Cancer Associated Thrombosis (CAT)

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Questions and Answers

A 65-year-old patient with metastatic pancreatic cancer presents with acute onset of pleuritic chest pain and dyspnea. A CT pulmonary angiogram confirms a pulmonary embolism. Which of the following underlying mechanisms most directly contributes to this patient's increased risk of venous thromboembolism?

  • Endothelial damage from repeated venipuncture for chemotherapy administration.
  • Tumour-derived tissue factor activating the extrinsic coagulation pathway. (correct)
  • Reduced venous blood flow caused by tumour-related cachexia and immobility.
  • Increased platelet activation due to chemotherapy-induced myelosuppression.

A researcher is investigating the coagulation profiles of patients with different types of solid tumours. They hypothesize that patients with mucinous adenocarcinomas have a higher incidence of venous thromboembolism (VTE) compared to those with squamous cell carcinomas. Which of the following biological factors best explains this potential difference?

  • Variations in tumour-associated inflammation and cytokine release between mucinous and squamous cell histologies.
  • Differential activation of the intrinsic coagulation pathway due to tumour necrosis in squamous cell carcinomas.
  • Higher rates of chemotherapy-induced nausea and vomiting leading to dehydration and hemoconcentration in mucinous adenocarcinoma patients.
  • Increased expression of P-selectin ligands on mucinous adenocarcinoma cells, promoting platelet adhesion. (correct)

A patient with lung cancer develops a deep vein thrombosis (DVT) despite being on prophylactic low molecular weight heparin (LMWH) during hospitalization. Which of the following factors is the most likely reason for the failure of thromboprophylaxis in this scenario?

  • Pharmacokinetic alterations due to cancer or its treatment have reduced the effective LMWH concentration. (correct)
  • The patient has developed heparin-induced thrombocytopenia, paradoxically increasing thrombotic risk.
  • The patient's DVT is provoked by recent air travel, overriding the prophylactic effect of LMWH.
  • Cancer-associated hypercoagulability is inherently resistant to standard prophylactic LMWH dosing.

A 70-year-old patient with metastatic colorectal cancer and a recent diagnosis of deep vein thrombosis (DVT) is being considered for anticoagulation. He has a history of chronic kidney disease (CKD) with an estimated glomerular filtration rate (eGFR) of 25 mL/min. Which of the following anticoagulation strategies is most appropriate for this patient?

<p>Therapeutic dose low molecular weight heparin (LMWH), such as enoxaparin, with dose adjustment based on anti-Xa levels. (D)</p> Signup and view all the answers

In the management of cancer-associated venous thromboembolism (VTE), what is the primary rationale for considering extended or indefinite duration of anticoagulation therapy?

<p>To mitigate the increased risk of recurrent VTE associated with persistent cancer activity and treatment. (C)</p> Signup and view all the answers

Which of the following statements best describes the clinical utility of an Inferior Vena Cava (IVC) filter in the context of cancer-associated venous thromboembolism?

<p>IVC filters are considered in cancer patients with acute VTE when therapeutic anticoagulation is absolutely contraindicated. (C)</p> Signup and view all the answers

A patient with acute promyelocytic leukemia (APML) develops disseminated intravascular coagulation (DIC) and clinically significant bleeding during induction chemotherapy. Thrombosis is also a concern in APML-associated coagulopathy. What is the most critical initial step in managing this complex scenario?

<p>Rapidly initiate treatment for APML with all-trans retinoic acid (ATRA) and chemotherapy to address the underlying cause of DIC. (B)</p> Signup and view all the answers

A researcher is designing a clinical trial comparing direct oral anticoagulants (DOACs) to low molecular weight heparin (LMWH) for the treatment of cancer-associated thrombosis. Which of the following patient populations would be most appropriate to exclude from this trial to minimize confounding factors?

<p>Patients receiving concomitant medications known to be strong inhibitors of CYP3A4 and P-glycoprotein. (B)</p> Signup and view all the answers

A patient with metastatic prostate cancer and bone metastases develops sudden onset paraplegia. Imaging reveals epidural spinal cord compression and a newly diagnosed deep vein thrombosis (DVT) in the lower extremity. How does the presence of spinal cord compression influence the anticoagulation management of this patient's DVT?

<p>Standard anticoagulation for DVT should be initiated, but with careful monitoring for signs of bleeding into the spinal canal. (B)</p> Signup and view all the answers

Which of the following statements accurately reflects the relationship between cancer-associated thrombosis (CAT) and patient prognosis?

<p>CAT is associated with an increased risk of mortality in cancer patients, independent of cancer stage and other prognostic factors. (A)</p> Signup and view all the answers

According to the Khorana risk score for VTE in ambulatory cancer patients, which of the following factors contributes the highest number of points to the risk assessment?

<p>High-risk cancer type (e.g., stomach, pancreas). (B)</p> Signup and view all the answers

A patient with lymphoma is started on chemotherapy and is being assessed for VTE prophylaxis. According to guidelines, which of the following scenarios would be a strong indication for considering primary thromboprophylaxis in this ambulatory patient?

<p>Patient has a Khorana risk score of 3 or higher, indicating high risk. (A)</p> Signup and view all the answers

In the context of cancer-associated thrombosis, what is 'Trousseau's syndrome'?

<p>Venous thromboembolism that presents as the first clinical manifestation of an occult malignancy. (D)</p> Signup and view all the answers

Compared to patients without cancer, cancer patients with venous thromboembolism (VTE) exhibit which of the following characteristics regarding anticoagulation therapy?

<p>Higher rates of VTE recurrence despite being on anticoagulation. (D)</p> Signup and view all the answers

What is the primary rationale behind using low molecular weight heparin (LMWH) as a preferred initial anticoagulant over vitamin K antagonists (VKAs) like warfarin for the treatment of cancer-associated venous thromboembolism (VTE)?

<p>LMWH has demonstrated superior efficacy in preventing VTE recurrence and potentially improving survival in cancer patients with VTE. (B)</p> Signup and view all the answers

In a patient with cancer-associated thrombosis being treated with a direct oral anticoagulant (DOAC), which of the following clinical scenarios would raise the greatest concern for potential drug-drug interaction leading to reduced DOAC efficacy?

<p>Initiation of treatment with a strong CYP3A4 and P-glycoprotein inducer, such as rifampin. (C)</p> Signup and view all the answers

A patient with metastatic lung cancer and a central venous catheter (CVC) develops upper extremity deep vein thrombosis (UEDVT) related to the catheter. What is the recommended duration of anticoagulation therapy if the CVC remains in situ?

<p>Anticoagulation should be continued for as long as the CVC remains in place, plus at least 3 months after CVC removal. (D)</p> Signup and view all the answers

In the management of recurrent venous thromboembolism (VTE) in a cancer patient who is already receiving therapeutic low molecular weight heparin (LMWH), which of the following is the most appropriate next step?

<p>Increase the dose of LMWH by 20-25% and re-evaluate for underlying causes of recurrence. (B)</p> Signup and view all the answers

A patient with advanced cancer and thrombocytopenia (platelet count 30 x 10^9/L) develops an acute deep vein thrombosis (DVT). What is the most appropriate approach to anticoagulation in this patient?

<p>Administer prophylactic dose LMWH or 50% of the therapeutic dose due to thrombocytopenia-related bleeding risk. (B)</p> Signup and view all the answers

Which of the following statements regarding arterial thromboembolism prevention in patients with active cancer is most accurate?

<p>For patients with myeloproliferative neoplasms (MPNs), low-dose aspirin or low-dose DOAC may be considered for primary arterial thromboprophylaxis. (C)</p> Signup and view all the answers

In the context of V/Q scans for diagnosing pulmonary embolism (PE), a 'mismatch' typically indicates:

<p>Normal ventilation but reduced perfusion in a lung segment, raising suspicion for PE. (B)</p> Signup and view all the answers

According to the Wells' Score for Pulmonary Embolism (PE), which of the following clinical findings carries the highest point value?

<p>PE is as or more likely than an alternative diagnosis. (B)</p> Signup and view all the answers

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a long-term complication of pulmonary embolism (PE). What is the primary pathophysiological mechanism underlying CTEPH development?

<p>Failure of acute pulmonary emboli to resolve, resulting in persistent thrombus and vascular remodeling. (B)</p> Signup and view all the answers

Post-thrombotic syndrome (PTS) is a common complication following deep vein thrombosis (DVT). Which of the following best describes the underlying pathophysiology of PTS?

<p>Recanalization of the thrombosed vein with residual valve damage, causing venous reflux and ambulatory venous hypertension. (C)</p> Signup and view all the answers

In the context of cancer-associated thrombosis, which of the following statements regarding 'unprovoked' VTE and occult malignancy screening is most accurate?

<p>A limited screening strategy, including history, physical exam, basic blood tests, and age-appropriate cancer screening, is recommended for first unprovoked VTE. (C)</p> Signup and view all the answers

What is the primary mechanism by which tumour-secreted factors contribute to the hypercoagulable state in cancer-associated thrombosis?

<p>Inhibition of fibrinolysis by tumour-derived plasminogen activator inhibitor-1 (PAI-1). (B)</p> Signup and view all the answers

In cancer-associated thrombosis, the interplay between tumour cells, platelets, neutrophils and monocytes contributes to venous thrombosis. Which of the following best describes the role of neutrophils in this process?

<p>Neutrophils release neutrophil extracellular traps (NETs), which provide a scaffold for thrombus formation and platelet activation. (C)</p> Signup and view all the answers

Flashcards

Pulmonary Embolism (PE)

Blockage of arteries within the lungs, often caused by a dislodged Deep Vein Thrombosis

Deep Vein Thrombosis (DVT)

A blood clot that forms in a deep vein, commonly in the legs, causing pain and swelling

Ventilation Scan

A diagnostic test involving inhalation of radioactive gas to visualize air distribution in the lungs

Perfusion Scan

A diagnostic test using a radioactive tracer to show blood flow in the lung tissue

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Wells Criteria

A clinical prediction model combined with D-dimer testing, used to assess the probability of DVT or PE

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Post-Thrombotic Syndrome (PTS)

Damage to vein valves after DVT, develops in 1-2 years, leading to persistent pain and swelling

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Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Increased pressure in pulmonary arteries from residual clot after PE, leading to right heart failure, fatigue, and reduced exercise tolerance

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Virchow's Triad

Damage to vessel walls, immobility from bed rest, and hypercoagulability caused by cancer cells/therapies that promote thrombosis

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Trousseau's Syndrome

Spontaneous migratory blood clot associated with cancer

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Thrombosis in Cancer

Leading cause of death among cancer patients, second only to disease progression

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VTE Treatment Goal

Therapeutic anticoagulation with LMWH or DOACs minimizes new clots

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Therapeutic anticoagulation

Low-molecular-weight heparin (LMWH) or direct oral anticoagulants (DOACs).

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Treatment Considerations

Drug-drug interactions and toxicity

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VKA/DOAC

If this happens switch to LMWH

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Screening Strategy

The use of history, physical examination, basic blood tests, and chest radiography

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LMWH

The use of pharmacological prophylaxis with LMWH unless contraindicated.

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Arterial Thrombosis

No specific guidelines or recommendations are available.

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PICC/Portacath/Central line/Hickman line

This may need to be removed if it's functioning normally/needed

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IVC Filter

Device to prevent traveling clots

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Switch to LMWH

To manage recurrent VTE

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Study Notes

Learning Outcomes

  • Mechanisms of arterial and venous thrombosis formation should be described for cancer patients
  • Risk factors for thrombosis should be listed for cancer patients
  • Solid cancers associated with a high risk of thrombosis should be listed
  • Methods for preventing thrombosis should be listed
  • Clinical indications for an Inferior Vena Cava Filter should be described
  • Initial management of Cancer Associated Thrombosis should be described
  • Long term management of Cancer Associated Thrombosis should be described

Venous Thrombo-Embolism (VTE)

  • Deep Vein Thrombosis (DVT) forms in deep veins, often in the legs
  • People with DVT have pain, swelling, tenderness, or erythema in the affected limb
  • Pulmonary Embolism (PE) is a sudden, life-threatening blockage in a lung artery
  • PEs are commonly caused by a DVT part breaking off and traveling to the lung from a vein in the leg
  • Less common sites for VTE include upper limbs, cerebral veins, and splanchnic veins (mesenteric, hepatic, and portal veins)

VTE Diagnosis

  • Diagnosis starts with history and examination
  • A D-Dimer test should be considered alongside a clinical risk prediction model, like Wells Criteria for DVT or PE
  • Ultrasound for symptomatic limb veins is used to diagnose a DVT
  • CT Pulmonary Angiogram (CT-PA) is used for diagnosing PE, as is a Ventilation Perfusion (V/Q) scan
  • Ventilation Scan is part of a V/Q scan and uses inhaled radioactive gas to visualize air distribution in the lungs
  • Perfusion Scan is part of a V/Q scan and uses injected radioactive tracer to show blood flow in the lung tissue
  • Pulmonary embolism shows a mismatch where a lung segment is ventilated but not perfused due to blockage in a pulmonary artery

Well's Score for PE

  • Signs of DVT (swelling, etc) - 3 points
  • Heart Rate >100 - 1.5 points
  • Immobilisation >2 days or recent surgery (4 weeks) - 1.5 points
  • Previous DVT - 1.5 points
  • Haemoptysis - 1.0 points
  • Cancer - 1.0 points
  • PE as or more likely than other diagnosis - 3.0 points

  • 6 indicates high probability

  • 2-6 is medium probability
  • <2 is low probability

VTE Complications

  • Death
  • Recurrent VTE
  • Treatment-related issues, like bleeding
  • Post-Thrombotic Syndrome
  • Pulmonary Hypertension (CTEPH)

What if Anticoagulation Is Absolutely Contraindicated?

  • Acute PE/DVT may necessitate anticoagulation, however contraindications can exist
  • Examples of contraindications are active bleeding, severe thrombocytopenia or an emergency surgery requiring prolonged interruption
  • High risk of recurrence can lead to...
  • Consideration of a temporary IVC filter placement

IVC Filters

  • Metallic devices can be placed into the inferior vena cava under fluoroscopic guidance
  • Done to stop lower limb DVTs from traveling to pulmonary circulation
  • Complications must be beware of
  • Immediate: Misplacement 1.3%, Pneumothorax 0.02%,Hematoma 0.6%, Air embolism 0.2%, Carotid artery puncture 0.04%, AV fistula 0.02%
  • Early: insertion site thrombosis 8.5%, infection
  • Late: Recurrent DVT 21%, IVC thrombus 2-10%, Post-thrombotic syndrome 15-40%, IVC penetration 0.3%, Filter migration 0.3%, Filter tilting/fracture
  • IVC Filters should be placed only if indicated
  • Retrieval should be arranged when anticoagulation is established and/or risk of PE is passed
  • The longer the IVC filter remains in situ, the less chance of retrieval.

Central Line Associated Thrombosis

  • PICC/Portacath/Central line/Hickman line, all central lines may lead to thrombosis
  • Treatment does not necessitate immediate removal of the line if it is functioning normally
  • A minimum of 3 months anticoagulant therapy at a full dose is needed
  • Should the line remain in place, anticoagulation therapy needs to continue

Types of Catheters

  • Peripherally Inserted Central Catheter (PICC): a catheter inserted through a vein in the arm and advanced until the tip reaches a large vein near the heart
  • Used for long-term IV medications, nutrition, or chemotherapy
  • Portacath: a small, implantable device placed under the skin, usually in the chest, with a catheter leading into a vein near the heart
  • Allows easy access for IV treatments and blood draws, often used in cancer patients for chemotherapy
  • Central Line (Central Venous Catheter): A catheter is inserted into a large vein, typically the neck (internal jugular), chest (subclavian), or groin (femoral), and provides direct access to major veins
  • Hickman line: a type of central line inserted through the chest, with the catheter remaining outside the body for easy access

VTE Recurrence

  • Patients with cancer have a higher recurrence rate during anticoagulation
  • Possible Reasons for Recurring VTE:
  • Progressive disease
  • Extrinsic compression of a blood vessel
  • Surgery
  • Medication interaction
  • Interruption/Non-Compliance with medication
  • Weight Change leads to Under-dosing of LMWH
  • Malabsorption of a DOAC

How to Manage VTE Recurrence

  • Swap VKA/DOAC for LMWH
  • With LMWH, up the dose by 20-25%
  • Or, calculate whether weight dosing is therapeutic

Unprovoked VTE & Occult Malignancy

  • Thrombosis can be an early sign of hidden cancer
  • Occult cancer prevalence is low in first unprovoked VTE cases
  • Routine CT scans of the thorax, abdomen, and pelvis are not clinically beneficial for those with first unprovoked VTE
  • Limited screening instead should be done, including history, physical exam, basic blood tests, chest radiography, targeted investigations, and age/sex cancer screening

VTE Prevention in Patients with Active Cancer

  • If admitted, consider LMWH prophylaxis unless contraindicated
  • If admitted for acute medical illness LMWH throughout admission
  • If admitted for non-minor surgery LMWH throughout admission
  • If high-risk surgical patients extend to 28 days post-op, such as abdominal/pelvic cancer with open/laparoscopic surgery
  • Consider omitting LMWH prophylaxis if platelet count < 50 × 109/L
  • Consider assessing ambulatory patients starting systemic anti-cancer therapy with a validated risk assessment score (e.g. Khorana score)

Khorana Score for VTE Risk in Ambulatory Patients

  • Factors for scoring are the site of cancer, platelet count, hemoglobin levels/use of red cell growth factors, leukocyte count and BMI
  • Very high risk (stomach, pancreas) – 2 points
  • High risk (Lung, Lymphoma, Gynecologic, bladder, testicular) – 1 points
  • Intermed Risk - 1-2
  • High Risk ≥3

Arterial Thrombosis Prevention in Patients with Active Cancer

  • There are no specific guidelines for arterial thromboembolism prophylaxis or primary prevention in the cancer setting
  • An exception is Myeloproliferative Neoplasms (MPNs), where aspirin/low-dose DOAC + cytoreductive therapy/phlebotomy has proven to significantly reduce risk of cardiovascular events.

Unanswered Questions in CAT

  • What is the best anticoagulation duration for low-risk cancer VTE (e.g. Isolated Distal DVT/Low Risk PE)?
  • Is lowering DOAC dose after 6 months appropriate if the thrombus is resolved?
  • Could low-dose DOACs be used in CAT with ESKD or Thrombocytopenia (i.e. 6 months if resolution of thrombus?
  1. Could low dose DOACs be used in CAT with associated ESKD or Thrombocytopenia (i.e.

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