Updates in Thrombosis Dr. Ali Y. Al-Muhaini MBBch FRCP(C) Chairman of the Internal Medicine Department Head of the Division Of Clinical Hematology Jaber Al-Ahmed Al-Sabah Hospital
Today Introduction • Causes of VTE • Treatment Options • DVT & PE Treatment Guidelines ACCP 2016 • Can DOAC’s be Use in APLS ? • Can DOAC’s be Use in Malignancies ? • DOACs Reversal • Conclusion •
Introduction • What is deep vein thrombosis? • Thrombus formation within the deep venous system • It can occur in any vein • Most clinical events arise in the deep vessels of the legs, subsequently embolize to the lungs. • DVT is a frequent occurrence in the general population, with an estimated annual incidence rate of 0.1-0.2%.
Introduction • Of those who present with symptoms of possible DVT, ~25% have confirmed DVT • 80% are proximal and 20% have DVT limited to the calf • 50% of patients with documented DVT will have PE • In DVT limited to the calf, 20-30% may extend within 1-2 weeks of presentation • PE is found in 15% of adult patients who had been hospitalized
Today Introduction • Causes of VTE • Treatment Options • DVT & PE Treatment Guidelines ACCP 2016 • Can DOAC’s be Use in APLS ? • Can DOAC’s be Use in Malignancies ? • DOACs Reversal • Conclusion •
Introduction • Risk factors for VTE • Underlying , such as obesity, increasing age, previous VTE, etc. • Transient , such as acute trauma, immobility, surgery, etc. • Virchow’s triad describes the three broad factors that contribute to thrombosis, which are: • Vascular wall injury • Hypercoagulable state • Circulatory stasis
Classification of Risk factors for Thrombosis ACQUIRED FACTORS Strong risk (odds ratio > Moderate risk (odds ratio 2- Weak risk (odds ratio < 2) 10) 9) • Bed rest > three days • Immobility due to sitting • Surgery, especially orthopedic • Malignancy • Increasing age • Spinal cord injury • Presence of a central venous • Obesity • Hip or knee replacement catheter • Pregnancy/postpartum • Varicose veins • Major trauma • Oral contraceptives • Hormone replacement therapy • Hyperhomocysteinemia • Antiphospholipid antibody syndrome • Medical conditions • Stroke • Congestive heart failure • Inflammatory bowel disease
Classification of Risk factors for Thrombosis Classification of risk factors for Thrombosis Hereditary Haemostatic disorders 1. Factor V Leiden 2. Prothrombin G20210A variant 3. Protein C deficiency 4. Antithrombin deficiency 5. Protein S deficiency 6. Dysfibrinogenaemia Mixed hereditary / acquired disorders 1. Raised plasma levels of factor VIII 2. Raised plasma levels of fibrinogen 3. Raised plasma levels of homocysteine
Who To Test
Why to Test
Today Introduction • Causes of VTE • Treatment Options • DVT & PE Treatment Guidelines ACCP 2016 • Can DOAC’s be Use in APLS ? • Can DOAC’s be Use in Malignancies ? • DOACs Reversal • Conclusion •
Mode of Action
Conventional approach
Dual Drug Approach
Single Drug Approach • 15mg BID for the first 3 weeks Rivaroxaban then 20mg OD • 10mg BID for 1 week followed Apixaban by 5mg BID
Reasons Contributing for long term treatment
Reasons Contributing for long term Treatment
DOACs
DOACs
Betrixaban
Today Introduction • Causes of VTE • Treatment Options • DVT & PE Treatment Guidelines ACCP 2016 • Can DOAC’s be Use in APLS ? • Can DOAC’s be Use in Malignancies ? • DOACs Reversal • Conclusion •
Anticoagulation Guidelines 2016 For VTE without an associated cancer diagnosis, all direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, or edoxaban) are recommended over vitamin K antagonist (VKA) therapy (all Grade 2B) and VKA therapy is recommended over low molecular weight heparin (LMWH; Grade 2C). For VTE associated with cancer, LMWH is recommended over VKA (Grade 2B) or any direct oral anticoagulants (all Grade 2C). Anticoagulants should stop after 3 months of therapy in patients with an acute, proximal deep venous thrombosis (DVT) provoked by surgery rather than shorter or longer treatment courses (Grade 1B). Anticoagulants should also be stopped after 3 months in patients with a proximal DVT or pulmonary embolism (PE) provoked by a nonsurgical transient risk factor over shorter or longer courses (Grade 1B for high bleeding risk patients, Grade 2B for low or moderate bleeding risk patients).
Anticoagulation Guidelines 2016 Anticoagulation should be given for 3 months in patients with a first unprovoked VTE and a high risk of bleeding (Grade 1B), but should be extended without a scheduled stop date in patients with a low or moderate risk of bleeding (Grade 2B). For patients with acute VTE who are treated with anticoagulation, the guideline recommends against the use of an inferior vena cava filter (Grade 1B). For patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy, the guideline suggests the use of aspirin over no aspirin to prevent recurrent VTE if there are no contraindications to aspirin therapy (Grade 2B). For patients with acute DVT, the guideline recommends against the use of compression stockings routinely to prevent the post-thrombotic syndrome (Grade 2B).
Anticoagulation Guidelines 2016 For patient with subsegmental PE and no DVT, the guideline suggests clinical surveillance over anticoagulation when the risk of VTE recurrence is low (Grade 2C). The guideline recommends the use of anticoagulation over surveillance when the risk of VTE recurrence is high (Grade 2C). Thrombolysis should almost always be reserved for hypotensive patients, and should be given systemically, rather than catheter-directed. For isolated distal DVT of the leg, the choice between anticoagulation and serial ultrasound at 2 weeks should be made based on risk for thrombus extension, risk for bleeding, and patient preference. Home treatment is recommended for patients with low-risk PE. Patients should be switched to LMWH if they have recurrent VTE on another therapy; patients with recurrent VTE on LMWH should have their dose increased.
Today Introduction • Causes of VTE • Treatment Options • DVT & PE Treatment Guidelines ACCP 2016 • Can DOAC’s be Use in APLS ? • Can DOAC’s be Use in Malignancies ? • DOACs Reversal • Conclusion •
Can DOAC’s be Use in APLS ? Antiphospholipid Antibody Syndrome (APS) is defined by two major components: • Presence in the serum of at least one type of autoantibody (aPL) 3 month apart. • Lupus anticoagulants (LA) • Anticardiolipin antibodies • Antibodies to beta2-glycoprotein • The occurrence of at least one of the following clinical features: • Venous or arterial thromboses • Pregnancy morbidity.
GENERAL APPROACH TO THERAPY Heparin The mainstay of Direct oral anticoagulants treatment (DOACs) only Warfarin in special for APS situations include: Aspirin
GENERAL APPROACH TO THERAPY The approach to treating antiphospholipid syndrome (APS) varies with the clinical presentation. Recurrance rate with or without warfarin is up to 11% per year. The frequency of recurrent clinical events and the potentially devastating nature of these events are strong arguments for lifelong anticoagulation in most patients.
VTE in APLS • The initial treatment of VTE in patients with APS is the same as that for idiopathic thromboembolic disease. • The standard of care for both of these clinical complications is treatment with heparin, followed by warfarin. • The current standard of care for the long-term management of the APS is to maintain the INR between 2.0 and 3.0 for an initial venous thromboembolic event
Arterial Thrombosis • There is disagreement among experts regarding the optimal therapy of APS with arterial thrombosis • The combination of warfarin, with a target INR of 2.0 to 3.0, and low-dose aspirin (81 mg/day). • Other experts treat to a target INR of greater than 3.0
Duration of VKA Use • Indefinite antithrombotic therapy in patients with definite APS and thrombosis is recommended. • Treating for a more defined period in patients with a provoked first VTE, and a non- diagnostic or low-risk aPL profile
Treatment Failure If thrombotic events recur during warfarin therapy despite INR levels that are • within the target range of 2.0 to 3.0 the treatment alternatives include: Increasing the target INR (3.1 to 4.0) • Adding low-dose aspirin • Low molecular weight heparin (LMWH) • HCQ • The choice between these options is based in part upon patient • characteristics: Reliability to maintain a higher INR • Bleeding risk •
Can We Use DOAC’s in APLS ? • There has been interest in the use of DOACs for APS due to: • Convenience • Lack of need for laboratory monitoring • Decreased risk of bleeding • The available evidence suggests: • They are less effective than VKA for thrombosis prevention.
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