**4.1 Hospitalized cancer patients**

Risk of thrombotic events in cancer patients undergoing surgery is as high as 50% which can reduce about 50–80% by thromboprophylaxis agents [17]. Since recent decades, multiples guidelines support the using of venous thromboembolism (VTE) prophylactic drugs in hospitalized active cancer patients unless contraindications which intermittent pneumatic compression or graduated compression stockings are recommended in these cases **Table 1** [14, 19]. Although, it is uncertain if hospital


*\* Active bleeding that requires at least two units of blood products within 24 h.*

*\*\*Pregnancy is relative contraindication for warfarin.*

*\*\*\*International Society of Thrombosis and Homeostasis 2014 (ISTH) recommended thromboprophylaxis agents for patients with platelets more than 50,000/mm3 , individualize approach in cases with platelets 25,000–49,000/mm3 , and against pharmacologic therapy for platelet lesser than 25,000/mm3 , [14, 19, 20].*

#### **Table 1.**

*Relative contraindications for thromboprophylaxis drug in hospitalized cancer patients.*

admission for chemotherapy or bone marrow transplantation displays a risk for venous thromboembolism [20].

American Society of Clinical Oncology 2020 (ASCO) recommended pharmacological thromboprophylaxis for hospitalized cancer patients with acute medical illness, reduced mobility, or undergoing major surgery. However, it should not be advised thromboprophylaxis to patients admitted for minor procedures, chemotherapy infusion, or stem cell/bone marrow transplantation.

Low-molecular-weight heparin (LMWH), fondaparinux, unfractionated heparin (UFH) are proposed prophylaxis drugs by International Society of Thrombosis and Homeostasis 2014 (ISTH), International Initiative on Thrombosis and Cancer 2019 (IITC), and National Comprehensive Cancer Network 2020 [20]. American Society of Hematology 2021 (ASH) guideline recommended low molecular heparin weight (LMHW) over unfractionated heparin (UFH) in hospitalized cancer patients and LMWH or fondaparinux rather than UFH for cancer patients undergoing surgery [21]. They against use of direct oral anticoagulants (DOACs) as prophylactic drugs in these patients [20]. Trials showed the rate of thrombosis has been significantly lower with low-molecular-weight heparin (LMWH) than unfractionated heparin (UFH) without noticeable increase in major bleeding [19].

According to American Society of Clinical Oncology 2020 (ASCO), prophylactic drugs should be commenced preoperatively (one dose 12 hours prior or evening before procedure rather than one dose on the operating table) and continued for at least 7–10 days. Extended prophylaxis with low-molecular-weight heparin (LMWH) is advised up to 4 weeks postoperatively, for high-risk patients undergoing major open or laparascopic abdominal or pelvic cancer surgery [20, 21]. American Society of Hematology 2021 recommended discontinuing thromboprophylaxis at the time of discharge rather than continuing beyond it in hospitalized cancer patients due to medical illness [21].

Non-pharmacological prophylaxis should not be recommended for cancer patients undergoing cancer surgery unless contraindication for using of pharmacological prophylaxis. Combined prophylaxis (pharmacological and mechanical) may be effective for high-risk patients for thrombotic events [20]. American Society of Hematology

#### *Thrombotic Events in Cancer Patients DOI: http://dx.doi.org/10.5772/intechopen.109619*

2021 (ASH) also suggested pharmacological thromboprophylaxis over combination or mechanical prophylaxis. Although, it recommended mechanical thromboprophylaxis over pharmacological for cancer inpatient undergoing surgery with high bleeding risk. In contrast, early ambulation is over mechanical thromboprophylaxis in postsurgery cancer patients to the opinion of American Society of Hematology Guideline 2021 [21]. International Initiative on Thrombosis and Cancer 2019 (IITC) did not recommend inferior vena cava (IVC) filter for prophylaxis, routinely [20].

### **4.2 Ambulatory cancer patients**

Ambulatory cancer patients receiving chemotherapy have increased risk for thromboembolism [20]. Primary prophylaxis decreases the risk of thromboembolism events in these patients, but the related bleeding risk and frequent daily injection have increased [22] and absolute event rate is low in cancer outpatients, too. Thus, thromboprophylaxis is not recommended by guidelines for all ambulatory cancer patients, routinely [20].

Risk stratification can guide selection of ambulatory cancer patient at high risk of venous thromboembolism [23]. Khorana score (KRS) is used as an ideal, simple, and validated risk stratification tool since 2008, to identify patients at risk of venous thromboembolism (VTE) based on clinical and laboratory variables before starting new systematic therapy. It uses platelet and leukocyte counts, hemoglobin level, body mass index, and site of cancer as the predictor for thromboembolism events **Table 2**, [23, 24]. Two randomized trials evaluated the role of anticoagulant agents for primary prevention of venous thromboembolism based on Khorana scoring in outpatients with cancer and demonstrated reduction in incidence of venous thromboembolism [22]. Khorana score seems to be the best known risk stratification tool in recent years which is endorsed by the latest guidelines [23]. Based on Khorana score, score of 0 displays that the patients are at low risk of venous thromboembolism, a score of 1–2 associates with intermediate risk, and a score of ≥3 (maximum score is 6) indicates high-risk patients. This scoring classification relates to symptomatic venous thromboembolism risk of 0.3–1.5%, 1.8–4.8%, and 6.7–12.9% in ambulatory cancer patients under chemotherapy, respectively [25].

Some guidelines suggest Khorana score 3 points or higher as potential indication for anticoagulation but most recommend a threshold of equal and more than 2 points for anticoagulant agent using [22]. Floris T.M. Bosch et al. evaluated thromboprophylaxis effects in ambulatory cancer patients with intermediate risk (2 points) Khorana


#### **Table 2.**

*Khorana score for risk stratification in ambulatory cancer patients [24].*

score, intermediate to high risk (≥2 points) and high risk score (≥3 points) separately, as a systemic review and meta-analysis involving 4626 cancer patients in 2020. They showed significant reduction in venous thromboembolism in intermediate-, intermediate-to-high-, and high-risk patients with no important difference in major bleeding or all-cause mortality. These results explained the indication of thromboprophylaxis for ambulatory cancer patients with intermediate-to-high-risk Khorana score (≥2 points) to reducing the risk of venous thromboembolism [26].

American Society of Clinical Oncology 2020 (ASCO) recommended thromboprophylaxis with apixaban, rivaroxaban, or low-molecular-weight heparin (LMWH) for high-risk outpatients with cancer with Khorana score 2 points and higher, prior to starting a systemic chemotherapy regimen (strength of recommendation: moderate) [20]. Outpatients with multiple myeloma undergoing treatment with immonomodulatory drugs such as thalidomide or linalidomide-based regimens in combination with steroids or systemic chemotherapy drugs are at risk for venous thromboembolism. So, guidelines such as American Society of Clinical Oncology 2020 (ASCO) and International Initiative on Thrombosis and Cancer 2019 (IITC)) recommended lowdose aspirin or low-molecular-weight heparin (LMWH) for these patients as thromboprophylaxis [20]. American Society of Hematology 2021 (ASH) recommended fixed low-dose vitamin K antagonists (VKAs) in these patients, too [21].
