Anticoagulation

The anticoagulation treatment plan for DVT is categorized into three distinct phases:

Initial phase lasting up to 10 days, focused on swiftly initiating anticoagulation to prevent DVT and PE expansion;
Primary treatment phase for the first three months, aiming to sustain therapeutic anticoagulation levels, reduce early recurrent VTE risk, and halt DVT and PE progression; and
Extended treatment phase with no predetermined endpoint, intended to decrease the long-term likelihood of recurrent VTE.

Post primary treatment Prolonged anticoagulation may be necessary for specific high-risk patient groups.

Various Anticoagulants:

Anticoagulant	Target	Dose (Kindly also refer to ESVS 2021 guidelines mentioned below)	Dose adjustment	Management for bleeding
Indirect Anticoagulants
Unfractionated Heparin (UFH)	Factor Xa : IIa inhibition ratio (1:1)	Infusion - Non Body weight adjusted = 5000 IU (Bolus) then 1250-1280 IU/ hour (maintenance dose) - Body weight adjusted = 80 IU/kg (Bolus) then 18 IU/ kg/hour (maintenance dose) Subcutaneous - Fixed dose = 5000 IU (Bolus) then 17500 IU every 12 hour (maintenance dose); APTT adjusted - Adjusted dose = 333 IU/kg (Bolus) then 250 IU/ kg every 12 hour (maintenance dose)	See APTT related dose adjustment below	Protamine sulphate 1000 IU (10 mg) of protamine sulphate neutralize 1000 units of heparin by neutralizing Anti IIa activity
Low molecular weight heparin (LMWH)	Factor Xa : IIa inhibition ratio (2:1 and 4:1, depending on molecular weight of LMWH)	Subcutaneous 0.6 - 1.0 IU /ml B.D 1.0 - 2.0 IU/ml O.D		Protamine sulphate - partially neutralize 30 - 40% of LMWH (because of Anti Xa: Anti IIa ratio) - 0.5 - 1.0 mg for 1 mg of LMWH depending whether dose was given > 8 hour or < 8 hour respectively. - 100 IU (1 mg) of protamine sulphate neutralize 0.01 ml or 1 mg of LMWH by neutralizing Anti IIa activity
Fondaparinux	Factor Xa	Standard treatment dose 7.5 mg O.D	1. Weight < 50 kg, dose 5 mg O.D 2. Weight > 100 kg, dose 10 mg O.D 3. CrCl < 30 ml/minute - contraindicated
Vitamin K antagonists
Vitamin K antagonist (VKA)	Vit. K dependent clotting Factor (II, VII, IX, X)	Initial parenteral anticoagulation for at least 5 days using heparins or fondaparinux	INR adjusted OD dose. Target INR = 2.0 - 3.0	1. Vitamin K injection - major bleeding - 5 mg IV, non-major bleed 1-3 mg IV 2. Three factor PCC (prothrombin complex concentrate) - II, IX and X or Four Factor PCC - II, IX, X and VII (25-50 IU/kg) 3. Fresh frozen plasma is inferior to PCC as it produces suboptimal reversal 4. Patient with INR > 5.0 and no bleed = withhold 1-2 dose and reduce maintenance dose 5. Patient with INR > 8.0 and no bleed = oral Vitamin K 1-5 mg
Direct Oral Anticoagulants (DOAC)
Dabigatran	Thrombin (IIa)	Dose = 150 mg B.D (initial parenteral anticoagulation for at least 5 days)	1. Patients ≥ 80 years or concomitant verapamil reduced dose of - 110 mg B.D 2. Patient age 75-80 years, increased risk of bleeding, CrCl 30 - 50 ml/minute - either dosing regimen (150 mg BD or 110 mg BD) depending on thromboembolic risk. 3. CrCl < 30 ml/minute - contraindicated	Idarucizumab - humanized monoclonal antibody fragment IV dose = 2 x 2.5 g / 50 ml (for emergency / urgent interventions / uncontrolled bleeding)
Apixaban	Factor Xa	10 mg B.D x first 7 days (initial parenteral anticoagulation for at least 5 days) 5 mg B.D thereafter 2.5 mg B.D after 6 months (extended therapy)	CrCl (Creatine clearance) < 15-29 ml/minute - cautious use CrCl < 15 ml/minute - not recommended	Andexanet Alpha - modified rFXa peptide with no intrinsic pro-coagulatory activity - Rivaroxaban or apixaban (consumption > 7 hours prior, patient using low dose regimen) 400 mg IV bolus (30 mg/minute) followed by 2 hour IV infusion (dose 480 mg @ 4 mg/minute) - Rivaroxaban, LMWH or edoxaban (consumption < 7 hours prior or unknown time) 800 mg IV bolus (30 mg/minute) followed by 2 hour IV infusion (dose 960 mg @ 8 mg/minute) PCC is recommended where if Andexanet alpha is not available
Edoxaban	Factor Xa	60 mg O.D (Initial parenteral anticoagulation for at least 5 days)	CrCl < 30-50 ml/minute - dose reduced to 30 mg O.D
Rivaroxaban	Factor Xa	- 15 mg B.D x first 3 weeks - 20 mg O.D thereafter - 10 mg O.D after 6 months (extended therapy) Consume with food for better bioavailability.	CrCl < 15-49 ml/minute - dose adjustment according to risk of bleeding or thromboembolism (no fixed dose adjustment, dose of either 20 or 25 mg O.D can be used)


  
    APTT
    Ratio APTT/normal value
    Dose adjustment
  
  
    < 35 sec
    < 1.2
    80 IU/kg bolus then increase 4 IU/kg/h
  
  
    35 to 45 sec
    1.2 to 1.5
    40 IU/kg bolus then increase 2 IU/kg/h
  
  
    46 to 70 sec
    1.5 to 2.5 (should be reached within 24 hours of initiating the therapy, lower APTT is associated with high incidence of recurrent DVT)
    No change
  
  
    71 to 90 sec
    2.5 to 3.0
    Decrease 2 IU/kg/h
  
  
    > 90 sec
    > 3.0
    Infusion withhold for 2 hours then decrease 3 IU/kg/hour

APTT	Ratio APTT/normal value	Dose adjustment
< 35 sec	< 1.2	80 IU/kg bolus then increase 4 IU/kg/h
35 to 45 sec	1.2 to 1.5	40 IU/kg bolus then increase 2 IU/kg/h
46 to 70 sec	1.5 to 2.5 (should be reached within 24 hours of initiating the therapy, lower APTT is associated with high incidence of recurrent DVT)	No change
71 to 90 sec	2.5 to 3.0	Decrease 2 IU/kg/h
> 90 sec	> 3.0	Infusion withhold for 2 hours then decrease 3 IU/kg/hour

Case based anticoagulation use:

Anticoagulation	Factor	Keypoint
Unfractionated Heparin (UFH)	1. Thrombolytic therapy 2. Special clinical situation - Severe renal insufficiency - Hemodialysis - Pending Intervention - Critically ill patients	More literature and greater experience
Low molecular weight heparin (LMWH)	1. Cancer 2. Pregnancy 3. Liver disease and coagulopathy	1. Extensive VTE, metastatic cancer, very symptomatic, vomiting on cancer chemotherapy 2. Potential to cross placenta by other agents 3. DOAC are contraindicated if INR is raised (due to liver disease), VKA is also difficult to control.
Vitamin K anticoagulant (VKA)	1. Renal disease and creatinine clearance < 30 mL/min 2. Poor compliance	1. DOAC and LMWH are not recommended in severe renal impairment 2. INR monitoring is required.
Rivaroxaban, apixaban	Parenteral therapy to be avoided	VKA, dabigatran and edoxaban require initial parenteral therapy
Rivaroxaban, edoxaban, VKA	Once daily oral therapy prefered
Rivaroxaban, edoxaban, apixaban and VKA	Coronary artery disease	1. Coronary events appear to occur more often with dabigatran than with VKA
Apixaban and VKA	Dyspepsia or history of GI bleed	Rivaroxaban, edoxaban and dabigatran are associated with GI bleeding
VKA, UFH	Reversal agent needed

Contraindications to anticoagulation therapy:


Risk Factors for bleeding (patients on anticoagulant therapy - Low risk, moderate risk and high risk categories)	1. Age > 65 years 2. Previous history of bleeding 3. Cancer 4. Metastatic cancer 5. Renal failure 6 Liver failure 7. Thrombocytopenia 8. Previous stroke 9. Diabetes 10. Anaemia 11. Antiplatelet therapy 12. Poor anticoagulant control 13. Comorbidity and reduced functional capacity 14. Recent surgery 15. Frequent falls 16. Alcohol abuse 17. Nonsteroidal anti-inflammatory drug
Major Contraindications	1. Structural intracranial disease 2. Previous intracranial hemorrhage 3. Ischemic stroke within 3 months 4. Active bleeding 5. Recent brain or spinal surgery 6. Recent head trauma with fracture or brain injury 7. Bleeding diathesis
Relative contraindications	1. Systolic BP >180 2. Diastolic BP >110 3. Recent bleeding (non-intracranial) 4. Recent surgery or invasive procedure 5. Anticoagulated (eg, VKA therapy) 6. Traumatic cardiopulmonary resuscitation 7. Pericarditis or pericardial fluid 8. Diabetic retinopathy 9. Pregnancy 10. Age >75 y 11. Low body weight (eg, <60 kg)

ESVS 2021 clinical practice recommendations:

Here are the key points from ESVS 2021 clinical practice recommendations:

Diagnosis and Pre-Test Probability:

Consider pre-test probability when DVT is suspected.
Use validated diagnostic pathways.
First-line imaging modality is ultrasound (USG).
Suspected calf DVT should undergo whole leg ultrasound.
Inconclusive assessments may require CT venography, MR venography, or venography.

Anticoagulation Management:

Anticoagulant therapy should be tailored based on the risk factors and type of DVT.
Use DOACs over VKA for principal treatment, especially in provoked proximal DVT.
Extended anticoagulation should be considered based on bleeding risk assessment.
Cancer-associated DVT is initially managed with LMWH.
Unprovoked DVT management may involve extended anticoagulation with DOACs.
Dose adjustments for anticoagulants are needed in under/overweight and CKD patients.

Specific DVT Scenarios:

Superficial vein thrombosis (SVT) ≥ 3cm from deep system: Fondaparinux or intermediate dose of LMWH.
Symptomatic calf DVT: Consider DOACs over LMWH and VKA.
Iliofemoral DVT: Early thrombus removal could be considered.
Triple positive antiphospholipid syndrome: VKA with target INR 2-3.
Lower limb SVT: Consider ablation after acute phase.
Catheter-related thrombosis: Consider catheter removal, anticoagulation.
Young adults with severe upper limb DVT: Thrombolysis within two weeks.

Pregnancy and DVT:

Pregnant women: Therapeutic dose of LMWH.
Near due date with DVT: Temporary IVC filter may be considered.

Additional Considerations:

Residual vein obstruction and D-dimer for extended anticoagulation.
Aspirin not recommended for extended antithrombotic therapy in unprovoked DVT.
Routine IVC filter use, early thrombus removal not recommended.
Thrombophilia testing not routine for provoked DVT.
Isolated lower limb SVT < 5cm without high-risk features may not need anticoagulation.
Superficial venous interventions not routinely recommended.
Routine examination for occult PE not needed in asymptomatic DVT patients.

Duration of Treatment:

Extended anticoagulation may be considered for unprovoked DVT, especially beyond 3 months.
Unprovoked DVT with low risk of recurrence: Reduced-dose DOACs for extended periods.
Cancer-associated DVT: Transition to DOACs after 3-6 months of LMWH.
CKD patients treated with anticoagulants need regular renal function assessment.

Remember that individual cases may vary, and these points should be considered within the context of clinical judgment and guidelines.

Class	Level
I	A	1. Patient with unprovoked DVT, clinical examination and sex specific cancer screening should be performed rather than performing routine extensive screening for occult malignancy. 2. Most patients with DVT management as outpatient is recommended. 3. Provoked proximal DVT with major transient risk factor - 3 month anticoagulant therapy is preferred over short treatment. 4. Provoked proximal DVT, DOAC are preferred over VKA for principal treatment phase 5. Unprovoked proximal DVT, DOAC is preferred over LMWH followed by VKA for principal treatment phase. 6. Unprovoked proximal DVT with low or moderate bleeding risk factor, anticoagulant therapy beyond 3 month can be provided reevaluation of bleeding risk. 7. Early compression at 30-40 mm Hg with compression stockings or multilayer bandage is recommended to reduce pain, oedema and residual obstruction in patients with proximal deep thrombosis. 8. Proximal DVT with limited symptoms and signs as described in Villalta score, below knee stocking is recommended for 6 to 12 months. 9. Symptomatic calf DVT requiring anticoagulant treatment, 3 month therapy is recommended over shorter duration. 10. Cancer associated DVT, LMWH is recommended for initial and principal phase anticoagulation.
	B	1. 2nd or subsequent unprovoked DVT, extended anticoagulation beyond 3 months is recommended. 2. Symptomatic calf DVT not receiving any anticoagulation, clinical reassessment and repeat whole limb USG after 1 week is recommended. 3. Suspected superficial vein thrombosis of lower limb, whole leg USG is recommended to determine thrombus extend and exclude asymptomatic DVT. 4. Lower limb superficial vein thrombosis ≥ 3cm from deep venous system and ≥ 5 cm in length, fondaparinux 2.5 mg once daily is recommended. 5. Lower limb superficial vein thrombosis ≥ 3cm from deep venous system and ≥ 5 cm in length, 45 days of anticoagulation is recommended. 6. Pregnant woman with DVT, therapeutic dose of LMWH is recommended during pregnancy for at least 3 months or 6 weeks post partum.
	C	1. When DVT is suspected, pre-test probability is recommended. 2. Use a validated diagnostic pathway. 3. USG is recommended as first imaging modality. 4. Suspected calf DVT, whole leg ultrasound is recommended. 5. Unprovoked DVT anticoagulant therapy beyond 3 months can be considered after assessment of bleeding risk. 6. Proximal DVT with contraindication to anticoagulant therapy during initial or principal phase, temporary IVC filter insertion is recommended. 7. DVT treated with early thrombus removal with or without stenting, duration of anticoagulation should be at least as long as if the patient was treated by anticoagulation alone. 8. Calf DVT requiring anticoagulation, DOAC is recommended over LMWH followed by VKA. 9. Lower limb superficial vein thrombosis ≤ 3cm from deep venous system therapeutic anticoagulation is recommended. 10. Upper limb deep vein thrombosis USG as initial imaging is recommended. 11. Upper limb deep vein thrombosis anticoagulation for 3months is recommended. 12. Active cancer associated DVT, switching from LMWH to DOAC is recommended after 3-6 months of extended anticoagulation treatment. 13. Patient with DVT and high risk for thrombophilia full dose extended anticoagulation therapy is recommended with periodic evaluation. 14. DVT with CKD treated with LMWH, fondaparinux and DOAC need periodic assessment of renal functions. 15. Dose adjustment for UFH, LMWH and fondaparinux is recommended in under and over weight DVT patients undergoing anticoagulation therapy.
IIa	A	1. Provoked proximal DVT with major transient risk factor - 3 month anticoagulant therapy is preferred over 6 month or longer treatment. 2. Proximal DVT use of below knee compression stocking is considered to reduce the risk of post-thrombotic syndrome. 3. Selected patients with symptomatic iliofemoral DVT, early thrombus removal strategy should be considered. 4. Cancer associated DVT not located in GI or GU system, approved DOAC for initial, principal and extended phase can be considered.
	B	1. Unprovoked proximal DVT with anticoagulant therapy beyond 3 months DOAC should be preferred over VKA. 2. Unprovoked proximal DVT with extended anticoagulant therapy beyond 6 months and not a high risk of recurrence for VTE, reduced dose DOAC is preferred apixaban (2.5 mg twice daily) or rivaroxaban (10 mg once daily). 3. Lower limb superficial vein thrombosis ≥ 3cm from deep venous system and ≥ 5 cm in length, intermediate dose of LMWH can be considered as alternative to fondaparinux. 4. DVT with antiphospholipid syndrome who are triple positive with history of arterial and small vessel thrombosis, VKA should be used with target INR between 2-3.
	C	1. Patients with likely pre-test probability and negative compression USG, repeat USG after 5-7 days. 2. Patients with Proximal deep vein thrombosis CT venography, MR venography or Venography should be considered over USG due to inconclusive assessment. 3. Patient with unprovoked DVT and first degree relative with history of VTE, consider testing for hereditary thrombophilia. 4. Patients with unprovoked DVT, testing for antiphospholipid antibodies should be considered prior to termination of anticoagulation management. 5. Provoked proximal DVT with persistent risk factor other than malignancy anticoagulation beyond 3 month should be considered with regular evaluation for thrombotic/bleeding risk. 6. Iliofemoral DVT undergoing early thrombus removal, therapy of choice should be based on judgement of treating physician. 7. Calf DVT, anticoagulation should be based on symptoms, risk factor for progression and bleeding risk. 8. Symptomatic calf DVT and active cancer, anticoagulation beyond 3 months should be considered. 9. Lower limb superficial vein thrombosis, ablation of incompetent superficial vein should be considered once the acute inflammatory and prothrombotic phase ends (at least 3 months after most recent thrombotic event). 10. Catheter related thrombosis, catheter removal should be considered, when it is not needed, non-functional, anticoagulation is contraindicated, symptoms are not resolving after anticoagulation, limb or life threatening thrombosis. 11. Catheter related thrombosis, anticoagulation with LMWH or LMWH followed by VKA should be considered for a minimum of 3 months. 12. DVT with CKD, dose reduction and monitoring anticoagulant levels is recommended as most anticoagulants have renal excretion.
IIb	A
	B	1. Residual vein obstruction on USG and/or D dimer level can be considered prior to initiating extended anticoagulation in DVT patients. 2. Pregnant women with DVT < 2 weeks before due date of delivery, a temporary IVC filter may be considered.
	C	1. Provoked proximal DVT with minor transient risk factor - anticoagulant therapy beyond 3 month after evaluation for thrombotic and bleeding risk. 2. Patient with DVT, repeat whole limb USG at end of anticoagulation therapy to establish new baseline anatomic status. 3. Lower limb superficial vein thrombosis with high risk clinical and/or anatomical feature, 3 months of anticoagulation should be considered. 4. Young adults with upper limb deep vein thrombosis with severe symptoms thrombolysis should be considered within first two weeks. 5. Upper limb deep vein thrombosis by early thrombus removal, first rib resection may be considered if there is clear evidence of venous thoracic outlet syndrome.
III	A	1. Unprovoked DVT aspirin is not recommended for extended antithrombotic therapy.
	B	1. Patient on anticoagulation therapy for DVT, routine use of IVC filter is not recommended. 2. DVT limited to femoral, popliteal or calf veins, early thrombus removal is not recommended. 3. Pregnant women with suspected DVT, use of D dimer and well score is not recommended. 4. DVT with antiphospholipid syndrome who are triple positive with history of arterial and small vessel thrombosis, DOAC should not be used.
	C	1. Patient with DVT without sign and symptoms for PE, routine examination to detect occult PE is not recommended. 2. For patients with provoked DVT thrombophilia testing is not recommended. 3. For patients with unprovoked DVT routine testing for hereditary thrombophilia is not recommended. 4. Isolated lower limb superficial venous thrombosis < 5 cm in length on USG and lacking high risk feature such as malignancy, thrombophilia or proximity to deep venous system do not require anticoagulation. 5. Lower limb superficial vein thrombosis acute superficial venous intervention is not recommended. 6. Patient with symptomatic primary upper limb deep vein thrombosis early thrombus removal is not recommended.

Researches and Publications:

Studies/ Trails		Author's Conclusion
DOAC
The Einstein-DVT and Einstein-PE studies	Rivaroxaban vs Enoxaparin followed by a vitamin K antagonist	Both studies found that rivaroxaban was non-inferior to standard therapy (enoxaparin followed by a vitamin K antagonist) in terms of efficacy and safety, and had a lower risk of bleeding.
The EINSTEIN CHOICE and EINSTEIN -Extension study	Once-daily rivaroxaban (at doses of 20 mg or 10 mg) vs 100 mg of aspirin	Both studies found that rivaroxaban was more effective than aspirin in preventing recurrent VTE, with a similar safety profile.
The EINSTEIN-Jr study	Rivaroxaban versus standard anticoagulants	The study found that bodyweight-adjusted rivaroxaban was effective and safe for the treatment of venous thromboembolism in children.
AMPLIFY study	Aapixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) vs conventional therapy (subcutaneous enoxaparin, followed by warfarin)	A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding.
AMPLIFY-EXT study	Apixaban (2.5 mg and 5 mg, twice daily) vs placebo for patients who have complete anticoagulation therapy for 6-12 months for VTE	Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding.
The RE-COVER and RE-COVER II studies	Dabigatran versus warfarin for acute VTE	For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring.
RE-MEDY study	Dabigatran at a dose of 150 mg twice daily with warfarin (active-control study) or with placebo (placebo-control study) in patients with venous thromboembolism who had completed at least 3 initial months of therapy	Dabigatran was effective in the extended treatment of venous thromboembolism and carried a lower risk of major or clinically relevant bleeding than warfarin but a higher risk than placebo.
The MAGELLAN study	Rivaroxaban (extended period), vs subcutaneous enoxaparin administered for a standard period, followed by placebo.	In acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding.
Catheter directed thrombolysis
ATTRACT trial	Acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting)	Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding.
CaVenT trial	Catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life.	Additional catheter-directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter-directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life.
TORPEDO study	PEVI + anticoagulation vs anticoagulation alone	In patients with proximal DVT, PEVI is superior to anticoagulation alone in the reduction of VTE and PTS. This benefit, which appears early in the course of treatment, extends to >2.5 years.
DVT and PE in cancer patients
Hokusai-VTE Cancer Study	Edoxaban vs LMWH	Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin.
CATCH study	Long-term tinzaparin versus warfarin for treatment of acute venous thromboembolism in cancer patients	Use of long-term LMWH as the preferred treatment for cancer-associated VTE due to a lower risk of clinically relevant major bleeding and a significant reduction in recurrent DVT
CLOT study	Efficacy of a LMWH vs DOAC in preventing recurrent thrombosis in patients with cance	In patients with cancer and acute venous thromboembolism, dalteparin (LMWH) was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding
Main LITE study	Long-term therapeutic tinzaparin subcutaneously once daily with usual-care long-term vitamin-K-antagonist therapy for 3 months.	Long-term low-molecular-weight heparin is more effective than vitamin-K-antagonist therapy for preventing recurrent venous thromboembolism in patients with cancer and proximal venous thrombosis
CANTHANOX study	Subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months	Warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer. Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients
Superficial vein thrombosis
The CALISTO study	Fondaparinux vs Placebo	Fondaparinux at a dose of 2.5 mg once a day for 45 days was effective in the treatment of patients with acute, symptomatic superficial-vein thrombosis of the legs and did not have serious side effects.
Other Studies
The GARFIELD-VTE registry	Treatment for VTE was anticoagulant (AC) therapy alone in 90.9% of patients; 5.1% received thrombolytic and/or surgical/mechanical therapy ± AC and 4.0% received no therapy.	This global registry highlight the heterogeneity in characteristics and management of VTE patients
The PEGeD study	Pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP	A combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up.
DACUS study	Patients with a first episode of deep vein thrombosis, treated with oral anticoagulant (OAT) for 3 months, were managed according to residual venous thrombosis (RVT) findings. Those with RVT were randomized to either stop or continue anticoagulants for 9 additional months, whereas in those without RVT, OAT was stopped.	Absence of RVT identifies a group of patients at very low risk for recurrent thrombosis who can safely stop OAT
Calf DVT
The CACTUS study	Efficacy and safety of anticoagulant treatment for patients with acute symptomatic deep vein thrombosis (DVT) of the calf	Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk outpatients with symptomatic calf DVT, but did increase the risk of bleeding. Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective.
DOTAVK study	Short oral anticoagulant course (3 months for proximal deep vein thrombosis [P-DVT] and/or pulmonary embolism [PE]; 6 weeks for isolated calf DVT [C-DVT]) v/s long course of therapy (6 months for P-DVT/PE; 12 weeks for C-DVT).	After isolated C-DVT, 6 weeks of oral anticoagulation is sufficient. For P-DVT or PE, we demonstrated an equivalence between 3 and 6 months of anticoagulant therapy. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient.
ACT trail	Dalteparin vs VKA for 3 months for calf DVT excluding cancer associated DVT	No difference at 3 months
IVC Filter studies
PREPIC trail	Patients with proximal deep-vein thrombosis who were at risk for pulmonary embolism to receive a vena caval filter (200 patients) or no filter (200 patients), and to receive low-molecular-weight heparin (enoxaparin, 195 patients) or unfractionated heparin (205 patients)	In high-risk patients with proximal deep-vein thrombosis, the initial beneficial effect of vena caval filters for the prevention of pulmonary embolism was counterbalanced by an excess of recurrent deep-vein thrombosis, without any difference in mortality. Our data also confirmed that low-molecular-weight heparin was as effective and safe as unfractionated heparin for the prevention of pulmonary embolism.
FILTER PEVI study	Evaluate the necessity of and recommend indications for inferior vena cava (IVC) filter implantation during percutaneous endovenous intervention (PEVI) for deep venous thrombosis (DVT).	IVC filter implantation during PEVI reduces the risk of iatrogenic PE by eightfold without a mortality benefit. A selective approach may be exercised in filter implantation during PEVI.

References