Summary
Definition
History and exam
Key diagnostic factors
- calf swelling
- pain or tenderness along deep venous system
- chest pain
- tachypnea
- breathlessness
- hypotension
- tachycardia
Other diagnostic factors
- family history of venous thromboembolism (VTE)
Risk factors
- history of unprovoked venous thromboembolism
- increasing age
- pregnancy/postpartum
- obesity
- smoking
- malignancy
- acute inflammatory state
- antiphospholipid antibodies (aPLs)
- myeloproliferative disorders
- nephrotic syndrome
- Behcet disease
- HIV infection
- disseminated intravascular coagulation
- paroxysmal nocturnal hemoglobinuria
- heparin-induced thrombocytopenia
- estrogen-containing oral birth control pill/hormone replacement therapy/selective estrogen receptor modulator therapy
- chemotherapy
- surgery
- long-haul flight (>4 hours)
- antithrombin deficiency
- protein C deficiency
- protein S deficiency
- plasminogen deficiency
- elevated fibrinogen
- dysfibrinogenemia
- factor V Leiden
- prothrombin gene mutation (G-20210-A; also referred to as F2 c.*97G>A variant)
- elevated factor VIII levels (>150 U/L)
- elevated levels of factor IX or XI
- hyperhomocysteinemia
- sickle cell disease
- elevated levels of thrombin-activatable fibrinolysis inhibitor (TAFI)
Diagnostic tests
1st tests to order
- CBC
- peripheral blood smear
- activated partial thromboplastin time (aPTT)
- fibrinogen
- prothrombin time (PT)
- D-dimer
- serum albumin
- serum creatinine
- serum cholesterol
- serum triglycerides
Tests to avoid
- homocysteine level
Tests to consider
- heritable thrombophilia test
- polymerase chain reaction (PCR) for factor V Leiden
- antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, anti-beta-2 glycoprotein 1 antibodies)
- factor VIII level
- myeloproliferative neoplasm panel
- flow cytometry for paroxysmal nocturnal hemoglobinuria
- heparin-induced thrombocytopenia (HIT) test
- chest x-ray
- abdominal CT
- abdominal ultrasound
- tumor markers
- 24-hour urine collection for protein, or spot urine for protein/creatinine ratio
Treatment algorithm
nonpregnant: no cancer and with an acute medical illness
nonpregnant: with cancer
nonpregnant: undergoing nonorthopedic surgery
nonpregnant: undergoing orthopedic surgery
nonpregnant with major trauma
pregnant
Contributors
Authors
Lara N. Roberts, MBBS, MD (Res), FRCP, FRCPath
Consultant Haematologist
King's Thrombosis Centre
King's College Hospital
London
UK
Disclosures
LNR has received speaker fees from Bayer and Viatris.
Roopen Arya, BMBCh (Oxon), MA, PhD, FRCP, FRCPath
Professor of Thrombosis and Haemostasis
King's Thrombosis Centre
King's College NHS Foundation Trust
London
UK
Disclosures
RA declares that he has no competing interests.
Peer reviewers
Beverly Hunt, FRCP, FRCPath, MD
Professor of Thrombosis & Haemostasis
King's College
Consultant
Departments of Haematology, Pathology & Rheumatology
Lead in Blood Sciences
Guy's & St Thomas' NHS Foundation Trust
London
UK
Disclosures
BH declares that she has no competing interests.
Per Morten Sandset, MD, PhD
Senior Consultant and Head of Department
Oslo University Hospital Ullevål
Department of Hematology
Professor in Hematology
University of Oslo
Oslo
Norway
Disclosures
PMS declares that he has no competing interests.
Michael Bromberg, MD, PhD
Associate Professor
Director of Hematologic Malignancies
Medicine and Pharmacology
Temple University School of Medicine
Philadelphia
PA
Disclosures
MB declares that he has no competing interests.
References
Key articles
Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e691S-736S.Full text Abstract
American College of Chest Physicians. Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. CHEST. 2012;141(suppl 2):e1-801.Full text
Arachchillage DJ, Mackillop L, Chandratheva A, et al. Thrombophilia testing: A British Society for Haematology guideline. Br J Haematol. 2022 Aug;198(3):443-58.Full text Abstract
Anderson DR, Morgano GP, Bennett C, et al. American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients. Blood Adv. 2019 Dec 10;3(23):3898-944.Full text Abstract
Key NS, Khorana AA, Kuderer NM, et al. Venous Thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol. 2023 Jun 1;41(16):3063-71.Full text Abstract
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: cancer-associated venous thromboembolic disease [internet publication].Full text
Reference articles
A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
Guidelines
- NCCN clinical practice guidelines in oncology: cancer-associated venous thromboembolic disease
- Venous thromboembolism in cancer patients: clinical practice guideline
More GuidelinesPatient information
Deep vein thrombosis
Sickle cell disease
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