Thrombotische Mikroangiopathien nach extrakorporaler Zirkulation: Wichtige Differenzialdiagnose

Zusammenfassung: Thrombotische Mikroangiopathien sind durch Thrombozytenaktivierung, Endothelzellschädigung, Hämolyse und mikrovaskuläre Okklusionen gekennzeichnet. Es handelt sich hierbei um eine Gruppe von Erkrankungen, deren Hauptvertreter die thrombotische thrombozytopenische Purpura (TTP) und das hämolytisch-urämische Syndrom (HUS) sind. Klinisch bestehen bei den Patienten eine mikroangiopathische hämolytische Anämie mit Thrombozytopenie und okklusionsbedingte Organischämien in variabler Ausprägung. Die Symptomatik der einzelnen Krankheitsbilder überschneidet sich häufig, sodass eine eindeutige Zuordnung anhand klinischer Kriterien oft schwierig ist. Aufgrund einer hohen Mortalität, insbesondere der TTP, sind eine schnelle Diagnostik und Therapie erforderlich. Es wird über 2Patienten mit thrombotischen Mikroangiopathien nach kardiochirurgischen Eingriffen berichtet. Da TTP, HUS und eine medikamentöse Ätiologie weitgehend ausgeschlossen wurden, wurde ein Zusammenhang zwischen der extrakorporalen Zirkulation während dem herzchirurgischen Eingriff und der thrombotischen Mikroangiopathie vermute

Langzeitmedikation und perioperatives Management

Zusammenfassung: Anästhesisten und Operateure sehen sich zunehmend mit Patienten konfrontiert, die unter einer medikamentösen Dauertherapie stehen. Ein Teil dieser Medikamente können mit Anästhetika oder anästhesiologischen und/oder chirurgischen Interventionen interagieren. Als Folge können Komplikationen wie Blutungen, Ischämien, Infektionen oder schwere Kreislaufreaktionen auftreten. Andererseits birgt oft gerade das perioperative Absetzen von Medikamenten die größere Gefahr. Der Anteil ambulant durchgeführter Operationen hat in den letzten Jahren stark zugenommen und wird voraussichtlich auch in Zukunft zunehmen. Seit Einführung der Fallpauschalen (in der Schweiz bevorstehend) wird der Patient in der Regel erst am Vortag der Operation stationär aufgenommen. Somit sind sowohl zuweisende Ärzte als auch Anästhesisten und Operateure gezwungen, sich frühzeitig mit Fragen der perioperativen Pharmakotherapie auseinanderzusetzen. Dieser Übersichtsartikel behandelt das Management der wichtigsten Medikamentenklassen während der perioperativen Phase. Neben kardial und zentral wirksamen Medikamenten und Wirkstoffen, welche auf die Hämostase und das endokrine System wirken, werden Spezialfälle wie Immunsuppressiva und Phytopharmaka behandel

Standardized Management Protocol in Severe Postpartum Hemorrhage: A Single-Center Study.

Severe postpartum hemorrhage (sPPH) is an obstetric emergency that needs prompt and effective therapy to reduce the risk of complications. In this study, women who developed sPPH (study cohort, n = 27) were treated according to a standardized management protocol prescribing sequential administration of uterotonic drugs, crystalloids, tranexamic acid, labile blood products, low-dose fibrinogen, and recombinant activated factor VII (rFVIIa). This group was compared to patients treated with different strategies during 2 preceding periods: an in-house guideline regulating the administration of rFVIIa (historical cohort 1, n = 20) and no specific guideline (historical cohort 2, n = 27). The management protocol was used over 33 months. The study cohort had a lower estimated blood loss ( P = .004) and required less red blood cell concentrates ( P = .007), fresh frozen plasma units ( P = .004), and platelet concentrates ( P = .020) compared to historical cohort 1 and historical cohort 2, respectively. The necessity of emergency postpartum hysterectomy was lower in the study group ( P = .012). In conclusion, in patients with sPPH treated with this standardized management protocol, we observed a decreased requirement of labile blood products and lower need to proceed to emergency postpartum hysterectomy

Acquired haemophilia A in the postpartum and risk of relapse in subsequent pregnancies: A systematic literature review.

About 1%-5% of acquired haemophilia A cases affect mothers in the postpartum setting. This study delineates the characteristics of this disease, specific to the postpartum setting, notably relapse in subsequent pregnancies. Report of two cases and literature study (1946-2019), yielding 73 articles describing 174 cases (total 176 cases). Patients were aged 29.9 years (17-41) and 69% primigravidae. Diagnosis was made at a median of 60 days after delivery (range 0-308). Bleeding types were obstetrical (43.4%), cutaneous (41.3%), and muscular (36.7%). In >90% of the cases, FVIII at diagnosis was <1% (range 0%-8%). FVIII inhibitor was documented in 75.4% cases (median titre of 20 BU/ml, range 1-621). Haemostatic treatment was necessary in 57.1% using fresh frozen plasma (16%), factor concentrate (27.6%) and/or bypassing agents (37.4%). Immunosuppressive treatment was administered in 90.8%, mostly steroids (85.3%), alone or combined with immunosuppressants (27%). Rituximab was used mostly as a second line treatment. Only 24 patients (13.6%) had documented subsequent pregnancies and 6 (22.2%) suffered haemophilia recurrence during pregnancy. This study allows better definition of: (1) clinical and laboratory characteristics of postpartum acquired haemophilia, (2) response to therapy, and (3) the risk of relapse for subsequent pregnancies

Impact of rivaroxaban on point-of-care assays.

Point-of-care testing (POCT) is regularly used to assess haemostasis in various clinical settings. The impact of rivaroxaban on those POCT is still elusive. We aimed to study the effects of rivaroxaban on most commonly used POCT assays. Blood samples were taken before, 3h, and 24h after administration of 20mg rivaroxaban to 20 healthy volunteers as part of a prospective, multicenter validation study (clinicaltrials.govNCT01710267). Blood samples were analysed with thromboelastometry (ROTEM®), two platelet function assays (INNOVANCE® PFA-200 and Multiplate®), and the CoaguChek® XS. Rivaroxaban plasma levels were determined using liquid chromatography-mass spectrometry. Rivaroxaban significantly modified some thromboelastometry parameters (CT INTEM: mean difference 56.1s, 95% CI: 41.8, 70.3; CT EXTEM: 47.5s, 95% CI: 37.8, 57.1; CT HEPTEM: 50.1s, 95% CI: 34.7, 65.6), and CoaguChek® XS parameters (prothrombin time: mean difference 3.8s, 95% CI: 3.3, 4.2; INR: 0.32, 95% CI: 0.27, 0.38; prothrombin ratio: -36.1%, 95% CI: -32.3, -39.9). CT EXTEM and INR showed a moderate correlation with rivaroxaban plasma levels (r=0.83; 95% CI 0.69, 0.9 and r=0.83; 95% CI 0.70, 0.91, respectively) and a high sensitivity to detect rivaroxaban treatment at peak levels (0.95; 95% CI: 0.76, 1.0 and 0.90, 95% CI 0.70, 0.99, respectively). Rivaroxaban 20mg treatment significantly alters ROTEM® and CoaguChek® XS parameters. Even though POCT do not allow precise quantification of rivaroxaban plasma concentration, CT EXTEM and CoaguChek XS detect the presence of rivaroxaban at peak level with a high sensitivity

Management of bleeding events and invasive procedures in patients with haemophilia A without inhibitors treated with emicizumab.

Emicizumab (Hemlibra®, Hoffmann-La Roche, Switzerland) is now available for haemophilia A patients with or without factor VIII inhibitors. Management of bleeding events and replacement therapy for invasive procedures have to be adapted. To provide a practical guidance for the management of breakthrough bleeding events and elective or urgent surgery in adult and paediatric patients with haemophilia A without inhibitors treated with emicizumab. Based on the available literature and the experiences collected from adult and paediatric patients treated in Switzerland, the Working Party on Haemostasis of the Swiss Society of Haematology and the Swiss Haemophilia Network worked together to reach a consensus on the management of bleeding events and invasive procedures. Minor bleeding events and invasive procedures associated with low bleeding risk can be treated without factor replacement therapy in most cases, whereas major bleeding events and high-risk surgery require additional factor VIII replacement at usual doses, at least for the first days. Emicizumab treatment should be continued throughout the procedure and during the postoperative period. Elective major surgery should be planned according to emicizumab dosing for patients with a once-a-month posology. Of note, so far only few data are available on the management of major bleeds and surgery in patients with haemophilia A treated with emicizumab and this practical guidance will have to be regularly updated with growing experience. &nbsp

Pretransplant Genetic Susceptibility: Clinical Relevance in Transplant-Associated Thrombotic Microangiopathy

Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). We hypothesized that pretransplant genetic susceptibility is evident in adult TA-TMA and further investigated the association of TMA-associated variants with clinical outcomes. We studied 40 patients with TA-TMA, donors of 18 patients and 40 control non-TMA HCT recipients, without significant differences in transplant characteristics. Genomic DNA from pretransplant peripheral blood was sequenced for TMA-associated genes. Donors presented significantly lower frequency of rare variants and variants in exonic/splicing/untranslated region (UTR) regions, compared with TA-TMA patients. Controls also showed a significantly lower frequency of rare variants in ADAMTS13, CD46, CFH, and CFI. The majority of TA-TMA patients (31/40) presented with pathogenic or likely pathogenic variants. Patients refractory to conventional treatment (62%) and patients that succumbed to transplant-related mortality (65%) were significantly enriched for variants in exonic/splicing/UTR regions. In conclusion, increased incidence of pathogenic, rare and variants in exonic/splicing/UTR regions of TA-TMA patients suggests genetic susceptibility not evident in controls or donors. Notably, variants in exonic/splicing/UTR regions were associated with poor response and survival. Therefore, pretransplant genomic screening may be useful to intensify monitoring and early intervention in patients at high risk for TA-TMA. © 2020 Georg Thieme Verlag. All rights reserved