Bring A Nuanced Approach to Venous Thromboembolism Management

Michelle T. Chi, MD

Despite the frequency of a blood clot located in the vein, or venous thromboembolism (VTE) among patients with cancer, ¹ appropriate management of acute VTE can depend on various factors. When caring for a patient with acute VTE, it is important for a provider to consider the characteristics of the clot, as well as the patient’s bleeding risk.

Step 1: Consider Characteristics of the Clot

Hematologists are often consulted to assess for underlying etiologies of VTE, for recommendations about duration of anticoagulation, or for assistance with selecting agents for therapeutic anticoagulation. Many factors contribute to this multifaceted evaluation, such as collecting a thorough medical history from the patient with consideration to pertinent, ongoing risk factors for the development of thrombosis. These basic pieces of information can help a hematologist determine whether additional laboratory testing is warranted.

One of the first steps is to evaluate the location of the thrombus, which can provide important clues about the underlying disease state. The most common VTEs are lower-extremity deep vein thrombosis (DVT) and pulmonary embolism (PE). However, uncommon thrombi such as those found in the cerebral venous, splanchnic venous, and portal vein may alert the hematologist to the possibility of an underlying cause. These thrombi warrant consideration for underlying precipitants such as myeloproliferative disorders, paroxysmal nocturnal hemoglobinuria, catastrophic thrombin-generating states, underlying liver disease, malignancy, and other conditions.

In addition, it is important to determine whether a clot was precipitated by known risk factors for thrombosis. These were historically called “provoked” clots, though recent nomenclature trends have been moving away from this term. This information can identify transient risk factors, such as estrogen exposure from oral contraceptive use, perioperative states, and illness-related immobility. In these situations, current guidelines typically recommend definitive courses of anticoagulation after transient risk factors have been removed.

Conversely, patients may have ongoing thrombotic risk factors, such as active inflammatory bowel disease, cancer, or others. In these cases, extended-duration anticoagulation may be warranted following a more in-depth assessment of the individual risks and benefits of continuing anticoagulation.

It may be easier to characterize potential thrombotic risk factors around the time of initial VTE diagnosis. Patients and family members may be more likely to recall potential thrombosis triggers in the acute setting; thus, inpatient hematology consultation may be beneficial in identifying risk factors. However, some patients may be too ill to provide this detailed history at the time of the initial event and may benefit from outpatient follow-up intervals to clarify risk factors and discuss thrombosis history in detail.

Step 2: Consider Bleeding Risk

Bleeding is the most common adverse effect of any anticoagulant medication. Assessing bleeding risk will help determine whether anticoagulation should be started, optimize choice of anticoagulant, and potentially inform the duration of anticoagulation. For most patients with an acute VTE, the benefits of initiating anticoagulation outweigh the risks of bleeding. Exceptions may include acute central nervous system bleeding events concurrent with an acute VTE, when the addition of anticoagulation may result in life-threatening expansion or hemorrhage.

Some gastrointestinal (GI) bleeds may become life-threatening with the addition of anticoagulation. Areas of anatomic abnormality such as arterio-venous malformations, ulcers, and tumors tend to bleed more readily with the addition of anticoagulation. Definitively managing an underlying anatomic abnormality may help the patient tolerate anticoagulation and decrease the risk of bleeding. Examples may include a resection or radiation of an oozing site of malignancy or an endoscopic intervention on a GI bleed. It is important to remember that bleeding issues at the time of initial evaluation may prohibit anticoagulation for several weeks.

Frequent reassessment of tolerance for a particular anticoagulant provides an opportunity to individualize the approach for each patient. If a patient is taking an injectable anticoagulant such as enoxaparin, it may be useful to assess the patient within 2 to 4 weeks of starting injectable anticoagulants to ensure they are tolerating the injections.

Other factors that may increase bleeding risk include age 60 years or older, history of prior bleeding, active cancer, chronic hepatic or renal disease, thrombocytopenia, anemia, and other comorbidities including hypertension, poor functional capacity, and recent surgery. Use of the externally validated VTE-BLEED score may provide a frame-work for the identification of patients at risk for major bleeding during long-term anticoagulation.^2,3

Step 3: Consider Anticoagulation Options in Special Populations

There are certain patient populations or circumstances that may affect approaches to management of VTE.⁴ Patients with acute DVT and absolute contraindications to anticoagulation caused by concurrent acute bleeding may be considered for retrievable inferior vena cava (IVC) filter placement. It is paramount to ensure prompt removal of IVC filters once anticoagulation can be restarted, as there is mounting evidence of harm from lack of retrieval.⁴ Of note, the 2019 American Society of Clinical Oncology Clinical Practice Update did not recommend IVC filters for patients with a chronic DVT diagnosed more than 4 weeks prior.⁵

It is important to note that certain special populations with unique anticoagulation needs exist beyond the scope of this article, including patients who are pregnant, where low molecular weight heparins (LMWHs) or unfractionated heparins have long been the standard of care. Chronic kidney disease and hepatic disease are scenarios where the degree of organ dysfunction may dictate the choice of anticoagulation.6 Useful data for anticoagulation selection can be assessed by evaluation of the creatinine clearance, Child-Pugh score for cirrhosis, and review of the drug package insert for dosing guidance.

Direct oral anticoagulants may be relatively contraindicated in the setting of cirrhosis with a Child-Pugh score greater than B or C, depending on the agent. LMWHs are relatively contraindicated in renal insufficiency. Warfarin may be difficult to manage if the international normalized ratio is increased at baseline. Additional patient populations with specific anticoagulation considerations include patients with antiphospholipid antibody syndrome, active cancers, gastric bypass or other GI resection surgeries, and heparin-induced thrombocytopenia.^5,7-9

References

1. Centers for Disease Control and Prevention. What is venous thromboemolism? February 7, 2020. Accessed April 29, 2022. bit.ly3ywp9Ky
2. Kresoja KP, Ebner M, Rogge NIJ, et al. Prediction and prognostic importance of in-hospital major bleeding in a real-world cohoty of patients with pulmonary embolism. Int J Cardiol. 2019;1(290):144-149. doi: 10.1016/j/ijcard.2019.03.017
3. Klok FA, Barco S, Konstantinides SV. External validation of the VTE-BLEED score for predicting major bleeding in stable anticoagulated patients with venous thromboembolism. Thromb Haemost. 2017;117(6):1164-1170. doi:10.1160/TH16-10-0810
4. Choosing Wisely. IVC filters and acute VTE. October 30, 2018. https://www.choosingwisely.org/clinician-lists/american-society-hematology-inferior-vena-cava-filters-in-patients-with-acute-vte/. Accessed May 4, 2022
5. Becattini C, Agnelli G. Risk stratification and management of acute pulmonary embolism. Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):404-412. doi:10.1182/asheducation-2016.1.404
6. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020;38(5):496-520. doi:10.1200/JCO.19.01461
7. Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis adn pulmonary embolism. Blood Adv. 2020;4(19):4693-4738. doi:10.1182/bloodadvances.2020001830
8. Becattini C, Agnelli G. Acute treatment of venous theomboembolism. Blood. 2020;135(5):305-316. doi:10.1182/blood.2019001881
9. Lyman GH, Carrier M, Ay C, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv. 2021;5(4):927-974. doi:10.1182/bloodadvances.2020003442