Updated German S2k Guideline for Diagnosis and Therapy of Venous Thrombosis and Pulmonary Embolism: New Recommendations for Cancer Patients, including Anticoagulation with Low Molecular Weight Heparins and Direct Oral Anticoagulants – A Summary and Practical Guide for Oncology Professionals, based on the Latest Scientific Data and the Expertise of Numerous Specialist Societies.

2023-05-02 09:21:33

In February 2023 is the German S2k guideline diagnostics and therapy of venous thrombosis and pulmonary embolism newly published, with the participation of numerous scientific specialist societies. Compared to the previous version from 2015, the experts give updated recommendations – especially for cancer patients.

In the chapter “Malignancy-associated venous thromboembolism” of the guideline, interested parties can find out more about the scientific data. Important innovations for tumor patients relate to the treatment of venous thromboembolism (VTE) with anticoagulant drugs (anticoagulants): Overall, low molecular weight heparins and direct oral anticoagulants have gained in importance compared to traditional vitamin K antagonists.

In the following, we summarize why VTE is so important for people with cancer and what VTE therapy looks like for cancer patients. You can find many more details on the subject directly in the guideline¹.

Background: Venous thromboembolism in cancer

Some tumors form coagulation-activating factors that promote the formation of clots in blood vessels. The tumor itself can also trigger an acute thrombosis, for example due to local pressure or vascular growth. In addition, cancer treatments and patient-related factors increase the risk of venous thromboembolism.

The term venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism. Compared to patients without cancer, those with cancer have a four to seven times higher risk of VTE. It is estimated that around 20 percent of all cancer patients develop thrombosis².

Important to know: Most venous thromboembolism occurs within the first 6 months after cancer diagnosis.

Venous thromboembolism: risk factors

The causes of thromboembolic events can be very different. The following risk factors (selection) increase the risk of thrombosis in cancer patients^3,4:

• Type and stage of cancer: cancer of the pancreas, lung, kidney, ovary, testicle, brain and stomach; also for lymphomas and tumors in an advanced stage (metastasized)
• Type and intensity of cancer treatment: Surgery, radiation, chemotherapy, immunotherapy, anti-hormonal therapy, central venous access and transfusions
• patient-related factors: reduced mobility, history of venous thromboembolism, infections and older age

The individual probability of venous thromboembolism (VTE) can be determined using standardized recording and evaluation forms (risk score). Medical experience also plays a role.

For diagnostics in case of suspected VTE, read more in the current guideline¹. It is important to promptly clarify any suspicion of a VTE in tumor patients so that an individual therapeutic decision can be made. The patient’s medical condition must be adequately taken into account.

Venous thromboembolism: anticoagulation

In its sub-chapter “Anticoagulant therapy in malignant-associated VTE”, the S2k guidelines deal separately with the various phases of treatment:

• initial therapy (usually 1 to 3 weeks),
• maintenance therapy (for 3 to 6 months),
• thereafter if necessary Secondary prophylaxisto reduce the likelihood of VTE recurrence. It can also be continued in the long term – depending on the benefits, risks and wishes of the patient. A regular reassessment of the individual overall situation is recommended.

Anticoagulants such as factor Xa inhibitors are primarily used in cancer patients. There are several drugs available:

• indirect factor Xa inhibitors: low molecular weight heparin (LMWH), fondaparinux and unfractionated heparin (UFH). They are administered subcutaneously or intravenously, i.e. parenterally.
• direct factor Xa inhibitors: Abbreviation DXI, which includes apixaban, rivaroxaban and edoxaban. Together with the direct thrombin inhibitor dabigatran, these substances are also referred to as direct oral anticoagulants (DOAC).

The new guideline contains information on the possible change from LMWH to DXI or vice versa and on the question of how long anticoagulation should be continued in individual cases. Also worth mentioning is the new one Therapiealgorithmus (Fig. 6.3) on p. 141, which can help you to decide between oral and parenteral anticoagulant therapy.

conclusion for practice

Primary prophylaxis: example testicular cancer

Due to the increased VTE risk in men with testicular cancer receiving cisplatin therapy, the German S3 guideline recommends thrombosis prophylaxis³. The guideline of the European Society of Urology (EAU) also advises against – if possible – central venous catheters during first-line chemotherapy⁵.

The number of cancer-associated venous thromboembolisms (VTE) will tend to increase in the future, as modern oncological therapies prolong the lives of people with cancer.

In the meantime, the options for anticoagulation have expanded: In addition to heparins, oral medications can also be considered for the treatment and secondary prophylaxis of VTE. The evidence-based S2k guideline can support you in selecting a suitable therapy. For the individual therapy decision, it is also important to consider the following aspects:

• Safety (depending on the individual bleeding risk and substance-specific contraindications)
• Absorption with oral therapy and possible interactions with antitumor therapy
• Patient wishes and compliance (oral versus parenteral medication may be easier)

You might also be interested in: The S2k guideline does not deal with primary prophylaxis. Refer to the International Thrombosis and Cancer Initiative (ITAC) guideline for recommended measures to prevent a first VTE in cancer².

The latter also provides information about VTE therapy in tumor patients with COVID-19 disease: In short, the procedure does not differ – whether with or without corona infection.

For further reading: Sources used and in-depth information

guidelines

¹ Linnemann B, Blank W, Doenst T, Erbel C, Isfort P, Janssens U, Kalka C, Klamroth R, Kotzerke J, Ley S et al. Diagnosis and treatment of deep vein thrombosis and pulmonary embolism – AWMF-S2k guideline (status: 02/2023, retrieved on: 04/20/2023).

² Farge D, Frere C, Connors JM, Khorana AA, Kakkar A, Ay C, Muñoz A, Brenner B, Prata PH, Brilhante D et al. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol. 2022. Jul;23(7):e334-e347. doi: 10.1016/S1470-2045(22)00160-7.

³ Guideline program oncology (German Cancer Society, German Cancer Aid, AWMF): S3 guideline testicular tumorslong version 1.1, 2020, AWMF register number: 043/049OL (retrieved on: 04/20/2023).

⁴ Onkopedia guideline. Thromboembolism in Cancer Patients (formerly Venous Thromboembolism (VTE) in Cancer Patients). Riess H, Angelillo-Scherrer A, Alt-Epping B, Langer F, Wörmann B, Pabinger-Fasching I (status 11/2020, retrieved on: April 20, 2023).

⁵ Nicol D, Berney D, Boormans JL, di Nardo D, Fankhauser CD, Fischer S, Gremmels H, Heidenreich A, Leão R, Nicolai N et al. EAU Guidelines on Testicular Cancer (Status 03/2023, retrieved on: 04/20/2023).

Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, Wong SL, Balaban EP, Flowers CR, Gates LE et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update. J Clin Oncol. 2023 Apr 19:JCO2300294. doi: 10.1200/JCO.23.00294.

Further reviews and specialist publications

Falanga A, Ay C, Di Nisio M, Gerotziafas G, Jara-Palomares L, Langer F, Lecumberri R, Mandala M, Maraveyas A, Pabinger I et al. ESMO Guidelines Committee. Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline. Ann Oncol. 2023 Jan 10:S0923-7534(22)04786-X. doi: 10.1016/j.annonc.2022.12.014.

Moik F, Posch F, Zielinski C, Pabinger I, Ay C. Direct oral anticoagulants compared to low-molecular-weight heparin for the treatment of cancer-associated thrombosis: Updated systematic review and meta-analysis of randomized controlled trials. Res Pract Thromb Haemost. 2020 May 21;4(4):550-561. doi: 10.1002/rth2.12359.

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