Clot Waveform Analysis Demonstrates Low Blood Coagulation Ability in Patients with Idiopathic Thrombocytopenic Purpura

Wada, Hideo; Ichikawa, Yuhuko; Ezaki, Minoru; Shiraki, Katsuya; Moritani, Isao; Yamashita, Yoshiki; Matsumoto, Toshifumi; Masuya, Masahiro; Tawara, Isao; Shimpo, Hideto; Shimaoka, Motomu

doi:10.3390/jcm10245987

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…Routine APTT or PT using PPP cannot evaluate the effect of platelets on the coagulation system. When APTT is measured using PRP, the large amount of artificial phospholipids in the APTT reagent cancels out the effect of platelets on the coagulation reaction [22,31]. Fig.…”

Section: Why Several Modifications Are Neededmentioning

confidence: 99%

“…CWA-PT with APTT is useful for evaluating small amounts of FVIII and FVIII inhibitors [3,32,37], whereas sTF/FIXa can measure FVIII activity [29] and evaluate hypercoagulability in patients with neoplasms [38]. As sTF/FIXa uses PRP, it has been used to evaluate hemostatic abnormalities in idiopathic thrombocytopenic purpura [31]. Finally, CWA-sTF/FIXa diagnoses hypercoagulability, which shortens the peak time and increases the peak height in patients with cancer or acute cerebral infarction, and hypocoagulability, which prolongs the peak time or decreases the peak height in patients with thrombocytopenia or clotting factor deficiency [31,38] (Fig.…”

Section: Cwa-dilute Ptmentioning

confidence: 99%

“…Further investigations are needed to determine the optimal cutoff value of the peak height in CWA-sTF/FIXa for initiating anticoagulant therapy in patients with hypercoagulability. In PRP from patients with thrombocytopenia, decreased platelet membrane phospholipid concentrations may prolong the peak time and reduce the peak height in CWA-sTF/FIXa, suggesting that antiplatelet agents may not cause CWA abnormalities [1,31].…”

Section: Cwa-dilute Ptmentioning

confidence: 99%

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Clot Waveform Analysis for Hemostatic Abnormalities

et al. 2023

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Clot waveform analysis (CWA) observes changes in transparency in a plasma sample based on clotting tests such as activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). Evidence indicates that not only an abnormal waveform but also peak times and heights in derivative curves of CWA are useful for the evaluation of hemostatic abnormalities. Modified CWA, including the PT with APTT reagent, dilute PT (small amount of tissue factor [TF]-induced clotting factor IX [FIX] activation; sTF/FIXa), and dilute TT, has been proposed to evaluate physiological or pathological hemostasis. We review routine and modified CWA and their clinical applications. In CWA-sTF/FIXa, elevated peak heights indicate hypercoagulability in patients with cancer or thrombosis, whereas prolonged peak times indicate hypocoagulability in several conditions, including clotting factor deficiency and thrombocytopenia. CWA-dilute TT reflects the thrombin burst, whereas clot-fibrinolysis waveform analysis reflects both hemostasis and fibrinolysis. The relevance and usefulness of CWA-APTT and modified CWA should be further investigated in various diseases.

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Section: Why Several Modifications Are Neededmentioning

confidence: 99%

Section: Cwa-dilute Ptmentioning

confidence: 99%

Section: Cwa-dilute Ptmentioning

confidence: 99%

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Clot Waveform Analysis for Hemostatic Abnormalities

et al. 2023

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“…An optical automatic coagulation analyzer has been able to demonstrate the clot reaction curve of APTT [ 14 , 15 ], diluted prothrombin time (PT) [ 16 ] and thrombin time (TT) [ 17 ]. Such an analysis of the coagulation curve is called a clotting waveform analysis (CWA) [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

A Clot Waveform Analysis of Thrombin Time Using a Small Amount of Thrombin Is Useful for Evaluating the Clotting Activity of Plasma Independent of the Presence of Emicizumab

Wada

Shiraki²,

Matsumoto³

et al. 2022

JCM

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Objective: Although emicizumab is a bispecific, monoclonal antibody that has led to a significant improvement of treatment for hemophilia A patients with inhibitors, the routine monitoring of patients treated with emicizumab is difficult. Thrombin time (TT) reflects thrombin burst, which mainly depends on activation of factor V (FV) and FVIII. Methods: We, therefore, developed a method for evaluating clotting activity independent of the presence of emicizumab. Normal plasma (NP) or FVIII-deficient plasma (FVIIIDP) with and without emicizumab was measured using clot waveform analysis (CWA)-activated partial thromboplastin time (APTT) and TT. Results: Emicizumab caused clot formation in FVIIIDP using the CWA-APTT; however, the coagulation peaks of plasma with and without emicizumab measured by the CWA-TT did not differ to a statistically significant extent. Regarding the mixing tests with NP and FVIIIDP, CWA-APTT showed large differences between each mixing test in plasma with and without emicizumab, whereas the CWA-TT showed similar patterns in mixing plasma with and without emicizumab. Regarding the standard curve of FVIII activity, the CWA-APTT showed an FVIII-concentration-dependent increase; however, the values with each concentration of FVIII differed between samples with and without emicizumab, whereas CWA-TT showed FVIII-concentration-dependent fluctuations independent of the presence of emicizumab, and the values with each concentration of FVIII were similar in samples with and without emicizumab. Conclusions: As CWA-TT using a small amount of thrombin (0.5 IU/mL) can reflect thrombin burst and be useful for evaluating FVIII activity, independent of the presence of emicizumab, it is useful for monitoring clotting activity in patients with an anti-FVIII inhibitor treated with emicizumab.

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Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma

Patalakh,

Wandersee,

Schlüter

et al. 2024

Transfus Med Hemother

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Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized classical treatment approaches of various cancer entities, but are also associated with a number of side effects. One of these may be life-threatening clotting disorders with the risk of thrombotic or hemorrhagic complications, the mechanisms of which are still poorly understood. In the present study, we analyzed the direct effects of pembrolizumab, nivolumab, and ipilimumab on platelet aggregation as well as plasma coagulation followed by fibrinolysis in an ex vivo model. Methods: Microplate spectrometry was used to analyze aggregation, coagulation, and fibrinolysis in platelet-free (PFP) and platelet-rich (PRP) healthy donor plasma samples treated with pembrolizumab, nivolumab, ipilimumab, and appropriate isotype controls. Aggregation was induced by TRAP-6. Clotting of PFP and PRP followed by lysis was initiated with a tissue factor in a mixture of phosphatidylserine:phosphatidylcholine and the addition of t-PA. Among other parameters, the area under the curve (AUC) was used to compare the effect of ICIs on aggregation, coagulation, and fibrinolysis. Results: Upon direct contact with platelets, pembrolizumab stimulated platelet aggregation in PRP, while nivolumab and ipilimumab promoted disaggregation with corresponding changes in the AUC. Pembrolizumab and nivolumab, both PD-1 receptor inhibitors, had no effect on the plasma coagulation cascade. Ipilimumab, a CTLA-4 receptor inhibitor, significantly increased the rate of PRP clotting. When clotting was followed by lysis, all ICIs were found to prolong the growth of the PRP-derived fibrin clot and delay its elimination. This was manifested by an increase in AUC relative to control PRP. Conclusion: This study characterizes the potential impact of pembrolizumab, nivolumab, and ipilimumab on hemostasis. Nivolumab and ipilimumab are able to reduce aggregation and increase the procoagulant properties of platelets, which can cause side effects associated with hemostatic imbalance leading to thrombosis or bleeding. The observed ICI-specific effects may contribute to our understanding of the mechanisms by which ICI affects platelets and suggest how, in a clinical setting, to reduce coagulation disorders during ICI treatment in the future.

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Clot Waveform Analysis Demonstrates Low Blood Coagulation Ability in Patients with Idiopathic Thrombocytopenic Purpura

Cited by 6 publications

References 26 publications

Clot Waveform Analysis for Hemostatic Abnormalities

Clot Waveform Analysis for Hemostatic Abnormalities

A Clot Waveform Analysis of Thrombin Time Using a Small Amount of Thrombin Is Useful for Evaluating the Clotting Activity of Plasma Independent of the Presence of Emicizumab

Influence of the Immune Checkpoint Inhibitors on the Hemostatic Potential of Blood Plasma

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