ADAMTS13 activity in sickle cell disease

Schnog, John‐John B.; Hovinga, Johanna A. Kremer; Krieg, Soraya; Akın, Şakir; Lämmle, Bernhard; Brandjes, Dees P. M.; Gillavry, Melvin R. Mac; Muskiet, Faj; Duits, Ashley J.

doi:10.1002/ajh.20653

Cited by 56 publications

(56 citation statements)

References 41 publications

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“…This process may ultimately result in organ dysfunction as described previously in several other pathologies and invasive procedures including TTP and liver transplantation (4,5,(20)(21)(22)(23)(24). We speculate that the development of a VWF/ADAMTS13 unbalance during lung transplantation also facilitates thrombus formation within the allograft.…”

Section: Primary Hemostasis In Lung Transplantationsupporting

confidence: 59%

Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13

Hugenholtz

Ruitenbeek

Adelmeijer

et al. 2015

American Journal of Transplantation

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An unbalance between the platelet‐adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off‐pump lung transplantation. We analyzed plasma of 10 patients and distinguished lung transplantation‐specific effects from those generally accompanying open‐chest surgeries by comparing results with 11 patients undergoing off‐pump coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for reference values. VWF antigen levels as well as the VWF ristocetin cofactor activity/VWF antigen ratio increased during lung transplantation and after CABG surgery. An increase in VWF propeptide levels was paralleled by a decrease in ADAMTS13 activity. This was more pronounced during lung transplantation. Similarly, the capacity of plasma to support platelet aggregation under shear flow conditions in vitro was more increased during lung transplantation. The proportion of high molecular weight VWF multimers was elevated in both groups without evidence for ultra‐large VWF. VWF's collagen binding activity remained unchanged. In conclusion, a hyperactive primary hemostatic system develops during lung transplantation resulting both from a pronounced (functional) increase of the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet thrombosis within the allograft.

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Section: Primary Hemostasis In Lung Transplantationsupporting

confidence: 59%

Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13

Hugenholtz

Ruitenbeek

Adelmeijer

et al. 2015

American Journal of Transplantation

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“…A doubleblind randomized trial with tinzaparin in SCD patients during acute vaso-occlusive events documented a reduction of their severity and duration [97]. Studies with low dose of warfarin or acenocoumarol were reported to slightly reduce the frequency of acute pain events with decreased thrombin generation and fibrinolysis, however without reaching a significant clinical amelioration [98].…”

Section: Future Trendmentioning

confidence: 99%

Non-Conventional Pain Management for Sickle Cell Disease

Al-Jafar¹

2017

Ann Hematol Oncol

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Sickle cell disease is a congenital blood disorder affecting hemoglobin molecule. It leads to a rigid, sickle like shape red blood cell. Most people with sickle cell disease have severe painful episodes called vaso-occlusive crises. However, the frequency, severity, and duration of these crises vary tremendously. The pain is classified into two types, nociception pain which is intact peripheral or central nervous system and neuropathic pain which is initiated by dysfunction of the peripheral or central nervous system. Despite the pain being the most common complication of sickle cell disease, there is a lack of novel pain treatments. Pain killers including opioid have continued to be the main stay of therapy over the past several decades. A non-conventional treatments for pain were applied effectively to avoid the serious systemic side effects of the pharmaceutical pain killers.

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“…[8][9][10] Normally, ULVWF is cleaved rapidly by the metalloproteinase ADAMTS13 into smaller, less adhesive multimers, 11 preventing disastrous complications, such as thrombotic thrombocytopenic purpura. 12 Elevated plasma VWF levels have been reported in SCD, 13,14 but studies on the structure and reactivity of VWF in this disease are lacking.…”

Section: Introductionmentioning

confidence: 99%

The rate of hemolysis in sickle cell disease correlates with the quantity of active von Willebrand factor in the plasma

Chen

Hobbs

et al. 2011

Blood

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Vaso-occlusion, hemolysis, and oxidative stress are hallmarks of sickle cell disease (SCD). This pathology is accompanied by systemic endothelial activation, rendering the endothelium more adhesive for blood cells, including sickle erythrocytes. Activated endothelial cells display or secrete several adhesive molecules, including von Willebrand factor (VWF). We assessed several VWF parameters in SCD patients at baseline: multimer pattern, antigen concentration (VWF:Ag), activation factor (VWF:AF), and total active VWF (VWF:TA). VWF:AF was determined using a llama nanobody (AU/VWFa-11) that detects a platelet-binding conformation of the A1 domain; VWF:TA was calculated by multiplying VWF:Ag by VWF:AF. SCD plasma contained elevated VWF:Ag and ultralarge VWF multimers. VWF:TA, a measure of total VWF reactivity, correlated closely with hemolysis, as determined by serum lactate dehydrogenase. ADAMTS13 activity and antigen were normal in all patients. These findings suggest an important role for hyperreactive VWF in SCD pathology and connect SCD to other microangiopathies, particularly thrombotic thrombocytopenic purpura.

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ADAMTS13 activity in sickle cell disease

Cited by 56 publications

References 41 publications

Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13

Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13

Non-Conventional Pain Management for Sickle Cell Disease

The rate of hemolysis in sickle cell disease correlates with the quantity of active von Willebrand factor in the plasma

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