Low ADAMTS‐13 predicts adverse outcomes in hospitalized patients with suspected heparin‐induced thrombocytopenia

Chan, Meng; Zhao, Xinyang; Zheng, X. Long

doi:10.1002/rth2.12581

Cited by 8 publications

(9 citation statements)

References 70 publications

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“…A positive correlation between PF4 and VWF : Ag levels in type 2A VWD patients (r = 0.229, p = 0.010) was found, which might indicate a similar interaction in vivo (53). Low plasma ADAMTS13 activity or reduced ratio of ADAMTS13 activity to VWF antigen or activity was found prevalent in patients with suspected HIT (54), which suggests that PF4 may reduce VWF cleavage by inhibiting ADAMTS13 activity. Similarly, ADAMTS13 levels were reduced (p = 0.009) and the VWF/ADAMTS13 ratio was increased (p = 0.0004) in convalescent COVID-19 patients with dysregulated angiogenesis and immunothrombosis, while levels of PF4 (a putative protector of VWF) were also elevated (p = 0.0001) (55).…”

Section: Potential Role Of the Pf4-vwf Complex In Immune-associated T...mentioning

confidence: 79%

New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF

et al. 2023

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Platelet factor 4 (PF4), also known as chemokine (C-X-C motif) ligand 4 (CXCL4), is a specific protein synthesized from platelet α particles. The combination of PF4 and heparin to form antigenic complexes is an important mechanism in the pathogenesis of heparin-induced thrombocytopenia (HIT), but vaccine-induced immune thrombotic thrombocytopenia (VITT) related to the COVID-19 vaccine makes PF4 a research hotspot again. Similar to HIT, vaccines, bacteria, and other non-heparin exposure, PF4 can interact with negatively charged polyanions to form immune complexes and participate in thrombosis. These anions include cell surface mucopolysaccharides, platelet polyphosphates, DNA from endothelial cells, or von Willebrand factor (VWF). Among them, PF4–VWF, as a new immune complex, may induce and promote the formation of immune-associated thrombosis and is expected to become a new target and therapeutic direction. For both HIT and VITT, there is no effective and targeted treatment except discontinuation of suspected drugs. The research and development of targeted drugs based on the mechanism of action have become an unmet clinical need. Here, this study systematically reviewed the characteristics and pathophysiological mechanisms of PF4 and VWF, elaborated the potential mechanism of action of PF4–VWF complex in immune-associated thrombosis, summarized the current status of new drug research and development for PF4 and VWF, and discussed the possibility of this complex as a potential biomarker for early immune-associated thrombosis events. Moreover, the key points of basic research and clinical evaluation are put forward in the study.

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Section: Potential Role Of the Pf4-vwf Complex In Immune-associated T...mentioning

confidence: 79%

New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF

et al. 2023

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“…VTE is a known complication of surgery that remains as a notable cause of morbidity and mortality. Several studies have found that changes in the ratio of VWF to ADAMTS13 impact thrombosis potential in patients with various diseases [ 49 , 50 , 51 , 52 , 53 ]. The results of this study are consistent with the changes described in the literature and the relationship between VWF, ADAMTS13, and other surgeries [ 20 , 29 , 54 , 55 , 56 , 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Changes in Plasma Levels of ADAMTS13 and von Willebrand Factor in Patients Undergoing Elective Joint Arthroplasty

Schick

Williams

et al. 2022

JCM

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The risk of venous thromboembolic events (VTE) increases in patients undergoing total shoulder arthroplasty (TSA). However, there is no guidelines for prophylaxis. A decreased ratio of ADAMTS13 to VWF has been reported in patients with VTE. This study evaluates how TSA affects this ratio to better characterize timing of VTE risk and develop better guidelines for prophylactic treatment. Methods: Patients receiving TSA between 2016 and 2019 were recruited for this study following informed consent. Blood samples were collected at the clinic visit prior to surgery, postoperatively within one hour, at 24 h, 48 h, 2 and 6 weeks. Plasma levels of ADAMTS13 activity and VWF antigen were determined with a FRETS-VWF73 and an enzyme-linked immunoassay, respectively. Results: Of 22 patients included in the study, the mean age (± SD) was 68 ± 11 years. The most common diagnosis and surgery were osteoarthritis (68%) and reverse TSA (77%), respectively. Plasma ADAMTS13 activity was reduced immediately following surgery and remained lower than the baseline until postoperative day 2 (POD-2) (93.7 ± 28.5 IU/dL, p = 0.009). VWF antigen was the highest on POD-2 (253.2 ± 101.0%, p = 0.0034). The ADAMTS13/VWF ratio followed the same pattern, lowest on POD-2 (0.41 ± 0.20, p = 0.0016). All levels returned to baseline by two weeks. Conclusions: TSA resulted in low ADAMTS13 activity and high VWF acutely post-surgery day 2, suggesting that risk for VTE may be the highest during this period. ADAMTS13/VWF ratio is a useful marker to identify patients who may need proper anticoagulation after TSA.

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“…31,76 The relative deficiency of ADAMTS13 function is a risk factor for the increased mortality rate in these patients. 26,31,[74][75][76][77] Irradiation and/or malignancy may trigger endothelial release of ULVWF and suppress ADAMTS13 synthesis. [78][79][80] Low ADAMTS13 activity and high VWF levels were also shown to be independently associated with an increased mortality rate in patients with malignancy.…”

Section: Discussionmentioning

confidence: 99%

“…The cause of such a moderate deficiency of plasma ADAMTS13 activity is most likely the results of massive release of VWF from vascular endothelium and/or inhibition of ADAMTS13 biosynthesis and release. More recent studies have demonstrated the relative deficiency of plasma ADAMTS13 function (i.e., low ADAMTS13 and high VWF) in hospitalized patients with a suspected heparin‐induced thrombocytopenia 75 and in those with severe/critical COVID‐19, resulting from infection with SARS‐CoV‐2 31,76 . The relative deficiency of ADAMTS13 function is a risk factor for the increased mortality rate in these patients 26,31,74–77 …”

Section: Discussionmentioning

confidence: 99%

ADAMTS13 protease or lack of von Willebrand factor protects irradiation and melanoma‐induced thrombotic microangiopathy in zebrafish

Zheng

Cao

Zheng

2022

Journal of Thrombosis and Haemostasis

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Background: Severe deficiency of plasma ADAMTS13 activity may result in potentially fatal thrombotic thrombocytopenic purpura and relative deficiency of plasma ADAMTS13 activity may be associated with adverse outcomes of certain malignancies. Here, we report the role of ADAMTS13 or lack of von Willebrand factor (VWF) in reducing irradiation and melanoma-induced thrombotic microangiopathy (TMA) and mortality in zebrafish.Methods: Zebrafish melanoma cell line (ZMEL) was injected subcutaneously into wild-type (wt), adamts13 −/− (a13 −/− ), von Willebrand factor (vwf −/− ), and a13 −/− vwf −/− zebrafish following total body irradiation; the tumor growth, its gene expression pattern, the resulting thrombocytopenia, and the mortality were determined. Results:Total body irradiation at 30 Gy alone resulted in a transient thrombocytopenia in both wt and a13 −/− zebrafish. However, thrombocytopenia occurred earlier and more profound in a13 −/− than in wt zebrafish, which was resolved 2 weeks following irradiation alone. An inoculation of ZMEL following the irradiation resulted in more severe and persistent thrombocytopenia, as well as earlier death in a13 −/− than in wt zebrafish. The vwf −/− or a13 −/− vwf −/− zebrafish were protected from developing severe thrombocytopenia following the same maneuvers. RNA-sequencing revealed significant differentially expressed genes associated with oxidation-reduction, metabolism, lipid, fatty acid and cholesterol metabolic processes, steroid synthesis, and phospholipid efflux in the melanoma explanted from a13 −/− zebrafish compared with that from the wt controls. Conclusions:Our results indicated that plasma ADAMTS13 or lack of VWF may offer a significant protection against the development of irradiation-and/or melanomainduced TMA. Such a microenvironment may directly affect melanoma cell phenotypes via alternation in the oxidation-reduction and lipid metabolic pathways.

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Low ADAMTS‐13 predicts adverse outcomes in hospitalized patients with suspected heparin‐induced thrombocytopenia

Cited by 8 publications

References 70 publications

New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF

New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF

Changes in Plasma Levels of ADAMTS13 and von Willebrand Factor in Patients Undergoing Elective Joint Arthroplasty

ADAMTS13 protease or lack of von Willebrand factor protects irradiation and melanoma‐induced thrombotic microangiopathy in zebrafish

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