Venous thromboembolism in cancer.presentation
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Transcript of Venous thromboembolism in cancer.presentation
VENOUS THROMBOEMBOLISM IN MALIGNANCY PATIENT
MUSTAKIM.MD
Resident at Clinical Pathology Division Hasanuddin University
Makassar, Indonesia
CONTENTS
INTRODUCTION
EPIDEMIOLOGY AND RISK FACTOR
PATOPHYSIOLOGY
PREVENTION
TREATMENT PROGNOSIS
SUMMARY
CONTENT
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
Armand TrousseauDescribing the relationship between VTE & malignancy
Bouillard;recognised deep vein
Thrombosis in patients
w/malignancy
1823 1865
TROUSSEAU SYNDROME
Occult cancer in patients w/
idiopathic venous thromboembolism
Thrombophlebitis in patients
w/ malignancy
CONTENTS
INTRODUCTION
EPIDEMIOLOGY AND RISK FACTOR
PATOPHYSIOLOGY
PREVENTION
TREATMENT PROGNOSIS
SUMMARY
CONTENT
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
VTE AND RISK FACTOR
Age,sex,ethnicity,comorbid condition & prothrombotic mutation
type, site, stage & duration of malignancy
PATIENT RELATED FACTOR
TUMOR RELATED FACTOR
VTE AND RISK FACTOR ( CONT…)
Pharmacologic therapy Chemotherapeutic agent
TREATMENT RELATED FACTOR
Predictive model for chemotherapy associated VTE
VTE AND RISK FACTOR ( CONT…)
Hormonal agent Antiangiogenic agent Erythropoiesis-stimulating agent
Mechanical therapy
TREATMENT RELATED FACTOR
CONTENTSI. INTRODUCTION
II.EPIDEMIOLOGY AND RISK FACTOR
III.PATOPHYSIOLOGY
IV.PREVENTION
V.TREATMENT
VI.PROGNOSIS
VII.SUMMARY
Pathogenesis of Thrombosis in malignancy patientA Modification of Virchow’s Triad
1. Stasis– 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
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
Fibrinolytic activities:t-PA, u-PA, u-PAR, PAI-1, PAI-2
Procoagulant Activities
FIBRIN
Endothelial cells
IL-1, TNF-, a VEGF
Tumor cells
Monocyte
PMN leukocyte
Activation of coagulation
Platelets
Angiogenesis,Basement matrix degradation.
CONTENTI. INTRODUCTION
II.EPIDEMIOLOGY AND RISK FACTOR
III.PATOPHYSIOLOGY
IV.PREVENTION
V.TREATMENT
VI.PROGNOSIS
VII.SUMMARY
VTE : PREVENTION
AMBULATORY PATIENT W/ CHEMOTHERAPY
MEDICAL INPATIENT W/ CHEMOTHERAPY
MALIGNANCY PATIENT W/ SURGERY
PRIMARY PREVENTION
• 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 dexamethasoneMyeloma patients w/ 2 or more individual or myeloma risk factors
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
VTE : PREVENTION
AMBULATORY PATIENT W/ CHEMOTHERAPY
MEDICAL INPATIENT W/ CHEMOTHERAPY
CANCER SURGERY PATIENT
PRIMARY PREVENTION
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)
VTE : PREVENTION
AMBULATORY PATIENT W/ CHEMOTHERAPY
MEDICAL NPATIENT W/ CHEMOTHERAPY
MALIGNANCY PATIENT W/ SURGERY
PRIMARY PREVENTION
CANCER SURGERY INPATIENT
• electrical calf stimulation• intermitten pneumatic compression devices• graduated compression stocking• venous foot pump devices
Mechanical prophylaxis
Malignanct inpatient w/ surgery ( cont…)
• Modality prophylaxis for malignancy patient w/ surgery is not significantly different w/ medical in patient w/ chemotherapy
pharmacological
VTE PREVENTIONSECONDARY 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 &
bleedingLow molecular weight heparin
CONTENTI. INTRODUCTION
II.EPIDEMIOLOGY AND RISK FACTOR
III.PATOPHYSIOLOGY
IV.PREVENTION
V.TREATMENT
VI.PROGNOSIS
VII.SUMMARY
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
Goals therapy
VTE in Cancer : 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)
Anticoagulant Therapy
Therapeutic Anticoagulation Failure
Therapeutic INR
Switch to heparin (LMWH preferred)
or fondaparinux
Increase warfarin dose and treat with
parenteral agent until INR target achieved or consider switching to
heparin (LMWH preferred) or fondaparinux
Patient on
warfarin
Check INR
Sub-therapeutic
INR
Therapeutic Anticoagulation Failure
Therapeutic aPTT
Increase dose of heparin or Switch to LMWH or Switch to fondaparinux&Consider placement of IVC filter & Consider HIT
Increase dose of heparin to reach therapeutic
level
Patient on
heparin
Check aPTT levels
Sub-therapeutic
aPTT
CONTENTI. INTRODUCTION
II.EPIDEMIOLOGY AND RISK FACTOR
III.PATOPHYSIOLOGY
IV.PREVENTION
V.TREATMENT
VI.PROGNOSIS
VII.SUMMARY
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.
CONTENTI. INTRODUCTION
II.EPIDEMIOLOGY AND RISK FACTOR
III.PATOPHYSIOLOGY
IV.PREVENTION
V.TREATMENT
VI.PROGNOSIS
VII.SUMMARY
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
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
thatTHANK YOU
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.
• APC resistance = Activated Protein C resisten adalah kegagalan protein C aktiv merubah FVa menjadi FV,sehingga FVa menjadi bertumpuk yang memudahkan trombosis.