Immunthrombozytopenie - Onkopedia-Leitlinien Update: Empfehlungen einer gemeinsamen Arbeitsgruppe der DGHO, ÖGHO, SGH + SSH und GPOH

Matzdorff, Axel; Eberl, W.; Giagounidis, Aristoteles; Imbach, Paul; Pabinger, Ingrid; Wörmann, Bernhard

doi:10.1159/000356910

Cited by 8 publications

(25 citation statements)

References 62 publications

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“…1 D). In summary, we observe that in the absence of plate lets, UVB radiation provokes cutaneous bleeding (WHO bleed ing grade I; Matzdorff et al, 2014) in humans and in mice.…”

Section: Uvb-induced Inflammation Leads To Skin Hemorrhage During Thrmentioning

confidence: 64%

“…ITP patients may become resistant to various forms of ITP treatment, and specific antiinflammatory strategies with out compromising the overall immune status of the patient are clearly needed (Neunert et al, 2011;Izak and Bussel, 2014;Matzdorff et al, 2014). We show here that inflammatory neutrophil-endothelial cross talk induces tissue bleeding dur ing thrombocytopenia.…”

Section: (E) Representative Photographs and Quantification Of Bleedinmentioning

confidence: 68%

“…In thrombocytopenic patients, cutaneous bleeding (WHO bleeding grade I; Matzdorff et al, 2014) is obviously not as dreaded as pulmonary or cerebral hemorrhage (WHO bleed ing grade IV; Matzdorff et al, 2014). Lung hemorrhage, a major clinical complication of ITP, may be life threatening for thrombocytopenic patients.…”

Section: (E) Representative Photographs and Quantification Of Bleedinmentioning

confidence: 99%

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Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

Hillgruber¹,

Pöppelmann²,

Weishaupt³

et al. 2015

J Cell Biol

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Spontaneous organ hemorrhage is the major complication in thrombocytopenia with a potential fatal outcome. However, the exact mechanisms regulating vascular integrity are still unknown. Here, we demonstrate that neutrophils recruited to inflammatory sites are the cellular culprits inducing thrombocytopenic tissue hemorrhage. Exposure of thrombocytopenic mice to UVB light provokes cutaneous petechial bleeding. This phenomenon is also observed in immune-thrombocytopenic patients when tested for UVB tolerance. Mechanistically, we show, analyzing several inflammatory models, that it is neutrophil diapedesis through the endothelial barrier that is responsible for the bleeding defect. First, bleeding is triggered by neutrophil-mediated mechanisms, which act downstream of capturing, adhesion, and crawling on the blood vessel wall and require G i signaling in neutrophils. Second, mutating Y731 in the cytoplasmic tail of VE-cadherin, known to selectively affect leukocyte diapedesis, but not the induction of vascular permeability, attenuates bleeding. Third, and in line with this, simply destabilizing endothelial junctions by histamine did not trigger bleeding. We conclude that specifically targeting neutrophil diapedesis through the endothelial barrier may represent a new therapeutic avenue to prevent fatal bleeding in immune-thrombocytopenic patients.

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“…1 D). In summary, we observe that in the absence of plate lets, UVB radiation provokes cutaneous bleeding (WHO bleed ing grade I; Matzdorff et al, 2014) in humans and in mice.…”

Section: Uvb-induced Inflammation Leads To Skin Hemorrhage During Thrmentioning

confidence: 64%

Section: (E) Representative Photographs and Quantification Of Bleedinmentioning

confidence: 68%

Section: (E) Representative Photographs and Quantification Of Bleedinmentioning

confidence: 99%

See 1 more Smart Citation

Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

Hillgruber¹,

Pöppelmann²,

Weishaupt³

et al. 2015

J Cell Biol

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“…Especially secondary ITP due to indolent B-cell lymphomas, autoimmune diseases, human immunodeficiency virus, and hepatitis B and C have to be excluded [8]. Newly diagnosed, persistent, and chronic ITP have to be discriminated due to the high spontaneous remission rate of newly diagnosed ITP with different treatment approaches [8,9]. The goal of therapy in ITP is to prevent bleeding.…”

Section: Introductionmentioning

confidence: 99%

Outpatient Management of Patients with Immune Thrombocytopenia (ITP) by Hematologists 1995-2014

Weide

Feiten²,

Friesenhahn³

et al. 2015

Oncol Res Treat

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Background: The aim of this study was to evaluate the treatment reality for outpatients with immune thrombocytopenia (ITP) managed by hematologists in routine care. Patients and Methods: All patients with ITP diagnosed between 06/1995 and 12/2014 in a community-based oncology group practice in Germany were retrospectively analyzed. Results: 422 patients with a median age of 55 years (range 7-91 years) were evaluated. 57% were female and 43% male. Only 198 (47%) patients needed therapy. First-line therapy (n = 198) consisted of steroids in 81%, intravenous immunoglobulins (IVIG) in 12%, and IVIG plus steroids in 6%. Patients received a median of 2 (range 1-10) lines of therapy. The most frequently used treatment modalities were steroids in 93%, IVIG in 55%, splenectomy in 21%, and other immunosuppressive agents (OISA) in 23% of patients. Rituximab and thrombopoietin receptor agonists (TRAs) were used in 10% and 6% only. 9 (2%) patients needed hospitalization due to bleeding complications. 72% of patients achieved a durable remission after their last line of therapy. 1 (0.2%) patient died due to bleeding complications. Conclusion: The treatment modalities most frequently used are steroids, immunoglobulins, splenectomy, and OISA. Rituximab and TRAs are only used infrequently. 72% of ITP patients achieve durable remissions. The rate of hospital admissions due to bleeding complications and the ITP-related mortality are low. The majority of ITP patients can be safely managed by hematologists on an outpatient basis.

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“…45 In contrast, platelet transfusions are usually not effective, but transfusion of large amounts of platelets can result in cessation of bleeding and even an increased platelet count and are therefore recommended as first-line treatment (in addition to IVIG and corticosteroids) in ITP patients with life-threatening bleeding. 44,46,47 However, in this situation, often more than 5 therapeutic units are required before bleeding is controlled.…”

Section: Commentmentioning

confidence: 99%

How I evaluate and treat thrombocytopenia in the intensive care unit patient

Greinacher

Selleng

2016

Blood

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Multiple causes (pseudothrombocytopenia, hemodilution, increased consumption, decreased production, increased sequestration, and immune-mediated destruction of platelets) alone or in combination make thrombocytopenia very common in intensive care unit (ICU) patients. Persisting thrombocytopenia in critically ill patients is associated with, but not causative of, increased mortality. Identification of the underlying cause is key for management decisions in individual patients. While platelet transfusion might be indicated in patients with impaired platelet production or increased platelet destruction, it could be deleterious in patients with increased intravascular platelet activation. Sepsis and trauma are the most common causes of thrombocytopenia in the ICU. In these patients, treatment of the underlying disease will also increase platelet counts. Heparin-induced thrombocytopenia requires alternative anticoagulation at a therapeutic dose and immune thrombocytopenia immunomodulatory treatment. Thrombocytopenia with symptomatic bleeding at or above World Health Organization grade 2 or planned invasive procedures are established indications for platelet transfusions, while the evidence for a benefit of prophylactic platelet transfusions is weak and controversial. If the platelet count does not increase after transfusion of 2 fresh ABO blood group–identical platelet concentrates (therapeutic units), ongoing platelet consumption and high-titer anti-HLA class I antibodies should be considered. The latter requires transfusion of HLA-compatible platelet concentrates.

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Immunthrombozytopenie - Onkopedia-Leitlinien Update: Empfehlungen einer gemeinsamen Arbeitsgruppe der DGHO, ÖGHO, SGH + SSH und GPOH

Cited by 8 publications

References 62 publications

Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

Outpatient Management of Patients with Immune Thrombocytopenia (ITP) by Hematologists 1995-2014

How I evaluate and treat thrombocytopenia in the intensive care unit patient

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