MPN and thrombosis was hard enough . . . now there's COVID-19 thrombosis too

Abstract Both myeloproliferative neoplasms (MPNs) and coronavirus disease 2019 (COVID-19) are characterized by an intrinsic thrombotic risk. Little is known about the incidence and the outcome of thrombotic events in patients with MPN infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but common mechanisms of coagulation activation, typical of both disorders, suggest that these patients can be at particularly high risk. To define the best thromboprophylaxis and treatment regimens in both MPN and COVID-19, individual- and disease-specific thrombotic risk factors, bleeding risk, and concomitant specific treatments need to be considered. In this case-based review, an individualized approach is presented in a case of SARS-CoV-2 infection occurring in a man with polycythemia vera (PV). A primary anticoagulant thromboprophylaxis strategy and adjustment of his PV treatment were implemented. However, during the hospital stay, he experienced pulmonary embolism and therapeutic anticoagulation had to be set. Then his condition improved, and discharge was planned. Postdischarge decisions had to be made about the type and duration of venous thromboembolism treatment as well as the management of PV-specific drugs. The steps of our decisions and recommendations are presented.

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Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.763827 ◽

2021 ◽

Vol 8 ◽

Author(s):

Peter Jirak ◽

Zornitsa Shomanova ◽

Robert Larbig ◽

Daniel Dankl ◽

Nino Frank ◽

...

Keyword(s):

Risk Factors ◽

Critically Ill ◽

Critically Ill Patients ◽

Severe Pneumonia ◽

Thromboembolic Events ◽

Therapeutic Anticoagulation ◽

Tertiary Hospitals ◽

Ventricular Tachycardias ◽

Disease Specific ◽

Rhythm Monitoring

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins.Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%).Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

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Interferon Alpha Therapy Increases Pro-Thrombotic Biomarkers in Patients with Myeloproliferative Neoplasms

Cancers ◽

10.3390/cancers12040992 ◽

2020 ◽

Vol 12 (4) ◽

pp. 992

Author(s):

Dorothée Faille ◽

Lamia Lamrani ◽

Stéphane Loyau ◽

Marie-Geneviève Huisse ◽

Marie-Charlotte Bourrienne ◽

...

Keyword(s):

Interferon Alpha ◽

Myeloproliferative Neoplasms ◽

Anticoagulant Activity ◽

Protein S ◽

Pegylated Interferon ◽

Coagulation Activation ◽

Thrombotic Risk ◽

Interferon Alpha Therapy ◽

Increased Risk ◽

Ifn Therapy

Myeloproliferative neoplasms (MPN) are associated with an increased risk of arterial and venous thrombosis. Pegylated-interferon alpha (IFN) and hydroxyurea (HU) are commonly used to treat MPN, but their effect on hemostasis has not yet been studied. The aim of our study was to determine whether IFN and HU impact the biological hemostatic profile of MPN patients by studying markers of endothelial, platelet, and coagulation activation. A total of 85 patients (50 polycythemia vera and 35 essential thrombocythemia) were included: 28 treated with IFN, 35 with HU, and 22 with no cytoreductive drug (non-treated, NT). Von Willebrand factor, shear-induced platelet aggregation, factor VIII coagulant activity (FVIII:C), fibrinogen, and thrombin generation with and without exogenous thrombomodulin were significantly higher in IFN-treated patients compared to NT patients, while protein S anticoagulant activity was lower. In 10 patients in whom IFN therapy was discontinued, these hemostatic biomarkers returned to the values observed in NT patients, strongly suggesting an impact of IFN therapy on endothelial and coagulation activation. Overall, our study shows that treatment with IFN is associated with significant and reversible effects on the biological hemostatic profile of MPN patients. Whether they could be associated with an increased thrombotic risk remains to be determined in further randomized clinical studies.

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Thrombotic risk factors in Chinese Budd-Chiari syndrome patients

Thrombosis and Haemostasis ◽

10.1160/th12-10-0784 ◽

2013 ◽

Vol 109 (05) ◽

pp. 878-884 ◽

Cited By ~ 51

Author(s):

Chuangye He ◽

Zhanxin Yin ◽

Jing Niu ◽

Ming Bai ◽

Zhiping Yang ◽

...

Keyword(s):

Risk Factors ◽

Myeloproliferative Neoplasms ◽

Factor V Leiden ◽

Jak2 V617f ◽

Paroxysmal Nocturnal Haemoglobinuria ◽

Prothrombin G20210a ◽

Factor V ◽

Factor V Leiden Mutation ◽

Thrombotic Risk ◽

G20210a Mutation

SummaryIn Western countries, thrombotic risk factors for Budd-Chiari syndrome (BCS) are very common, including factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, paroxysmal nocturnal haemoglobinuria, etc. However, the data regarding thrombotic risk factors in Chinese BCS patients are extremely limited. An observational study was conducted to examine this issue. A total of 246 BCS patients who were consecutively admitted to our department between July 1999 and December 2011 were invited to be examined for thrombotic risk factors. Of these, 169 patients were enrolled. Neither factor V Leiden mutation nor prothrombin G20210A mutation was found in any of 136 patients tested. JAK2 V617F mutation was positive in four of 169 patients tested. Neither MPL W515L/K mutation nor JAK2 exon 12 mutation was found in any of 135 patients tested. Overt myeloproliferative neoplasms were diagnosed in five patients (polycythemia vera, n=3; essential thrombocythemia, n=1; idiopathic myelofibrosis, n=1). Two of them had positive JAK2 V617F mutation. Both CD55 and CD59 deficiencies were found in one of 166 patients tested. This patient had a previous history of paroxysmal nocturnal haemoglobinuria before BCS. Anticardiolipin IgG antibodies were positive or weakly positive in six of 166 patients tested. Hyperhomocysteinaemia was found in 64 of 128 patients tested. 5,10-methylenetetrahydrofolate reductase C677T mutation was found in 96 of 135 patients tested. In conclusion, factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, and paroxysmal nocturnal haemoglobinuria are very rare in Chinese BCS patients, suggesting that the etiological distribution of BCS might be different between Western countries and China.

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Higher incidence of stroke in severe COVID-19 is not associated with a higher burden of arrhythmias: comparison to other types of severe pneumonia

European Heart Journal ◽

10.1093/eurheartj/ehab724.0287 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

P Jirak ◽

Z Shomanova ◽

R Larbig ◽

D Dankl ◽

N Frank ◽

...

Keyword(s):

Risk Factors ◽

Critically Ill ◽

Severe Pneumonia ◽

Thromboembolic Events ◽

Funding Sources ◽

Therapeutic Anticoagulation ◽

Tertiary Hospitals ◽

Ventricular Tachycardias ◽

Disease Specific ◽

Rhythm Monitoring

Abstract Background Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias, and stroke during rhythm monitoring in critically ill COVID-19, compared to severe pneumonias of other origin. Methods Recruited were 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n=60 COVID-19, matched according to risk factors for occurrence of arrhythmias to n=60 patients from a retrospective consecutive cohort of severe pneumonias of other origin. Results Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared to nonCOVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4%, p=ns and asystole 5.0 vs. 3.3%, p=ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0% p=ns). AF was even more common in nonCOVID-19 (AF 18.3 vs. 43.3%, p=0.003; newly onset AF 10.0 vs. 30.0%, p=0.006) which resulted in higher need for electrical cardioversion (6.7 vs. 20.0%, p=0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p=0.042). These events happened also in absence of AF (50%) and with TAC (50%). Conclusion Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonias of other origin. A contrasting higher incidence of stroke independent of arrhythmias observed also with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

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Thrombophilic Risk of Factor V Leiden, Prothrombin G20210A, MTHFR, and Calreticulin Mutations in Essential Thrombocythemia Egyptian Patients

Advances in Hematology ◽

10.1155/2020/7695129 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Mohamed S. El-Ghonemy ◽

Solafa El Sharawy ◽

Maryan Waheeb Fahmi ◽

Shaimaa El-Ashwah ◽

May Denewer ◽

...

Keyword(s):

Risk Factors ◽

Essential Thrombocythemia ◽

Myeloproliferative Neoplasms ◽

Factor V Leiden ◽

Prothrombin G20210a ◽

Control Group ◽

Fibrinogen Concentration ◽

Factor V ◽

Thrombotic Risk ◽

Prothrombin Gene

Objectives. Essential thrombocythemia (ET) is one of the myeloproliferative neoplasms characterized by a sustained elevation of platelet numbers with a tendency for thrombosis and hemorrhage. The aim of this work is to establish the relation between calreticulin, factor V Leiden, prothrombin G20210A, and MTHFR mutations in ET patients and the thrombotic risk of these patients. Methods. This study was carried out on 120 ET patients and 40 apparently healthy individuals as a control group. Results. There were increases in WBCs, PLT counts, PT, fibrinogen concentration factor V Leiden, and MTHFR mutation in ET patients as compared to the control group (P<0.05). Also, there were increases in WBCs, PLT counts, and hematocrit value in thrombosed ET patients as compared to the nonthrombosed ones (P<0.05). On the contrary, there was no significantly statistical difference in ET patients with JAK2 V617F positive mutation versus the JAK2 negative group (P>0.05) and in patients with cardiovascular risk factors versus patients with noncardiovascular risk factors (P>0.05). ET patients with factor V Leiden, prothrombin gene, and CALR mutations were more prone to thrombosis (odds ratio 5.6, 5.7 and 4.7, respectively). On the contrary, JAk2V 617F and MTHFR mutations have no effect on the thrombotic state of those patients. Conclusion. There is a significant increase risk of thrombosis in ET patients with CALR mutation, thrombophilic mutations, as well as factor V Leiden and prothrombin gene mutation with a risk of developing leukemic transformation.

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The Approach to Thrombosis Prevention across the Spectrum of Philadelphia-Negative Classic Myeloproliferative Neoplasms

Hemato ◽

10.3390/hemato2030025 ◽

2021 ◽

Vol 2 (3) ◽

pp. 392-402

Author(s):

Steffen Koschmieder

Keyword(s):

High Risk ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Neoplasm ◽

Primary Myelofibrosis ◽

Thrombotic Risk ◽

Increased Risk ◽

Individualized Approach ◽

Night Sweats ◽

Thrombotic Complications

Patients with myeloproliferative neoplasm (MPN) are potentially facing diminished life expectancy and decreased quality of life, due to thromboembolic and hemorrhagic complications, progression to myelofibrosis or acute leukemia with ensuing signs of hematopoietic insufficiency, and disturbing symptoms such as pruritus, night sweats, and bone pain. In patients with essential thrombocythemia (ET) or polycythemia vera (PV), current guidelines recommend both primary and secondary measures to prevent thrombosis. These include acetylsalicylic acid (ASA) for patients with intermediate- or high-risk ET and all patients with PV, unless they have contraindications for ASA use, and phlebotomy for all PV patients. A target hematocrit level below 45% is demonstrated to be associated with decreased cardiovascular events in PV. In addition, cytoreductive therapy is shown to reduce the rate of thrombotic complications in high-risk ET and high-risk PV patients. In patients with prefibrotic primary myelofibrosis (pre-PMF), similar measures are recommended as in those with ET. Patients with overt PMF may be at increased risk of bleeding and thus require a more individualized approach to thrombosis prevention. This review summarizes the thrombotic risk factors and primary and secondary preventive measures against thrombosis in MPN.

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Prevention and Management of Thrombosis in BCR/ABL-Negative Myeloproliferative Neoplasms

Hämostaseologie ◽

10.1055/a-1334-3259 ◽

2021 ◽

Vol 41 (01) ◽

pp. 048-057

Author(s):

Anna Falanga ◽

Marina Marchetti ◽

Francesca Schieppati

Keyword(s):

Risk Factors ◽

Endothelial Cells ◽

Stem Cell ◽

Management Strategy ◽

Blood Clotting ◽

Myeloproliferative Neoplasms ◽

Primary Myelofibrosis ◽

Hematopoietic Stem ◽

Thrombotic Risk ◽

Prevention And Treatment

AbstractMyeloproliferative neoplasms (MPNs) are clonal disorders of the hematopoietic stem cell. Classical BCR/ABL-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Thrombotic events are a major cause of morbidity and mortality in these patients. Pathogenesis of blood clotting activation involves various abnormalities of platelets, erythrocytes, and leukocytes, as well as dysfunctions of endothelial cells. Patients with MPN can be stratified in “high risk” or “low risk” of thrombosis according to established risk factors. ET and PV clinical management is highly dependent on the patient's thrombotic risk, and a risk-oriented management strategy to treat these diseases is strongly recommended. In this review, we give an overview of risk factors, pathogenesis, and thrombosis prevention and treatment in MPN.

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Role of acquired and hereditary thrombotic risk factors in patients with ischemic colitis

Gastroenterology ◽

10.1016/s0016-5085(01)81398-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A282-A282

Author(s):

I KOUTROUBAKIS ◽

A SFIRIDAKI ◽

A THEODOROPOULOU ◽

A LIVADIOTAKI ◽

P DIMOULIOS ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Colitis ◽

Thrombotic Risk

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Hemmkörperentwicklung bei Hämophilie-Patienten nach Präparate wechsel

Hämostaseologie ◽

10.1055/s-0037-1619773 ◽

2012 ◽

Vol 32 (S 01) ◽

pp. S39-S42 ◽

Cited By ~ 1

Author(s):

S. Kocher ◽

G. Asmelash ◽

V. Makki ◽

S. Müller ◽

S. Krekeler ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Observational Study ◽

Retrospective Observational Study ◽

Frequent Change ◽

Patient Age ◽

Treatment Regimens ◽

Patient Âgé ◽

The Relationship ◽

Observation Period

SummaryThe retrospective observational study surveys the relationship between development of inhibitors in the treatment of haemophilia patients and risk factors such as changing FVIII products. A total of 119 patients were included in this study, 198 changes of FVIII products were evaluated. Results: During the observation period of 12 months none of the patients developed an inhibitor, which was temporally associated with a change of FVIII products. A frequent change of FVIII products didn’t lead to an increase in inhibitor risk. The change between plasmatic and recombinant preparations could not be confirmed as a risk factor. Furthermore, no correlation between treatment regimens, severity, patient age and comorbidities of the patients could be found.

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Risk Factors for Bleeding during Treatment of Acute Venous Thromboembolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650643 ◽

1996 ◽

Vol 76 (05) ◽

pp. 682-688 ◽

Cited By ~ 33

Author(s):

Jos P J Wester ◽

Harold W de Valk ◽

Karel H Nieuwenhuis ◽

Catherine B Brouwer ◽

Yolanda van der Graaf ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Surface Area ◽

Body Surface Area ◽

Body Surface ◽

Small Body ◽

Bleeding Risk ◽

Risk Scores ◽

Risk Of Bleeding ◽

Acute Venous Thromboembolism

Summary Objective: Identification of risk factors for bleeding and prospective evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism. Design: Secondary analysis of a prospective, randomized, assessor-blind, multicenter clinical trial. Setting: One university and 2 regional teaching hospitals. Patients: 188 patients treated with heparin or danaparoid for acute venous thromboembolism. Measurements: The presenting clinical features, the doses of the drugs, and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding. In addition, the recently developed Utrecht bleeding risk score and Landefeld bleeding risk index were evaluated prospectively. Results: Major bleeding occurred in 4 patients (2.1%) and minor bleeding in 101 patients (53.7%). For all (major and minor combined) bleeding, body surface area ≤2 m2 (odds ratio 2.3, 95% Cl 1.2-4.4; p = 0.01), and malignancy (odds ratio 2.4, 95% Cl 1.1-4.9; p = 0.02) were confirmed to be independent risk factors. An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin, independent of the concomitant activated partial thromboplastin time ratios. Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders. Conclusions: A small body surface area and malignancy were associated with a higher frequency of bleeding. The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding. In patients with a small body surface area or in patients with malignancy, it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy.

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