thrombosis

Essential Thrombocythemia: A Review

Alex Haga — Mon, 03 Feb 2025 23:59:34 +0000

Date Added:

February 3, 2025

Journal/Publication:

JAMA

Publication Date:

January 27, 2025

URL:

Essential Thrombocythemia: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.25349

Keywords

thrombocythemia

essential thrombocythemia

PMID (1):

39869325

MeSH

Thrombocythemia

Essential

Primary Myelofibrosis

thrombosis

An evidence-based summary of what is known about essential thrombocythemia. James W. Mold, MD, MPH

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Importance: Essential 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.

Observations: Patients 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.

Conclusions: Essential 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.

Author/s:

Ayalew Tefferi, Naseema Gangat, Giuseppe Gaetano Loscocco, Paola Guglielmelli

Diagnosis and Treatment of Polycythemia Vera: A Review

Erin Blanchette — Wed, 20 Nov 2024 22:28:21 +0000

Date Added:

November 20, 2024

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

November 18, 2024

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.20377

Keywords

Venous Thromboembolism

Leukemias

PMID (1):

39556352

MeSH

Primary Myelofibrosis

Leukemia, Myeloid, Acute

A review of the diagnosis and treatment of polycythemia vera. James W. Mold, MD, MPH

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Importance: Polycythemia vera (PV), a myeloproliferative neoplasm characterized by an increased red blood cell mass and increased risk of thrombosis, affects approximately 65 000 people in the US, with an annual incidence of 0.5 to 4.0 cases per 100 000 persons.

Observations: Erythrocytosis (hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women) is a required diagnostic criterion, although thrombocytosis (53%) and leukocytosis (49%) are common. Patients may have pruritus (33%), erythromelalgia (5.3%), transient visual changes (14%), and splenomegaly (36%) with abdominal discomfort. More than 95% of patients have a JAK2 gene variant, which helps distinguish PV from secondary causes of erythrocytosis, such as tobacco smoking or sleep apnea. Among 7 cohorts (1545 individuals), the median survival from diagnosis was 14.1 to 27.6 years. Prior to or at the time of PV diagnosis, arterial thrombosis occurred in 16% of patients and 7% had venous thrombotic events, which could involve unusual sites, such as splanchnic veins. PV is also associated with an increased bleeding risk, especially in patients with acquired von Willebrand disease, which can occur with extreme thrombocytosis (platelet count, ≥1000 × 109/L). All patients with PV should receive therapeutic phlebotomy (goal hematocrit, <45%) and low-dose aspirin (if no contraindications). Patients who are at higher risk of thrombosis include those aged 60 years or older or with a prior thrombosis. These patients and those with persistent PV symptoms may benefit from cytoreductive therapy with hydroxyurea or interferon to lower thrombosis risk and decrease symptoms. Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. About 12.7% of patients with PV develop myelofibrosis and 6.8% develop acute myeloid leukemia.

Conclusions and Relevance: PV is a myeloproliferative neoplasm characterized by erythrocytosis and is almost universally associated with a JAK2 gene variant. PV is associated with an increased risk of arterial and venous thrombosis, hemorrhage, myelofibrosis, and acute myeloid leukemia. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

Author/s:

Douglas Tremblay, Marina Kremyanskaya, John Mascarenhas, Ronald Hoffman

Diagnosing acute aortic syndrome: a Canadian clinical practice guideline

Brian Desmarais — Wed, 22 Jul 2020 16:32:28 +0000

Date Added:

July 22, 2020

Journal/Publication:

Canadian medical Association Journal

Publication Date:

July 20, 2020

Issue:

Volume:

192

URL:

Diagnosing acute aortic syndrome: a Canadian clinical practice guideline

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.1503/cmaj.200021

MeSH

thrombosis

Aorta

Aneurysm, Dissecting

A guideline from Canada on diagnosis of acute aortic syndrome (dissection, thrombosis, or perforating ulceration of the aorta). James W. Mold, MD, MPH

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Not available.

Author/s:

Ohle, R., Yan, J.W., Yadav, K., Cournoyer, A., Savage, D.W., Jetty, P., Atoui, R.

Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial

Brian Desmarais — Thu, 17 Oct 2019 14:29:29 +0000

Date Added:

October 17, 2019

Journal/Publication:

Annals of Internal Medicine

Publication Date:

October 15, 2019

URL:

Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome: A Randomized Noninferiority Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.7326/M19-0291

Keywords

MeSH

International Normalized Ratio

Antiphospholipid Syndrome

Rivaroxaban apparently doesn’t work as well as warfarin at preventing recurrent venous thrombosis in patients with antiphospholipid syndrome. That suggests to me that patients should be tested for that condition before recommending a non-warfarin option. James W. Mold, MD, MPH

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BACKGROUND:

The potential role of new oral anticoagulants in antiphospholipid antibody syndrome (APS) remains uncertain.

OBJECTIVE:

To determine whether rivaroxaban is noninferior to dose-adjusted vitamin K antagonists (VKAs) for thrombotic APS.

DESIGN:

3-year, open-label, randomized noninferiority trial. (EU Clinical Trials Register: EUDRA [European Union Drug Regulatory Authorities] code 2010-019764-36).

SETTING:

6 university hospitals in Spain.

PARTICIPANTS:

190 adults (aged 18 to 75 years) with thrombotic APS.

INTERVENTION:

Rivaroxaban (20 mg/d or 15 mg/d, according to renal function) versus dose-adjusted VKAs (target international normalized ratio, 2.0 to 3.0, or 3.1 to 4.0 in patients with a history of recurrent thrombosis).

MEASUREMENTS:

The primary efficacy outcome was the proportion of patients with new thrombotic events; the primary safety outcome was major bleeding. The prespecified noninferiority margin for risk ratio (RR) was 1.40. Secondary outcomes included time to thrombosis, type of thrombosis, changes in biomarker levels, cardiovascular death, and nonmajor bleeding.

RESULTS:

After 3 years of follow-up, recurrent thrombosis occurred in 11 patients (11.6%) in the rivaroxaban group and 6 (6.3%) in the VKA group (RR in the rivaroxaban group, 1.83 [95% CI, 0.71 to 4.76]). Stroke occurred more commonly in patients receiving rivaroxaban (9 events) than in those receiving VKAs (0 events) (corrected RR, 19.00 [CI, 1.12 to 321.9]). Major bleeding occurred in 6 patients (6.3%) in the rivaroxaban group and 7 (7.4%) in the VKA group (RR, 0.86 [CI, 0.30 to 2.46]). Post hoc analysis suggested an increased risk for recurrent thrombosis in rivaroxaban-treated patients with previous arterial thrombosis, livedo racemosa, or APS-related cardiac valvular disease.

LIMITATION:

Anticoagulation intensity was not measured in the rivaroxaban group.

CONCLUSION:

Rivaroxaban did not show noninferiority to dose-adjusted VKAs for thrombotic APS and, in fact, showed a non-statistically significant near doubling of the risk for recurrent thrombosis.

PRIMARY FUNDING SOURCE:

Bayer Hispania.

Author/s:

Ordi-Ros, J, Sáez-Comet, L., Pérez-Conesa, M., Vidal, X., Riera-Mestre, A., Castro-Salomó, A., Cuquet-Pedragosa, J., Ortiz-Santamaria, V., Mauri-Plana, M., Solé, C., Cortés-Hernández, J.

Left Atrial Appendages Occlusion: Current Status and Prospective

Brian Desmarais — Mon, 05 Aug 2019 18:23:22 +0000

Date Added:

August 5, 2019

Journal/Publication:

Korean Circulation Journal

Publication Date:

August 28, 2018

Issue:

Volume:

Pages:

692-704

URL:

Left Atrial Appendages Occlusion: Current Status and Prospective

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.4070/kcj.2018.0231

Keywords

Watchman device

left atrial appendage

MeSH

For those wanting to know more about the Watchman device and other approaches to left atrial appendage occlusion for prevention of stroke due to atrial fibrillation, this was the best recent review article I could find. James W. Mold, MD, MPH

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Stroke continues to be a major cause of morbidity and mortality in atrial fibrillation (AF) patients. Oral anticoagulation (OAC) provides protection against stroke and peripheral embolization in AF but significant proportion of patients could not be started on anticoagulation because of bleeding complications. Left atrial appendage harbors clot in about 90% of nonvalvular AF. The advent of left atrial appendage occlusion (LAAO) techniques has provided these patients with alternative to OAC for stroke prophylaxis. Multiple LAAO devices are currently available with Watchman and Amulet being the most commonly used in clinical practice. Randomized studies are available for Watchman device only. Data on Amplatzer Cardiac Plug, Amulet and Lariat devices are limited by the paucity of randomized data. Long-term data on different LAAO techniques are showing promising results. Device related thrombosis continues to be a serious complication associated with LAAO. Future studies should look into comparative effectiveness between different LAAO techniques, optimal patient selection, risk of complications, and anticoagulant treatment after LAAO. This article aims to provide current available evidence on efficacy and safety of different LAAO devices and future prospective.

Author/s:

Sharma, S.P., Park, P., Lakkireddy, D.

Anticoagulant Comparison Chart

Tracy Ashby — Mon, 10 Dec 2018 06:00:00 +0000

Date Added:

December 10, 2018

Publisher:

North American Thrombosis Forum

Publication Date:

January 3, 2018

URL:

Anticoagulant Comparison Chart

Type:

Clinical Decision Aids

Format:

Article

Keywords

MeSH

A table comparing currently available oral anticoagulants.

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After being diagnosed with a blood clot, navigating the different medications can be confusing. NATF has designed a chart comparing the different anticoagulant medications, which include warfarin and the direct oral anticoagulants (DOACs).

This is a great tool for patients to use when talking to their doctors about which medication is right for them.

Author/s:

North American Thrombosis Forum