Platelet Function and Factor 8 in Uremia

Park, Hee Sook; Kim, Moo Won; Kim, Tae Joon; Hwang, Seung Duk; Lee, Hi Bahl

doi:10.3904/kjim.1987.2.1.74

Cited by 2 publications

(3 citation statements)

References 27 publications

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“…[ 10 11 ] None of our patients had low vWF:Ag concentration, and 10 patients (22.2%) had values above the normal range. Other authors have also found the concentration of vWF:Ag to be normal[ 12 13 ] or elevated[ 14 15 ] in renal failure. The structure of vWF multimers has also been shown to be normal in renal failure.…”

Section: Discussionmentioning

confidence: 99%

Hemostatic abnormalities in severe renal failure: Do they bark or bite?

Mohapatra

Valson

Gopal³

et al. 2018

Indian J Nephrol

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Abnormal primary hemostasis is believed to be the most significant contributor to uremic bleeding. This study aimed to describe the prevalence and profile of primary and secondary hemostatic disorders in patients with chronic kidney disease (CKD) Stages 4 and 5 and to determine their association if any, with degree of uremia. Stages 4 and 5 predialysis CKD patients attending nephrology outpatient clinic were prospectively recruited and the following bleeding parameters were measured in all patients: platelet count, bleeding time (BT), Factor VIII assay, von Willebrand factor antigen (vWF:Ag), vWF:ristocetin cofactor activity (vWF:RCo), ratio of vWF:ristocetin cofactor activity to vWF antigen (vWF:RCo/vWF:Ag), prothrombin time (PT), and activated partial thromboplastin time (aPTT). Forty-five patients (80%, males) with a mean age of 39.4 years, 82% (n = 37) in Stage 5 CKD, were recruited for the study. The prevalence of thrombocytopenia was significantly higher among patients from West Bengal (15/26, 57.7%) compared to other study patients (2/19, 10.5%; P = 0.001); however, all had macrothrombocytes with normal BT, suggestive of the Harris syndrome. Factor VIII, vWF:Ag, vWF:RCo, vWF:RCo/vWF:Ag ratio, BT, PT, and aPTT were abnormal in 0 (0%), 0 (0%), 0 (0%), 4 (8.8%), 1 (2.2%), 7 (15.6%), and 5 (11.1%) patients, respectively. Except for thrombocytopenia, the prevalence of hemostatic abnormalities did not differ between CKD Stages 4 and 5. Hemostatic abnormalities are uncommon in Stages 4–5 CKD and except for thrombocytopenia, are not associated with degree of uremia. Constitutional macrothrombocytopenia is associated with normal BT even in CKD.

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Section: Discussionmentioning

confidence: 99%

Hemostatic abnormalities in severe renal failure: Do they bark or bite?

Mohapatra

Valson

Gopal³

et al. 2018

Indian J Nephrol

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“…21 A reduced protein tethering and platelet adhesion to subendothelial surfaces has been reported, while binding to collagen was normal 22,23 and the concentration of the vWF:FVIII complex was higher in ESKD group than in healthy volunteers. 24 The impact of carbamylation on von Willebrand factor (vWF) functionality and its implications for platelet adhesion remain largely unexplored. This study aims to elucidate whether carbamylation of vWF establishes a mechanistic connection between uremia and coagulation dysfunction in patients with end-stage kidney disease (ESKD).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…coagulation cascade, with the vWF:FVIII complex circulating in an inactive form in plasma. 24 In the context of ESKD, there is an upsurge in circulating levels of the vWF:FVIII complex. Notably, our study revealed that carbamylation of FVIII in vitro enhances its binding to vWF, potentially contributing to the elevated plasma levels of the complex as observed in ESKD.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Carbamylation Is Instrumental in End-Stage Kidney Disease Coagulopathies: The Impact on von Willebrand Factor and Platelet Functionality

Babickova,

Kałucka,

Kaminska

et al. 2024

Thromb Haemost

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Chronic kidney disease (CKD) is a progressive, irreversible and incurable condition characterized by high morbidity and mortality, affecting approximately one-tenth of the global population. Rise of urea-derived cyanate levels in CKD patients, severalfold higher in comparison to those found in healthy individuals, leads to an increased rate of carbamylation of lysine residues of proteins and peptides. This post-translational modification plays an important role in the progression of kidney failure but also in the onset of CKD-related complications, including previously reported coagulopathies. In this study we have explored the impact of carbamylation on the functionality of von Willebrand factor (vWF), pivotal player in hemostasis, and its implications for platelet adhesion. Using mass spectrometry we detected the vWF’s lysine residues most susceptible to carbamylation. This modification has in turn affected vWF’s interactions with its key binding partners: decreased binding to collagen types I/III but increased the affinity to factor FVIII, while its binding to fibrinogen remained unchanged. Carbamylation of vWF impeded vWF-blood platelet binding, but carbamylation of platelets led to their increased thrombin-dependent activation as observed by enhanced phosphatidylserine exposure, improved their binding to vascular endothelium, at the same time decreasing the production of the prothrombotic mediator, thromboxane A2. Our findings highlight the multifaceted impact of carbamylation on vWF and platelets, disturbing the delicate balance of coagulation cascade. These alterations could contribute to the complex hemostatic imbalance in ESKD, underscoring the need for further research to fully understand these mechanisms and their clinical implications.

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Platelet Function and Factor 8 in Uremia

Cited by 2 publications

References 27 publications

Hemostatic abnormalities in severe renal failure: Do they bark or bite?

Hemostatic abnormalities in severe renal failure: Do they bark or bite?

Carbamylation Is Instrumental in End-Stage Kidney Disease Coagulopathies: The Impact on von Willebrand Factor and Platelet Functionality

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