Jürgen Koscielny

Diagnosis and treatment of peripartum bleeding

Abstract Severe peripartum hemorrhage (PPH) contributes to maternal morbidity and mortality and is one of the most frequent emergencies in obstetrics, occurring at a prevalence of 0.5–5.0%. Detection of antepartum risk factors is essential in order to implement preventive measures. Proper training of obstetric staff and publication of recommendations and guidelines can effectively reduce the frequency of PPH and its resulting morbidity and mortality. Therefore, an interdisciplinary expert committee was formed, with members from Germany, Austria, and Switzerland, to summarize recent scientific findings. An up-to-date presentation of the importance of embolization and of the diagnosis of coagulopathy in PPH is provided. Furthermore, the committee recommends changes in the management of PPH including new surgical options and the off-label use of recombinant factor VIIa.

Capillary Microscopic and Rheological Dimensions for the Diagnosis of von Willebrand Disease in Comparison to other Haemorrhagic Diatheses

It is known that angiodysplasia influence macrocirculation as well as microcirculation in patients with vWD. In the present study it was examined if intravital capillary microscopic dimensions (morphologic and dynamic) in skin (nailfold) in combination with rheologic parameters could give indications for the presence of vWD in patients with haemorrhagic diathesis. Patients with vWD (n = 100; 92 type 1: definite type 1:78 and possible type 1:14: 8 type 2A) have in comparison to patients with other haemorrhagic diathesis [thrombocytopathy (n = 122), thrombocytopenia (n = 101). severe haemophilia A (n = 50) and severe haemophilia B (n = 20). congenital dysfibrinogenaemia (n = 22), oral anticoagulation with phenprocoumone (n = 112)] and to apparently healthy subjects (n = 100) a significantly increased capillary torquation (median index: 3.5), a venolar and an arteriolar capillary dilatation (median: 16.5 microm; median: 15.1 microm) and the highest part of microscopic bleedings (extravasates) with 40% in the video capillary microscopy as morphological changes. Only the congenital dysfibrinogenaemia appears with a larger dilatation in venolar capillaries (median: 14.5 microm). Microscopic bleedings are much less common in other haemorrhagic diatheses with a frequency between 4% and 13%. In the vWD a significantly reduced duration of reactive hyperaemia (median: 150 sec). This is the only dynamic change that can be taken as a possible hint for a loss of flexibility within the precapillary vessels. A significantly reduced plasma viscosity (< 1.25 mPas) is typical for the vWD due to the increase of the shear stress in blood plasma because of the reduction of vWF-activities. Changes of the capillary morphology (dilatation, extravasates, capillary torquation) and the hypoplasmaviscosity are most sensitive for the vWD (75%, 65%, 40%, 80%) with a fairly high specifity (up to 93%) and a positive predictive value of 99%. As a conclusion it seems reasonable to discuss the introduction of video capillary microscopy as a screening test for haemostasiological and angiological centers.

S3-Leitlinie zum Umgang mit Antikoagulation bei Operationen an der Haut.

Hintergrund: Immer häufiger sind Patienten aufgrund verschiedener Erkrankungen auf die Einnahme von Antikoagulanzien und Thrombozytenaggregationshemmern angewiesen. Besteht bei diesen Patienten die Notwendigkeit einer Operation an der Haut, stellt sich die Frage des perioperativen Umgangs mit Antikoagulation.

More on: platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function.

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Elimination kinetics of different hydroxyethyl starches and effects on blood fluidity

In a single blind randomized cross-over study 6 volunteers each received infusions of 500 m1 of 6 different types of hydroxyethyl starch (HES) solutions. Between the test periods there was a regular wash-out phase of 3 months. The concentration and molecular weight distribution of the intravascular HES-molecules as well as the blood fluidity were determined before and up to 24 hours after the infusions. The C2/C6 substitution ratio and the molar substitution exert an essential influence on the elimination of the HES-molecules. An increase in the C2/C6 substitution ratio from 4.6 to 10.8 with unchanged molecular weight (MW) and molar substitution brings about an increase in the half-life of the elimination in the 13 -phase t1I2-13 from 10.4 to 19.5 hours. In case a high C2/C6 substitution ratio is combined with a high molar substitution (0.62 instead of 0.5), half-life rises up to 36.1 hours. Whereas the molecular weights of all medium-molecular HEStypes (MW 200,000) decrease, the medium molecular weight of the

Rivaroxaban and hemostasis in emergency care.

Rivaroxaban is an oral, direct Factor Xa inhibitor, approved for the prevention and treatment of several thromboembolic disorders. Rivaroxaban does not require routine coagulation monitoring and has a short half-life. However, confirmation of rivaroxaban levels may be required in circumstances such as life-threatening bleeding or perioperative management. Here, we explore the management strategies in patients receiving rivaroxaban who have a bleeding emergency or require emergency surgery. Rivaroxaban plasma concentrations can be assessed quantitatively using anti-Factor Xa chromogenic assays, or qualitatively using prothrombin time assays (using rivaroxaban-sensitive reagents). In patients receiving long-term rivaroxaban therapy who require elective surgery, discontinuation of rivaroxaban 20–30 hours beforehand is normally sufficient to minimize bleeding risk. For emergency surgery, we advise against prophylactic use of hemostatic blood products, even with high rivaroxaban concentrations. Temporary rivaroxaban discontinuation is recommended if minor bleeding occurs; for severe bleeding, rivaroxaban withdrawal may be necessary, along with compression or appropriate surgical treatment. Supportive measures such as blood product administration might be beneficial. Life-threatening bleeding demands comprehensive hemostasis management, including potential use of agents such as prothrombin complex concentrate. Patients taking rivaroxaban who require emergency care for bleeding or surgery can be managed using established protocols and individualized assessment.

Blood rheology at term in normal pregnancy and in patients with adverse outcome events.

Plasma volume expansion of more than 1.5 l and sustainable activation of the hemostatic system that results in a steady rise of the fibrinogen/fibrin turnover are contemporary physiological events during normal pregnancy. In contrast, adverse outcome of pregnancy i.e. pre-eclampsia commonly coincide with hemo concentration and over activation of blood coagulation both of which alter blood rheology. On the basis of 4,985 consecutively recorded singleton pregnancies values range of blood rheological parameters in women with normal and complicated outcome of pregnancy at the time of their delivery were compared. Plasma viscosity (pv) was determined using KSPV 1 Fresenius and RBC aggregation (stasis: E0 and low shear: E1) using MA1-Aggregometer; Myrenne. Seventy-nine point four percent (n=3,959) had normal pregnancy outcome and 1,026 with adverse outcome of pregnancy had pre-eclampsia (8.4%; n=423), had newborn with a birth-weight < 2,500 g (9.5%; n=473), had early-birth before week 37 (9.3%; n=464), and/or were diagnosed with intra uterine growth retardation (IUGR) (5.0%; n=250). In women with normal pregnancy outcome mean (+/-SD) of pv was 1.31+/-0.09 mPa s, of E0 was 21.6+/-5.3, and of E1 was 38.4+/-7.9 while in women with adverse outcome means for rheological parameters were statistically significantly different i.e. pv: 1.32+/-0.08 mPa s; p=0.006, E0: 22.1+/-5.5; p=0.002 and E1: 39.5+/-8.5; p=0.0006. Subgroup analysis revealed statistical significant lower pv in women who either had pre term delivery or a low birth-weight child (p<0.005) as compared to women who had normal pregnancy outcome while patients with pre-eclampsia had markedly higher low shear and stasis RBC aggregation (p<0.0001). None of the rheological results at term were correlated with either maternal age (r<0.04), BMI (r<0.09), maternal weight gain until delivery (r<0.04), or fetal outcome such as APGAR-score (r<0.09) art. pH in the umbilical cord (-0.05<r<0.04), fetal birth-weight (r<0.04). Women who did vs. did not receive iron supplementation during pregnancy had lower pv (p<0.0001) and higher E0 (p<0.01) while smokers vs. non-smokers had lower E0 (p=0.0002). There was a strong correlation between hemoglobin concentrations and pv at term (spearman r=0.15; p<0.0001). To our knowledge this is the largest trial that consecutively assessed blood rheological parameters in pregnant women at term. Distribution of pv and RBC aggregation was studied in women with normal and complicated pregnancy. We found lower pv and increased RBC aggregation in patients with different adverse outcome of pregnancy compared to normal pregnancy. Interestingly, in pre-eclampsia hemo concentration and increased fibrinogen turnover due to enhanced coagulation activation are weighty co factors of pv but were associated with lower pv in patients with pre-eclampsia. However, coincidental increased RBC aggregation and hemo concentration may potentially derogate blood flow in the materno-fetal unit that is commonly traceable using vessel duplex ultra sound in pre-eclampsia.

Comparison of blood flow to the cutaneous temperature and redness after topical application of benzyl nicotinate

The topical application of drugs, such as nicotinates, affects cutaneous blood flow. Such a biological response, which is dependent on the drug and the individual, can be measured noninvasively using laser Doppler flowmetry. We illustrate the kinetics of vasodilation caused by topically applied benzyl nicotinate using a new frequency-selective laser Doppler flowmeter. This flowmeter measures the blood flow in the superficial dermal plexus and the deeper lying larger capillaries simultaneously and indirectly by determining the flow velocity. Both sets of data are compared with the skin temperature and redness. Four biological parameters are measured consecutively on a skin area treated with gel containing benzyl nicotinate and on an untreated control area. A linear relationship between both blood flows is observed. However, no correlation is obtained between the microcirculation with either the cutaneous temperature or the redness. These results indicate the transport of the drug in the blood from the upper to the deeper capillaries. Cutaneous temperature and redness are unsuitable parameters to measure the kinetics of the blood flow after topical application of drugs.

S3 guidelines for the management of anticoagulation in cutaneous surgery.

An increasing number of patients are being treated with anticoagulants and platelet inhibitors. Whenever surgical procedures of the skin are required, questions arise regarding the perioperative management of anticoagulation.

Präinterventionelle Änderung der Gerinnungsmedikation

Hintergrund: Die Differentialdiagnostik und Therapie von perioperativen Blutungen besitzt besonders bei Eingriffen mit hohen Blutverlusten einen hohen Stellenwert, z.B. in der Viszeralchirurgie. Insbesondere die präoperative Erfassung von hämorrhagischen Diathesen und einer gerinnungshemmenden Medikation trägt effektiv zur Minimierung von Komplikationen wie Hämatomen, sekundären Infektionen und Blutverlusten bei. Methode: Pharmakologische Aspekte, bereits vorliegende Konsensus-Empfehlungen und Leitlinien, Erfahrungen sowie Empfehlungen der Hersteller und der Zulassungsbehörden wurden genutzt. Ergebnisse: Bei Elektiveingriffen unter Langzeitantikoagulation ist zur Normalisierung des Blutungsrisikos bei normaler Nieren- und Leberfunktion ein Absetzen der Gerinnungsmedikation vor der Operation ausreichend, ein längerer Abstand ist bei eingeschränkter Nieren- und Leberfunktion sowie bei hohem Lebensalter zu berücksichtigen. Bei Patienten mit positiver standardisierter Blutungsanamnese durch die Einnahme von gerinnungshemmenden Medikamenten sollte auf der Basis einer individuellen Nutzen-Risiko-Abwägung (Individualmedizin) interdisziplinär das perioperative Weiterführen oder Absetzen von Gerinnungshemmern festgelegt werden. Da die Halbwertszeit aber interindividuell unterschiedlich und zum Teil unvorhersehbar sein kann, insbesondere bei Patienten mit verminderter Elimination (z.B. Niereninsuffizienz), kann in Einzelfällen ein geeigneter laboranalytischer Wirkungsnachweis als zusätzliche Entscheidungshilfe die Terminierung der Intervention unterstützen. Aus hämostaseologischer Sicht besteht die Indikation zum bereits präoperativen Management einer hämorrhagischen Diathese. Die Maßnahmen richten sich nach der jeweiligen Defizienz. Schlussfolgerungen: Elektive Eingriffe müssen sorgfältig geplant werden, besonders bei Patienten mit Gerinnungsmedikation oder hämorrhagischer Diathese.