Iron Deficiency as an Important Predictor of Arterial and Venous Thrombosis, Myocarditis, and Atrial Fibrillation in COVID-19 and Influenza.

Risk of Arterial and Venous Thrombosis in 11,155 Patients with Myeloproliferative Neoplasms and 44,620 Matched Controls; A Population-Based Study

Elevated Risk of Venous but Not Arterial Thrombosis in Waldenström’s Macroglobulinemia and Lymphoplasmacytic Lymphoma

Arterial Thrombosis and Cancer: Implications for Screening and Risk Modification

No Risk of Arterial or Venous Thrombosis in Monoclonal Gammopathy of Undetermined Significance: Results from a Population-Based Study

Arterial disease and venous thrombosis: are they related, and if so, what should we do about it?

Arterial and venous thrombosis by high platelet count and high hematocrit: 108 521 individuals from the Copenhagen General Population Study

Red Blood Transfusion Does Not Increase Risk for Venous or Arterial Thrombosis

An “Endothelialized” Microfluidic System That Distinguishes Procoagulant Mechanisms in Arterial and Venous Thrombosis

Recent Advances in the Understanding of Thrombosis.

e18599 Background: Polycythemia vera (PCV) is a myeloproliferative neoplasm defined by the clonal proliferation of hematopoietic progenitor cells. PCV is associated with an increased risk of thrombosis, which is stratified according to patient age and thrombosis history. Secondary malignancies (SM) develop in 8.4% of PCV patients. While cancer-associated thrombosis is an evolving field, the risk of thrombosis among PCV patients with SM is not well described. Methods: This study is a secondary analysis of data from a previously conducted study approved by the University of Illinois College of Medicine Peoria IRB. We identified 145 JAK2-positive adult patients (2015 - 2024) with elevated hemoglobin (≥160 g/L for females, ≥165 g/L for males) and no cancer history prior to PCV diagnosis. The relative risk (RR) of venous and arterial thrombosis among patients with SM compared to those without SM was calculated. Results: The rate of SM was 238.0 per 1000 person-years, with Myelodysplastic Disease (55.8%), Myeloid Leukemia (11.5%) and Lung Cancer (9.6%) being the most common. There were no statistically significant differences in age, gender and race between patients who developed SM compared to those who did not. Patients with SM had a greater overall risk of arterial (RR: 1.11, 95% CI: 1.09 - 1.13) and venous thrombosis (RR: 1.09, 95% CI: 1.07 - 1.10), as shown in Table 1. PCV patients with SM were less likely to have pulmonary embolisms (PE) (RR: 0.79, 95% CI: 0 0.78 - 0.81). Conclusions: This study demonstrated an anticipated increased risk of thrombosis among PCV patients with SM, except for PE. However, this study did not compare thrombotic risk factors, rates of PCV treatment, or details of individual clotting events between groups. This analysis is also limited by a small sample size. Future studies should evaluate the risks and benefits of antithrombotic prophylaxis among PCV patients with SM. Providers could consider these findings when stratifying the risk of thrombosis and individualizing treatment decisions. The incidence and relative risk of thrombosis among Polycythemia Vera (PCV) patients with secondary malignancies (SM) compared to those with Polycythemia Vera only. PCV with SM (n/1000 person years) PCV only (n/1000 person years) Relative Risk 95% Confidence Interval Arterial Thrombosis 278.49 251.09 1.11 1.09, 1.13 STEMI/NSTEMI 282.87 229.27 1.23 1.22, 1.25 TIA/CVA 276.73 255.96 1.08 1.07, 1.10 Venous Thrombosis 291.99 268.63 1.09 1.07, 1.10 DVT 309.30 273.68 1.13 1.11, 1.15 PE 201.71 254.53 0.79 0.78, 0.81 Thrombosis incidence is expressed per 100,000 person-years. CI: 95% Confidence Interval; DVT: Deep Vein Thrombosis; NSTEMI: Non-ST-Elevation Myocardial Infarction; PE: Pulmonary Embolism; RR: PCV: Polycythemia Vera; Relative Risk; SM: Secondary Malignancies; STEMI: ST-Elevation Myocardial Infarction; TIA/CVA: Transient Ischemic Attack/Cerebrovascular Accident.

Mutations and Thrombosis in Essential Thrombocythemia and Polycythemia Vera: Mayo-Careggi Alliance Study

Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. The risk of venous thrombosis during low-dose oral contraceptive use is three- to sixfold increased compared with that of nonusers. The association is not only attributed to the estrogen component of the pill: the risk is twice as high for desogestrel and gestodene (third generation) containing oral contraceptives as for levonorgestrel (second generation) containing oral contraceptives. The risk of venous thrombosis is highest in the first year of use and in women with genetic or acquired risk factors for thrombosis. Both venous or arterial thrombosis are unrelated to duration of use or past use of combined oral contraceptives. The risk of myocardial infarction and stroke during low-dose oral contraceptive use is two- to fivefold increased relative to that of nonusers. The risk of arterial thrombosis induced by oral contraceptive use is more pronounced in smokers and women with hypertension, diabetes, and hypercholesterolemia. All types of thrombosis have strongly age-dependent incidences, and therefore in absolute figures the risks and effects of risk factors increase with age. The lowering of the estrogen dose in combined oral contraceptives from 50 microg to 20-30 microg in the last decade did not clearly reduce the risk of venous thrombosis, myocardial infarction, stroke, or peripheral arterial disease. For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is unlikely to counterbalance the adverse effect of third generation contraceptives on venous thrombosis.

ImportanceEssential thrombocythemia, a clonal myeloproliferative neoplasm with excessive platelet production, is associated with an increased risk of thrombosis and bleeding. The annual incidence rate of essential thrombocythemia in the US is 1.5/100 000 persons.ObservationsPatients with essential thrombocythemia have a persistent platelet count of 450 × 109/L or greater. The differential diagnosis includes myeloproliferative neoplasms (polycythemia vera, primary myelofibrosis, chronic myeloid leukemia); inflammatory conditions such as rheumatoid arthritis and systemic lupus erythematosus; infections; splenectomy; iron deficiency anemia; and solid tumors such as lung cancer. Approximately 90% of individuals with essential thrombocythemia have genetic variants that upregulate the JAK-STAT (signal transducer and activator of transcription 5) signaling pathway, including Janus kinase 2 (JAK2, 64%), calreticulin (CALR, 23%), and myeloproliferative leukemia virus oncogene (MPL, 4%). The median age at diagnosis of essential thrombocythemia is 59 years. The median overall survival exceeds 35 years in those diagnosed at 40 years or younger. Patients with essential thrombocythemia are at increased risk of arterial thrombosis (11%), venous thrombosis (7%), and hemorrhagic complications (8%). Thrombosis risk is increased among those with a history of thrombosis, age older than 60 years, a JAK2 gene variant, and cardiovascular risk factors (eg, hypertension, diabetes mellitus, hyperlipidemias, tobacco use). Use of aspirin (81-100 mg/d) is suggested for most patients with essential thrombocythemia to lower thrombosis risk. In a retrospective study of 300 affected patients with a low thrombosis risk (younger than 60 years with no prior thrombosis), those not taking aspirin (100 mg/d) had a risk of arterial thrombosis of 9.4/1000 patient-years and a venous thrombosis risk of 8.2/1000 patient years; cardiovascular risk factors were associated with a higher risk of arterial thrombi (incidence rate ratio, 2.5 [95% CI, 1.02-6.1]), and a JAK2 gene variant was associated with increased risk of venous thrombosis (incidence rate ratio, 4.0 [95% CI, 1.2-12.9]). In a randomized trial of 114 patients at higher risk for thrombosis (age older than 60 years or a prior thrombotic event), cytoreduction with hydroxyurea significantly lowered the risk of arterial or venous thrombotic events compared with no cytoreductive therapy (3.6% vs 24%; P < .01). At a median of 8.5 years from diagnosis, approximately 10% of patients with essential thrombocythemia develop myelofibrosis and about 3% develop acute myeloid leukemia.ConclusionsEssential thrombocythemia is a rare clonal myeloproliferative neoplasm associated with an increased risk of venous and arterial thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. Based on individual risk factors for thrombosis, persons with essential thrombocythemia may be treated with low-dose aspirin, either alone or in combination with a cytoreductive drug such as hydroxyurea.

Immune checkpoint inhibitors (ICPi) have been associated with a prothrombotic and pro-atherogenic tendency which could lead to an increased risk of thrombosis. The aim of this study was to investigate the incidence of venous and arterial thrombosis (myocardial infarction or ischemic stroke) in patients who used ICPi as compared with the general population. Furthermore, we investigated the association between the occurrence of venous or arterial thrombosis and mortality. Patients receiving immune checkpoint inhibitors ICPi between January 1, 2013, and May 31, 2020, at the University Medical Center Utrecht, the Netherlands, were included in this study. Indirect standardization was used to compare the incidence rates of venous and arterial thrombosis in patients who used ICPi to the age- and sex weighted incidence rates in the general population. Time-dependent Cox proportional hazard regression model was used to calculate Hazard ratios (HRs) with 95% CIs to investigate the association between the occurrence of a venous or arterial event after start of an ICPi and mortality. The age- and sex weighted incidence rates in 663 patients who used ICPi as compared to the general population was 22.7-fold (95% CI 16.6-31.0) increased for venous thrombosis, 3.0-fold (95% CI 1.2-7.1) increased for myocardial infarction, and 3.2-fold (95% CI 1.6-5.7) increased for ischemic stroke. After adjustment, the all-cause mortality risk was 2.3-fold (95% CI 1.5-3.5) increased for patients who were diagnosed with venous thrombosis during follow-up and 2.2-fold (95% CI 1.1-4.1) increased for patients who were diagnosed with arterial thrombosis during follow-up as compared with patients without venous or arterial thrombosis during follow-up. Patients receiving ICPi have elevated risks of venous thrombosis and arterial thrombosis. Occurrence of venous thrombosis or arterial thrombosis during treatment with ICPi is associated with an increased mortality risk.

Absolute risk of venous and arterial thrombosis in HIV-infected patients and effects of combination antiretroviral therapy.