Sabine Eichinger

Clinical significance of lupus anticoagulants in children

OBJECTIVES To determine the spectrum of associated clinical manifestations and time course of lupus anticoagulants (LA) in children. STUDY DESIGN Retrospective study of 95 consecutive children (46 boys and 47 girls), with a median age of 5.3 years (range, 1.7 to 17.1 years), diagnosed with presence of LA at a hemostasis referral center; 83 were followed up over a median of 2.9 years (range, 6 weeks to 21.6 years). RESULTS At diagnosis, 80 of 95 (84%) children were free of symptoms, and presence of LA was found incidentally. Nine children (10%) had bleeding symptoms, 5 (5%) had thrombotic events, and 1 had systemic lupus erythematosus. Among the patients with bleeding, 5 had transient severe hypoprothrombinemia after adenovirus infections, and 3 had thrombocytopenia. None of the children who were initially free of symptoms had bleeding, thrombotic complications, or autoimmune disease subsequently. At follow-up, 48 of 83 (58%) patients had normal activated partial thromboplastin time values after 1.9 years (5 weeks to 19.1 years). Thirty-two (38%) still had activated partial thromboplastin time elevations but did not fulfill all criteria for presence of LA after 3.2 years (7.4 months to 9.3 years). Three (4%) patients, who had presented with thrombosis, had persistent positive LA, anti-cardiolipin, and antinuclear antibodies after 1.4, 2.8, and 7.5 years, respectively. One of these had recurrent thrombosis. CONCLUSIONS In most children the presence of LA did not lead to clinical complications and was transient. Bleeding occurred with additional hypoprothrombinemia or thrombocytopenia. Thrombosis was rare and strongly associated with persistently positive LA.

Preeclampsia and Fetal Loss in Women With a History of Venous Thromboembolism

Abstract—A higher prevalence of risk factors for venous thromboembolism (VTE) has been found in women with preeclampsia and fetal loss. We investigated whether women with a history of VTE have a higher prevalence of pregnancy-associated complications compared with control subjects. In 395 patients with a history of VTE and in 313 control women, the prevalence of complications during pregnancy and the mean birth weight of viable infants were evaluated. The prevalence of pregnancy-induced hypertension and preeclampsia was higher in patients (5.1% and 3.0%, respectively) compared with control subjects (1.3% each). The odds ratio was 4.13 for pregnancy-induced hypertension (95% CI 1.4 to 12.22, P =0.0058) and 2.43 for preeclampsia (95% CI 0.78 to 7.6, P =0.133). Stillbirth was slightly more frequent in patients (4.3%) than in control subjects (3.2%); the difference was not statistically significant. Miscarriage was equally frequent in patients (21.8%) and control subjects (21.3%). The birth weight of viable infants born to patients was, on average, 109 g lower than that of the infants born to the control subjects (P =0.014) after adjustment for the mother’s body mass index. Our study demonstrates that women with a predisposition to VTE have, overall, a good chance for a successful pregnancy outcome. However, the findings from our study support the assumption that a predisposition to venous thrombosis is associated with a higher risk for complications during pregnancy and lower infant birth weight.

Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate

In HIV-infected subjects with haemophilia, CD4 counts seem to fall more slowly in those on high-purity factor VIII (FVIII) than on intermediate-purity product. We evaluated whether risks for AIDS or death were associated with either product among 411 HIV-infected individuals. The relative hazard of AIDS was slightly elevated for both current (1.34) [corrected] and cumulative (1.01 per month) use of high-purity products (neither significant). The corresponding hazards for death were 1.49 and 1.03 (neither significant). Thus we found no evidence that high-purity FVIII concentrates retard the development of AIDS.

The risk of recurrent venous thromboembolism: The Austrian Study on Recurrent Venous Thromboembolism

ZusammenfassungDie venöse Thromboembolie (VTE) ist eine chronische Erkrankung. Nach Beendigung der oralen Antikoagulantientherapie erleidet ca. ein Drittel der Patienten ein neuerliches thromboembolisches Ereignis. 5% dieser Patienten sterben an der Pulmonalembolie. Die Austrian Study on Recurrent Venous Thromboembolism (AUREC) ist eine prospektive Kohortenstudie und hat zum Ziel, die Gesamtrezidivrate der VTE, den prädiktiven Wert von Laboruntersuchungen, die Bedeutung von angeborenen und erworbenen thrombotischen Risikofaktoren und den Einfluss einer länger dauernden bzw. modifizierten sekundären Thromboseprophylaxe auf das Rezidivrisiko von Hochrisikopatienten zu untersuchen. Bislang gelang es den AUREC Untersuchern Subgruppen von Patienten mit einem erhöhten Rezidivrisiko zu identifizieren. Patienten mit einer anamnestischen VTE, erhöhten Faktor VIII-, Faktor IX- und Faktor XI-Spiegeln, einer anamnestischen Pulmonalembolie oder einer oberflächlichen Venenthrombose nach VTE sowie Patienten mit Hyperhomocysteinämie. Patienten mit der Faktor V Leiden Mutation oder der G20210A Mutation im Prothrombingen haben kein erhöhtes Rezidivrisiko und benötigen daher keine länger dauernde Sekundärprophylaxe. Zur Zeit werden interventionelle Studien bei Patienten mit hohem Faktor VIII oder Hyperhomocysteinämie durchgeführt um zu untersuchen, ob eine länger dauernde Sekundärprophylaxe mit oralen Antikoagulantien oder die Verabreichung von Folsäure, Vitamin B6 und Vitamin B12 das Rezidivrisiko senken.AbstractVenous thromboembolism (VTE) is a chronic disease. After withdrawal of oral anticoagulation at least a third of patients will experience a subsequent episode of venous thrombosis. Of these patients, approximately 5% will die from pulmonary embolism. The Austrian Study on Recurrent Venous Thromboembolism (AUREC) is a prospective cohort study aiming to investigate the overall rate of recurrent VTE, the predictive value of laboratory assays, the importance of acquired or congenital risk factors for thrombosis and the impact of extended or modified secondary thromboprophylaxis on the risk of recurrence among high-risk patients. So far, the AUREC investigators have identified subgroups of patients with a particular high risk of recurrence: patients with a history of venous thrombosis, elevated levels of coagulation factors VIII, IX and XI, pulmonary embolism or superficial venous thrombosis and a history of venous thrombosis and hyperhomocysteinemia. Patients with a history of venous thrombosis and mutations in genes encoding for coagulation factors (factor V Leiden, factor II, G20210A) do not have an enhanced risk of recurrence and, thus, do not qualify for extended secondary thromboprophylaxis. At present, interventional trials are in progress in patients with high factor VIII or hyperhomocysteinemia in order to investigate if these patient groups might benefit from extended oral anticoagulation or vitamin supplementation, respectively.

EVALUATION OF BEDSIDE PROTHROMBIN TIME AND ACTIVATED PARTIAL THROMBOPLASTIN TIME MEASUREMENT BY COAGULATION ANALYZER COAGUCHECK PLUS® IN VARIOUS CLINICAL SETTINGS

In the present study CoaguCheck Plus (CCP), a coagulation test system using whole blood, was evaluated with respect to its comparability with widely distributed conventional routine coagulation assays. A correlation of r = 0.997 (p < 0.0001) was found between INR of CCP-prothrombin time (CCP-PT) and Thrombotest (KC-1 analyzer) in patients on oral anticoagulant therapy. A correlation of r = 0.899 (p < 0.001) between CCP-aPTT and Actin ES aPTT (STA analyzer) was found in heparinized patients. Impaired hepatic hepatic coagulation factor synthesis in liver cirrhosis patients was detected by CCP-PT with a sensitivity of 0.75 and by Normotest (STA analyzer) with a sensitivity of 0.92. Those patients with normal CCP-PT values and liver disease had, only mild reductions (> 30% of normals) in coagulation factors II, V, VII or X. CCP-aPTT was also performed in patients with a deficiency in the so called endogenous coagulation factors VIII, IX, XI and XII. CCP-aPTT showed a sensitivity similar to that of Actin FS aPTT in the detection even of mild deficiencies in factors VIII, IX and XII; factor XI deficiency was however detected only in patients with severe (< 12% of normals) disease; lupus anticoagulants were detected with a high sensitivity.

Effects of Recombinant Hirudin (r-Hirudin, HBW 023) on Coagulation and Platelet Activation In Vivo Comparison With Unfractionated Heparin and a Low-Molecular-Weight Heparin Preparation (Fragmin)

In a double-blind, randomized, crossover study, we investigated in 15 healthy male volunteers the effects of recombinant (r-) hirudin (HBW 023, 0.35 mg/kg body wt SC), unfractionated heparin (UFH, HeparinNovo; 150 IU/kg body wt SC), and a low-molecular-weight heparin preparation (LMWH, Fragmin; 75 IU/kg body wt SC) on coagulation and platelet activation in vivo by measuring specific coagulation-activation peptides (prothrombin fragment 1 + 2 [F1 + 2], thrombin-antithrombin-III complex [TAT], and beta-thromboglobulin [beta-TG]) in bleeding-time blood (activated state) and venous blood (basal state). In bleeding-time blood, r-hirudin and the heparin preparations significantly inhibited formation of both TAT and F1 + 2. However, the inhibitory effect of r-hirudin on F1 + 2 generation was short-lived and weaker compared with that of UFH and LMWH, and the TAT-to-F1 + 2 ratio was significantly lower after r-hirudin than after UFH or LMWH. Thus, in vivo, when the coagulation system is in an activated state, r-hirudin exerts its anticoagulant effects predominantly by inhibiting thrombin (factor IIa), whereas UFH and LMWH are directed against both factors Xa and IIa. A different mode of action for UFH and LMWH was not detectable. In venous blood, r-hirudin caused a moderate reduction in TAT formation and an increase (at 1 hour) rather than a decrease in F1 + 2 generation. Formation of TAT and F1 + 2 was suppressed at various time points following both UFH and LMWH. There was no difference in the TAT-to-F1 + 2 ratio after r-hirudin and heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Leitlinien für die venöse Thromboembolieprophylaxe in Österreich

Venous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special high-risk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.SummaryVenous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special highrisk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.ZusammenfassungVenöse Thromboembolien treten bei einem bedeutenden Anteil von Patienten in typischen Risikosituationen (z.B. Operation oder Trauma) auf. Durch gerinnungshemmende Medikamente, insbesondere die niedermolekularen Heparine, ist es möglich, die Anzahl an venösen Thrombosen, Pulmonalembolien und Tod durch Pulmonalembolie in diesen speziellen Risikosituationen zu senken. Nur die breite und richtige Anwendung von Antithrombotika stellt sicher, dass die Patienten in den jeweiligen Risikosituationen effektiv vor venösen Thromboembolien geschützt werden. Leitlinien (Guidelines) sind integrativer Bestandteil des Qualitätsmanagements und stellen die Anwendung evidenzbasierter Medizin sicher. Der Konsensus zur Durchführung der Thromboseprophylaxe in Österreich wurde von 23 Experten aus dem Gebiet der Hämostaseologie, Angiologie, Chirurgie, Orthopädie, Inneren Medizin, Anästhesiologie und Pharmakologie erarbeitet. Basierend auf den Guidelines des American College of Chest Physicians wurden die Vorschläge für die Durchführung der Thromboseprophylaxe auf den Gebieten Allgemeinchirurgie, Orthopädische Chirurgie, Unfallchirurgie und Innere Medizin erarbeitet. Es werden die Indikationen, die Art der Antithrombotika, Dosis und Dauer in den verschiedenen Indikationen vorgeschlagen. Die Erstellung der Österreichischen Leitlinien für die Venöse Thromboembolieprophylaxe soll durch eine Harmonisierung des Vorgehens ein größeres Maß an Sicherheit in Organisationsstrukturen für den Arzt, den Pflegebereich und den Patienten schaffen.

Austrian Guidelines for Prophylaxis of Venous Thromboembolism

Venous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special high-risk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.SummaryVenous thromboembolism occurs in a significant number of patients in typical risk situations (e.g. surgery or trauma). However, in these special highrisk situations anticoagulants, particularly low molecular weight heparin, allow for a decrease in the number of venous thromboses, pulmonary embolisms and deaths caused by pulmonary embolism. Only the wide-spread and adequate use of antithrombotics can safeguard against venous thromboembolism in these various risk situations. Guidelines constitute an integrative part of quality management and ensure the application of evidence-based medicine. The present consensus on thrombosis prophylaxis in Austria has been elaborated by 23 experts in the fields of hemostasis research, angiology, surgery, orthopedics, internal medicine, anaesthesiology and pharmacology. The recommendations for the management of thrombosis prophylaxis in the fields of general surgery, orthopaedic and trauma surgery and internal medicine have been elaborated drawing on the Guidelines issued by the American College of Chest Physicians. Included are recommendations on indications as well as the choice of antithrombotics, dose and duration of therapy for the various conditions. The Austrian Guidelines for Venous Thromboembolism Prophylaxis are meant to be a basis for standardising procedures in the above-mentioned fields, thus contributing to an improved management of risk situations by physicians and health care staff and providing more safety for patients.ZusammenfassungVenöse Thromboembolien treten bei einem bedeutenden Anteil von Patienten in typischen Risikosituationen (z.B. Operation oder Trauma) auf. Durch gerinnungshemmende Medikamente, insbesondere die niedermolekularen Heparine, ist es möglich, die Anzahl an venösen Thrombosen, Pulmonalembolien und Tod durch Pulmonalembolie in diesen speziellen Risikosituationen zu senken. Nur die breite und richtige Anwendung von Antithrombotika stellt sicher, dass die Patienten in den jeweiligen Risikosituationen effektiv vor venösen Thromboembolien geschützt werden. Leitlinien (Guidelines) sind integrativer Bestandteil des Qualitätsmanagements und stellen die Anwendung evidenzbasierter Medizin sicher. Der Konsensus zur Durchführung der Thromboseprophylaxe in Österreich wurde von 23 Experten aus dem Gebiet der Hämostaseologie, Angiologie, Chirurgie, Orthopädie, Inneren Medizin, Anästhesiologie und Pharmakologie erarbeitet. Basierend auf den Guidelines des American College of Chest Physicians wurden die Vorschläge für die Durchführung der Thromboseprophylaxe auf den Gebieten Allgemeinchirurgie, Orthopädische Chirurgie, Unfallchirurgie und Innere Medizin erarbeitet. Es werden die Indikationen, die Art der Antithrombotika, Dosis und Dauer in den verschiedenen Indikationen vorgeschlagen. Die Erstellung der Österreichischen Leitlinien für die Venöse Thromboembolieprophylaxe soll durch eine Harmonisierung des Vorgehens ein größeres Maß an Sicherheit in Organisationsstrukturen für den Arzt, den Pflegebereich und den Patienten schaffen.

Eingriff-spezifische Thromboseprophylaxe beim Erwachsenen

According to the concept of Virchow, alterations of the blood flow, vascular injury and hypercoagulability of the blood (due to inherited or acquired thrombophilia or as a consequence of perioperative coagulation activation) are causally related to the risk of venous thrombosis. The overall risk of venous thromboembolic events in the perioperative setting ranges between <10% and >50%. The risk is highest in patients undergoing major orthopaedic surgery or cancer surgery. The aim of perioperative thrombosis prophylaxis is to reduce perioperative morbidity and mortality. The article discusses patient- and intervention-dependent thromboprophylactic measures. Recent recommendations for non-pharmacological and pharmacological prophylaxis are presented including the information on the beginning and duration of anticoagulation. Management strategies for patients undergoing abdominal and orthopaedic surgery as well as special aspects of the neurosurgical population and of cancer surgery are highlighted.SummaryAccording to the concept of Virchow, alterations of the blood flow, vascular injury and hypercoagulability of the blood (due to inherited or acquired thrombophilia or as a consequence of perioperative coagulation activation) are causally related to the risk of venous thrombosis. The overall risk of venous thromboembolic events in the perioperative setting ranges between <10% and >50%. The risk is highest in patients undergoing major orthopaedic surgery or cancer surgery. The aim of perioperative thrombosis prophylaxis is to reduce perioperative morbidity and mortality. The article discusses patient- and intervention-dependent thromboprophylactic measures. Recent recommendations for non-pharmacological and pharmacological prophylaxis are presented including the information on the beginning and duration of anticoagulation. Management strategies for patients undergoing abdominal and orthopaedic surgery as well as special aspects of the neurosurgical population and of cancer surgery are highlighted.ZusammenfassungVeränderungen des Blutflusses, Gefäßwandverletzungen und eine gesteigerte Gerinnbarkeit des Blutes durch angeborene oder erworbene Thrombophilie oder durch die perioperative Gerinnungsaktivierung tragen gemäß dem Konzept von Virchow ursächlich zur Entstehung von perioperativen Venenthrombosen bei. Je nach Art des Eingriffs beträgt das Risiko zwischen <10% und >50%. Das Risiko ist nach großen orthopädischen Eingriffen und bei Tumoroperationen am höchsten. Ziel einer standardisierten perioperativen Thromboseprophylaxe ist, die postoperative Morbidität und Mortalität zu senken. Dieser Artikel beschreibt Patienten- und Eingriff-spezifische Maßnahmen zur Thromboseprophylaxe. Aktuelle Empfehlungen zur mechanischen und pharmakologischen Prophylaxe einschließlich Beginn und Dauer der Antikoagulation werden dargestellt. Neben der Thromboseprophylaxe für allgemeinchirurgische und große orthopädische Eingriffe wird die Problematik auch am Beispiel neurochirurgischen Interventionen und der Tumorchirurgie beleuchtet.

CorrespondenceDeep vein thrombosis

Deep vein thrombosis and its sequelae pulmonary embolism and post-thrombotic syndrome are some of the most common disorders. A thrombus either arises spontaneously or is caused by clinical conditions including surgery, trauma, or prolonged bed rest. In these instances, prophylaxis with low-dose anticoagulation is effective. Diagnosis of deep vein thrombosis relies on imaging techniques such as ultrasonography or venography. Only about 25% of symptomatic patients have a thrombus. Thus, clinical risk assessment and D-dimer measurement are used to rule out deep vein thrombosis. Thrombus progression and embolisation can be prevented by low-molecular-weight heparin followed by vitamin K antagonists. Use of these antagonists for 3-6 months is sufficient for many patients. Those with antithrombin deficiency, the lupus anticoagulant, homozygous or combined defects, or with previous deep vein thrombosis can benefit from indefinite anticoagulation. In cancer patients, low-molecular-weight heparin is more effective than and is at least as safe as vitamin K antagonists. Women seem to have a lower thrombosis risk than men, but pregnancy or use of oral contraceptives or hormone replacement therapy represent important risk factors.