Venous thromboembolism in cancer.presentation

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Venous thromboembolism in cancer.presentation

  1. 1. VENOUS THROMBOEMBOLISM IN MALIGNANCY PATIENT MUSTAKIM.MD Resident at Clinical Pathology Division Hasanuddin University Makassar, Indonesia
  2. 2. CONTENTS CONTENT INTRODUCTION PREVENTION EPIDEMIOLOGY AND RISK FACTOR PATOPHYSIOLOGY TREATMENT PROGNOSIS SUMMARY
  3. 3. Thrombosis is a general term for the formation or presence of a thrombus (a clot of coagulated blood) in a blood vessel Thrombus can develop in vein,artery,heart & microcirculation Thrombosis is much more prevalent in patients w/malignancy & predominantly of the venous circulation
  4. 4. 1823 Bouillard; recognised deep vein Thrombosis in patients w/malignancy 1865 Armand Trousseau Describing the relationship between VTE & malignancy
  5. 5. Occult cancer in patients w/ idiopathic venous thromboembolism Thrombophlebitis in patients w/ malignancy TROUSSEAU SYNDROME
  6. 6. CONTENTS CONTENT INTRODUCTION PREVENTION EPIDEMIOLOGY AND RISK FACTOR PATOPHYSIOLOGY TREATMENT PROGNOSIS SUMMARY
  7. 7. VTE and malignancy : Epidemiology • Of all cases of VTE: – About 18% occur in malignancy patients – About 10-17% patients ,in which no underlying cause of VTE, will go on to have the diagnosis of a new malignancy within two years • Of all patients w/ malignancy – 15% will have symptomatic VTE – As many as 30- 50% have VTE at autopsy • Compared to patients without malignancy: – Higher risk of first and recurrent VTE (about 7- fold increased ) – In certain malignancy risk for VTE increased 28-fold
  8. 8. VTE AND RISK FACTOR PATIENT RELATED FACTOR Age,sex,ethnicity,comorbid condition & prothrombotic mutation TUMOR RELATED FACTOR type, site, stage & duration of malignancy
  9. 9. VTE AND RISK FACTOR ( CONT…) TREATMENT RELATED FACTOR  Pharmacologic therapy  Chemotherapeutic agent 
  10. 10. Predictive model for chemotherapy associated VTE
  11. 11. VTE AND RISK FACTOR ( CONT…) TREATMENT RELATED FACTOR  Hormonal agent  Antiangiogenic agent  Erythropoiesis-stimulating agent Mechanical therapy 
  12. 12. CONTENTS I. INTRODUCTION II.EPIDEMIOLOGY AND RISK FACTOR III.PATOPHYSIOLOGY IV.PREVENTION V.TREATMENT VI.PROGNOSIS VII.SUMMARY
  13. 13. Pathogenesis of Thrombosis in malignancy patient 1. Stasis A Modification of Virchow’s Triad – Prolonged bed rest – Extrinsic compression of blood vessels by tumor 2. Vascular Injury – Direct invasion by tumor – Prolonged use of central venous catheters – Endothelial damage by chemotherapy drugs – Effect of tumor cytokines on vascular endothelium 3. Hypercoagulability – Tumor-associated procoagulants & cytokines (tissue factor, CP, TNF , IL-1 , VEGF, etc.) – Impaired endothelial cell defense mechanisms (APC resistance; deficiencies of AT, Protein C and S) – Enhanced selectin/integrin-mediated, adhesive interactions between tumor cells,vascular endothelial cells, platelets & host macrophages
  14. 14. VTE: PATHOPHYSIOLOGY Cont…….  The PRINCIPAL prothrombotic properties of tumor cell : Capacity of tumor cell to interact w/ host blood cells; endothelial, leukocytes & platelet. Capacity of tumor cell to produce & release its own procoagulant & fibrinolytic activities, beside proinflammatory cytokines
  15. 15. Tumor cells Angiogenesis, Basement matrix degradation. Fibrinolytic activities: t-PA, u-PA, u-PAR, PAI-1, PAI-2 Procoagulant Activities IL-1, TNFVEGF PMN leukocyte Activation of coagulation FIBRIN Platelets Monocyte Endothelial cells
  16. 16. CONTENT I. INTRODUCTION II.EPIDEMIOLOGY AND RISK FACTOR III.PATOPHYSIOLOGY IV.PREVENTION V.TREATMENT VI.PROGNOSIS VII.SUMMARY
  17. 17. VTE : PREVENTION PRIMARY PREVENTION AMBULATORY PATIENT W/ CHEMOTHERAPY MEDICAL INPATIENT W/ CHEMOTHERAPY MALIGNANCY PATIENT W/ SURGERY
  18. 18. • Ambulatory Patient with Chemotherapy NCCN Recommended VTE prophylaxis in high risk setting : Patient receiving highly thrombotic antiangiogenic therapy (i.e., thalidomide/ lenalidomide in combination w/ high dose dexamethasone Myeloma patients w/ 2 or more individual or myeloma risk factors
  19. 19. Ambulatory Patient (Cont….) Modality for prophylaxis:  Low dose warfarin (1mg for 6 weeks ) adjusted to INR 1,3-1,9 Enoxaparin 1mg/kg SC every 24 hour for at least 3 months. Apixaban
  20. 20. VTE : PREVENTION PRIMARY PREVENTION AMBULATORY PATIENT W/ CHEMOTHERAPY MEDICAL INPATIENT W/ CHEMOTHERAPY CANCER SURGERY PATIENT
  21. 21. Medical Inpatient with chemotherapy NCCN recommended : • Enoxaparin, 40 mg sc daily • Tinzaparin, 4500 units (fixed dose) sc daily or 75 units/kg sc daily • Dalteparin, 5000 units sc daily • Fondaparinux ; 2.5 mg sc daily • Unfractionated heparin:5000 units sc 3 times daily • Warfarin (adjusted to INR 2-3)
  22. 22. VTE : PREVENTION PRIMARY PREVENTION AMBULATORY PATIENT W/ CHEMOTHERAPY MEDICAL NPATIENT W/ CHEMOTHERAPY MALIGNANCY PATIENT W/ SURGERY
  23. 23. CANCER SURGERY INPATIENT Mechanical prophylaxis • • • • electrical calf stimulation intermitten pneumatic compression devices graduated compression stocking venous foot pump devices
  24. 24. Malignanct inpatient w/ surgery ( cont…) pharmacological • Modality prophylaxis for malignancy patient w/ surgery is not significantly different w/ medical in patient w/ chemotherapy
  25. 25. VTE PREVENTION SECONDARY PREVENTION Warfarin ●Difficulty maintaining tight therapeutic control, due to anorexia, vomiting, drug interactions ●Frequent interruptions for thrombocytopenia & procedures ●Difficulty in venous access for monitoring ● Increased risk of both recurrence & bleeding Low molecular weight heparin
  26. 26. CONTENT I. INTRODUCTION II.EPIDEMIOLOGY AND RISK FACTOR III.PATOPHYSIOLOGY IV.PREVENTION V.TREATMENT VI.PROGNOSIS VII.SUMMARY
  27. 27. THERAPY Goals therapy (1)Preventing fatal PE (2) Reducing short-term morbidities associated w/ acute leg or lung thrombus (3) Preventing recurrent VTE (4) Preventing the long-term sequelae of VTE
  28. 28. VTE in Cancer : Therapy Anticoagulant Therapy Acute Management  Dalteparin (200 units/kg subcutaneous daily Enoxaparin (1 mg/kg subcutaneous every 12 hours) (4-5 days,continuated with warfarin if INR >2,0. Tinzaparin :175 u/kg sc daily  Fondaparinux (5 mg [< 50 kg]; 7.5 mg [50-100 kg]; 10 mg [> 100 kg] subcutaneous daily)  Unfractionated Heparin : 5000 IU load,or 80 U/kg load, then 18 U/kg/h (aPTT 0f 2-2,5Xcontrol)
  29. 29. Therapeutic Anticoagulation Failure Therapeutic INR Patient on warfarin Switch to heparin (LMWH preferred) or fondaparinux Check INR Subtherapeutic INR Increase warfarin dose and treat with parenteral agent until INR target achieved or consider switching to heparin (LMWH preferred) or fondaparinux
  30. 30. Therapeutic Anticoagulation Failure Therapeutic aPTT Patient on heparin Increase dose of heparin or Switch to LMWH or Switch to fondaparinux&Consider placement of IVC filter & Consider HIT Check aPTT levels Subtherapeutic aPTT Increase dose of heparin to reach therapeutic level
  31. 31. CONTENT I. INTRODUCTION II.EPIDEMIOLOGY AND RISK FACTOR III.PATOPHYSIOLOGY IV.PREVENTION V.TREATMENT VI.PROGNOSIS VII.SUMMARY
  32. 32. PROGNOSIS ►Survival after VTE is lower than expected in malignancy patients. ►VTE : 2nd most common cause of death in hospitalized patients w/ malignancy(tied with infection) ►Survival among active cancer patients with VTE differs by gender.
  33. 33. CONTENT I. INTRODUCTION II.EPIDEMIOLOGY AND RISK FACTOR III.PATOPHYSIOLOGY IV.PREVENTION V.TREATMENT VI.PROGNOSIS VII.SUMMARY
  34. 34. SUMMARY ►VTE : 2nd most common cause of death in hospitalized malignancy patient ► Risk factors for VTE in the setting of malignancy have been well characterized: solid tumors, chemotherapy, surgery, thrombocytopenia ► Long-term secondary prevention w/ LMWH has been shown to produce better outcomes than warfarin ► malignancy patients are under-prophylaxed for VTE
  35. 35. SUMMARY (Cont….)  Effective VTE prophylaxis in malignancy patients usually requires anticoagulation w/ LMWH but when bleeding risk is too high, use mechanical measures.  VTE prophylaxis in malignancy patients is under-utilized & requires increased vigilance and prophylaxis-focused intervention
  36. 36. that THANK YOU
  37. 37. Trombosis lebih sering pada vena dibanding arteri because: • Aliran darah pada vena lebih lambat dibandingkan arteri. • Trombus pada arteri : trombus putih karena terdiri dari trombin bersifat lebih kuat tidak mudah lepas,pada vena trombus merah terbentuk dari fibrin mudah lepas menjadi emboli.
  38. 38. • APC resistance = Activated Protein C resisten adalah kegagalan protein C aktiv merubah FVa menjadi FV,sehingga FVa menjadi bertumpuk yang memudahkan trombosis.

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