Prolongation of bleeding time by acute hemolysis in rats: a role for nitric oxide

1997 ◽  
Vol 272 (6) ◽  
pp. H2875-H2884 ◽  
Author(s):  
T. Wollny ◽  
L. Iacoviello ◽  
W. Buczko ◽  
G. de Gaetano ◽  
M. B. Donati
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Platelet Aggregation ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Platelet Adhesion ◽  
Bleeding Time ◽  
Ex Vivo ◽  
White Blood Cells

The present study was aimed at clarifying the interaction between red blood cell trauma and bleeding observed in some clinical conditions. Acute hemolysis provoked by distilled water injection was followed by a significant prolongation of the "template" bleeding time in rats. Comparable effects were observed after injection of an isotonic lysate of washed red blood cells. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) formation from L-arginine, normalized bleeding time when given to rats before hemolysis induction. The occurrence of hemolysis decreased ex vivo platelet adhesion to collagen without affecting platelet aggregation and induced a transient drop in blood pressure, the latter occurring during the first minute after injection. L-NAME pretreatment increased ex vivo platelet adhesion but did not affect either platelet aggregation or fall in blood pressure. All the effects of L-NAME were blunted by treating the animals with the NO precursor L-arginine but not D-arginine. Incubation of the erythrocyte lysate with apyrase prevented the prolongation of bleeding time induced by the hemolysate. Moreover, ADP administration, at doses that did not increase hemoglobin levels, induced effects similar to those observed after hemolysis (on template bleeding time and ex vivo platelet adhesion), which were also reversed by L-NAME and restored by L-arginine. ADP is abundantly released from (hemo)lysed red blood cells and is known to stimulate release of NO, a potent vasodilator and inhibitor of platelet adhesion. ADP-dependent NO release could be responsible for bleeding time prolongation, due to abnormalities in platelet-vessel wall interaction, during acute hemolysis. Lysis of white blood cells may also contribute to prolongation of bleeding time. Because ADP could not be detected in these cells, we postulate that other mechanisms also can be involved in bleeding time prolongation after blood cell activation in vivo.

The Effect of Red Blood Cells on the ADP-induced Aggregation of Human Platelets in Flow Through Tubes

1990 ◽  
Vol 63 (01) ◽  
pp. 112-121 ◽  
Author(s):  
David N Bell ◽  
Samira Spain ◽  
Harry L Goldsmith
Keyword(s):  
Platelet Aggregation ◽  
Shear Rate ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Platelet Rich Plasma ◽  
Mean Transit Time ◽  
White Blood Cells ◽  
Aggregate Size ◽  
Human Platelets ◽  
Induced Aggregation

SummaryThe effect of red blood cells, rbc, and shear rate on the ADPinduced aggregation of platelets in whole blood, WB, flowing through polyethylene tubing was studied using a previously described technique (1). Effluent WB was collected into 0.5% glutaraldehyde and the red blood cells removed by centrifugation through Percoll. At 23°C the rate of single platelet aggregtion was upt to 9× greater in WB than previously found in platelet-rich plasma (2) at mean tube shear rates Ḡ = 41.9,335, and 1,920 s−1, and at both 0.2 and 1.0 µM ADP. At 0.2 pM ADP, the rate of aggregation was greatest at Ḡ = 41.9 s−1 over the first 1.7 s mean transit time through the flow tube, t, but decreased steadily with time. At Ḡ ≥335 s−1 the rate of aggregation increased between t = 1.7 and 8.6 s; however, aggregate size decreased with increasing shear rate. At 1.0 µM ADP, the initial rate of single platelet aggregation was still highest at Ḡ = 41.9 s1 where large aggregates up to several millimeters in diameter containing rbc formed by t = 43 s. At this ADP concentration, aggregate size was still limited at Ḡ ≥335 s−1 but the rate of single platelet aggregation was markedly greater than at 0.2 pM ADP. By t = 43 s, no single platelets remained and rbc were not incorporated into aggregates. Although aggregate size increased slowly, large aggregates eventually formed. White blood cells were not significantly incorporated into aggregates at any shear rate or ADP concentration. Since the present technique did not induce platelet thromboxane A2 formation or cause cell lysis, these experiments provide evidence for a purely mechanical effect of rbc in augmenting platelet aggregation in WB.

scholarly journals PO-283 Correlation Analysis between Blood Cell Viability, Five Elements and Competition Performance of Elite Men’s Rowers

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Junbei Bai
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Aerobic Capacity ◽  
Red Blood Cell ◽  
Iron Content ◽  
Blood Cells ◽  
White Blood Cells ◽  
Cell Activity ◽  
Ordinary People ◽  
Five Elements

Objective To observe the national elite male rowers blood, red blood cell activity and serum copper, zinc, calcium, magnesium and iron content of the five elements, and compared with the ordinary people. Aimed to investigate the between athletes, athletes and ordinary differences between the two sets of indicators and to explore the impact of element contents in red blood cell activity and five factors. Trying to bring two sets of indicators and specific combining ability, used in training on the monitoring function, and for the future to provide some references for further study. Methods It was included 22 athletes and 22 ordinary men, as the research object, in the collection of blood, measuring red blood cell activity in the blood content of the five elements, simultaneous measurement of physical indicators , will be doing all the data at the differences between the two groups compared to the group to do correlation analysis. The recent record of 2000m, 6000m rowing Dynamometer test results, and red blood cell activity associated with the five elements of content analysis. Results 1. Athletes indicators related to aerobic exercise were significantly higher than ordinary people. The white blood cells of athletes group were average.It shows that athletes have high aerobic capacity, while white blood cells are more stable than normal people. The members of the national rowing men's iron, magnesium content was significantly higher than ordinary group, the iron content is higher than the normal reference value; blood calcium levels were significantly lower than ordinary people, and lower than the normal reference value. The total number of red blood cells and the number of living cells was very significant positive correlation in two groups subjects; Red blood cell activity and red blood cell diameter is proportional, and red blood cell roundness in inverse proportion to the relationship; from this experiment a special ability to see red blood cell activity and there is no correlation. In both groups, hemoglobin was positively correlated with iron content, while iron was positively correlated with copper content. Conclusions 1. Increasing the number and volume of red blood cells can effectively increase the activity of red blood cells; red blood cell activity has no correlation with specific ability, and can not be used as an indicator to determine specific ability. The content of iron and magnesium in rowers is higher than that in ordinary people, which indicates that the adjustment of aerobic capacity and nerve control is very effective. The lower calcium content indicates that the injury caused by calcium loss should be prevented and the urgency of calcium supplementation should be emphasized. In training, we should pay attention to increasing hemoglobin content and aerobic capacity by supplementing iron. We can further consider the effect of supplementing copper to promote iron supplementation.

Unique Antiplatelet Effects of a Novel S-Nitrosoderivative of a Recombinant Fragment of von Willebrand Factor, AR545C: In Vitro and Ex Vivo Inhibition of Platelet Function

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1693-1700
Author(s):  
Aida Inbal ◽  
Osnat Gurevitz ◽  
Ilia Tamarin ◽  
Regina Eskaraev ◽  
Angela Chetrit ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Aggregate Formation ◽  
Recombinant Fragment ◽  
Von Willebrand ◽  
Willebrand Factor

The recombinant fragment of von Willebrand factor (vWF) spanning Ala444 to Asp730 and containing an Arg545Cys mutation (denoted AR545C) has antithrombotic properties that are principally a consequence of its ability to inhibit platelet adhesion to subendothelial matrix. Endothelial-derived nitric oxide (NO) can also inhibit platelet function, both as a consequence of inhibiting adhesion as well as activation and aggregation. Nitric oxide can react with thiol functional groups in the presence of oxygen to form S-nitrosothiols, which are naturally occurring NO derivatives that prolong the biological actions of NO. Because AR545C has a single free cysteine (Cys545), we attempted to synthesize the S-nitroso-derivative of AR545C and to characterize its antiplatelet effects. We successfully synthesized S-nitroso-AR545C and found that it contained 0.96 mol S-NO per mole peptide. S-nitroso-AR545C was approximately 5-fold more potent at inhibiting platelet agglutination than was the unmodified peptide (IC50 = 0.02 ± 0.006 μmol/L v 0.1 ± 0.03 μmol/L, P = .001). In addition and by contrast, S-nitroso-AR545C was a powerful inhibitor of adenosine diphosphate–induced platelet aggregation (IC50 = 0.018 ± 0.002 μmol/L), while AR545C had no effect on aggregation. These effects were confirmed in studies of adhesion to and aggregation on extracellular matrix under conditions of shear stress in a cone-plate viscometer, where 1.5 μmol/L S-nitroso-AR545C inhibited platelet adhesion by 83% and essentially completely inhibited aggregate formation, while the same concentration of AR545C inhibited platelet adhesion by 74% and had significantly lesser effect on aggregate formation on matrix (P ≤ .004 for each parameter by ANOVA). In an ex vivo rabbit model, we also found that S-nitroso-AR545C had a more marked and more durable inhibitory effect on botrocetin-induced platelet aggregation than did AR545C, and these differences were also reflected in the extent and duration of effect on the prolongation of the bleeding time in these animals. These data show that S-nitroso-AR545C has significant and unique antiplatelet effects, inhibiting both adhesion and aggregation, by blocking platelet GPIb receptor through the AR545C moiety and elevating platelet cyclic 3′,5′-guanosine monophosphate through the -SNO moiety. These observations suggest that this NO-modified fragment of vWF may have potential therapeutic benefits as a unique antithrombotic agent.

scholarly journals PO-277 Nitric oxide generation in red blood cells induced by exercise

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Zhenghui Zha ◽  
Yuli Zhang
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Red Blood Cells ◽  
Blood Vessels ◽  
Blood Cells ◽  
White Blood Cells ◽  
Pi3k Pathway ◽  
No Production ◽  
Hemodynamic Changes ◽  
Enzyme Source

Objective Vascular endothelial nitric oxide synthase (NOS) is considered to be the main enzyme source for NO production in blood vessels, and studies have shown that RBC may also express NOS and produce NO. The purpose of this study was to summarize the expression of NOS in vascular red blood cells caused by changes in hemodynamics, and to improve the bioavailability of NO, and to lay a theoretical foundation for exploring the mechanism of exercise to improve vasodilation. Methods A literature review method was used to analyze related studies on exercise and RBC-NOS published in recent years. Results Intravascular NO is one of the most important vascular signaling molecules, which has the function of relaxing blood vessels. NO is produced during the conversion of L-arginine into L-citrulline, which is mainly dependent on the regulation of vascular eNOS. RBC can express NOS under certain action, and RBC-NOS is mainly located on RBC membrane and cytoplasm; The regulatory mechanisms of RBC-NOS and eNOS have similarities and differences: RBC-NOS and eNOS are both dependent on Ca2+ regulation and phosphorylation of Serine 1177  via the PI3K pathway; however, since red blood cells do not have nuclei, endoplasmic reticulum and Golgi, they do not have other mechanisms of action of eNOS. Therefore, the vascular endothelium is not the only source of NO production. Red blood cells, white blood cells and platelets can produce NO. The amount of NO produced by red blood cells is significantly higher than that of white blood cells and platelets，it is another major source of NO production in blood vessels.The level of wall shear stress is the main determinant of NOS expression in blood vessels: On the one hand, exercise training can cause hemodynamic changes, increased shear stress, and induce changes in eNOS and RBC-NOS levels, increase NO bioavailability, and participate in the regulation of vasodilation.On the other hand, moderate-intensity exercise causes NO produced by RBC to increase red blood cell deformability and participate in vascular regulation. Conclusions 1.Erythrocyte is an enzyme source that relies on hemodynamics to release NO from the blood vessel wall. It is regulated by Ca2+ and phosphorylates ser1177 through the PI3K pathway to participate in the regulation of the body. 2.Hemodynamic changes caused by exercise training can simultaneously induce the expression of eNOS and RBC-NOS, increase the bioavailability of NO, and jointly mediate vasodilation.

Effects of Magnesium on Platelet Aggregation and Adhesion

1994 ◽  
Vol 72 (06) ◽  
pp. 912-918 ◽  
Author(s):  
M Gawaz ◽  
I Ott ◽  
A J Reininger ◽  
F-J Neumann
Keyword(s):  
Myocardial Infarction ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Adhesion ◽  
Bleeding Time ◽  
Magnesium Deficiency ◽  
Ex Vivo ◽  
Surface Expression ◽  
Activated Platelets

SummaryMagnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+(4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p <0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p <0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.

Blood Cell Versus Vascular Endothelial Cell Contributions to Nitrite Homeostasis and Blood Pressure Regulation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4601-4601
Author(s):  
Katherine C Wood ◽  
Virginia B Liu ◽  
Audrey Noguchi ◽  
Xunde Wang ◽  
Nalini Raghavachari ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Cell ◽  
Whole Blood ◽  
Blood Cells ◽  
Pressure Regulation ◽  
Chimeric Mice ◽  
Blood Pressures ◽  
Plasma Nitrite ◽  
Positive Controls

Abstract Mice genetically deficient in constitutive nitric oxide synthase (eNOS) are hypertensive compared to normal C57Bl6 (wild type) mice, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. The objective of this study was to use molecular methodologies to determine the contribution of eNOS in circulating blood cells to the intravascular pool of nitrite, a metabolite and storage form of nitric oxide (NO•) with powerful vasorelaxant activity, and to the regulation of blood pressure under physiological conditions. We used bone marrow transplant to create chimeric mice genetically deficient in eNOS in either circulating blood cells (−/+) or vascular endothelium (+/−), confirmed by flow cytometry, western blot, RT-PCR and immunohistochemistry. Nitrite concentrations in whole blood and plasma of chimeras were quantified using ozone-based reductive chemiluminescence. Mean arterial and diastolic blood pressures of chimeras were assessed in the absence/presence of NOS stimulation with oral L-Arginine or NOS inhibition with oral L-Name. A highly significant inverse correlation between plasma nitrite concentrations and blood pressures was noted across all groups of chimeric mice. Importantly, in agreement with higher blood pressures in −/+ chimeras compared to eNOS positive controls (+/+ chimeras globally competent for eNOS), significantly reduced whole blood and plasma nitrite concentrations were also measured. Blood pressure responses to NOS inhibition or stimulation were intact in all chimera groups except eNOS negative controls (−/− chimeras globally deficient for eNOS) and, importantly, blunted in −/+ chimeras compared to eNOS positive controls. These findings indicate a functional blood cell eNOS that is a major contributor to circulating nitrite concentrations and plays a critical role in vascular homeostasis.

scholarly journals Humanized Von Willebrand Factor-Glycoprotein Ibα Interaction in Mouse Models of Hemostasis and Thrombosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 558-558 ◽  
Author(s):  
Sachiko Kanaji ◽  
Jennifer N Orje ◽  
Yuichi Kamikubo ◽  
Taisuke Kanaji ◽  
Jeremy Mattson ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Adhesion ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Mouse Strains ◽  
Wild Type ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Introduction: The interaction between von Willebrand Factor (VWF) and platelet glycoprotein (GP) Ibα is key for initiating the response to vascular injury that leads to hemostasis or, in pathological conditions, may be a cause of thrombosis. VWF binding to GPIbα occurs through the A1 domain (VWFA1) and its role in platelet adhesion and aggregation becomes progressively more important with increasing shear rates, i.e., in arterioles or pathologically stenosed arteries. Owing to the key role in platelet adhesion/aggregation under arterial flow conditions, VWFA1 has been considered an obvious target for antithrombotic intervention. However, efforts to develop this concept have been complicated by the lack of suitable animal models due to species-specificity in VWFA1-GPIb binding. To obviate the problem, we have generated new mouse strains with humanized VWF-GPIb interaction and characterized the resulting phenotypes in experimental ex vivo and in vivo models of hemostasis and thrombosis. Methods: In the human VWF gene, and in the mouse Vwf ortholog, exon 28 encodes domains A1 and A2, including the VWFA1 GPIb-binding site. We generated a knock-in mouse by targeted insertion of human VWF exon 28 (VWFh28) into the mouse Vwf exon28 locus such that mouse platelet GPIbα (M1) interacted with mouse VWF containing human A1 domain (HA); the strain was designated M1HA (Table). These mice were cross-bred with the previously described transgenic strain (mGPIbαnull;hIbαTg) in which human GPIbα is expressed on the platelet surface in the context of the mouse GPIb-IX-V complex (strain designation: H1MA). The resulting strain was thus designated H1HA, with humanized GPIb-VWF interaction. The unmodified wild type mouse strain used for reference was designated M1MA (Table). All mouse strains were in C57BL/6 genetic background. VWF plasma concentration was measured by ELISA and function ex vivo was evaluated by ristocetin-induced platelet aggregation. In vivo, we measured the tail bleeding time to gauge hemostatic efficiency as well as the propensity to support pathological thrombosis in the carotid artery injured by exposure to ferric chloride. Results: Plasma of VWFh28 mice expressing mouse or human platelet GPIbα had VWF levels (M1HA: 876.4 ± 209.5 mU/ml, n = 16; H1HA: 848.9 ± 121.0 mU/ml, n = 15) not significantly different from wild type mice (M1MA: 1022 ± 267.4 mU/ml, n = 23). Addition of 1.5 mg/ml ristocetin into platelet-rich plasma (PRP) from M1MA, M1HA and H1MA mice elicited no response; only in PRP of H1HA mice did ristocetin cause platelet aggregation that, as in human PRP, was inhibited by the anti-human VWFA1 monoclonal antibody, NMC-4. The tail bleeding time was abnormally prolonged in the M1HA strain expressing human VWFA1/mouse GPIbα, but normal in the H1HA strain expressing human VWFA1/human GPIbα (6.0 ± 3.8 min vs. 1.5 ± 0.9 min; n = 12); the latter was similar to the bleeding time in the M1MA strain (1.0 ± 0.1 min, n = 10). Thrombus formation (time to occlusion) following a carotid artery injury with 9% FeCl3∙6H2O was greatly delayed in the M1HA strain (1760.0 ± 538.5 s, n = 6) but similar to WT M1MA in the H1HA strain (485.2 ± 63.7 s vs. 598.3 ± 84.0 s, n = 6, respectively). Conclusions: Knock-in of human VWF exon 28 into the mouse Vwf locus led to successful biosynthesis of chimeric mouse-human VWF protein in vivo under endogenous promoter control, maintaining normal physiologic expression in endothelial cells and megakaryocytes/platelets. Tail bleeding time and in vivo thrombosis assays confirmed the normal functional interaction of mouse VWF containing human A1 domain with hGPIbα. Moreover, the normal response to ristocetin with platelet aggregation, and inhibition of the latter by the specific NMC4 antibody, indicates that the "humanized" H1HA mouse strain could be a powerful tool to select and develop new interventions for the diagnosis and treatment of hemostatic and thrombotic disorders. Table Table. Disclosures No relevant conflicts of interest to declare.

scholarly journals Continuous changes in biological levels of complete blood count in a high altitude area of China

2020 ◽  
Vol 8 ◽  
pp. 205031212093133 ◽  
Author(s):  
Xuan Luo ◽  
Lei Feng ◽  
XueJing Bai ◽  
JiangXian Zhu ◽  
GuanCheng Zhao ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Complete Blood Count ◽  
White Blood Cells ◽  
Age Groups ◽  
Reference Interval ◽  
Distribution Width ◽  
Men And Women ◽  
Cell Parameters

Objectives: We aimed to establish a new reference interval of blood cell parameters by classifying and counting blood Cells of 16- to 85-year-old healthy volunteers and observing continuous changes with age. Methods: We analyzed the blood cell parameters of 42,678 cases (men, 24,406; women, 18,272), and compared the blood cell parameters of men and women in different age groups using an independent samples t-test. Using limits of 2.5%–97.5%, a 90% confidence interval was used to develop new reference intervals. Results: Counts of blood cell parameters, including white blood Cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood Cells, hemoglobin, hematocrit, distribution width of red blood Cells and platelets, were found to differ between men and women in different age groups. These parameters were used to establish a new reference interval of blood Cells. Conclusion: The blood cell parameters of both men and women changed with increasing age. The reference interval that we established will provide more accurate basic evidence for clinical diagnosis and treatment of diseases.

scholarly journals AI-enabled microscopic blood analysis for microfluidic COVID-19 haematology

2020 ◽  
Author(s):  
Tiancheng Xia ◽  
Richard Fu ◽  
Nanlin Jin ◽  
Paul Chazot ◽  
Plamen Angelov ◽  
...  
Keyword(s):  
Deep Learning ◽  
Blood Cell ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Point Of Care ◽  
White Blood Cells ◽  
Blood Analysis ◽  
Cell Analysis ◽  
Learning Methods ◽  
Cell Counts

Microscopic blood cell analysis is an important methodology for medical diagnosis, and complete blood cell counts (CBCs) are one of the routine tests operated in hospitals. Results of the CBCs include amounts of red blood cells, white blood cells and platelets in a unit blood sample. It is possible to diagnose diseases such as anemia when the numbers or shapes of red blood cells become abnormal. The percentage of white blood cells is one of the important indicators of many severe illnesses such as infection and cancer. The amounts of platelets are decreased when the patient suffers hemophilia. Doctors often use these as criteria to monitor the general health conditions and recovery stages of the patients in the hospital. However, many hospitals are relying on expensive hematology analyzers to perform these tests, and these procedures are often time consuming. There is a huge demand for an automated, fast and easily used CBCs method in order to avoid redundant procedures and minimize patients’ burden on costs of healthcare. In this research, we investigate a new CBC detection method by using deep neural networks, and discuss state of the art machine learning methods in order to meet the medical usage requirements. The approach we applied in this work is based on YOLOv3 algorithm, and our experimental results show the applied deep learning algorithms have a great potential for CBCs tests, promising for deployment of deep learning methods into microfluidic point-of-care medical devices. As a case of study, we applied our blood cell detector to the blood samples of COVID-19 patients, where blood cell clots are a typical symptom of COVID-19.

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