What medications can cause Deep Vein Thrombosis (DVT)?

Medications That Can Cause Deep Vein Thrombosis (DVT)

Hormonal therapies, chemotherapy agents, and immunomodulatory drugs are the primary medication classes that significantly increase DVT risk, with combined estrogen-progestin formulations, thalidomide/lenalidomide combinations, and antiangiogenic agents posing the highest thrombotic risk.

Hormonal Medications

Hormone Replacement Therapy (HRT)

• Combined estrogen-progestin HRT carries a greater than 2-fold increased risk for DVT (OR = 2.70) compared to non-users 1
• Estrogen-only HRT shows a lower but still elevated risk (OR = 1.22), though not statistically significant 1
• All forms of HRT are associated with a 2- to 6-fold increased relative risk of VTE 2

Oral Contraceptives

• Combined oral contraceptives increase VTE risk, with the magnitude varying by progestin type 3
• Third-generation progestins (desogestrel, gestodene) carry higher VTE risk than levonorgestrel-containing formulations 2
• The risk is exponentially higher in women with inherited hypercoagulable states 2

Selective Estrogen Receptor Modulators (SERMs)

• Tamoxifen and raloxifene increase VTE risk when used for estrogen receptor-positive cancer prevention and treatment 3

Cancer Treatment Medications

Chemotherapy Agents

• Cytotoxic chemotherapy increases DVT risk with odds ratios of 6.5 in treated patients versus 4.1 in untreated cancer patients (both compared to non-cancer patients) 3
• The annual VTE incidence reaches 15% in colorectal cancer patients receiving chemotherapy 3
• Chemotherapy promotes VTE through multiple mechanisms: acute vessel wall damage, endothelial injury, decreased natural coagulation inhibitors, and platelet activation 3

Immunomodulatory/Antiangiogenic Agents

• Thalidomide combined with doxorubicin and/or dexamethasone shows VTE rates up to 34% in multiple myeloma patients 3
• Lenalidomide with high-dose dexamethasone carries particularly high thrombotic risk in relapsed myeloma 3
• Bevacizumab increases VTE risk by 33% relative to chemotherapy alone, with overall VTE incidence of 11.9% (any grade) and 6.3% (high-grade) 3
• These agents cause thrombosis through endothelial cell and platelet activation plus vascular endothelial damage 3

Hormonal Cancer Therapies

• Diethylstilbestrol phosphate combined with doxorubicin for hormone-refractory prostate cancer increases VTE risk versus doxorubicin alone 3

Supportive Care Medications

Erythropoiesis-Stimulating Agents (ESAs)

• ESAs are associated with VTE development in cancer patients 3
• Concomitant use of erythropoietin with other thrombogenic therapies (e.g., lenalidomide) further amplifies VTE risk 3
• Hemoglobin <10 g/dL or ESA use contributes 1 point to the Khorana VTE risk score 3

High-Risk Medication Combinations

Multiple Myeloma Regimens

• Highest risk: thalidomide/lenalidomide + high-dose dexamethasone (≥480 mg/month) + doxorubicin or multiagent chemotherapy 3
• These combinations require prophylactic anticoagulation with warfarin (INR 2-3) or LMWH 3

Cancer + Hormonal Therapy

• The thrombogenic effect of antiangiogenic agents is amplified by co-administration of chemotherapy and steroids 3

Important Clinical Caveats

Risk stratification is essential: Not all patients on these medications require prophylaxis, but those with multiple risk factors need aggressive prevention 3

Key additional risk factors that compound medication-related DVT risk include:

• Previous VTE history 3
• Active malignancy (especially pancreatic, gastric, brain, lung, lymphoma, gynecologic) 3
• Immobilization 3
• Central venous catheters 3
• Advanced age (>75 years) 3
• Obesity (BMI ≥35 kg/m²) 3

Prophylaxis considerations: For high-risk cancer outpatients receiving highly thrombogenic regimens (particularly thalidomide/lenalidomide with high-dose dexamethasone or multiagent chemotherapy), prophylactic LMWH or warfarin should be strongly considered 3. Lower-risk patients may use aspirin prophylaxis, though LMWH is preferred for those with ≥2 risk factors 3.

Monitoring: Patients on these medications should be educated about DVT symptoms (leg swelling, pain, warmth) and PE symptoms (sudden dyspnea, chest pain) requiring immediate medical attention 3.