glanzmann-Naegeli thrombasthenia]. / Zur Diagnostik der Hämophilie und des von Willebrand-Jürgens-Syndroms (vWJS). 3. Mitteilung: Untersuchungsergebnisse bei Patienten mit vWJS, Merkmalsträgern eines vWJS und Patienten mit Thrombasthenie Glanzmann-Naegeli.

By means of genealogical and laboratory-diagnostic examinations in the district of Magdeburg 59 patients with a von-Willebrand-Jürgens-syndrome and 2 patients with thrombasthenia were detected. On the basis of the laboratory data and the severity of the inclination to haemorrhage in patients with von-Willebrand-Jürgens-syndrome a subdivision into type I (severe from), type I (easy form) and type II was made. The diagnosis was rendered difficult by the appearance of clinically asymptomatic carriers of signs. The experiences hitherto made in the dispensary care and the use of the laboratory programme are estimated.

[Diagnosis of hemophilia and von Willebrand-Jürgens syndrome. 1. Organization of a dispensary for patients with hemorrhagic diatheses and a laboratory program]. / Zur Diagnostik der Hämophilie und des von Willebrand-Jürgens-Syndroms. 1. Mitteilung: Aufbau eines Dispensaires für Patienten mit hämorrhagischen Diathesen und Laborprogramm.

Tasks and organisation of a dispensary for patients with hereditary haemorrhagic diatheses are explained. A laboratory programme which was used for the diagnostics of these diseases, particularly of haemophilia and von Willebrand-Jürgens syndrome, is demonstrated.

[Monitoring of heparin therapy with activated recalcification time]. / Uberwachung der Heparintherapie mit der aktivierten Rekalzifizierungszeit.

In in-vivo- and in-vitro-examinations the activated recalcification time, the recalcification time of the plasma, the partial thromboplastin time and the thrombin time were compared concerning their suitability for the control of a heparin therapy. The laboratory methods tested considerably differed in their sensitivity compared with heparin and in the possibility of a quantitative statement. The use of a certain laboratory method depends on the indication for a heparin therapy and on the heparin concentration in the blood to be expected. While thrombin time, recalcification time of the plasma and the partial thromboplastin time are suited only for the proof of lower heparin concentrations, the activated recalcification time allows also the proof of higher heparin concentrations in the blood.